Agent for inhibiting pruritus comprising sphingosine and use thereof

Abstract

Provided is a novel agent which can induce an effect of inhibiting the expression of an itch-related gene and which can be mainly applied to human skin or the like. The agent for inhibiting pruritus according to the present invention contains sphingosine base.

Description

Technical Field

[0001] The present invention relates to an agent for suppressing pruritus comprising a sphingosine base and use thereof. Background Art

[0002] The stratum corneum, the outermost layer of the skin, has a barrier function that prevents water from evaporating from the inside of the skin and defends against the invasion of foreign substances such as allergens and bacteria from the outside. In normal skin, the stratum corneum has intercellular lipids in the gaps between keratinocytes, and ceramide accounts for about 50% of the intercellular lipids. The reduction of ceramide is associated with atopic dermatitis, dry skin in winter, and aging, and causes a decrease in barrier function. Therefore, in order to improve the barrier function of the skin, various studies have been conducted on cosmetics and external preparations focusing on ceramide (Patent Document 1).

[0003] Prior art literature Patent Literature Patent Document 1: Japanese Patent No. 6959204 Summary of the invention

[0004] Technical problem to be solved by the invention Therefore, an object of the present invention is to provide a novel agent that can induce the effect of suppressing the expression of itch-related genes and can be applied mainly to human skin, etc.

[0005] Technical solutions for solving technical problems In order to achieve the above-mentioned object, the agent for suppressing itch of the present invention (hereinafter, also referred to as “itch suppressant”) contains a sphingosine base.

[0006] The agent for inhibiting TARC (Thymus and Activation-Regulated Chemokine) gene expression of the present invention (hereinafter, also referred to as “TARC gene expression inhibitor”) contains a sphingosine base.

[0007] The agent for inhibiting TSLP (thymic stromallymphopoietin) gene expression of the present invention (hereinafter, also referred to as “TSLP gene expression inhibitor”) contains a sphingosine base.

[0008] The agent for inhibiting IL-31RA gene expression of the present invention (hereinafter, also referred to as “IL-31RA gene expression inhibitor”) contains a sphingoid base.

[0009] Effects of the Invention According to the present invention, a novel agent capable of inducing an inhibitory effect on itch-related genes and applicable mainly to human skin and the like can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 This is a graph showing the amount of TARC produced by HaCaT cells in Example 1.

[0011] Figure 2 This is a graph showing the gene expression level of TSLP in NHEK cells in Example 1.

[0012] Figure 3 This is a graph showing the gene expression level of TSLP in NHEK cells in Example 1.

[0013] Figure 4 This is a graph showing the amount of TSLP produced by NHEK cells in Example 1.

[0014] Figure 5 This is a graph showing the gene expression level of IL-31RA in NHEK cells in Example 1.

[0015] Figure 6 This is a graph showing the amount of LTB4 produced by NHEK cells in Example 1.

[0016] Figure 7 This is a graph showing the gene expression level of TSLP in NHEK cells in Example 2.

[0017] Figure 8 This is a graph showing the gene expression level of IL-31RA in NHEK cells in Example 2.

[0018] Fig. 9 This is a graph showing the gene expression level of IL-8 in NHEK cells in Example 2. DETAILED DESCRIPTION

[0019] Hereinafter, the present invention will be specifically described with reference to examples. Hereinafter, each disclosure can refer to the description of other disclosures unless otherwise specified.

[0020] <Agent or composition for suppressing pruritus comprising sphingosine base> In a certain embodiment, the present invention provides an agent or composition for suppressing pruritus. The agent for suppressing pruritus of the present invention comprises a sphingoid base. In addition, the composition for suppressing pruritus of the present invention comprises a sphingoid base. In the following description, unless otherwise specified, the description of each agent of the present invention can be cited to the description of each corresponding composition.

[0021] The present inventors have conducted intensive studies and found that sphingoid base, which is a component of ceramide, shows an effect of suppressing the expression of genes related to itch (itch-related genes, biomarker genes) in keratinocytes, thereby establishing the present invention. Therefore, according to the agent or composition for suppressing itch of the present invention, for example, it is possible to suppress the expression of genes that show association with itch, and thus it is expected that it can suppress skin itch.

[0022] In the present invention, "sphingoid base" refers to a long-chain alcohol having an amino group, that is, a long-chain amino alcohol. The sphingoid base may be derived from, for example, an animal or a plant. The sphingoid base may be represented by, for example, the following formula (1). In the following formula (1), R 1 is a saturated or unsaturated hydrocarbon group. Examples of the sphingoid base include sphingosine, sphinganine, sphingadienine, and sphingenin. Examples of the sphingoid base include isomers. Examples of the isomers of the sphingoid base include 4,8-sphingadienine (4-8-sphingadienine) in which the double bonds at positions 4 and 8 are cis:cis, cis:trans, trans:cis, or trans:trans. Examples of the sphingoid base include 4-hydroxy-8-sphingenin. The number of carbon atoms in the sphingoid base is, for example, 12 to 20, and more preferably 18. As specific examples, the sphingoid bases include animal-derived sphingoid bases such as C18-sphingosine (d18:1), Sph3), dihydrosphingosine (d18:0), and phytosphingosine (t18:0); (4E,8Z)-dienesphingosine (trans-4-cis-8-sphingadienine, (d18:2), Sph1), (8Z)-4-hydroxysphingosine (4 -Hydroxy-cis-8-sphingenin, (t18:1), Sph2), 8-sphingosine (d18:1) and the like, and C20-sphingosine (C20-sphingosine, (d20:1), Sph4) and the like, from the viewpoint of being able to more strongly inhibit the expression of the above-mentioned biomarker genes, preferably 4,8-diene sphingosine, and more preferably (4E,8Z)-diene sphingosine.

[0023] [Chemistry 1]

[0024] [Chemistry 2]

[0025] [Chemistry 3]

[0026] [Chemistry 4]

[0027] [Chemistry 5]

[0028] In the present invention, the sphingoid base may be, for example, a component that can free the sphingoid base by being decomposed by an enzyme or the like in vivo. As the component that can free the sphingoid base, for example, ceramide, sphingolipids, etc. may be cited. The ceramide is decomposed by ceramidase in vivo, thereby freeing the sphingoid base. In addition, the sphingolipid is decomposed by sphingomyelinase or glucosylceramidase in vivo, thereby freeing ceramide, and the ceramide is further decomposed by the ceramidase, thereby freeing the sphingoid base. Therefore, the ceramide and the sphingolipid may also be referred to as precursors, precursor substances, or prodrugs of the sphingoid base, for example.

[0029] The above-mentioned "ceramide" refers to a compound composed of a sphingosine base part and a fatty acid part, and the above-mentioned sphingosine base part and the above-mentioned fatty acid part are bonded. In the above-mentioned ceramide, as shown in the following formula (6), the above-mentioned sphingosine base part and the above-mentioned fatty acid part are covalently bonded via an amide bond. The above-mentioned ceramide, for example, can be represented by the following formula (6). The above-mentioned sphingosine base part refers to the part of the above-mentioned ceramide that is derived from a sphingosine base. The above-mentioned sphingosine base part, for example, can include an amino group (NH 2 ) is separated from a hydrogen atom. In addition, the fatty acid portion refers to a portion of the ceramide derived from a fatty acid. In the following formula (6), R 2 For example, a saturated or unsaturated straight chain hydrocarbon group, a ω -Hydroxylated saturated or unsaturated straight chain hydrocarbon groups, or ester-terminated ω-Hydroxylated saturated or unsaturated straight-chain hydrocarbon group. The number of carbon atoms in the above-mentioned fatty acid part is, for example, 16 to 24. The source of the above-mentioned fatty acid part can be, for example, palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), nervonic acid (24:1), etc. The above-mentioned fatty acid part can be, for example, a group formed by the detachment of a hydroxyl group (OH) in the above-mentioned fatty acid. The above-mentioned ceramide can be, for example, N-acylsphingosine (ceramide), N-acylsphingosine (dihydroceramide), N-acylsphingosine (phytoceramide), etc. The ceramide is preferably a ceramide in which the sphingosine base part is derived from 4,8-dienesphingosine, and more preferably a ceramide in which the sphingosine base part is derived from (4E,8Z)-dienesphingosine, from the viewpoint of being able to more strongly inhibit the expression of the biomarker gene.

[0030] [Chemistry 6]

[0031] The above-mentioned sphingolipid refers to a lipid (complex lipid) in which the above-mentioned ceramide is further bonded to a group containing a sugar or a phosphate. In the case where the above-mentioned sphingolipid is a lipid in which the above-mentioned ceramide is bonded to a sugar, the primary alcohol of the above-mentioned ceramide and the group containing a sugar are covalently bonded via a glycosidic bond. In the case where the above-mentioned sphingolipid is a lipid in which the above-mentioned ceramide is bonded to a group containing a phosphate, as shown in the following formula (7), the primary alcohol of the above-mentioned ceramide and the group containing a phosphate are covalently bonded via an ester bond. Examples of the above-mentioned sphingolipid include glycosphingolipids and sphingomyelin. The above-mentioned sphingolipids can be represented by the following formula (7). In the following formula (7), in R 3 When is a group derived from sugar, the sphingolipid can be referred to as glycosphingolipid. 3 In the case of a group containing a phosphate, the sphingolipid may be referred to as sphingomyelin.

[0032] [Chemistry 7]

[0033] The above-mentioned glycosphingolipids, for example, can also be referred to as compounds in which the above-mentioned ceramides also have a sugar part. The above-mentioned sugar part refers to the part of the above-mentioned glycosphingolipids that is derived from sugar. Examples of the above-mentioned sugars include glucose, galactose and lactose. When the above-mentioned ceramide is bonded to glucose, the above-mentioned glycosphingolipids are called glucosylceramides. When the above-mentioned ceramide is bonded to galactose, the above-mentioned glycosphingolipids are called galactosylceramides. When the above-mentioned ceramide is bonded to lactose, the above-mentioned glycosphingolipids are called lactosylceramides. The above-mentioned sugar part is preferably derived from glucose.

[0034] The sphingomyelin can also be referred to as a compound in which a phosphoric acid compound is ester-bonded to the ceramide. Examples of the phosphoric acid compound include phosphorylcholine and the like. When the ceramide and phosphorylcholine are bonded, the sphingomyelin is referred to as sphingomyelin.

[0035] The sphingoid base, the ceramide, or the sphingolipid (hereinafter collectively referred to as "sphingoid base component") may be a compound obtained by separation or purification, or may be a composition containing the sphingoid base component. In addition, the sphingoid base component may be prepared by itself, or a commercial product may be used. When a commercial product is used as the sphingoid base, (4E, 8Z)-dienesphingosine (Nagara Science), (8Z)-4-hydroxy-sphingosine (Nagara Science), C18-sphingosine (Nagara Science), C20-sphingosine (Nagara Science), etc. may be used. When a commercial product is used as the ceramide, natural plant glucosylceramide (Glucosylceramide, Nagara Science (URL: https: / / www.funakoshi.co.jp / contents / 3459)) and the like may be used. When a commercial product is used as the sphingolipid, sphingomyelin (Olbracht Serdary Research Laboratories (URL: https: / / www.funakoshi.co.jp / contents / 3311)) etc. can be used. The composition containing the sphingoid base component includes, for example, an extract containing the sphingoid base component; a crude purified product of the extract, a dried product of the extract, a freeze-dried product of the extract, a spray-dried product of the extract, etc.

