Itching inhibitor, histamine production inhibitor, and keratinization normalizing agent

Abstract

The present disclosure relates to an itching inhibitor containing selenium disulfide.

Description

Itching suppressant, histamine production inhibitor, and keratinization normalizer

[0001] The present invention relates to an anti-itch agent, an inhibitor of histamine production, and an agent for normalizing keratinization.

[0002] Itching is usually caused by the production of itch-causing substances (itch mediators such as histamine). Various studies have been conducted on ingredients that suppress itching. For example, Patent Document 1 discloses an itching suppressant containing diethylene glycol oligomer dimer dilinoleate as an active ingredient.

[0003] JP 2015-81234 A

[0004] An object of the present invention is to provide a novel anti-itch agent and a novel histamine production inhibitor.

[0005] The present inventors have found that selenium disulfide inhibits histamine production and itching, and the present invention is based on these novel findings.

[0006] The present invention provides, for example, the following inventions. [1] An itch suppressant comprising selenium disulfide. [2] The itch suppressant according to [1], comprising the selenium disulfide as an active ingredient. [3] The itch suppressant according to [1] or [2], wherein the selenium disulfide has an average particle size of 60 μm or less. [4] The itch suppressant according to any of [1] to [3], which is an external preparation. [5] The itch suppressant according to any of [1] to [4], which is an external preparation for the scalp. [6] The itch suppressant according to any of [1] to [5], which suppresses scalp itch while suppressing changes in the scalp bacterial flora. [7] A histamine production inhibitor comprising selenium disulfide as an active ingredient. [8] The histamine production inhibitor according to [1], comprising the selenium disulfide as an active ingredient. [9] The histamine production inhibitor according to [8], wherein the selenium disulfide has an average particle size of 60 μm or less.

[10] The histamine production inhibitor according to [8] or [9], which is based on the L-histidine decarboxylase inhibitory activity of Staphylococcus capitis.

[11] The histamine production inhibitor according to any of [8] to

[10] , which is an external preparation for the scalp.

[12] A keratinization normalizer comprising selenium disulfide.

[13] The keratinization normalizer according to

[12] , which comprises the selenium disulfide as an active ingredient.

[14] The keratinization normalizer according to

[12] or

[13] , wherein the selenium disulfide has an average particle size of 60 μm or less.

[15] The keratinization normalizer according to any of

[12] to

[14] , which is an external preparation.

[16] The keratinization normalizer according to any of

[12] to

[15] , which is an external preparation for the scalp.

[0007] According to the present invention, a novel anti-itch agent can be provided. According to the present invention, a novel histamine production inhibitor can be provided.

[0008] Graph showing the evaluation results of the histamine production inhibitory effect of selenium disulfide. Graph showing the evaluation results of the itching inhibitory effect of selenium disulfide. Graph showing the results of a questionnaire on the frequency of itching experienced by subjects at the start of an itching evaluation test. Graph showing the evaluation results of the durability of the itching inhibitory effect when using Selsun Anti-Dandruff Shampoo With Selenium Sulfide (Example 1), a product containing selenium disulfide. Graph showing the evaluation results of the durability of the itching inhibitory effect when using Product A (Example 2), which contains selenium disulfide. Graph showing the evaluation results of the durability of the itching inhibitory effect when using a placebo (Comparative Example 1) not containing selenium disulfide. ΔΔC in Test Example 3 Ｔ 1 is a graph showing the results of evaluation of relative gene expression levels by the method.

[0009] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The following describes in detail the embodiments of the present invention, but the present invention is not limited to the following embodiments.

[0010] [Itch suppressant] The itch suppressant according to this embodiment is selenium disulfide (SeS ２ "Itch" refers to an unpleasant sensation on the skin accompanied by scratching behavior. The itch suppressant may contain selenium disulfide as an active ingredient. The "active ingredient" in the itch suppressant refers to a component that exerts an itch suppressing effect.

