Thymic stromal lymphopoietin expression inhibitor, external composition for skin, cosmetic, and pharmaceutical

Abstract

To provide a thymic stromal lymphopoietin expression inhibitor, an external composition for skin or the like that can inhibit the expression of thymic stromal lymphopoietin (TSLP).SOLUTION: The present invention provides a thymic stromal lymphopoietin expression inhibitor, an external composition for skin or the like, comprising at least one selected from a mannuronic acid oligomer methylsilanol ester, a heparinoid, and a middle-molecular-weight hyaluronic acid having a molecular weight of 50,000 or more and 400,000 or less.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an inhibitor of thymic stromal lymphopoietin expression, a composition for external use on the skin, a cosmetic, and a pharmaceutical, which are used, for example, by application to the skin. [Background technology]

[0002] Thymic stromal lymphopoietin (TSLP) is a cytokine secreted by cells of patients with allergic diseases such as atopic dermatitis, promoting excessive activation of immune cells. TSLP is known to be one of the causative agents of allergic reactions. It is believed that suppressing the expression of TSLP may enable the prevention and treatment of allergic diseases such as atopic dermatitis.

[0003] Conventionally, preparations that suppress the expression of thymic stromal lymphopoietin (TSLP) are known, for example, to contain an aqueous extract of hops as an active ingredient (Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2011 / 070970 Summary of the Invention [Problem to be solved by the invention]

[0005] However, TSLP expression inhibitors containing the above-mentioned active ingredients have not yet been fully investigated. Therefore, there is a need for TSLP expression inhibitors containing active ingredients that can inhibit the expression of TSLP.

[0006] In view of the above-mentioned needs, an objective of the present invention is to provide an expression inhibitor of thymic stromal lymphopoietin (TSLP) that can suppress the expression of TSLP, as well as topical skin compositions, cosmetics, and pharmaceuticals that contain such an expression inhibitor. [Means for solving the problem]

[0007] The thymic stromal lymphopoietin expression inhibitor of the present invention is characterized by containing at least one of N-acetylcysteine, an ester compound having at least a mannuronate methylsilanol ester structure in the molecule, a heparin-like substance, and a medium molecular weight hyaluronic acid having a molecular weight of 50,000 or more and 400,000 or less.

[0008] The expression inhibitor according to the present invention preferably contains at least one of the N-acetylcysteine, the ester compound, and the heparinoid. The expression inhibitor according to the present invention preferably contains at least two of the N-acetylcysteine, the ester compound, and the heparinoid.

[0009] The external skin composition, cosmetic, and pharmaceutical according to the present invention each contain the above-mentioned thymic stromal lymphopoietin expression inhibitor. [Effects of the Invention]

[0010] The expression of thymic stromal lymphopoietin (TSLP) can be suppressed by the thymic stromal lymphopoietin expression inhibitor, external skin composition, cosmetic, and pharmaceutical of the present invention. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a graph showing the rate of suppression of thymic stromal lymphopoietin (TSLP) expression by each component. [Figure 2] FIG. 2 is a graph showing the rate of suppression of thymic stromal lymphopoietin (TSLP) expression by medium-molecular-weight hyaluronic acid and the like. [Figure 3] FIG. 3 is a graph showing the expression suppression rate of thymic stromal lymphopoietin (TSLP) by N-acetylcysteine ​​and heparinoids. [Figure 4] FIG. 4 is a graph showing the rate of suppression of thymic stromal lymphopoietin (TSLP) expression by an ester compound having at least a methyl mannuronate silanol ester structure in the molecule and a heparinoid. [Figure 5] FIG. 5 is a graph showing the rate of suppression of thymic stromal lymphopoietin (TSLP) expression by an ester compound having at least a methyl mannuronate silanol ester structure in the molecule and a heparinoid. DETAILED DESCRIPTION OF THE INVENTION

[0012]

[0023] The present invention relates to an inhibitor of thymic stromal lymphopoietin (TSLP) expression, and to an external skin composition, cosmetic, and pharmaceutical product containing the inhibitor. Hereinafter, the TSLP expression inhibitor, external skin composition, cosmetic, and pharmaceutical product may each be referred to simply as a "composition."