[0036] The extract containing the above-mentioned sphingoid base component can be produced, for example, by subjecting the plant containing the above-mentioned sphingoid base component to solvent extraction. Examples of plants containing the above-mentioned sphingoid base include rice, corn, konjac, soybeans, wheat, and yeast. Examples of plants containing the above-mentioned ceramide include rice, corn, konjac, soybeans, wheat, and yeast. Examples of plants containing the above-mentioned sphingolipids include rice, corn, konjac, soybeans, wheat, and yeast. One or more of the above-mentioned plants may be used. The plant material provided for the above-mentioned extraction may be an individual plant or a part of the plant. Examples of the parts of the above-mentioned plants include roots, rhizomes, leaves, stems, flowers, whole plants, or mixtures thereof. The above-mentioned material may be the collected plant itself, or a processed product obtained by drying and / or pulverizing. When the extract containing the sphingoid base contains the ceramide or the sphingolipid, the extract containing the sphingoid base can be further contacted with ceramidase to generate the sphingoid base from the ceramide or the sphingolipid in the extract.

[0037] Examples of the solvent used for the extraction of the sphingoid base component include aqueous solvents such as water and buffer; lower alcohols or water-containing lower alcohols such as methanol, ethanol, propanol, isopropanol, butanol, and isobutanol; polyols or water-containing polyols such as propylene glycol, 1,3-butanediol, 1,2-butanediol, 1,4-butanediol, 1,5-pentanediol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,3,5-pentanetriol, glycerol, and polyethylene glycol (for example, with a molecular weight of 100 to 100,000); organic solvents such as acetone, ethyl acetate, diethyl ether, dimethyl ether, ethyl methyl ether, dioxane, hexane, acetonitrile, xylene, benzene, chloroform, carbon tetrachloride, phenol, and toluene; and acids (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, etc.) or bases (sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia, etc.) whose equivalent concentration is appropriately adjusted. The above solvents may be used alone or in combination of two or more.

[0038] The treatment of the above-mentioned treated material includes, for example: decomposition based on the addition of acid (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, organic acid, etc.) or alkali (sodium hydroxide, calcium hydroxide, ammonia, etc.); fermentation or metabolic conversion based on microorganisms; component adsorption based on ion exchange resins, activated carbon, diatomaceous earth, etc.; chromatographic separation using various separation modes (ion exchange, hydrophilic adsorption, hydrophobic adsorption, size exclusion, ligand exchange, affinity, etc.); filtration using filter paper, membrane filter, or ultrafiltration membrane, etc.; pressurization or decompression; heating or cooling: drying or freeze drying; pH adjustment; deodorization; decolorization; long-term static storage, etc. The above-mentioned treatments can be implemented alone or in combination.

[0039] The above-mentioned "pruritus" means itching. Examples of the above-mentioned skin diseases accompanied by itching include dry skin, atopic dermatitis, contact dermatitis, and fungal skin infections.

[0040] The above-mentioned "suppression of itch" refers to the suppression of itching. The above-mentioned suppression of itch can be evaluated, for example, directly or indirectly. In the case of the above-mentioned direct evaluation, the above-mentioned suppression of itch can be evaluated, for example, by using a model animal (for example, an atopic dermatitis model) or a patch test, by the aggravation, deterioration, or cessation of the enhancement of itch, or improvement of itch in the subject to whom the object is administered. In the case of the above-mentioned indirect evaluation, the above-mentioned suppression of itch can be evaluated, for example, by measuring the expression level of itch-related genes, specifically, by suppressing the expression of the above-mentioned itch-related genes.

[0041] The itch-related gene is a gene that is related to the induction of itch or the formation of a skin condition that is prone to itch. Examples of the itch-related gene include the TARC gene, the TSLP gene, and the IL-31RA gene.

[0042] The above-mentioned "TARC (Thymus and Activation-Regulated Chemokine)" is a type of chemokine that causes cells such as white blood cells to migrate to tissues. It is known that the expression of the TARC gene is induced in atopic dermatitis, etc., and the production of TARC is induced and increased. In addition, it is known that TARC induces lymphocytes (Th2 cells) that cause allergic inflammation, causing allergic reactions to be hyperactive. The above-mentioned TARC is also used as a marker in atopic dermatitis.

[0043] As an example of the TARC gene, mRNA encoded by the human TARC gene, for example, includes a polynucleotide comprising a base sequence registered in Genbank with accession number: NM_002987.3, etc. As the expression level of the TARC gene, the expression level of any one or two or more isoforms of the TARC gene can be measured, or the expression of all isoforms can be measured.

[0044] The above-mentioned "TSLP (Thymic stromal lymphopoietin)" is a cytokine. It is known that the expression of TSLP gene is induced in atopic dermatitis, etc., and the production of TSLP is induced and increased. In addition, TSLP is known to induce lymphocytes (Th2 cells) that cause allergic inflammation, and exacerbate allergic reactions.

[0045] As an example of the TSLP gene, mRNA encoded by the human TSLP gene, for example, includes a polynucleotide comprising a base sequence registered in the GenBank with the accession number: NM_033035.5, etc. As the expression level of the TSLP gene, the expression level of any one or more isoforms of the TSLP gene can be measured, or the expression of all isoforms can be measured.

[0046] The above-mentioned "IL-31RA (Interleukin-31, interleukin 31 receptor)" is a receptor for T cell cytokine IL-31 secreted by Th2 cells, etc. It is known that itching is induced when IL-31 binds to IL-31RA.

[0047] As an example of the IL-31RA gene, mRNA encoded by the human IL-31RA gene, for example, a polynucleotide comprising a base sequence registered in the GenBank with the accession number: NM_001242636.2, etc. As the expression level of the IL-31RA gene, the expression level of any one or two or more isoforms of the IL-31RA gene may be measured, or the expression of all isoforms may be measured.

[0048] The above-mentioned "IL-8 (Interleukin-8, interleukin 8)" is a type of cytokine (chemokine) that migrates in neutrophils. IL-8 is known to be the cause of inflammatory reactions. IL-8 is also called CXCL8.

[0049] As an example of the above-mentioned IL-8 gene, mRNA encoded by human IL-8 gene, for example, can be cited: a polynucleotide comprising a base sequence registered in the gene bank with accession number: NM_001354840.3, etc. As the expression level of the above-mentioned IL-8 gene, the expression level of any one or more isoforms of the IL-8 gene can be measured, and the expression of all isoforms can also be measured.

[0050] In the present invention, "inhibiting the expression of a gene" means that the expression level of the target gene is inhibited or reduced, and may also mean that the target gene is changed from an expressed state to a non-expressed state. The expression of the target gene can be evaluated by, for example, measuring the expression level of the mRNA of the target gene by quantitative PCR according to Example 1 or 2 described later. In the case where the target gene has multiple isoforms, the expression level of the target gene can be measured by measuring the expression level of any one or two or more isoforms of the target gene, or by measuring the expression of all isoforms, preferably the latter.

[0051] The above-mentioned "gene" can exist in the form of RNA (e.g., mRNA) or DNA (e.g., cDNA or genomic DNA). DNA can be double-stranded or single-stranded. In this specification, the above-mentioned "gene" can include additional sequences such as the sequence of the untranslated region (UTR).

[0052] The above-mentioned “keratinocyte” refers to a cell having the ability to differentiate into basal cells, spinous cells, granular cells, and corneocytes constituting the epidermis.

[0053] The antipruritic agent according to the present invention can, for example, inhibit the production of leukotriene B4 by keratinocytes. The inhibition of the production of leukotriene B4 can be evaluated, for example, according to Example 1 (6) described below. The antipruritic agent according to the present invention can, for example, inhibit pruritus by inhibiting the production of leukotriene B4.

[0054] The antipruritic agent of the present invention can suppress pruritus by, for example, administering it to a subject. The use conditions (administration conditions) of the antipruritic agent of the present invention are not particularly limited, and for example, the administration form, administration time, and administration amount can be appropriately set according to the type of the subject.

[0055] The pruritus suppressant of the present invention can be used, for example, in vivo Use, also can be in in vitro use.

[0056] The subject to which the antipruritic agent of the present invention is administered is not particularly limited. in vivo When the antipruritic agent of the present invention is used, the subject of administration may be, for example, a human or a non-human animal other than a human. Examples of the non-human animal include mammals such as mice, rats, rabbits, dogs, sheep, horses, cats, goats, monkeys, guinea pigs, and birds. in vitro When the antipruritic agent of the present invention is used, the administration subject may be, for example, cells, tissues, organs, etc., the cells may be, for example, cells collected from a living body, cultured cells, etc., and the tissues or organs may be, for example, tissues (biological tissues) or organs collected from a living body, etc.

[0057] In the following skin external preparation (for example, a coating agent or composition for transdermal administration or to the skin) or the following oral administration agent or oral administration composition containing the pruritus suppressing agent of the present invention, the amount of the sphingoid base to be blended may be an effective amount as long as it exhibits the pruritus suppressing effect. The blending amount (upper limit and lower limit) of the sphingoid base is, for example, as follows. It should be noted that in the following examples, the upper limit and the lower limit can be arbitrarily combined.

[0058] Lower limit: 0.1 μ g / ml Upper limit: 5 μ g / ml, preferably 1 μ g / ml The administration method of the pruritus suppressant of the present invention may include oral administration or parenteral administration. The parenteral administration may include transdermal administration, application (contact) to the skin, etc. The application to the skin may include application to the oral mucosa, that is, application or contact to the epithelial cells in the oral cavity. In addition, the application to the skin may include administration or injection into the skin or subcutaneous through the skin surface in addition to or instead of application to the skin surface. Administration or injection into the skin through the skin surface may be performed, for example, using a microneedle.

[0059] The dosage form of the antipruritic agent of the present invention is not particularly limited, and can be appropriately determined according to the above-mentioned administration method. The above-mentioned dosage form includes, for example, liquid and solid. When the above-mentioned administration method is oral administration, the above-mentioned dosage form includes, for example, tablets, pills, capsules, granules, powders, liquids, etc.

[0060] The antipruritic agent of the present invention may contain additives as needed. When used as a composition, the additives preferably contain pharmaceutically acceptable additives or pharmaceutically acceptable carriers. The additives are not particularly limited, and examples thereof include base materials, excipients, colorants, lubricants, binders, disintegrants, stabilizers, coating agents, preservatives, flavoring agents such as fragrances, etc. In the present invention, the amount of the additives is not particularly limited as long as it does not hinder the function of sphingosine base or ceramide.

[0061] Examples of the excipient include: sugar derivatives such as lactose, lactose hydrate, saccharide, glucose, mannitol, sorbitol, etc.; corn starch, potato starch, αStarch derivatives such as starch and dextrin; cellulose derivatives such as crystalline cellulose; gum arabic; dextran; organic excipients such as pullulan; silicate derivatives such as light silicic anhydride, synthetic aluminum silicate, calcium silicate, magnesium aluminosilicate; phosphates such as calcium hydrogen phosphate; carbonates such as calcium carbonate; and inorganic excipients such as sulfates such as calcium sulfate. Examples of the above-mentioned colorants include yellow ferric oxide. Examples of the above-mentioned lubricants include metal stearates such as stearic acid, calcium stearate, and magnesium stearate; talc; polyethylene glycol; silicon dioxide; hydrogenated vegetable oil, etc. Examples of the above-mentioned flavoring agents include spices such as cocoa powder, menthol, aromatic powder, peppermint oil, borneol, and cinnamon powder, sweeteners, acidulants, etc. Examples of the above-mentioned binders include hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl pyrrolidone, and polyethylene glycol (Macrogol). Examples of the above disintegrant include: cellulose derivatives such as carboxymethyl cellulose and carboxymethyl cellulose calcium; chemically modified starches and chemically modified celluloses such as carboxymethyl starch, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, and sodium starch glycolate. Examples of the above stabilizer include: parabens such as methyl paraben and propyl paraben; alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid; sorbic acid, and the like. Examples of the above coating agent include: polyethylene glycols such as hypromellose and polyethylene glycol 6000, talc, and titanium oxide.