[0011] The particle size of the selenium disulfide may be 200 μm or less, 100 μm or less, 70 μm or less, 60 μm or less, 50 μm or less, or 30 μm or less. The particle size of the selenium disulfide may be 1 μm or more, 5 μm or more, or 10 μm or more. The particle size of the selenium disulfide may be 1 μm to 200 μm, 1 μm to 100 μm, 1 μm to 70 μm, 1 μm to 60 μm, 1 μm to 50 μm, or 1 μm to 30 μm; 5 μm to 200 μm, 5 μm to 100 μm, 5 μm to 70 μm, 5 μm to 60 μm, 5 μm to 50 μm, or 5 μm to 30 μm; 10 μm to 200 μm, 10 μm to 100 μm, 10 μm to 70 μm, 10 μm to 60 μm, 10 μm to 50 μm, or 10 μm to 30 μm.

[0012] The average particle size of selenium disulfide can be measured using an optical microscope, a digital microscope, a laser diffraction / scattering particle size distribution analyzer, etc. A digital microscope is preferred.

[0013] The content of selenium disulfide can be appropriately set depending on the subject and area of ​​use, etc. For example, the content of selenium disulfide may be 0.10% by mass or more, 0.50% by mass or more, 0.80% by mass or more, or 0.95% by mass or more, and may be 5.00% by mass or less, 2.00% by mass or less, 1.50% by mass or less, or 1.10% by mass or less, based on the total mass of the itch suppressant. The content of selenium disulfide may be 0.10% by mass to 5.00% by mass, 0.10% by mass to 2.00% by mass, 0.10% by mass to 1.50% by mass, or 0.10% by mass to 1.10% by mass, based on the total mass of the itch suppressant, and may be 0.50% by mass to 5.00% by mass, 0.50% by mass to 2.00% by mass, 0.50% by mass to 1.50% by mass, or 0.50% by mass to 1.50% by mass. It may be 1.10% by mass, 0.80% to 5.00% by mass, 0.80% to 2.00% by mass, 0.80% to 1.50% by mass, or 0.80% to 1.10% by mass, 0.95% to 5.00% by mass, 0.95% to 2.00% by mass, 0.95% to 1.50% by mass, or 0.95% to 1.10% by mass.

[0014] The dosage form of the itch suppressant can be selected as desired depending on the intended use of the itch suppressant, and can be, for example, a liquid for external use, a liniment, a lotion, an ointment, a cream, a gel, a foam, etc. These dosage forms can be prepared according to known methods.

[0015] The itch suppressant may consist of selenium disulfide itself, or may contain, in addition to the above-mentioned selenium disulfide, other ingredients that are acceptable in the technical fields of pharmaceuticals, quasi-drugs, cosmetics, etc.