[0013] The composition of this embodiment contains at least one of N-acetylcysteine, an ester compound having at least a mannuronate methylsilanol ester structure in the molecule, a heparin-like substance, and a medium molecular weight hyaluronic acid having a molecular weight of 50,000 or more and 400,000 or less. The composition of this embodiment can suppress the expression of thymic stromal lymphopoietin (TSLP).

[0014] Preferably, the composition of this embodiment contains at least one of N-acetylcysteine, the above-mentioned ester compound, and a heparinoid. More preferably, the composition of this embodiment contains at least two of N-acetylcysteine, the ester compound, and a heparinoid. As a result, the composition of this embodiment can further suppress the expression of thymic stromal lymphopoietin (TSLP).

[0015] The above-mentioned N-acetylcysteine ​​(hereinafter sometimes referred to as NAC) is also known as N-acetyl-L-cysteine.

[0016] The composition of the present embodiment preferably contains the above-mentioned N-acetylcysteine ​​in an amount of 0.01% by mass or more and 10.00% by mass or less (on a dry matter basis).

[0017] The above-mentioned ester compound (hereinafter sometimes referred to as ALG) is an esterification reaction product of a compound having at least a mannuronic acid unit in the molecule with methylsilanol. In other words, the above-mentioned ester compound is a compound in which methylsilanol is esterified to at least a portion of the carboxy groups of a mannuronic acid polymer. The above ester compound is, for example, an ester compound of methylsilanol and alginic acid having L-guluronic acid and D-mannuronic acid in the molecule. The above ester compound is preferably an ester compound of a D-mannuronic acid oligomer and methylsilanol (mannuronic acid oligomer methylsilanol ester). The ester compound may be an ester compound of alginic acid oligomer and methylsilanol.

[0018] The ester compound may have a carboxy group in the molecule. In other words, the ester compound may be one in which some of the carboxy groups before the esterification reaction are esterified. Note that the ester compound may be one in which all of the carboxy groups are esterified. The molecular weight of the ester compound is not particularly limited.

[0019] ALG can be, for example, a commercially available product. An example of a commercially available product containing ALG is "Algicium C" (manufactured by Eximol).

[0020] The composition of the present embodiment preferably contains the above ester compound in an amount of 0.0001% by mass or more and 0.1000% by mass or less (on a dry basis).

[0021] The above-mentioned heparinoids (hereinafter referred to as HPD) are active medical ingredients used in prescription drugs. Heparinoids are defined in the Japanese Pharmacopoeia's Non-Diluted Pharmaceutical Standards and consist primarily of polysulfate esters of chondroitin sulfate. Heparinoids are a group of substances that can exert the same effects as heparin, which inhibits blood clotting and the formation of thrombi. Examples of the heparin-like substances include sulfated plant oligosaccharides and polysaccharides, specifically polysulfates prepared from alginic acid, pectin, xylan, starch, or dextran, or sulfated animal glycosaminoglycans. Examples of substances that may be included in heparinoids include the following: Examples of suitable polysaccharide sulfates include pentosan polysulfate (e.g., sodium pentosan sulfonate), xylan sulfate (e.g., β-1,4-D-xylan-2,3-bis(hydrogensulfate), xylan poly(hydrogensulfate), and its sodium salts), dextran sulfate, chitin sulfate, chondroitin polysulfate (also known as polysulfate mucopolysaccharide), polyvinyl sulfonic acid (also known as polyethylene sulfonic acid), sodium aporate, polygalacturonic acid sulfate (methyl ester methyl glucoside), alginate sulfate (e.g., sodium alginate sulfate), and polymannuronic acid sulfate.