[0062] When the antipruritic composition of the present invention is an orally administered composition, specific examples of the orally administered composition include beverages, foods, pharmaceuticals (drugs), quasi-drugs (drugs), and the like.

[0063] When the antipruritic agent or composition of the present invention is a substance for transdermal administration or application to the skin (hereinafter, also referred to as "topical skin preparation"), the form of the above-mentioned topical skin preparation may include, depending on the use form, ampoules, capsules, powders, granules, liquids, gels, foams, emulsions, tablets, mists, sprays, etc. The above-mentioned use forms may include, for example: pharmaceuticals (categories); quasi-pharmaceuticals (categories); topical or systemic topical skin preparations; pharmaceutical and / or cosmetic preparations applied to the scalp and hair; bath agents used by adding to bath water; other preparations, etc. The above-mentioned topical or systemic topical skin preparations may include, for example: basic cosmetics such as lotions, emulsions, creams, ointments, lotions, oils, facial masks, solid soaps, liquid soaps, hand sanitizers or skin cleansers, massage agents, cleansing agents, hair removal agents, depilatory agents, shaving treatment agents, aftershaves, pre-shaves, shaving creams, foundations, lipsticks, blushes, eyeshadows, eyeliner creams, mascaras, etc. makeup cosmetics, perfumes, nail agents, nail polishes, nail polish removers, cataplasms, plaster agents, tape agents, sheet agents, patches, aerosol agents, mouthwashes such as toothpastes and mouthwashes, etc. The above-mentioned pharmaceutical and / or cosmetic preparations applied to the scalp and hair may include, for example: shampoos, hair conditioners, hair treatment agents, hair pretreatment agents, permanent wave solutions, hair dyes, hair styling agents, hot oil agents, hair growth and hair nourishing agents, cataplasms, plaster agents, tape agents, sheet agents, aerosol agents, etc. The above-mentioned other preparations may include, for example: antiperspirants or deodorants, antiperspirants, sanitary products, sanitary pads, wet wipes, etc.

[0064] The above-mentioned topical skin preparation can be arbitrarily selected and / or used in combination with the following exemplified ingredients and / or additives as needed within the range that does not interfere with the antipruritic effect for manufacturing.

[0065] (1) Various oils Avocado oil, almond oil, anise oil, perilla oil, olive oil, orange oil, orange roughy oil, sesame oil, cocoa butter, chamomile oil, carrot oil, cucumber oil, beef tallow fatty acid, candlenut oil, safflower oil, shea butter, liquid shea butter, soybean oil, camellia oil, corn oil, rapeseed oil, peach kernel oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, palm oil, palm kernel oil, Japan wax, coconut oil, beef tallow, lard, squalene, squalane, shark liver alkane or hydrogenated products (hardened oils, etc.) of these oils, etc.

[0066] (2) Waxes Beeswax, carnauba wax, cetyl wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, lignite wax, shellac wax, rice bran wax, etc.

[0067] (3) Mineral oils Liquid paraffin, vaseline, paraffin, ozokerite, ceresin, microcrystalline wax, etc.

[0068] (4) Fatty acids Natural fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxystearic acid, undecylenic acid, tall oil, lanolin fatty acid, and synthetic fatty acids such as isononanoic acid, caproic acid, 2-ethylbutyric acid, isovaleric acid, 2-methylvaleric acid, 2-ethylhexanoic acid, and isovaleric acid.

[0069] (5) Alcohols Natural alcohols such as ethanol, isopropyl alcohol, lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterols, phenoxyethanol, and synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, and 2-octyldodecanol.

[0070] (6) Polyols Ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol, 1,3-butylene glycol, pentylene glycol, glycerol, pentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, maltitol, etc.

[0071] (7) Esters Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyl decyl dimethyl octanoate, cetyl lactate, myristyl lactate, diethyl phthalate, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, etc.

[0072] (8) Metal soaps Aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, zinc undecylenate, etc.

[0073] (9) Gum, sugar or water-soluble polymer compounds Arabic gum, benzoin gum, dammar gum, guaiac, Irish moss, karaya gum, tragacanth gum, carob bean gum, quince seed, agar, casein, lactose, fructose, sucrose or its esters, trehalose or its derivatives, dextrin, gelatin, pectin, starch, carrageenan, carboxymethyl chitin or chitosan, hydroxyalkyl (C2-C4) chitin or chitosan with alkylene (C2-C4) oxide added by ethylene oxide, low molecular weight chitin or chitosan, chitosan salt, chitosan sulfate or chitosan, phosphorylated chitosan cellulose or chitosan, alginic acid or its salt, hyaluronic acid or its salt, chondroitin sulfate or its salt, heparin, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate, polyalkylene oxide such as polyethylene oxide or polypropylene oxide or their cross-linked polymers, carboxyvinyl polymers, polyethylene imine, etc.

[0074] (10) Surfactants Anionic surfactants (alkyl carboxylates, alkyl sulfonates, alkyl sulfate ester salts, alkyl phosphate ester salts), cationic surfactants (alkyl amine salts, alkyl quaternary ammonium salts), amphoteric surfactants: carboxylic acid type amphoteric surfactants (amino type, betaine type), sulfate type amphoteric surfactants, sulfonic acid type amphoteric surfactants, phosphate type amphoteric surfactants, nonionic surfactants (ether type nonionic surfactants, ether ester type nonionic surfactants, ester type nonionic surfactants, block polymer type nonionic surfactants, nitrogen-containing nonionic surfactants), other surfactants (natural surfactants, protein hydrolyzate derivatives, polymer surfactants, titanium and silicon-containing surfactants, fluorinated carbon surfactants), etc.

[0075] (11) Various vitamins Vitamin A family: retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), vitamin B family: thiamine hydrochloride, thiamine sulfate (vitamin B1), riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, niacin, pantothenic acid, biotin, choline, inositol, vitamin C family: vitamin C acid or its derivatives, vitamin D family: ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotachysterol, vitamin E family: vitamin E or its derivatives, ubiquinones, vitamin K family: phytomenadione (vitamin K1), menaquinone (vitamin K2), 2-menadione (vitamin K3), hydromenaquinone (vitamin K4), others: essential fatty acids (vitamin F), carnitine, ferulic acid, γ - Oryzanol, orotic acid, vitamin P (rutin, erythritol, hesperidin), vitamin U, etc.

[0076] (12) Various amino acids Valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine, and their sulfates, phosphates, nitrates, citrates, or amino acid derivatives such as pyrrolidonecarboxylic acid, etc.

[0077] (13) Additives The above-mentioned external skin preparation may further contain various additives derived from animals or plants. The above-mentioned additives may be processed according to conventional methods according to the type and form of the product to be added, and may be arbitrarily selected and added from various raw materials. The above-mentioned processing may be, for example, arbitrarily selected and / or combined treatments such as pulverization, milling, washing, hydrolysis, fermentation, purification, squeezing, extraction, fractionation, filtration, drying, powderization, granulation, dissolution, sterilization, pH adjustment, deodorization, and decolorization.

[0078] The solvent used in the above extraction can be selected based on the purpose of use, type, or subsequent processing of the product to be provided. The above extraction solvent is preferably selected from, for example, water, methanol, ethanol, propanol, isopropanol, butanol, isobutanol and other lower alcohols or aqueous lower alcohols, propylene glycol, 1,3-butanediol, glycerol and other polyols or aqueous polyols, acetone, ethyl acetate and other organic solvents, or a mixture of two or more. Among them, the above extraction solvent, for example, in the case where it is not preferred to contain an organic solvent depending on the purpose, can be used only water, or ethanol that is easily removed after extraction can be used alone or in the form of any mixture with water, or the solvent after squeezing extraction can be used.

[0079] When the additives derived from plant or animal raw materials are used in external preparations or cosmetics for systemic or local use, the external preparations for skin, for example, protect the skin and hair, and in addition to the beauty effects such as moisturizing, improvement of touch and feel, imparting softness, relieving irritation, relieving stress caused by fragrance, cell activation (prevention of cell aging), inhibition of inflammation, improvement of skin quality and hair quality, prevention of skin roughness and its improvement, hair growth, hair growth, prevention of hair loss, imparting gloss, cleansing effect, relief of fatigue, promotion of blood flow, warm bath effect, etc., can also be expected to have fragrance, deodorizing, thickening, antiseptic, buffering and the like.

[0080] The above-mentioned external preparation for skin can expect various cosmetic and medicinal effects of various raw materials known so far in addition to the above, and by combining them, the effect aimed at by the present invention can be enhanced, and a product expected to have multifunctional effects can be made.

[0081] <Agent or composition for inhibiting TARC gene expression> In another embodiment, the present invention provides an agent or composition capable of inhibiting TARC gene expression. The agent for inhibiting TARC gene expression of the present invention comprises a sphingoid base. The composition for inhibiting TARC gene expression of the present invention comprises a sphingoid base. According to the TARC gene expression inhibitor or composition of the present invention, the effect of inhibiting itching can be obtained.

[0082] The above-mentioned "inhibiting TARC gene expression" means that the expression level of the above-mentioned TARC gene is inhibited or reduced, and may also mean that the above-mentioned TARC gene changes from an expressed state to a non-expressed state. The expression of the above-mentioned TARC gene can be evaluated, for example, by measuring the expression level of the mRNA of the TARC gene according to Example 1 described below.

[0083] The expression inhibitor of the TARC gene of the present invention can, for example, be used to inhibit the expression of the TARC gene by administering it to a subject. Thus, the expression inhibitor of the TARC gene of the present invention can, for example, obtain an effect of inhibiting itching. The conditions for use of the expression inhibitor of the TARC gene of the present invention (administration conditions) can refer to the description of the conditions for use of the agent for inhibiting itching of the present invention described above.

[0084] <Agent or composition for inhibiting TSLP gene expression> In another embodiment, the present invention provides an agent or composition capable of inhibiting TSLP gene expression. The agent for inhibiting TSLP gene expression of the present invention comprises a sphingoid base. The composition for inhibiting TSLP gene expression of the present invention comprises a sphingoid base. According to the TSLP gene expression inhibitor or composition of the present invention, an effect of inhibiting itching can be obtained.

[0085] The above-mentioned "inhibiting TSLP gene expression" means that the expression level of the above-mentioned TSLP gene is inhibited or reduced, and may also mean that the above-mentioned TSLP gene changes from an expressed state to a non-expressed state. The expression of the above-mentioned TSLP gene can be evaluated, for example, by measuring the expression level of TSLP gene mRNA according to Example 1 or 2 described below.

[0086] The TSLP gene expression inhibitor of the present invention can, for example, be used to an administration subject to inhibit the expression of the TSLP gene. Thus, the TSLP gene expression inhibitor of the present invention can, for example, achieve an effect of inhibiting pruritus. The conditions for use of the TSLP gene expression inhibitor of the present invention (administration conditions) can refer to the description of the conditions for use of the agent for inhibiting pruritus of the present invention described above.

[0087] <Agent or Composition for Inhibiting IL-31RA Gene Expression> In another embodiment, the present invention provides an agent or composition capable of inhibiting IL-31RA gene expression. The agent for inhibiting IL-31RA gene expression of the present invention comprises a sphingoid base. The composition for inhibiting IL-31RA gene expression of the present invention comprises a sphingoid base. According to the IL-31RA gene expression inhibitor or composition of the present invention, an effect of inhibiting itching can be obtained.

[0088] The above-mentioned “inhibition of IL-31RA gene expression” refers to the inhibition or reduction of the expression level of the above-mentioned IL-31RA gene, and may also refer to the change of the above-mentioned IL-31RA gene from an expressed state to a non-expressed state. The expression of the above-mentioned IL-31RA gene can be evaluated, for example, by measuring the expression level of the IL-31RA gene mRNA according to Example 1 or 2 described below.