[0016] Other ingredients include, for example, antibacterial agents (e.g., zinc pyrithione, piroctone olamine, isopropylmethylphenol, dequalinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, alkyldiaminoethylglycine hydrochloride, cetylpyridinium chloride, sodium benzoate, ethanol, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, and biguanide compounds), keratin softeners / keratolytic agents (e.g., salicylic acid), hair conditioning agents or film-forming agents (e.g., polyquaternium-73, polyquaternium-10), and nium-10, etc.), emollients (phthalic acid distearylamide, etc.), anti-inflammatory agents (glycyrrhizic acid, glycyrrhetinic acid, tranexamic acid, ε-aminocaproic acid, allantoin, derivatives thereof, and salts thereof, etc.), vitamins (tocopherol acetate, panthenol, etc.), antipruritic agents (crotamiton, ichthammol, moctamol, thymolic acid and pharmacologically acceptable salts thereof, etc.), moisturizers, refreshing agents, emulsifiers, emulsion stabilizers (bentonite, etc.), pearlizing agents (titanium oxide, glycol distearate, etc.), bases or carriers, polyhydric alcohols (1,3-butylene glycol, propylene glycol, glycerin, etc.), anionic surfactants (sodium lauryl sulfate, triethanolamine lauryl sulfate, ammonium lauryl sulfate, and other alkyl sulfate ester salts;Polyoxyethylene alkyl sulfate ether salts such as ammonium laureth sulfate and sodium laureth sulfate; acylation products of coconut oil fatty acids with alkylated amino acids having 1 to 4 carbon atoms, such as coconut oil fatty acid acyl sarcosine (also called cocoyl sarcosine), coconut oil fatty acid acyl methyl alanine (also called cocoyl methyl alanine) and salts thereof; acylation products of coconut oil fatty acids with sulfur-containing amino acid derivatives, such as coconut oil fatty acid acyltaurine (also called cocoyl taurine), coconut oil fatty acid acyl isethionate (cocoyl isethionate) and salts thereof; acyl glutamic acid glutamates (C8 to C22 alkanoyl glutamates such as cocoyl glutamate), acyl glycines (C8 to C22 alkanoyl glycines such as cocoyl glycine), acylalanines (C8 to C22 alkanoyl alanine salts such as cocoyl alanine), acyl alkyl alanines (C8 to C22 alkanoyl alkyl alanine salts such as lauroyl methyl alanine), acylaspartates (C8 to C22 alkanoyl aspartates such as lauroyl aspartate), monoalkyl phosphates (C8 to C22 alkyl alkyl alanines), acyl aspartates (C8 to C22 alkanoyl aspartates such as lauroyl aspartate), monoalkyl phosphates (C8 to C22 alkyl alkyl alanines ... alkyl alan amino acid-based anionic surfactants such as acyl sarcosinate (C8 to C22 alkanoyl sarcosinate such as cocoyl sarcosinate); etc.), nonionic surfactants (coconut oil fatty acid diethanolamide (cocamide DEA), coconut oil fatty acid monoethanolamide (cocamide MEA), lauric acid monoethanolamide (lauramide MEA), lauric acid diethanolamide (lauramide DEA), lauric acid monoisopropanolamide (lauramide MIPA), palmitic acid monoethanolamide (paltamide MEA), palmitic acid diethanolamide (paltamide MIPA), palmitic acid monoethanolamide (paltamide MEA), palmitic acid diethanolamide (lauramide MIPA), palmitic acid monoethanolamide (paltamide MIPA), palmitic acid diethanolamide (lauramide MIPA), palmitic acid monoethanolamide (laur ... fatty acid alkanolamides such as acetic acid diethanolamide (palutamide DEA), coconut oil fatty acid methylethanolamide (cocamidomethyl MEA), etc.; (C12-15) polyethylene glycol alkyl ethers such as Palace-3, Steareth-100, Beheneth-30, etc.; amphoteric surfactants (cocamidopropyl betaine, lauramidopropyl hydroxysultaine, lauramidopropylamine oxide, hydroxyalkyl (C12-14) hydroxyethyl sarcosine, lauramidopropyl betaine, lauryl betaine, etc.);Cationic polymers (polyquaternium-73, polyquaternium-10, polyquaternium-7, polyquaternium-22, polyquaternium-47, polyquaternium-53, cationized guar gum [guar hydroxypropyltrimonium chloride], etc.), thickeners (cellulose-based thickeners such as hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydrophobized hydroxypropyl methylcellulose, carboxymethyl cellulose, etc.; vinyl-based thickeners such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, etc.; guar gum, locust bean gum, carrageenan, xanthan gum, acrylates / alkyl methacrylate copolymer, bentonite, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer, etc.), dispersants (non-surfactants, etc.), antiseptics / preservatives (benzoic acid-based preservatives such as sodium benzoate, benzoic acid, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, and methyl parahydroxybenzoate (methylparaben); phenoxyethanol, propyl iodide butylcarbamate, etc.), silicone agents (dimethylpolysiloxane (dimethicone), amino-modified silicone, polyether-modified silicone, Examples of the other ingredients include aminopolyether-modified silicone, methylphenylpolysiloxane, fatty acid-modified silicone, alkoxy-modified silicone, and alkyl-modified silicone), antioxidants, chelating agents (EDTA disodium salt, EDTA calcium disodium salt, and the like), salts (sodium chloride, and the like), colorants (Orange 205, and the like), pH adjusters (organic acids such as citric acid, sodium citrate, lactic acid, sodium lactate, succinic acid, and sodium succinate, and the like), fragrances, solubilizers, water, and the like. Other ingredients may be used singly or in combination of two or more.