[0022] The composition of this embodiment preferably contains the above-mentioned heparinoid in an amount of 0.01% by mass or more and 1.00% by mass or less (on a dry matter basis).

[0023] The above-mentioned medium-molecular-weight hyaluronic acid (hereinafter sometimes referred to as HAF) is a mucopolysaccharide polymer compound having a chain structure in which disaccharide units, each of which is composed of N-acetylglucosamine and glucuronic acid, are linked together. The above-mentioned medium-molecular-weight hyaluronic acid can be obtained by a common method. For example, the above-mentioned medium-molecular-weight hyaluronic acid can be obtained by hydrolyzing high-molecular-weight hyaluronic acid (e.g., molecular weight of 1 million) produced by fermentation using microorganisms with enzymes or dilute acids, followed by dialysis.

[0024] The medium-molecular-weight hyaluronic acid may be in the form of a salt, such as a sodium salt, potassium salt, ammonium salt, magnesium salt, calcium salt, zinc salt, or aluminum salt.

[0025] The molecular weight of the above-mentioned medium molecular weight hyaluronic acid is more than 50,000 and less than 400,000.The molecular weight of the above-mentioned medium molecular weight hyaluronic acid is preferably more than 50,000 and less than 200,000, more preferably less than 150,000.As the raw material containing the above-mentioned medium molecular weight hyaluronic acid, the raw material that the proportion of the medium molecular weight hyaluronic acid that is more than 50,000 and less than 400,000 is 20% or more can be used.Preferably, the raw material that the proportion of the medium molecular weight hyaluronic acid that is more than 50,000 and less than 400,000 is 30% or more, more preferably 40% or more can be used. The raw material containing the medium-molecular-weight hyaluronic acid may further contain hyaluronic acid having a molecular weight of less than 50,000, or may further contain hyaluronic acid having a molecular weight of more than 400,000.

[0026] When the composition of the present embodiment contains hyaluronic acid, the proportion of the above-mentioned medium molecular weight hyaluronic acid to the total hyaluronic acid can be 15% or more, 20% or more, 30% or more, 40% or more, or 50% or more.Furthermore, this proportion can be 90% or less, 80% or less, or 70% or less.This proportion is calculated as follows: In the chart of the hyaluronic acid (including low molecular weight to high molecular weight) contained in the composition of the present embodiment measured by gel permeation chromatography (GPC measurement), the integral molecular weight distribution is made from the peak area of ​​the molecular weight range of 2,000 to 13,000,000, and the content ratio of the integral distribution value of the molecular weight range of 50,000 to 400,000 is calculated based on this.Therefore, the proportion of the medium molecular weight hyaluronic acid that is above-mentioned and molecular weight is above 50,000 to 400,000 is calculated.The GPC measurement conditions and the calculation method of above-mentioned proportion will be explained in detail later.

[0027] When the composition of the present embodiment comprises the above-mentioned medium molecular weight hyaluronic acid, when the composition is measured by GPC under the conditions described below, in the chart, the peak of hyaluronic acid appears in the range of molecular weight 50,000 or more and 400,000 or less.In this GPC measurement chart, among the peaks of hyaluronic acid that can appear in the range of 2,000 or more and 13,000,000 or less, preferably the peak that appears in the range of molecular weight 50,000 or more and 400,000 or less is the highest (largest).

[0028] As the medium-molecular-weight hyaluronic acid, commercially available products can be used, such as "Hyaluronic Acid Na-FCH-SU" manufactured by Kikkoman Biochemifa Corporation.