[0089] The IL-31RA gene expression inhibitor of the present invention can, for example, be used to inhibit the expression of the IL-31RA gene by administering it to a subject. Thus, the IL-31RA gene expression inhibitor of the present invention can, for example, achieve an effect of inhibiting pruritus. The conditions for use of the IL-31RA gene expression inhibitor of the present invention (administration conditions) can refer to the description of the conditions for use of the agent for inhibiting pruritus of the present invention described above.

[0090] <Agent or composition for inhibiting IL-8 gene expression> In another embodiment, the present invention provides an agent or composition capable of inhibiting IL-8 gene expression. The agent for inhibiting IL-8 gene expression of the present invention comprises a sphingoid base. The composition for inhibiting IL-8 gene expression of the present invention comprises a sphingoid base. According to the IL-8 gene expression inhibitor or composition of the present invention, the effect of inhibiting itching can be obtained.

[0091] The above-mentioned "inhibition of IL-8 gene expression" refers to the inhibition or reduction of the expression level of the above-mentioned IL-8 gene, and may also refer to the change of the above-mentioned IL-8 gene from an expressed state to a non-expressed state. The expression of the above-mentioned IL-8 gene can be evaluated, for example, by measuring the expression level of the mRNA of the IL-8 gene according to Example 2 described below.

[0092] The IL-8 gene expression inhibitor of the present invention can, for example, be used to inhibit the expression of the IL-8 gene by administering it to a subject. Thus, the IL-8 gene expression inhibitor of the present invention can, for example, obtain an effect of inhibiting itching. The conditions for use of the IL-8 gene expression inhibitor of the present invention (administration conditions) can refer to the description of the conditions for use of the agent for inhibiting itching of the present invention described above.

[0093] <Methods to suppress itching> In another embodiment, the present invention discloses a method for suppressing pruritus. The method for suppressing pruritus of the present invention uses the above-mentioned agent and / or composition for suppressing pruritus of the present invention. According to the method for suppressing pruritus of the present invention, for example, an effect of suppressing pruritus can be expected.

[0094] The method for suppressing pruritus of the present invention comprises a step of applying the above-mentioned agent and / or composition for suppressing pruritus of the present invention to a subject. The above-mentioned application may be, for example, contact with the skin or administration.

[0095] In the method for suppressing itching of the present invention, the above-mentioned use step can be performed, for example, in vitro or in vivo The subject (administration subject) and administration conditions of the method for suppressing pruritus of the present invention can refer to the description of the administration subject and administration conditions in the agent and / or composition for suppressing pruritus of the present invention, for example.

[0096] <Method for inhibiting TARC gene expression> In another embodiment, the present invention discloses a method for inhibiting TARC gene expression. The method for inhibiting TARC gene expression of the present invention uses the above-mentioned TARC gene expression inhibitor and / or composition of the present invention. According to the method for inhibiting TARC gene expression of the present invention, for example, it is expected that the effect of inhibiting itching can be obtained by inhibiting the expression of TARC gene.

[0097] The method of inhibiting TARC gene expression of the present invention comprises a step of applying the TARC gene expression inhibitor and / or composition of the present invention to a subject. The application may be, for example, contact with the skin or administration.

[0098] In the method for inhibiting TARC gene expression of the present invention, the above-mentioned using step can be performed, for example, in vitro or in vivo The subject (administration subject) and administration conditions of the method for inhibiting TARC gene expression of the present invention can refer to the description of the administration subject and administration conditions in the agent and / or composition for inhibiting pruritus of the present invention, for example.

[0099] <Method for Inhibiting TSLP Gene Expression> In another embodiment, the present invention discloses a method for inhibiting TSLP gene expression. The method for inhibiting TSLP gene expression of the present invention uses the TSLP gene expression inhibitor and / or composition of the present invention. According to the method for inhibiting TSLP gene expression of the present invention, for example, it is expected that the effect of inhibiting itching can be obtained by inhibiting the expression of TSLP gene.

[0100] The method of inhibiting TSLP gene expression of the present invention comprises a step of applying the TSLP gene expression inhibitor and / or composition of the present invention to a subject. The application may be, for example, contact with the skin or administration.

[0101] In the method for inhibiting TSLP gene expression of the present invention, the above-mentioned using step can be performed, for example, in vitro or in vivo The subject (administration subject) and administration conditions of the method for inhibiting TSLP gene expression of the present invention can refer to the description of the administration subject and administration conditions in the agent and / or composition for inhibiting pruritus of the present invention, for example.

[0102] <Method for inhibiting IL-31RA gene expression> In another embodiment, the present invention discloses a method for inhibiting IL-31RA gene expression. The method for inhibiting IL-31RA gene expression of the present invention uses the above-mentioned IL-31RA gene expression inhibitor and / or composition of the present invention. According to the method for inhibiting IL-31RA gene expression of the present invention, for example, it is expected that the effect of inhibiting itching can be obtained by inhibiting the expression of IL-31RA gene.

[0103] The method of inhibiting IL-31RA gene expression of the present invention comprises a step of applying the IL-31RA gene expression inhibitor and / or composition of the present invention to a subject. The application may be, for example, contact with the skin or administration.

[0104] In the method for inhibiting IL-31RA gene expression of the present invention, the above-mentioned using step can be performed, for example, in vitro or body Inside The subject (administration subject) and administration conditions of the method for inhibiting IL-31RA gene expression of the present invention can refer to the description of the administration subject and administration conditions in the agent and / or composition for suppressing pruritus of the present invention, for example.

[0105] <Method for inhibiting IL-8 gene expression> In another embodiment, the present invention discloses a method for inhibiting IL-8 gene expression. The method for inhibiting IL-8 gene expression of the present invention uses the above-mentioned IL-8 gene expression inhibitor and / or composition of the present invention. According to the method for inhibiting IL-8 gene expression of the present invention, for example, it is expected that the effect of inhibiting itching can be obtained by inhibiting the expression of IL-8 gene.

[0106] The method of inhibiting IL-8 gene expression of the present invention comprises a step of applying the IL-8 gene expression inhibitor and / or composition of the present invention to a subject. The application may be, for example, contact with the skin or administration.

[0107] In the method for inhibiting IL-8 gene expression of the present invention, the above-mentioned using step can be performed, for example, in vitro or in vivo The subject (administration subject) and administration conditions of the method for inhibiting IL-8 gene expression of the present invention can refer to the description of the administration subject and administration conditions in the agent and / or composition for inhibiting pruritus of the present invention, for example.

[0108] <Purpose> The present invention is the use of an agent for suppressing pruritus and / or a composition for suppressing pruritus. The present invention is the use of an inhibitor of expression of the TARC gene and / or a composition for suppressing TARC gene expression. The present invention is the use of an inhibitor of expression of the TSLP gene and / or a composition for suppressing TSLP gene expression. The present invention is the use of an inhibitor of expression of the IL-31RA gene and / or a composition for suppressing IL-31RA gene expression. The present invention is the use of an inhibitor of expression of the IL-8 gene and / or a composition for suppressing IL-8 gene expression.

[0109] The present invention is the use of an agent and / or composition for suppressing pruritus in the manufacture of an agent for suppressing pruritus or a composition for suppressing pruritus. The present invention is the use of an inhibitor of expression of the TARC gene and / or a composition in the manufacture of an agent for suppressing the expression of the TARC gene or a composition for suppressing the expression of the TARC gene. The present invention is the use of an inhibitor of expression of the TSLP gene and / or a composition in the manufacture of an agent for suppressing the expression of the TSLP gene or a composition for suppressing the expression of the TSLP gene. The present invention is the use of an inhibitor of expression of the IL-31RA gene and / or a composition in the manufacture of an agent for suppressing the expression of the IL-31RA gene or a composition for suppressing the expression of the IL-31RA gene. The present invention is the use of an inhibitor of expression of the IL-8 gene and / or a composition in the manufacture of an agent for suppressing the expression of the IL-8 gene or a composition for suppressing the expression of the IL-8 gene.

[0110] Example Next, examples of the present invention are described. However, the present invention is not limited to the following examples. Commercially available reagents are used based on these schemes unless otherwise specified. It should be noted that "mol / l" is sometimes also marked as "M".

[0111] [Example 1] It was confirmed that sphingosine base exhibited an effect of suppressing itching.

[0112] (1) TARC production test HaCaT cells, which are human keratinocytes, were inoculated in a 24-well plate. The culture medium used was DMEM culture medium (041-29775, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., the same as in the examples below) containing 10% FBS. After the above inoculation, the HaCaT cells were cultured until they reached 90% confluence. After the above culture, the culture medium in each well was replaced with serum-free DMEM. After the above replacement, the HaCaT cells were cultured for 24 hours. After the above culture, 1 μ g / ml phytoceramide (Fcer, PHYTOCERA NW-10, manufactured by Ichimaru Natural Beauty Co., Ltd.), 0.1 μg / ml glucosylceramide (Gcer, manufactured by Nagara Science), or 1 μ g / ml of sphingosine bases (Sph1: (4E,8Z)-dienesphingosine, Sph2: (8Z)-4-hydroxy-sphingosine, manufactured by Nagara Science Co., Ltd.), and cultured for 1 hour. After the above culture, TNF-α was added as a stimulating factor in such a manner that each 10 ng / ml α and IFN γ , cultured for 16 hours. After the above culture, the culture supernatant was recovered and ELISA was performed using Human IL-6 Quantikine ELISA Kit (manufactured by R&D System). Based on the results of the above ELISA, the amount of TARC produced was quantified. Each group was implemented with 3 samples (n=3). It should be noted that statistical analysis was performed using Turky's test. These results are shown in Figure 1 .

[0113] Figure 1 This is a graph showing the amount of TARC produced in HaCaT cells. Figure 1 In the graph, the vertical axis represents the amount of TARC produced (pg / ml), and the horizontal axis represents the type of sample.

[0114] Figure 1 The values ​​on the vertical axis in the graph represent the values ​​of each group in terms of the amount of TARC production corrected by the number of cells.

[0115] Figure 1 The values ​​on the vertical axis are as follows.

[0116] Control group: 6.59, non-additive group: 695.05, 1 μ g / ml Fcer group: 596.88, 0.1 μ g / ml Gcer group: 665.62, 1 μ g / ml Sph1 group: 590.90, 1 μ g / ml Sph2 group: 646.62.

[0117] like Figure 1 As shown, the amount of TARC production in the Fcer (rice-derived glucosylceramide) group or Sph1 group was significantly reduced compared to the group without addition (negative control). These results indicate that rice-derived glucosylceramide and Sph1 inhibit TARC production in keratinocytes.

[0118] (2) Test of TSLP gene expression level (I) It is known that rice-derived glucosylceramide and Sph1 show an inhibitory effect on TARC production in keratinocytes, but there are reports that TARC is not produced in normal keratinocytes. Therefore, a test of gene expression of TSLP, which is a biomarker of itch, was conducted. Specifically, 1.0×10 5 NHEK cells (KK-4009, frozen NHEK (NB), derived from newborns, manufactured by Kurabo Co., Ltd.) as human keratinocytes were inoculated in a cells / well manner. The culture medium used was KBM (trademark) medium (calcium-free phenol red, 00195769, manufactured by Lonza Co., Ltd., the same in the following examples). After the above inoculation, the NHEK cells were cultured until they were confluent. After the above culture, the culture medium of each well was replaced with KBM (trademark) medium containing BPE (bovine pituitary extract), insulin, EGF (epidermal growth factor), antibiotics (GA-1000) and 0.06 mmol / l calcium. After the above replacement, the NHEK cells were cultured for 24 hours. After the above culture, a concentration of 1 μ After the above culture, TNF-α was added as a stimulating factor to a final concentration of 10 ng / ml. α and INF γ , cultured for 6 hours. After the above culture, the culture supernatant was recovered and the mRNA was purified using RNeasy MiniKit (manufactured by QIAGEN) according to the attached protocol. After the above purification, reverse transcription reaction was performed using PrimeScript MasterMix (manufactured by TaKaRa). Next, qRT-PCR was performed using the following primer set for TSLP gene and primer set for RPS gene according to the method described in TB Green Master Mix (manufactured by TaKaRa). The PCR apparatus used was LightCycler (registered trademark) 96 (manufactured by Roche). The expression level of the TSLP gene is a relative value relative to the expression level of the internal standard gene (RPS18 gene). Data analysis was performed using the attached software. Statistical analysis was performed using JMP8, using Turky's test and Dunnett's test. These results are shown in Figure 2 .