[0017] The itch suppressant can be suitably used for hairy animals, which are animals having hair on the body surface. Target animals for the itch suppressant include, for example, humans, monkeys, dogs, cats, etc. The target animals for the itch suppressant are preferably humans or companion animals such as dogs or cats, and more preferably humans or dogs.

[0018] The itch suppressant can suppress itch by directly applying it to a necessary area on the body surface. Therefore, the itch suppressant can be suitably used as an external preparation (external preparation composition). The itch suppressant as an external preparation can also be referred to as an external preparation composition for itch suppression containing selenium disulfide.

[0019] The topical preparation may be an topical preparation applied to a hair growth site on the body surface, and is preferably an topical preparation for the scalp that is applied to the scalp.

[0020] Examples of uses of the itch suppressant include cleansing cosmetics (for example, shampoos, body shampoos, rinses, and treatments) and animal cleansers.

[0021] The antipruritic agent may be packaged in a container. Examples of the container shape include bottles, tubes, jars, droppers, dispensers, pumps, pouches, cheer packs, and sachets. Examples of container materials include polyethylene terephthalate, polypropylene, polyethylene (such as HDPE, LDPE, and LLDPE), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, and metal (such as aluminum). Taking into consideration the strength, flexibility, weather resistance, and stability of the components contained in the container, containers containing these materials may be subjected to various coating treatments, or these materials may be combined, for example, by mixing, to form container materials, or layers made of these materials may be laminated to form container materials. Furthermore, those skilled in the art can appropriately select the diameter and material of the nozzle and formulation discharge port of the container in order to adjust the amount of formulation discharged from the container or reduce adhesion of the formulation to the container.

[0022] The method of use of the itch suppressant can be selected appropriately depending on the skin condition, age, sex, etc. of the subject. The itch suppressant may be used periodically, or may be used when itching occurs. When used periodically, the frequency of use of the itch suppressant may be, for example, once or more times a day, or once or more times every few days (e.g., 2 to 7 days). The amount of the itch suppressant used can be appropriately determined depending on the application site and the condition of the application site, etc. The itch suppressant may be used continuously for a predetermined period. The period for continuous use of the itch suppressant may be 1 to 7 times a week, 1 to 5 times a week, 1 to 3 times a week, 2 to 3 times a week, or twice a week or more.

[0023] When used in humans, the itch suppressant can be used, for example, on healthy individuals who have developed itch or on patients who have developed itch.

[0024] The itch suppressant according to this embodiment contains selenium disulfide, and thus can suppress itch while suppressing the extinction of resident bacteria present on the body surface of an animal. Therefore, the itch suppressant according to this embodiment exerts an itch suppression effect without causing further skin troubles caused by an imbalance in the bacterial flora on the body surface. The itch suppressant according to this embodiment can be suitably used to suppress scalp itch while suppressing changes in the bacterial flora on the scalp.

[0025] The itch suppressant according to this embodiment contains selenium disulfide, and therefore the itch suppressant effect can be maintained for a predetermined period of time even after use has ceased.

[0026] [Histamine Production Inhibitor] The itch suppressant may be based on a histamine production inhibitory effect, particularly a histamine production inhibitory effect due to L-histidine decarboxylase (HDC) inhibition. As one embodiment of the present invention, there is provided a histamine production inhibitor containing selenium disulfide. The histamine production inhibitor may contain selenium disulfide as an active ingredient. The "active ingredient" in the histamine production inhibitor means a component that exerts a histamine production inhibitory effect.