[0029] The molecular weight is measured by gel permeation chromatography (GPC) under the following conditions: <Molecular weight measurement by gel permeation chromatography (GPC)> (1) Pretreatment method The sample is dissolved in the eluent and then filtered through a 0.45 μm membrane filter to prepare a measurement solution. (2) Measurement conditions Measuring equipment: Shimadzu Corporation, product name "GPC-HPLC Controller SCL-10AVP" Column: TSK gel GM PWXL x 2 + G2500 PWXL x 1 (7.8 mm I.D. x 300 mm x 3) Eluent: 200mM sodium nitrate aqueous solution Flow rate: 1.0mL / min. Detector: RI detector (Viscotek LR125 Laser Refractometer) Column temperature: 40℃ Injection volume: 200μL Molecular weight standard: pullulan-glucose standard (American Polymer Standards Corp.) (3) Molecular weight measurement Molecular weight: Conversion value of the above standard pullulan / glucose Molecular weight calculation: Attached software data analysis software "Multistation GPC-8020" (Tosoh Corporation) The above molecular weights are converted values ​​based on standard pullulan and glucose measured by GPC. The percentage (content) of the above medium-molecular-weight hyaluronic acid is calculated based on the results of GPC measurement as follows. Specifically, the elution time is converted to molecular weight using a calibration curve from the GPC measurement results, and the peak area is calculated to determine the concentration fraction for each elution time. The concentration fractions are sequentially integrated, and the content percentage of the target molecular weight range is determined using an integrated molecular weight distribution curve, with molecular weight (logarithmic value) on the horizontal axis and integrated concentration fraction on the vertical axis. Specifically, based on the integrated molecular weight distribution curve for hyaluronic acid in the molecular weight range of 2,000 to 13,000,000, the integrated distribution value for the fraction fractionated in the molecular weight range of 5,000 to 400,000 is calculated and used as the content (%).

[0030] The composition of the present embodiment preferably contains the above-mentioned medium-molecular-weight hyaluronic acid in an amount of 0.01% by mass or more and 5.00% by mass or less (on a dry matter basis).

[0031] The composition of the present embodiment may contain at least one of N-acetylcysteine, an ester compound having at least a mannuronate methylsilanol ester structure in its molecule, a heparinoid, and hydrolyzed hyaluronic acid in a total amount of 0.0001% by mass or more, 0.0010% by mass or more, 0.0100% by mass or more, or 0.1000% by mass or more. Note that the composition of the present embodiment may contain at least one of the above in a total amount of 10% by mass or less, 5% by mass or less, 2% by mass or less, or 1% by mass or less.

[0032] The composition of this embodiment preferably contains at least one of the above-mentioned ester compound (ALG) and heparinoid (HPD), which can further suppress the expression of thymic stromal lymphopoietin (TSLP).

[0033] The composition of this embodiment preferably contains the above-mentioned ester compound (ALG) and a heparinoid (HPD). The mass ratio of the heparinoid (HPD) to the above-mentioned ester compound (ALG) is preferably 15 or more, more preferably 20 or more, and even more preferably 25 or more. This mass ratio is preferably 150 or less, more preferably 120 or less, and even more preferably 100 or less. This allows for better suppression of thymic stromal lymphopoietin (TSLP) expression.

[0034] The composition of this embodiment preferably contains at least a heparinoid (HPD) and further contains at least one of N-acetylcysteine ​​(NAC) and the above-mentioned ester compound (ALG), thereby further suppressing the expression of thymic stromal lymphopoietin (TSLP).

[0035] The composition of this embodiment preferably contains N-acetylcysteine ​​(NAC) and a heparinoid (HPD). The mass ratio of N-acetylcysteine ​​(NAC) to heparinoid (HPD) is preferably 2 or more and 6 or less, and more preferably 3 or more and 5 or less. This allows for better suppression of thymic stromal lymphopoietin (TSLP) expression.

[0036] The composition may further contain surfactants, thickeners, preservatives, etc. in addition to the above components.

[0037] The properties and appearance of the composition of this embodiment are not particularly limited. The composition of this embodiment may be, for example, a liquid, semi-solid (gel, cream, etc.), or solid (powder, tablet, sheet, etc.). The composition of this embodiment may be contained in the contents of an aerosol product.

[0038] The composition of the present embodiment can be produced by mixing and stirring the components to be blended. A conventional stirring device can be used. If necessary, the mixture may be stirred while being heated.