[0119] TSLP gene primer set Forward primer (SEQ ID NO. 1) 5′-TAGCAATCGGCCACATTGCCT-3′ Reverse primer (SEQ ID NO: 2) 5'-GAAGCGACGCCACAATCCTTG-3' Primer set for RPS18 gene Forward primer (SEQ ID NO: 5) 5'-TTTGCGAGTACTCAACACCAACA-3' Reverse primer (SEQ ID NO: 6) 5'-GAGCATATCTTCGGCCCACAC-3' Figure 2 This is a graph showing the gene expression level of TSLP in NHEK cells. Figure 2 In (A), the vertical axis represents the relative value of TSLP gene expression level, and the horizontal axis represents the type of sample. Figure 2 In (B), the vertical axis represents the relative value of TSLP gene expression level, and the horizontal axis represents the type of sample.

[0120] Figure 2 The numerical values ​​on the vertical axes in (A) and (B) represent the values ​​of each group, with the value of the control group being 1.0 (1.00).

[0121] Figure 2 The numerical values ​​of the vertical axis of (A) are as follows.

[0122] · Group not added: 6.99, 1 μ g / ml Fcer group: 7.03.

[0123] Figure 2 The numerical values ​​of the vertical axis of (B) are as follows.

[0124] · Group not added: 6.99, 1 μ g / ml Sph1 group: 4.72.

[0125] like Figure 2 As shown in (A), in the Fcer group, the expression level of TSLP gene did not change compared with the group without addition (negative control). Figure 2 As shown in (B), in the Sph1 group, the TSLP gene expression level was significantly suppressed compared to the group without addition (negative control). From the above, it can be seen that Sph1 suppresses the TSLP gene expression in keratinocytes.

[0126] (3) Test of TSLP gene expression level (II) Next, Poly(I:C), which acts on TLR3 to promote TSLP production, was used instead of inflammatory cytokines (TNF α and INF γ ) was used to test the gene expression of TSLP. Specifically, 1.0×10 5NHEK cells were inoculated in cells / well format. KBM (trademark) medium was used as the culture medium. After the above inoculation, the NHEK cells were cultured until they were confluent. After the above culture, the culture medium of each well was replaced with KBM (trademark) medium containing BPE (bovine pituitary extract), insulin, EGF (epidermal growth factor), antibiotics (GA-1000) and 0.06mM calcium. After the above replacement, the NHEK cells were cultured for 24 hours. After the above culture, 1 μ g / ml of plant ceramide (Fcer) or sphingoid base (Sph1) and culture for 1 hour. μ g / ml, Poly (I: C) was added and cultured for 16 hours. After the above culture, the culture supernatant was recovered, and mRNA was purified according to the described protocol using RNeasy Mini Kit (manufactured by QIAGEN). After the above purification, reverse transcription reaction was performed using PrimeScript Master Mix (manufactured by TaKaRa). Then, qRT-PCR was performed using the above TSLP gene primer set and the above RPS gene primer set according to the method described in TB Green MasterMix (manufactured by TaKaRa). The PCR device used was LightCycler (registered trademark) 96 (manufactured by Roche). The gene expression level of the above TSLP gene is a relative value relative to the expression level of the internal standard gene (RPS18 gene). In addition, the protein level was detected by centrifugation after recovering the above culture supernatant to remove the debris. After the above removal, ELISA was performed using Human TSLPQuantikine ELISA Kit (manufactured by R&D System). According to the results of the above ELISA, the production amount of TSLP was quantified. Statistical analysis was performed using JMP8 and Turky test. These results are shown in Figure 3 and Figure 4 .

[0127] Figure 3 This is a graph showing the gene expression level of TSLP in NHEK cells. Figure 3 In (A), the vertical axis represents the relative value of TSLP gene expression level, and the horizontal axis represents the type of sample. Figure 3 In (B), the vertical axis represents the relative value of TSLP gene expression level, and the horizontal axis represents the type of sample.

[0128] Figure 3 The numerical values ​​on the vertical axes in (A) and (B) represent the values ​​of each group, with the value of the control group being 1.0 (1.00).

[0129] Figure 3 The numerical values ​​of the vertical axis of (A) are as follows.

[0130] · Group not added: 389.03, 1 μ g / ml Fcer group: 331.34.

[0131] Figure 3 The numerical values ​​of the vertical axis of (B) are as follows.

[0132] · Group not added: 389.03, 1 μ g / ml Sph1 group: 231.40.

[0133] like Figure 3 As shown in (A), in the Fcer group, the TSLP gene expression level did not change compared to the non-added (negative control) group. Figure 3 As shown in (B), in the Sph1 group, the TSLP gene expression level was significantly suppressed compared to the group without addition (negative control). From the above, it can be seen that Sph1 suppresses the TSLP gene expression in keratinocytes.

[0134] Figure 4 This is a graph showing the amount of TSLP produced in NHEK cells. Figure 4 In (A), the vertical axis represents the amount of TSLP produced, and the horizontal axis represents the type of sample. Figure 4 In (B), the vertical axis represents the TSLP generation amount, and the horizontal axis represents the type of sample.

[0135] Figure 4 The values ​​on the vertical axis in the graph represent the values ​​of each group in terms of TSLP production amount corrected by the number of cells.

[0136] Figure 4 The numerical values ​​of the vertical axis of (A) are as follows.

[0137] Control group: 9.02, non-additive group: 56.51, 1 μ g / ml Fcer group: 54.69.

[0138] Figure 4 The numerical values ​​of the vertical axis of (B) are as follows.

[0139] Control group: 9.02, non-additive group: 56.51, 1 μ g / ml Sph1 group: 42.68.

[0140] like Figure 4 As shown in (A), in the Fcer group, the production of TSLP did not change compared to the group without addition (negative control). Figure 4As shown in (B), in the Sph1 group, the production of TSLP was significantly suppressed compared to the group without addition (negative control). From the above, it can be seen that Sph1 suppresses the production of TSLP in keratinocytes.

[0141] (4) Test of IL-31RA gene expression It has been reported that IL-31 receptor A (IL-31RA) is expressed in epidermal cells, and that the addition of IL-31 to epidermal cells promotes the production of leukotriene B4 (LTB4). IL-31RA antibodies and inhibitors improve itching and inhibit the production of LTB4. Therefore, in addition to Sph1 inhibiting TSLP gene expression and protein production, we also studied whether Sph1 helps inhibit IL-31RA gene expression. Specifically, 1.0×10 5 NHEK cells were inoculated in cells / well format. KBM (trademark) medium was used as the culture medium. After the above inoculation, the NHEK cells were cultured until they were confluent. After the above culture, the culture medium of each well was replaced with KBM (trademark) medium containing BPE (bovine pituitary extract), insulin, EGF (epidermal growth factor), antibiotics (GA-1000) and 0.06mmol / l calcium. After the above replacement, the NHEK cells were cultured for 24 hours. After the above culture, 0.1 μ g / ml, 0.5 μ g / ml, or 1 μ g / ml of phytoceramide (Fcer) or sphingoid base (Sph1) and culture for 1 hour. After the above culture, TNF was added to a final concentration of 10 ng / ml. α and INF γ , cultured for 6 hours. After the above-mentioned culture, the culture supernatant was recovered, and the mRNA was purified according to the described protocol using the RNeasy Mini Kit (manufactured by QIAGEN). After the above-mentioned purification, a reverse transcription reaction was performed using PrimeScript Master Mix (manufactured by TaKaRa). Next, qRT-PCR was performed using the following primer set for the IL-31RA gene and the above-mentioned primer set for the RPS gene according to the method described in TBGreen Master Mix (manufactured by TaKaRa). The PCR apparatus used was LightCycler (registered trademark) 96 (manufactured by Roche). The expression level of the above-mentioned IL-31RA gene is a relative value relative to the expression level of the internal standard gene (RPS18 gene). The attached software was used for data analysis. Statistical analysis was performed using JMP8 and the Turky test. These results are shown in Figure 5 .

[0142] Primer set for IL-31RA gene Forward primer (SEQ ID NO: 3) 5'-TGAGTTGGCGCCTGTTTCAT-3' Reverse primer (SEQ ID NO: 4) 5'-TTTGACTCCTTGACCGCACA-3' Figure 5 This is a graph showing the gene expression level of IL-31RA in NHEK cells. Figure 5 In (A), the vertical axis represents the relative value of IL-31RA gene expression level, and the horizontal axis represents the type of sample. Figure 5 In (B), the vertical axis represents the relative value of IL-31RA gene expression level, and the horizontal axis represents the concentration of added Sph1.

[0143] Figure 5 The numerical values ​​on the vertical axes in (A) and (B) represent the values ​​of each group, with the value of the control group being 1.0 (1.00).

[0144] Figure 5 The numerical values ​​of the ordinate of (A) are as follows.

[0145] No added group: 18.76, 0.1 μ g / ml Fcer group: 17.68, 0.5 μ g / ml Fcer group: 15.76, 1 μ g / mlFcer group: 15.38.

[0146] Figure 5 The values ​​of the ordinate of (B) are as follows.

[0147] No added group: 18.76, 0.1 μ g / ml Sph1 group: 15.05, 0.5 μ g / ml Sph1 group: 12.55, 1 μ g / mlSph1 group: 10.06.

[0148] like Figure 5 As shown in (A), in the Fcer group, compared with the group without addition (negative control), at 0.5 μ g / ml or 1 μ When Fcer was added at a concentration of 100 g / ml, the gene expression of IL-31RA was significantly suppressed. Figure 5 (B) As shown, in the Sph1 group, compared with the group without addition (negative control), at 0.1 μ g / ml, 0.5 μ g / ml or 1 μWhen Sph1 was added at a concentration of 1.5 g / ml, the gene expression level of IL-31RA was significantly suppressed. From the above, it was found that Sph1 suppresses the gene expression of IL-31RA in keratinocytes.

[0149] (5) Leukotriene B4 production test We investigated whether inhibition of IL-31RA gene expression by Sph1 could inhibit the production of leukotriene B4 (LTB4) that causes pruritus. Specifically, 1.0×10 5 NHEK cells were inoculated in cells / well format. KBM (trademark) medium was used as the culture medium. After the above inoculation, the NHEK cells were cultured until they were confluent. After the above culture, the culture medium in each well was replaced with KBM (trademark) medium containing BPE (bovine pituitary extract), insulin, EGF (epidermal growth factor), antibiotics (GA-1000) and 0.06 mM calcium. After the above replacement, the NHEK cells were cultured for 24 hours. After the above culture, 0.5 μ g / ml or 1 μ After the above culture, TNF was added to a final concentration of 10 ng / ml. α and INF γ , cultured for 16 hours. After the above culture, the medium was replaced with KBM (trademark) medium containing IL-31 (100 ng / ml), BPE (bovine pituitary extract), insulin, EGF (epidermal growth factor), antibiotics (GA-1000) and 0.06 mM calcium. After the above replacement, the NHEK cells were cultured for 1 hour. After the above culture, the culture supernatant was recovered and centrifuged to remove the debris. After the above removal, ELISA was performed using Leukotoriene B4 EIA Kit (520111, manufactured by Cayman Chemical (seller: Fujifilm Wako Pure Chemical, 513-92091)). Based on the results of the above ELISA, the amount of LTB4 produced was quantified. Statistical analysis was performed using Student's t-test. These results are shown in Figure 6 .