[0027] The specific embodiments of the histamine production inhibitor, such as the average particle size and content of selenium disulfide, can be the same as those described above as the specific embodiments of the itching inhibitor.

[0028] The histamine production inhibitor may be a histamine production inhibitor that inhibits HDC. The histamine production inhibitor may be based on the histamine production inhibitory effect of Staphylococcus bacteria, which are normal bacteria present on the body surface of animals, by inhibiting HDC.

[0029] Examples of Staphylococcus bacteria include Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus aureus, Staphylococcus hominis, Staphylococcus caprae, Staphylococcus saccharolyticus, Staphylococcus warneri, Staphylococcus pasteuri, Staphylococcus spp. ... Staphylococcus haemolyticus (S. haemolyticus), Staphylococcus lugdunensis (S. lugdunensis), Staphylococcus auricularis (S. auricularis), Staphylococcus saprophyticus (S. saprophyticus), Staphylococcus cohnii (S. cohnii), Staphylococcus xylosus (S. xylosus), and Staphylococcus simulans (S. simulans) are included.

[0030] The histamine production inhibitor according to this embodiment has the effect of inhibiting histamine production by inhibiting the HDC of Staphylococcus capitis, a normal flora of the scalp, and therefore can be suitably used as an external preparation for the scalp.

[0031] The histamine production inhibitor according to this embodiment contains selenium disulfide, and therefore can suppress histamine production while inhibiting the extinction of resident bacteria present on the body surface of an animal. Therefore, the histamine production inhibitor according to this embodiment exhibits a histamine production inhibitory effect without causing further skin troubles caused by an imbalance in the bacterial flora on the body surface. The histamine production inhibitor according to this embodiment can be suitably used to suppress histamine production while inhibiting changes in the scalp bacterial flora.

[0032] The histamine production inhibitor according to this embodiment contains selenium disulfide, and therefore the histamine production inhibitory effect can be maintained for a predetermined period of time even after use has ceased.

[0033] In addition to suppressing itching, the histamine production inhibitor can also be used to suppress inflammation (for example, suppression of eczema and erythema (redness of the scalp)) and normalize skin keratinization.

[0034] [Keratinization Normalizer] One embodiment of the present invention provides a keratinization normalizer containing selenium disulfide. The keratinization normalizer may contain selenium disulfide as an active ingredient. The "active ingredient" in the keratinization normalizer refers to a component that exhibits a keratinization normalizing effect. As used herein, "keratinization" refers to the phenomenon in which keratinocytes that divide in the basal layer of the epidermis are pushed toward the outermost surface of the skin and become keratinocytes in the outermost stratum corneum. The keratinization normalizer is an agent that normalizes disrupted keratinization or maintains normal keratinization. The keratinization normalizer of this embodiment can improve skin barrier function by normalizing keratinization, and can prevent or suppress the penetration of external irritants by improving the skin barrier function associated with keratinization normalization. Keratinization normalization can be evaluated by checking the expression levels of genes (e.g., KRT1 and KRT10) that are keratinization biomarkers.

[0035] The specific aspects of the keratinization normalizing agent, such as the average particle size and content of selenium disulfide, can be the same as those described above as the specific aspects of the itching suppressant and histamine production suppressant.

[0036] The present invention can be considered as an invention relating to each of the following embodiments, since it contains selenium disulfide, which exhibits an itching suppression effect, a histamine suppression effect, and a keratinization normalization effect. The specific aspects of the invention relating to each of the following embodiments can be applied as described above.

[0037] One embodiment of the present invention provides a use of selenium disulfide for suppressing itch. One embodiment of the present invention provides selenium disulfide for use in suppressing itch. One embodiment of the present invention provides a method for suppressing itch, comprising the step of applying selenium disulfide to the skin.