[0039] The composition of the present embodiment may be used for the prevention or treatment of atopic dermatitis, for the prevention or treatment of allergic inflammation in the skin, or for the prevention or treatment of inflammation caused by sensitive skin or a rash.

[0040] The composition of this embodiment is usually used by applying it to the skin. For example, the composition may be applied to the skin of the face, neck, limbs, scalp, hair, or mucous membranes of the nostrils, lips, ears, genitals, anus, etc. It may also be incorporated into a bath additive or a skin patch. The composition may be classified as a cosmetic, quasi-drug, pharmaceutical, or the like under the Pharmaceutical and Medical Device Act, but may not be particularly restricted. The composition may be used in several fields.

[0041] The thymic stromal lymphopoietin expression inhibitor, topical skin composition, cosmetic, and pharmaceutical of the present invention are as exemplified above, but the present invention is not limited to the above-exemplified embodiments. Furthermore, the present invention can employ various forms commonly used in topical skin compositions, cosmetics, pharmaceuticals, etc., as long as the effects of the present invention are not impaired. [Example]

[0042] The present invention will now be described in more detail with reference to examples, but the present invention is not limited to these examples.

[0043] The performance of each composition was evaluated as follows: Details of each component contained in the composition are shown below.

[0044] [Details of each ingredient used] Dipotassium glycyrrhizinate, dry powder, commercially available Silanediol salicylate dry powder commercially available N-acetylglucosamine dry powder commercially available ε-Aminocaproic acid, dry powder, commercially available γ-Oryzanol solution (100% by mass) commercially available Aphanothece saccharin polysaccharide solution containing 0.5% by mass (commercially available) -Ingredients containing medium molecular weight hyaluronic acid (53.9% of the total hyaluronic acid is medium molecular weight hyaluronic acid) Product name: "Hyaluronic acid Na-FCH-SU" (manufactured by Kikkoman Biochemifa Corporation) Mannuronic acid oligomer methylsilanol ester 1.0% by mass solution Product name: "Argicium C" (manufactured by Eximol) Heparinoids, dry powder, commercially available Product name: "Extra-Regulatory Heparinoid (For Manufacturing Use Only)" (manufactured by API Co., Ltd.) N-acetylcysteine ​​dry powder Product name: "N-acetyl-L-cysteine" (manufactured by Nippon Rika Pharmaceuticals)

[0045] <TSLP expression suppression by each component alone> [Experimental Method] Normal human neonatal foreskin epidermal keratinocytes (Kurabo Industries, Ltd.) were seeded at 10,000 cells / well in a 96-well plate and cultured until confluent. Because TSLP is not expressed in normal human neonatal foreskin epidermal keratinocytes, TNF-α (R&D), IL-4 (R&D), IL-13 (R&D), and Poly;IC (R&D) were added as TSLP expression inducers and cultured for 24 hours to induce TSLP expression. The TSLP secretion level without stimulation was 0, whereas the TSLP secretion level with the TSLP expression inducers was 419 pg / mL. To evaluate the TSLP expression-inhibitory effect of each test component, the test component was added when the TSLP expression-inducing stimulant was added. Regardless of whether the component was in dry powder or solution form, the component was added at a concentration of 0.1% (mass / volume). After 24 hours of culture, the culture supernatant was collected. The amount of TSLP secreted in the collected culture supernatant was measured using a Human TSLP ELISA kit (Thermo Scientific). The TSLP expression level calculated by the ELISA assay was corrected by the cell count calculated by Cell Counting Kit-8 (Dojindo Laboratories), and the resulting value was used for analysis. The analytical value obtained with TSLP expression-inducing stimulation alone was set at 100%, and the analytical value for each test component was expressed as a relative value to evaluate the TSLP expression-inhibitory effect. [result] As shown in Figure 1, N-acetylcysteine, mannuronic acid oligomer methylsilanol ester, heparinoids, and medium-molecular-weight hyaluronic acid were all able to suppress TSLP expression independently.