[0150] Figure 6 This is a graph showing the amount of LTB4 produced in NHEK cells. Figure 6 In the graph, the vertical axis represents the amount of LTB4 produced (pg / ml), and the horizontal axis represents the type of sample.

[0151] Figure 6 The values ​​on the vertical axis represent the values ​​of each group in terms of LTB4 production corrected by the number of cells.

[0152] Figure 6 The values ​​of the vertical axis are as follows.

[0153] Control group: 31.65, non-additive group: 47.60, 0.5 μ g / ml Sph1 group: 30.42, 1 μ g / ml Sph1 group: 26.68.

[0154] like Figure 6 As shown, in the Sph1 group, the production of LTB4 was significantly suppressed compared to the non-added (negative control) group. From the above, it can be seen that Sph1 inhibits the production of LTB4 in epidermal keratinocytes. These results suggest that Sph1 inhibits the production of LTB4 via IL-31 by inhibiting the expression of IL-31RA, thereby suppressing itching.

[0155] In addition, information such as the sequences of the primers used in the above-mentioned Example 1(2), Example 1(3) and Example 1(4) is also shown in the following Table 1.

[0156] [Table 1]

[0157] [Example 2] The structural type of glucosylceramide contained in the rice-derived glucosylceramide was analyzed, and the composition ratio of the sphingoid base species contained in the glucosylceramide was estimated from the analysis results. Furthermore, it was confirmed whether the sphingoid base contained in the rice-derived glucosylceramide exerted an effect of suppressing itching.

[0158] (1) Analysis of the structure of glucosylceramide The structural type of glucosylceramide contained in the glucosylceramide derived from rice was analyzed to infer the type of sphingoid base contained in the glucosylceramide derived from rice. Specifically, 100 mg of glucosylceramide derived from rice (PHYTOCERA, NW-10, Lot No.121520, manufactured by Ichimaru Natural Beauty Co., Ltd.) was added to 3 ml of purified water and ultrasonicated to dissolve it. After the above dissolution, 18 ml of methanol was slowly added and ultrasonicated. Then, it was cooled, and chloroform was added to make a total of 50 ml to perform extraction. After the above extraction, the extract was filtered and the filtrate was concentrated to dryness. After the above concentration to dryness, 50 ml of methanol was added to dissolve it. After the above dissolution, it was concentrated to dryness again. Then, methanol was added to make a total of 50 ml, and 0.45 μThe filtrate was filtered through a membrane filter of 1000 μm. The filtrate obtained by the above filtration was used as a test sample. Liquid chromatography was performed using the above filtrate and the standard reagents shown in Table 2 below (manufactured by Nagara Science Co., Ltd.) to measure the amount of each glucosylceramide. The above liquid chromatography was performed under the conditions shown in Table 3 below. The results are shown in Tables 4 and 5 below.

[0159] [Table 2]

[0160] [Table 3]

[0161] [Table 4]

[0162] [Table 5]

[0163] As shown in Tables 4 and 5, it can be seen that the rice-derived glucosylceramide contains 81% of diene sphingosine (d18:2) (Sph1) and 12.6% of (8Z)-4-hydroxy-sphingosine (t18:1) (Sph2). As shown above, the rice-derived glucosylceramide (PHYTOCERA, NW-10, Lot No. 121520, manufactured by Ichimaru Natural Beauty Co., Ltd.) mainly contains diene sphingosine.

[0164] (2) Test of TSLP gene expression We investigated whether sphingoid bases derived from rice glucosylceramide, which mainly contain diene sphingosine, inhibit the expression of the TSLP gene, which is one of the biomarkers of itch. Specifically, 1.0×10 5 NHEK cells (KK-4009, frozen NHEK (NB), derived from newborns, manufactured by Kurabo) as human keratinocytes were inoculated in a cells / well manner. After the above inoculation, the NHEK cells were cultured until they were confluent. After the above culture, the culture medium of each well was replaced with KBM (trademark) culture medium containing BPE (bovine pituitary extract), insulin, EGF (epidermal growth factor), antibiotics (GA-1000) and 0.06mmol / l calcium. After the above replacement, the NHEK cells were cultured for 24 hours. After the above culture, a concentration of 0.1 μ g / ml, 0.5 μ g / ml or 1 μg / ml of Sph1 or rice-derived glucosylceramide (tSph) was cultured for 1 hour. After the above culture, TNFα and INFγ were added as stimulatory factors in a manner to give 1ng / ml (final concentration) respectively, and cultured for 6 hours. After the above culture, qRT-PCR and analysis were performed in the same manner as in Example 1 (2). These results are shown in Figure 7 .

[0165] Figure 7 This is a graph showing the gene expression level of TSLP in NHEK cells. Figure 7 In (A), the vertical axis represents the relative value of TSLP gene expression level, and the horizontal axis represents the type of sample. Figure 7 In (B), the vertical axis represents the relative value of TSLP gene expression level, and the horizontal axis represents the type of sample.

[0166] Figure 7 (A) and Figure 7 The numerical values ​​on the vertical axis in (B) represent the values ​​of each group, with the value of the control group being 1.0 (1.00).

[0167] Figure 7 The numerical values ​​of the vertical axis of (A) are as follows.

[0168] · Group not added: 7.31, 0.1 μ g / ml Sph1 group: 4.37, 0.5 μ g / ml Sph1 group: 3.98, 1 μ g / ml Sph1 group: 3.87.

[0169] Figure 7 The numerical values ​​of the vertical axis of (B) are as follows.

[0170] · Group not added: 7.31, 0.1 μ g / ml tSph group: 4.02, 0.5 μ g / ml tSph group: 4.79, 1 μ g / ml tSph group: 3.59.

[0171] like Figure 7 As shown in (A), in the Sph1 group, at any concentration, the TSLP gene expression level was significantly suppressed compared to the group without addition (negative control). Figure 7 As shown in (B), in the tSph group, the TSLP gene expression level was significantly suppressed at all concentrations compared to the non-added (negative control) group. From the above, it can be seen that not only Sph1 but also tSph suppresses the TSLP gene expression in keratinocytes.

[0172] (3) Test of IL-31RA gene expression We investigated whether sphingoid bases containing rice-derived glucosylceramide, which mainly contains diene sphingosine, contribute to the suppression of IL-31RA gene expression in addition to the suppression of TSLP gene expression. Specifically, NHEK cells (KK-4009, frozen NHEK (NB), derived from newborns, manufactured by Kurabo) were used as cells, and ceramide was used at a concentration of 0.1 μ g / ml, 0.5 μ g / ml, or 1 μ g / ml of Sph1 or rice-derived glucosylceramide (tSph), and TNF-α at 1 ng / ml (final concentration) as cytokines α and INF γ , except for this, qRT-PCR and analysis were performed in the same manner as in Example 1 (4) above. These results are shown in Figure 8 .

[0173] Figure 8 This is a graph showing the gene expression level of IL-31RA in NHEK cells. Figure 8 In (A), the vertical axis represents the relative value of IL-31RA gene expression level, and the horizontal axis represents the type of sample. Figure 8 In (B), the vertical axis represents the relative value of IL-31RA gene expression level, and the horizontal axis represents the type of sample.

[0174] Figure 8 (A) and Figure 8 The numerical values ​​on the vertical axis in (B) represent the values ​​of each group, with the value of the control group being 1.0 (1.00).

[0175] Figure 8 The numerical values ​​of the vertical axis of (A) are as follows.

[0176] · Group not added: 9.50, 0.1 μ g / ml Sph1 group: 5.84, 0.5 μ g / ml Sph1 group: 5.04, 1 μ g / ml Sph1 group: 4.55.

[0177] Figure 8 The numerical values ​​of the vertical axis of (B) are as follows.

[0178] · Group not added: 9.50, 0.1 μ g / ml tSph group: 5.74, 0.5 μ g / ml tSph group: 5.67, 1 μ g / ml tSph group: 4.09.

[0179] like Figure 8 As shown in (A), in the Sph1 group, at any concentration, the gene expression of IL-31RA was significantly suppressed compared with the group without addition (negative control). Figure 8 As shown in (B), in the tSph group, the IL-31RA gene expression level was significantly suppressed at all concentrations compared to the non-added (negative control) group. The above results show that not only Sph1 but also tSph suppresses the IL-31RA gene expression in keratinocytes.

[0180] (4) Test of IL-8 gene expression We investigated whether Sph1 and rice-derived glucosylceramide, which mainly contains diene sphingosine, inhibit the gene expression of IL-8, which is a biomarker of inflammation. Specifically, 1.0×10 5 NHEK cells (KK-4009, frozen NHEK (NB), derived from newborns, manufactured by Kurabo) were inoculated in cells / well format. KBM (trademark) medium was used as the culture medium. After the above inoculation, the NHEK cells were cultured until they were confluent. After the above culture, the culture medium of each well was replaced with KBM (trademark) medium containing BPE (bovine pituitary extract), insulin, EGF (epidermal growth factor), antibiotics (GA-1000) and 0.06mmol / l calcium. After the above replacement, the NHEK cells were cultured for 24 hours. After the above culture, a concentration of 0.5 μ g / ml or 1 μ g / ml of Sph1, or 1 μ g / ml of rice-derived glucosylceramide (tSph) and cultured for 1 hour. After the above culture, TNF was added to a final concentration of 1 ng / ml. α and INF γ, cultured for 6 hours. After the above culture, the culture supernatant was recovered and the mRNA was purified using the RNeasy Mini Kit (manufactured by QIAGEN) according to the attached protocol. After the above purification, a reverse transcription reaction was performed using PrimeScript Master Mix (manufactured by TaKaRa). Next, qRT-PCR was performed using the following primer set for the IL-8 gene and primer set for the RPS gene according to the method described in TB Green Master Mix (manufactured by TaKaRa). The PCR apparatus used was LightCycler (registered trademark) 96 (manufactured by Roche). The expression level of the IL-8 gene is a relative value relative to the expression level of the internal standard gene (RPS18 gene). Data analysis was performed using the attached software. Statistical analysis was performed using JMP8, using the Turky test and Dunnett's test. These results are shown in Fig. 9 .

[0181] IL-8 gene primer set Forward primer (SEQ ID NO: 7) 5'-AAATTGAGGCCAAGGGCCA-3' Reverse primer (SEQ ID NO: 8) 5'-AACCAAGGCACAGTGGAACA-3' Fig. 9 This is a graph showing the gene expression level of IL-8 in NHEK cells. Fig. 9 In (A), the vertical axis represents the relative value of IL-8 gene expression level, and the horizontal axis represents the type of sample. Fig. 9 In (B), the vertical axis represents the relative value of IL-8 gene expression level, and the horizontal axis represents the type of sample.

[0182] Fig. 9 (A) and Fig. 9 The numerical values ​​on the vertical axis in (B) represent the values ​​of each group, with the value of the control group being 1.0 (1.00).

[0183] Fig. 9 The numerical values ​​of the vertical axis of (A) are as follows.

[0184] · Group not added: 110.61, 0.5 μ g / ml Sph1 group: 64.96, 1 μ g / ml Sph1 group: 47.49.

[0185] Fig. 9 The numerical values ​​of the vertical axis of (B) are as follows.

[0186] · Group not added: 110.61, 1 μg / ml tSph group: 58.25.