[0038] One embodiment of the present invention provides a use of selenium disulfide for inhibiting histamine production. One embodiment of the present invention provides selenium disulfide for use in inhibiting histamine production. One embodiment of the present invention provides a method for inhibiting histamine production, comprising the step of applying selenium disulfide to the skin.

[0039] One embodiment of the present invention provides a use of selenium disulfide for normalizing keratinization.One embodiment of the present invention provides selenium disulfide for use in normalizing keratinization.One embodiment of the present invention provides a method for normalizing keratinization, comprising the step of applying selenium disulfide to skin.

[0040] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to the following examples.

[0041] Test Example 1: Histamine production test, viable cell count test Staphylococcus capitis (NBRC115304) was inoculated into a BHI liquid medium (manufactured by Becton Dickinson) and shaken at 37°C for 24 hours to prepare a pre-preculture solution. 100 μL of this solution was inoculated into a new BHI liquid medium and shaken at 37°C for 16 hours to prepare a preculture solution (OD660 ≒ 1.5). 10 μL of this solution was further inoculated into a new BHI liquid medium and shaken at 37°C for 16 hours to prepare a preculture solution (OD660 ≒ 1.5). ５ The mixture was diluted 2-fold to obtain a bacterial solution for inoculation.

[0042] Selenium disulfide was weighed into a 15 mL plastic tube (Corning Incorporated), and 5 mL of BHI liquid medium supplemented with L-histidine (Fujifilm Wako Pure Chemical Industries, Ltd.) to a concentration of 0.2% was dispensed. Sonication was performed for 2 minutes to disperse the selenium disulfide. 50 μL of the inoculum solution was then dispensed into aliquots, gently vortexed, plugged with dry-heat sterilized absorbent cotton, and placed under anaerobic conditions using an Anaeropack Kenki (Mitsubishi Gas Chemical Company, Inc.). After static incubation at 37°C for 3 days, bacterial counts were measured using SCD agar medium (Atect Co., Ltd.). After filter sterilization, histamine quantification was performed using Check Color Histamine (Kikkoman Biochemifa Corporation). Histamine quantification was also performed on BHI liquid medium supplemented with 0.2% histidine as a control. The results of the bacterial count and histamine determination are shown in Table 1 and FIG.

[0043]

[0044] As shown in Table 1 and FIG. 1, it was confirmed that the inclusion of selenium disulfide suppressed histamine production without significantly reducing the number of viable bacteria.

[0045] Test Example 2: Verification of Itch-Suppressing Effect The itch-suppressing effect of test products 1 to 3 shown below and the persistence of the itch-suppressing effect after discontinuation of use were evaluated by questionnaire. Test method: Subjects with an ASFS (Scalp Sepsis Score) score of 24 or higher were selected using the ASFS evaluation method. After obtaining informed consent from all subjects, 12 subjects were assigned to each test product and asked to wash their hair with the designated test product three times a week. Questionnaires were administered on days 0 and 28 of use. Furthermore, similar questionnaires were administered on day 35, one week after discontinuation of use, and on day 42, two weeks after discontinuation of use, to evaluate the persistence of the effect. A two-week washout period was provided before the start of the test. This test was conducted in compliance with the "ethical principles and GCP based on the Declaration of Helsinki."

[0046] The average particle size was measured at 400x magnification using a microscope VHX-7100 (manufactured by Keyence Corporation).

[0047] Test products: 1. Comparative Example 1 (placebo) 2. Example 1 (Selsun Anti-Dandruff Shampoo with Selenium Sulfide, selenium disulfide content: 1.0%, average particle size: 19 μm) 3. Example 2 (Product A, average particle size: 23 μm)

[0048] Tables 2 and 3 show the components contained in Comparative Example 1 and Examples 1 and 2. In Tables 2 and 3, "-" indicates that the component is not contained, and "◯" indicates that the component is contained.