[0046] <TSLP expression suppression by medium-molecular-weight hyaluronic acid> [Details of each hyaluronic acid used] N-acetylglucosamine (dry powder) Product name: "N-acetyl-D-glucosamine (for cosmetics)" (manufactured by Koyo Chemical Co., Ltd.) - Raw materials (dry powder form) mainly containing oligohyaluronic acid (molecular weight less than 50,000) Product name: "Hyalo Oligo" (Kewpie Corporation) Medium molecular weight hyaluronic acid content: Less than 15% (11.9% of total hyaluronic acid) - Raw materials (dry powder) containing mainly medium molecular weight hyaluronic acid (molecular weight between 50,000 and 400,000) Product name: "Hyaluronic acid Na-FCH-SU" (manufactured by Kikkoman Biochemifa Corporation) Medium molecular weight hyaluronic acid content: 53.9% (vs. total hyaluronic acid) - Raw materials containing mainly high molecular weight hyaluronic acid (molecular weight 500,000 to 700,000) (high molecular weight hyaluronic acid) (dry powder) Product name: "Sodium Hyaluronate-FCH-60" (manufactured by Kikkoman Biochemifa Corporation) Medium molecular weight hyaluronic acid content: Less than 15% (14.3% of total hyaluronic acid) [Experimental Method] Normal human neonatal foreskin epidermal keratinocytes (Kurabo Industries, Ltd.) were seeded at 10,000 cells / well in a 96-well plate and cultured until confluent. Because TSLP is not expressed in normal human neonatal foreskin epidermal keratinocytes, TSLP expression was induced by adding TNF-α (R&D), IL-4 (R&D), IL-13 (R&D), Poly;IC (R&D), and Flagellin (Sigma) as TSLP expression inducers. The cells were cultured for 24 hours to induce TSLP expression. The amount of TSLP secreted without stimulation was 0, whereas the amount of TSLP secreted with TSLP expression inducer was 510 pg / mL. To evaluate the TSLP expression inhibitory effect of each test component, each test component was added to the TSLP expression-inducing stimulant. Each test component was added to a dry powder concentration of 0.1% (mass / volume). After 24 hours of culture, the culture supernatant was collected. The amount of TSLP secreted in the collected culture supernatant was measured using a Human TSLP ELISA kit (Thermo Scientific). The value obtained by correcting the TSLP expression level calculated by the above ELISA measurement with the number of cells calculated by Cell counting kit-8 (Dojindo Laboratories) was used for analysis. The TSLP expression inhibitory effect was evaluated by expressing the analysis value for each test component as a relative value with the analysis value in the case of only the TSLP expression induction stimulus set as 100%. [Results] As shown in Fig. 2, medium molecular weight hyaluronic acid was able to suppress the expression of TSLP.

[0047] [TSLP expression inhibitory performance by N-acetylcysteine (NAC) and heparin-like substance (HPD)] [Details of each component used] It was formulated in the composition so that the total amount was equivalent to 0.1% [mass / volume] in terms of dry matter. · NAC was formulated alone · HPD was formulated alone · Both NAC and HPD were formulated [Experimental method] Normal human neonatal foreskin epidermal keratinocytes (manufactured by Kurabo Industries Ltd.) were seeded at 10,000 cells / well in a 96-well plate and cultured until confluent. Since TSLP is not expressed in normal human neonatal foreskin epidermal keratinocytes, TNF-α (manufactured by R&D), IL-4 (manufactured by R&D), IL-13 (manufactured by R&D), Poly;IC (manufactured by R&D), and Flagellin (manufactured by SIGMA) were added as TSLP expression induction stimulants, and the expression of TSLP was induced by culturing for 24 hours. As a result, the TSLP secretion amount in the case without stimulation was 0, whereas the TSLP secretion amount in the case with TSLP expression induction stimulation was 510 pg / mL. To evaluate the TSLP expression inhibitory effect of each test component, the test component was added when adding the above TSLP expression induction stimulant, and the culture supernatant was collected after culturing for 24 hours. The TSLP secretion amount in the collected culture supernatant was measured using a Human TSLP ELISA kit (manufactured by Thermo Scientific). The TSLP expression level calculated by the ELISA assay was corrected by the cell count calculated by Cell Counting Kit-8 (Dojindo Laboratories), and the resulting value was used for analysis. The analytical value obtained with TSLP expression-inducing stimulation alone was set at 100%, and the analytical value for each test component was expressed as a relative value to evaluate the TSLP expression-inhibitory effect. [result] As shown in Figure 3, the combination of N-acetylcysteine ​​(NAC) and heparinoid (HPD) synergistically suppressed TSLP expression.