[0187] like Fig. 9 As shown in (A), in the Sph1 group, compared with the group without addition (negative control), at 0.5 μ g / ml or 1 μ When Sph1 was added at a concentration of 100 g / ml, the gene expression of IL-8 was significantly suppressed. Fig. 9 (B) As shown, in the tSph group, compared with the group without addition (negative control), at 1 μ When tSph was added at a concentration of 100 g / ml, the gene expression of IL-8 was significantly suppressed. These results show that Sph1 and tSph suppress the gene expression of IL-8 in keratinocytes, that is, suppress inflammation.

[0188] In addition, information such as the sequences of the primers used in the above-mentioned Example 2 (4) is also shown in the following Table 6.

[0189] [Table 6]

[0190] The present invention has been described above with reference to the embodiments and examples, but the present invention is not limited to the above-described embodiments and examples. The configuration and details of the present invention can be modified in various ways that can be understood by those skilled in the art within the scope of the present invention.

[0191] The contents of patents, patent applications, and documents cited in this specification are incorporated herein by reference in the same manner as the contents specifically described in this specification.

[0192] This application claims the priority based on Japanese patent application No. 2022-181327 filed on November 11, 2022, the disclosure of which is incorporated herein in its entirety.

[0193] <Notes> A part or all of the above-mentioned embodiments and examples can be described as the following supplementary notes, but are not limited to the following.

[0194] <Agent for suppressing itching containing sphingosine base> (Note 1) An agent for suppressing pruritus, comprising a sphingosine base.

[0195] (Note 2) The reagent according to Supplementary Note 1, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0196] (Note 3) The reagent according to Supplementary Note 1, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxysphingosine, C18-sphingosine, and / or C20-sphingosine.

[0197] (Note 4) An agent for suppressing itching, comprising ceramide comprising a sphingosine base portion and a fatty acid portion.

[0198] (Note 5) The reagent according to Appendix 4, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or neuraminic acid (24:1).

[0199] (Note 6) The reagent according to Appendix 4 or 5, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0200] (Note 7) The reagent according to Appendix 4 or 5, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0201] (Note 8) The reagent according to any one of Appendixes 4 to 7, wherein the ceramide further includes a sugar moiety.

[0202] (Note 9) The reagent according to Supplementary Note 8, wherein the sugar part is derived from glucose.

[0203] (Note 10) A reagent for application to the skin, comprising the reagent according to any one of Supplementary Notes 1 to 9.

[0204] (Note 11) A reagent for oral administration, comprising the reagent according to any one of Supplementary Notes 1 to 9.

[0205] <Composition for suppressing itching comprising sphingosine base> (Note 12) A composition for suppressing itching, comprising a sphingosine base.

[0206] (Note 13) The composition according to Supplementary Note 12, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0207] (Note 14) The composition according to Appendix 12, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxysphingosine, C18-sphingosine, and / or C20-sphingosine.

[0208] (Note 15) A composition for suppressing itching, comprising ceramide comprising a sphingosine base portion and a fatty acid portion.

[0209] (Note 16) A composition according to Note 15, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or neuraminic acid (24:1).

[0210] (Note 17) The composition according to Appendix 15 or 16, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine and / or C20-sphingosine.

[0211] (Note 18) The composition according to Appendix 15 or 16, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0212] (Note 19) The composition according to any one of Appendix 15 to 18, wherein the ceramide further comprises a sugar moiety.

[0213] (Note 20) The composition according to Supplementary Note 19, wherein the sugar part is derived from glucose.

[0214] (Note 21) A composition for application to the skin, comprising the composition according to any one of Appendix 12 to 20.

[0215] (Note 22) A composition for oral administration, comprising the composition according to any one of Appendix 12 to 20.

[0216] (Note 23) The composition according to any one of Supplementary Notes 12 to 22, comprising the agent for suppressing itching according to any one of Supplementary Notes 1 to 11.

[0217] <Agents for Inhibiting TARC Gene Expression> (Note 24) An agent for inhibiting the expression of TARC (Thymus and Activation-Regulated Chemokine) gene, comprising a sphingosine base.

[0218] (Note 25) The reagent according to Supplementary Note 24, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0219] (Note 26) The reagent according to Supplementary Note 24, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxysphingosine, C18-sphingosine, and / or C20-sphingosine.

[0220] (Note 27) An agent for inhibiting TARC gene expression, comprising ceramide comprising a sphingoid base portion and a fatty acid portion.

[0221] (Note 28) The reagent according to Appendix 27, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or nervonic acid (24:1).

[0222] (Note 29) The reagent according to Supplementary Note 27 or 28, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0223] (Note 30) The reagent according to Supplementary Note 27 or 28, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0224] (Note 31) The reagent according to any one of Appendixes 27 to 30, wherein the ceramide further includes a sugar moiety.

[0225] (Note 32) The reagent according to Appendix 31, wherein the sugar part is derived from glucose.

[0226] (Note 33) An agent for application to the skin, comprising the agent according to any one of Supplementary Notes 24 to 32.

[0227] (Note 34) A reagent for oral administration, comprising the reagent according to any one of Appendix 24 to 32.

[0228] <Composition for inhibiting TARC gene expression> (Note 35) A composition for inhibiting the expression of TARC gene, comprising a sphingosine base.

[0229] (Note 36) The composition according to Supplementary Note 35, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0230] (Note 37) The composition according to Supplementary Note 35, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine and / or C20-sphingosine.

[0231] (Note 38) A composition for inhibiting TARC gene expression, comprising ceramide, wherein the ceramide comprises a sphingosine base portion and a fatty acid portion.

[0232] (Note 39) A composition according to Note 38, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or neuraminic acid (24:1).

[0233] (Note 40) The composition according to Supplementary Note 38 or 39, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0234] (Note 41) The composition according to Supplement 38 or 39, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0235] (Note 42) The composition according to any one of Appendix 38 to 41, wherein the ceramide further comprises a sugar moiety.

[0236] (Note 43) The composition according to Supplementary Note 42, wherein the sugar part is derived from glucose.

[0237] (Note 44) A composition for application to the skin, comprising the composition according to any one of Appendix 35 to 43.

[0238] (Note 45) A composition for oral administration, comprising the composition according to any one of Appendix 35 to 43.

[0239] (Note 46) The composition according to any one of Supplements 35 to 45, comprising the agent for inhibiting TARC gene expression according to any one of Supplements 24 to 34.

[0240] <Agents for Inhibiting TSLP Gene Expression> (Note 47) An agent for inhibiting TSLP (Thymic stromal lymphopoietin) gene expression, comprising a sphingosine base.

[0241] (Note 48) The reagent according to Supplementary Note 47, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0242] (Note 49) The reagent according to Supplementary Note 47, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxysphingosine, C18-sphingosine, and / or C20-sphingosine.

[0243] (Note 50) An agent for inhibiting TSLP gene expression, comprising ceramide comprising a sphingosine base portion and a fatty acid portion.

[0244] (Appendix 51) The reagent according to Note 50, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or neuraminic acid (24:1).

[0245] (Note 52) The reagent according to Supplementary Note 50 or 51, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0246] (Note 53) The reagent according to Supplementary Note 50 or 51, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0247] (Note 54) The reagent according to any one of Appendixes 50 to 53, wherein the ceramide further includes a sugar moiety.

[0248] (Note 55) The reagent according to Supplementary Note 54, wherein the sugar part is derived from glucose.

[0249] (Note 56) An agent for application to the skin, comprising the agent according to any one of Supplementary Notes 47 to 55.

[0250] (Note 57) A reagent for oral administration, comprising the reagent according to any one of Appendix 47 to 55.

[0251] <Composition for inhibiting TSLP gene expression> (Note 58) A composition for inhibiting TSLP gene expression, comprising a sphingosine base.

[0252] (Note 59) The composition according to Supplementary Note 58, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0253] (Note 60) The composition according to Supplementary Note 58, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0254] (Note 61) A composition for inhibiting TSLP gene expression, comprising ceramide, wherein the ceramide comprises a sphingosine base portion and a fatty acid portion.

[0255] (Note 62) A composition according to Note 61, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or neuraminic acid (24:1).

[0256] (Note 63) The composition according to Supplementary Note 61 or 62, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0257] (Note 64) The composition according to Supplementary Note 61 or 62, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0258] (Note 65) The composition according to any one of Appendix 61 to 64, wherein the ceramide further comprises a sugar moiety.

[0259] (Note 66) The composition according to Supplementary Note 65, wherein the sugar part is derived from glucose.

[0260] (Note 67) A composition for application to the skin, comprising the composition according to any one of Supplementary Notes 58 to 66.

[0261] (Note 68) A composition for oral administration, comprising the composition according to any one of Appendix 58 to 66.

[0262] (Note 69) The composition according to any one of Supplements 58 to 68, comprising the agent for inhibiting TSLP gene expression according to any one of Supplements 47 to 57.

[0263] <Agents for Inhibiting IL-31RA Gene Expression> (Note 70) An agent for inhibiting IL-31RA gene expression, comprising a sphingosine base.

[0264] (Supplementary Note 71) The reagent according to Supplementary Note 70, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0265] (Note 72) The reagent according to Supplementary Note 70, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxysphingosine, C18-sphingosine, and / or C20-sphingosine.

[0266] (Note 73) An agent for inhibiting IL-31RA gene expression, comprising ceramide comprising a sphingosine base portion and a fatty acid portion.

[0267] (Note 74) A reagent according to Note 73, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or neuraminic acid (24:1).

[0268] (Note 75) The reagent according to Supplementary Note 73 or 74, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0269] (Note 76) The reagent according to Supplementary Note 73 or 74, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0270] (Addendum 77) The reagent according to any one of Appendix 73 to 76, wherein the ceramide further includes a sugar moiety.

[0271] (Note 78) The reagent according to Supplementary Note 77, wherein the sugar part is derived from glucose.

[0272] (Addendum 79) A reagent for application to the skin, comprising the reagent according to any one of Supplementary Notes 70 to 78.

[0273] (Note 80) A reagent for oral administration, comprising the reagent according to any one of Supplementary Notes 70 to 78.

[0274] <Composition for Inhibiting IL-31RA Gene Expression> (Note 81) A composition for inhibiting IL-31RA gene expression, comprising a sphingosine base.

[0275] (Note 82) The composition according to Supplementary Note 81, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0276] (Note 83) The composition according to Supplementary Note 81, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0277] (Note 84) A composition for inhibiting IL-31RA gene expression, comprising ceramide, wherein the ceramide comprises a sphingosine base portion and a fatty acid portion.

[0278] (Note 85) A composition according to Note 84, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or neuraminic acid (24:1).

[0279] (Note 86) The composition according to Supplementary Note 84 or 85, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0280] (Addendum 87) The composition according to Supplementary Note 84 or 85, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0281] (Note 88) The composition according to any one of Appendixes 84 to 87, wherein the ceramide further comprises a sugar moiety.

[0282] (Addendum 89) The composition according to Supplementary Note 88, wherein the sugar part is derived from glucose.

[0283] (Note 90) A composition for application to the skin, comprising the composition according to any one of Appendix 81 to 89.

[0284] (Supplementary Note 91) A composition for oral administration, comprising the composition according to any one of Appendix 81 to 89.

[0285] (Supplementary Note 92) The composition according to any one of Supplements 81 to 91, comprising the agent for inhibiting IL-31RA gene expression according to any one of Supplements 70 to 80.

[0286] <Agents for Inhibiting IL-8 Gene Expression> (Note 93) An agent for inhibiting IL-8 gene expression, comprising a sphingosine base.

[0287] (Note 94) The reagent according to Supplementary Note 93, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0288] (Note 95) The reagent according to Supplementary Note 93, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxysphingosine, C18-sphingosine, and / or C20-sphingosine.