[0049]

[0050] The itching suppression effect of test products 1 to 3 was evaluated on the 28th day using the following five-point scale (1 (1. Very satisfied) to 3 (3. Neutral) to 5 (5. Very dissatisfied)). The results are shown in Figure 2. Evaluation criteria for itching suppression effect: 1. Very satisfied 2. Satisfied 3. Neutral 4. Not satisfied 5. Very dissatisfied

[0051] As shown in FIG. 2, it was confirmed that itching was suppressed when selenium disulfide was included.

[0052] Figure 3 shows the frequency of itching (initial value) experienced by users of each test product at the start of the test (day 0). The frequency of itching was evaluated using the following four-point scale (1 (always feels itchy) to 4 (feels itchy due to a specific trigger)). Evaluation criteria for frequency of itching: 1. Always 2. Often 3. Sometimes 4. After specific trigger

[0053] 4 to 6 show the evaluation results of the durability of the itching suppression effect on days 28, 35, and 42 when Test Product 2 (Example 1), Test Product 3 (Example 2), and Test Product 1 (Comparative Example 1) were used, respectively. The durability of the itching suppression effect was evaluated using the following four-point scale (1 (no itching) to 4 (very severe itching)). Evaluation criteria for the durability of the itching suppression effect: 1. None 2. Mild 3. Moderate 4. Severe

[0054] As shown in Figures 4 to 6, it was confirmed that the itching suppression effect was sustained when selenium disulfide was included.

[0055] <Test Example 3: KRT1 and KRT10 keratinization biomarker expression test> Staphylococcus Capitis (NBRC115304) was inoculated into LB liquid medium (manufactured by Becton Dickinson) and shaken at 37°C for 24 hours to prepare a pre-preculture solution. 100 μL of this solution was inoculated into a new BHI liquid medium and shaken at 37°C for 16 hours to prepare a preculture solution (OD660 ≒ 1.2). 10 μL of this solution was further inoculated into a new BHI liquid medium and shaken at 37°C for 16 hours to prepare a preculture solution (OD660 ≒ 1.2). ５ The mixture was diluted 2-fold to obtain a bacterial solution for inoculation.

[0056] Selenium disulfide was weighed into a 15 mL plastic tube (Corning Incorporated), and 5 mL of LB liquid medium supplemented with L-histidine (Fujifilm Wako Pure Chemical Industries, Ltd.) to a concentration of 0.2% was dispensed. Sonication was performed for 2 minutes to disperse the selenium disulfide. 50 μL of the inoculum solution was then dispensed into aliquots, gently vortexed, plugged with dry-heat sterilized absorbent cotton, and placed under anaerobic conditions using an Anaeropack Kenki (Mitsubishi Gas Chemical Company, Inc.). After static incubation at 37°C for 3 days, bacterial counts were measured using SCD agar medium (Atect Co., Ltd.). After filter sterilization, histamine quantification was performed using Check Color Histamine (Kikkoman Biochemifa Corporation).

[0057] Histamine (reagent) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was added to LB liquid medium containing 0.2% histidine so that the histamine concentration was the same as that in the culture supernatant containing 0.0% selenium disulfide.

[0058]

[0059] 100 μL of filter-sterilized LB liquid medium supernatant was applied to a three-dimensional cultured epidermal model (MatTek) equilibrated overnight and cultured for 48 hours. To confirm that bacterial metabolites did not affect the keratinization of the three-dimensional cultured epidermal model, a solution of histamine (reagent) (Fujifilm Wako Pure Chemical Industries, Ltd.) dissolved in LB medium supplemented with 0.2% histidine was also applied as a control (n=4). 100 μL of water for injection (Otsuka Pharmaceutical Factory, Inc.) was also applied in the same manner. After 48 hours, the three-dimensional cultured epidermal model was washed with PBS, and the three-dimensional cultured epidermal cell tissue was collected.

[0060] Total RNA purification from three-dimensionally cultured epidermal cell tissue can be performed by a standard method. Specifically, purification was performed using a silica membrane with the RNeasy Mini Kit (Qiagen), following the protocol.

[0061] Synthesis of single-stranded cDNA (reverse transcriptase reaction) Synthesis of single-stranded cDNA from purified total RNA can be performed according to standard methods. Specifically, ReverTra Ace (registered trademark) qPCR RT Master Mix with gDNA Remover (manufactured by Toyobo Co., Ltd.) was used, and the operation was performed according to the protocol. That is, 4 μL of 4 × DN Master Mix and 12 μL of RNA extract dilution were stored at 37 ° C for 5 minutes, then kept at 4 ° C., and 16 μL of this reaction solution and 4 μL of 5 × RT Master Mix were stored at 37 ° C for 15 minutes, 50 ° C for 5 minutes, 98 ° C for 5 minutes, and 4 ° C. to synthesize single-stranded cDNA.

[0062] PCR PCR can be performed according to a conventional method. Specifically, TaqMan® Fast Advanced Cells-to-CT ＴＭThe PCR was performed using a PCR kit (Thermo Fisher) and the operation was carried out according to the protocol. Specifically, 5 μL of Master Mix, 0.5 μL of Gene Expression Assay (20x) (Table 5 below), 2.5 μL of water, and 2 μL of cDNA synthesis solution were mixed. This mixture was dispensed into a 384-well PCR plate (Thermo Fisher), set in a thermal cycler, and PCR reaction was carried out with one cycle of "50°C for 2 minutes," one cycle of "95°C for 20 seconds," and 40 cycles of "95°C for 1 second, 60°C for 20 seconds." Using this result, GAPDH was used as the housekeeping gene, and ΔΔC Ｔ The relative gene expression levels were calculated and evaluated using the method.

[0063] Results Figure 7 shows the evaluation results. In Figure 7, "PC" stands for the positive control, which refers to a three-dimensional cultured epidermal model tissue to which a solution of histamine (reagent) dissolved in LB medium containing 0.2% histidine was applied. *: p<0.05, **: p<0.005

[0064] The lower the histamine concentration in the 3D cultured epidermal tissue, the higher the KRT1 and KRT10 gene expression levels, resulting in significant differences. Meanwhile, KRT5 and KRT14 did not show this behavior, and no significant differences were observed. The correlation between the increase in the keratinization biomarkers KRT1 and KRT10 and histamine levels suggests that lowering histamine levels leads to the normalization of skin keratinization.

Claims

1. An antipruritic agent containing selenium disulfide.

2. The itch suppressant according to claim 1, which contains selenium disulfide as an active ingredient.

3. The itch suppressant according to claim 1 or 2, wherein the average particle size of the selenium disulfide is 60 μm or less.

4. The antipruritic agent according to claim 1 or 2, which is an external preparation.

5. An antipruritic agent according to claim 1 or 2, which is an external preparation for the scalp.

6. An itching suppressant according to claim 1 or 2, which suppresses scalp itching while inhibiting changes in the scalp bacterial flora.

7. Histamine production inhibitors, including selenium disulfide.

8. The histamine production inhibitor according to claim 7, which contains selenium disulfide as an active ingredient.

9. The histamine production inhibitor according to claim 7 or 8, wherein the average particle size of the selenium disulfide is 60 μm or less.

10. The histamine production inhibitor according to claim 7 or 8, which is based on the inhibitory effect of L-histidine decarboxylase of Staphylococcus capitis.

11. A histamine production inhibitor according to claim 7 or 8, which is an external preparation for the scalp.

12. Keratinizing agents, including selenium disulfide.

13. The keratinization normalizing agent according to claim 12, comprising selenium disulfide as an active ingredient.

14. The keratinization normalizing agent according to claim 12 or 13, wherein the average particle size of the selenium disulfide is 60 μm or less.

15. The keratinization normalizing agent according to claim 12 or 13, which is an external preparation.

16. The keratinization normalizing agent according to claim 12 or 13, which is an external preparation for the scalp.

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