[0289] (Note 96) An agent for inhibiting IL-8 gene expression, comprising ceramide comprising a sphingosine base portion and a fatty acid portion.

[0290] (Addendum 97) A reagent according to Note 96, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or neuraminic acid (24:1).

[0291] (Note 98) The reagent according to Supplementary Note 96 or 97, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0292] (Addendum 99) The reagent according to Supplementary Note 96 or 97, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0293] (Note 100) The reagent according to any one of Appendix 96 to 99, wherein the ceramide further comprises a sugar moiety.

[0294] (Postscript 101) The reagent according to Supplementary Note 100, wherein the sugar part is derived from glucose.

[0295] (Note 102) A reagent for application to the skin, comprising the reagent according to any one of Supplementary Notes 93 to 101.

[0296] (Note 103) A reagent for oral administration, comprising the reagent according to any one of Supplementary Notes 93 to 101.

[0297] <Composition for inhibiting IL-8 gene expression> (Note 104) A composition for inhibiting IL-8 gene expression, comprising a sphingosine base.

[0298] (Note 105) The composition according to Supplement 104, wherein the sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0299] (Note 106) The composition according to Supplement 104, wherein the sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0300] (Note 107) A composition for inhibiting IL-8 gene expression, comprising ceramide, wherein the ceramide comprises a sphingosine base portion and a fatty acid portion.

[0301] (Note 108) A composition according to Note 107, wherein the fatty acid portion is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or neuraminic acid (24:1).

[0302] (Note 109) The composition according to Supplementary Note 107 or 108, wherein the sphingosine base part is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0303] (Note 110) The composition according to Supplement 107 or 108, wherein the sphingosine base part is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

[0304] (Supplementary Note 111) The composition according to any one of Appendix 107 to 110, wherein the ceramide further comprises a sugar moiety.

[0305] (Supplementary Note 112) The composition according to Supplementary Note 111, wherein the sugar part is derived from glucose.

[0306] (Note 113) A composition for application to the skin, comprising the composition according to any one of Appendix 104 to 112.

[0307] (Note 114) A composition for oral administration, comprising the composition according to any one of Appendix 104 to 112.

[0308] (Note 115) The composition according to any one of Supplementary Notes 104 to 114, comprising the agent for inhibiting IL-8 gene expression according to any one of Supplementary Notes 93 to 103.

[0309] <Methods to suppress itching> (Note 116) A method for suppressing pruritus, comprising using the agent for suppressing pruritus according to any one of Supplementary Notes 1 to 11 and / or the composition for suppressing pruritus according to any one of Supplementary Notes 12 to 23.

[0310] (Note 117) The method for suppressing pruritus according to Supplementary Note 116, comprising the step of using the agent for suppressing pruritus and / or the composition for suppressing pruritus on a subject.

[0311] (Note 118) The inhibition method according to Supplementary Note 116 or 117, wherein in vitro or in vivo use.

[0312] <Method for inhibiting TARC gene expression> (Supplementary Note 119) A method for inhibiting TARC gene expression, comprising using the agent for inhibiting TARC gene expression according to any one of Supplements 24 to 34 and / or the composition for inhibiting TARC gene expression according to any one of Supplements 35 to 46.

[0313] (Note 120) The inhibition method according to Supplementary Note 119, comprising the step of administering the agent for inhibiting TARC gene expression and / or the composition for inhibiting TARC gene expression to a subject.

[0314] (Supplementary Note 121) The inhibition method according to Supplement 119 or 120, wherein in vitro or in vivo use.

[0315] <Method for Inhibiting TSLP Gene Expression> (Note 122) A method for inhibiting TSLP gene expression, comprising using the agent for inhibiting TSLP gene expression described in any one of Supplements 47 to 57 and / or the composition for inhibiting TSLP gene expression described in any one of Supplements 58 to 69.

[0316] (Note 123) The inhibition method according to Supplementary Note 122, comprising administering the agent for inhibiting TSLP gene expression and / or the composition for inhibiting TSLP gene expression to a subject.

[0317] (Note 124) The inhibition method according to Supplement 122 or 123, wherein in vitro or in vivo use.

[0318] <Method for inhibiting IL-31RA gene expression> (Note 125) A method for inhibiting IL-31RA gene expression, comprising using the agent for inhibiting IL-31RA gene expression described in any one of Supplementary Notes 70 to 80 and / or the composition for inhibiting IL-31RA gene expression described in any one of Supplementary Notes 81 to 92.

[0319] (Note 126) The inhibition method according to Supplement 125, comprising the step of administering the agent for inhibiting IL-31RA gene expression and / or the composition for inhibiting IL-31RA gene expression to a subject.

[0320] (Note 127) The inhibition method according to Supplement 125 or 126, wherein in vitro or in vivo use.

[0321] <Method for inhibiting IL-8 gene expression> (Note 128) A method for inhibiting IL-8 gene expression, comprising using the agent for inhibiting IL-8 gene expression described in any one of Supplementary Notes 93 to 103 and / or the composition for inhibiting IL-8 gene expression described in any one of Supplementary Notes 104 to 115.

[0322] (Note 129) The inhibition method according to Supplementary Note 128, comprising the step of administering the agent for inhibiting IL-8 gene expression and / or the composition for inhibiting IL-8 gene expression to a subject.

[0323] (Note 130) The inhibition method according to Supplementary Note 128 or 129, wherein in vitro or in vivo use.

[0324] <Purpose> (Supplementary Note 131) Use of the agent for suppressing pruritus according to any one of Supplementary Notes 1 to 11 and / or the composition for suppressing pruritus according to any one of Supplementary Notes 12 to 23 for suppressing pruritus.

[0325] (Note 132) Use of the agent for suppressing TARC gene expression according to any one of Supplements 24 to 34 and / or the composition for suppressing TARC gene expression according to any one of Supplements 35 to 46 for suppressing TARC gene expression.

[0326] (Note 133) Use of the agent for suppressing TSLP gene expression according to any one of Supplementary Notes 47 to 57 and / or the composition for suppressing TSLP gene expression according to any one of Supplementary Notes 58 to 69 for suppressing TSLP gene expression.

[0327] (Note 134) Use of the agent for inhibiting IL-31RA gene expression according to any one of Supplementary Notes 70 to 80 and / or the composition for inhibiting IL-31RA gene expression according to any one of Supplementary Notes 81 to 92 for inhibiting IL-31RA gene expression.

[0328] (Note 135) Use of the agent for inhibiting IL-8 gene expression according to any one of Supplementary Notes 93 to 103 and / or the composition for inhibiting IL-8 gene expression according to any one of Supplementary Notes 104 to 115 for inhibiting IL-8 gene expression.

[0329] Industrial Applicability As described above, the present invention can provide a novel agent that can induce the effect of suppressing the expression of itch-related genes and can be mainly applied to human skin, etc. Therefore, it can be said that the present invention is very useful in the fields of pharmaceuticals, quasi-drugs, and external skin preparations, for example.

Claims

1. An agent for suppressing itching, It is characterized in that Contains sphingosine base.

2. The reagent according to claim 1, in, The sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

3. The reagent according to claim 1, in, The sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

4. An agent for suppressing itching, It is characterized in that Contains a ceramide comprising a sphingosine base portion and a fatty acid portion.

5. The reagent according to claim 4, in, The fatty acid moiety is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or nervonic acid (24:1).

6. The reagent according to claim 4 or 5, in, The sphingosine base portion is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

7. The reagent according to claim 4 or 5, in, The sphingosine base moiety is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

8. The reagent according to any one of claims 4 to 7, in, The ceramide also comprises a sugar moiety.

9. The reagent according to claim 8, in, The sugar moiety is derived from glucose.

10. An agent for application to the skin, It is characterized in that A reagent comprising the reagent according to any one of claims 1 to 9.

11. An agent for oral administration, It is characterized in that A reagent comprising the reagent according to any one of claims 1 to 9.

12. A composition for inhibiting itching, It is characterized in that Contains sphingosine base.

13. An agent for inhibiting the expression of TARC (Thymus and Activation-Regulated Chemokine) gene, It is characterized in that Contains sphingosine base.

14. The reagent according to claim 13, in, The sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

15. The reagent according to claim 13, in, The sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

16. An agent for inhibiting the expression of TARC gene, It is characterized in that Contains a ceramide comprising a sphingosine base portion and a fatty acid portion.

17. The reagent according to claim 16, in, The fatty acid moiety is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or nervonic acid (24:1).

18. The reagent according to claim 16 or 17, in, The sphingosine base portion is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

19. The reagent according to claim 16 or 17, in, The sphingosine base moiety is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

20. The reagent according to any one of claims 16 to 19, in, The ceramide also comprises a sugar moiety.

21. The reagent according to claim 20, in, The sugar moiety is derived from glucose.

22. An agent for application to the skin, It is characterized in that A reagent comprising the reagent according to any one of claims 13 to 21.

23. An agent for oral administration, It is characterized in that A reagent comprising the reagent according to any one of claims 13 to 21.

24. A composition for inhibiting TARC gene expression, It is characterized in that Contains sphingosine base.

25. An agent for inhibiting TSLP (Thymic stromal lymphopoietin) gene expression, It is characterized in that Contains sphingosine base.

26. The reagent according to claim 25, in, The sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

27. The reagent according to claim 25, in, The sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

28. An agent for inhibiting TSLP gene expression, It is characterized in that Contains a ceramide comprising a sphingosine base portion and a fatty acid portion.

29. The reagent according to claim 28, in, The fatty acid moiety is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or nervonic acid (24:1).

30. The reagent according to claim 28 or 29, in, The sphingosine base moiety is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

31. The reagent according to claim 28 or 29, in, The sphingosine base moiety is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

32. The reagent according to any one of claims 28 to 31, in, The ceramide also comprises a sugar moiety.

33. The reagent according to claim 32, in, The sugar moiety is derived from glucose.

34. An agent for application to the skin, It is characterized in that A reagent comprising the reagent according to any one of claims 25 to 33.

35. An agent for oral administration, It is characterized in that A reagent comprising the reagent according to any one of claims 25 to 33.

36. A composition for inhibiting TSLP gene expression, It is characterized in that Contains sphingosine base.

37. An agent for inhibiting IL-31RA gene expression, It is characterized in that Contains sphingosine base.

38. The reagent according to claim 37, in, The sphingosine base is 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

39. The reagent according to claim 37, in, The sphingosine base is (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

40. An agent for inhibiting IL-31RA gene expression, It is characterized in that Contains a ceramide comprising a sphingosine base portion and a fatty acid portion.

41. The reagent according to claim 40, in, The fatty acid moiety is derived from palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), arachidic acid (20:0), behenic acid (22:0), erucic acid (22:1), tricosanoic acid (23:0), tetracosanoic acid (24:0), or nervonic acid (24:1).

42. The reagent according to claim 40 or 41, in, The sphingosine base portion is derived from 4,8-dienesphingosine, 4-hydroxy-8-sphingosine, C18-sphingosine, and / or C20-sphingosine.

43. The reagent according to claim 40 or 41, in, The sphingosine base moiety is derived from (4E,8Z)-dienesphingosine, (8Z)-4-hydroxy-sphingosine, C18-sphingosine, and / or C20-sphingosine.

44. The reagent according to any one of claims 40 to 43, in, The ceramide also comprises a sugar moiety.

45. The reagent according to claim 44, in, The sugar moiety is derived from glucose.

46. ​​An agent for application to the skin, It is characterized in that A reagent comprising the reagent according to any one of claims 37 to 45.

47. An agent for oral administration, It is characterized in that A reagent comprising the reagent according to any one of claims 37 to 45.

48. A composition for inhibiting IL-31RA gene expression, It is characterized in that Contains sphingosine base.

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