[0048] <TSLP expression suppression by mannuronic acid oligomer methylsilanol ester (ALG) and heparinoid (HPD)> [Details of each ingredient used] Each component was blended into the composition so as to achieve the % concentration [mass / volume] shown in Figures 4 and 5, respectively, in terms of dry matter (solid content). - Formulated with ALG alone HPD alone Contains both ALG and HPD [Experimental Method] Normal human neonatal foreskin epidermal keratinocytes (Kurabo Industries, Ltd.) were seeded at 10,000 cells / well in a 96-well plate and cultured until confluent. Because TSLP is not expressed in normal human neonatal foreskin epidermal keratinocytes, TNF-α (R&D), IL-4 (R&D), IL-13 (R&D), Poly;IC (R&D), and Flagellin (Sigma) were added as TSLP expression inducers and the cells were cultured for 24 hours to induce TSLP expression. To evaluate the TSLP expression-inhibitory effect of each test component, the test component was added at the same time as the TSLP expression-inducing stimulant was added, and the culture supernatant was collected after 24 hours of culture. The amount of TSLP secreted in the collected culture supernatant was measured using a Human TSLP ELISA kit (Thermo Scientific). The TSLP expression level calculated by the ELISA assay was corrected by the cell count calculated by Cell Counting Kit-8 (Dojindo Laboratories), and the resulting value was used for analysis. The analytical value obtained with TSLP expression-inducing stimulation alone was set at 100%, and the analytical value for each test component was expressed as a relative value to evaluate the TSLP expression-inhibitory effect. [result] As shown in Figures 4 and 5, the combination of mannuronic acid oligomer methylsilanol ester (ALG) and heparinoid (HPD) synergistically suppressed TSLP expression.

[0049] As described above, the thymic stromal lymphopoietin (TSLP) expression inhibitor and topical skin composition of the present embodiment can inhibit the expression of TSLP, thereby preventing or ameliorating, for example, atopic dermatitis, skin itching, allergic inflammation, and inflammation caused by dryness or rash. [Industrial Applicability]

[0050] The thymic stromal lymphopoietin expression inhibitor, topical skin composition, cosmetic, and pharmaceutical of the present invention are applied to the skin for use, for example, to improve inflammation of atopic dermatitis, or to improve inflammation caused by contact allergic inflammation, dryness, or rash. The thymic stromal lymphopoietin expression inhibitor, topical skin composition, cosmetic, and pharmaceutical of the present invention are preferably used by, for example, applying directly to the stratum corneum, specifically, by applying to skin affected by atopic dermatitis.

Claims

1. An inhibitor of thymic stromal lymphopoietin expression, comprising at least one of mannuronic acid oligomer methylsilanol ester, heparin-like substance, and medium molecular weight hyaluronic acid having a molecular weight of 50,000 or more and 400,000 or less.

2. The thymic stromal lymphopoietin expression inhibitor according to claim 1 , comprising at least one of the mannuronic acid oligomer methylsilanol ester and the heparinoid.

3. The thymic stromal lymphopoietin expression inhibitor according to claim 1 , comprising the mannuronic acid oligomer methylsilanol ester and the heparinoid.

4. A composition for topical application to the skin, comprising a mannuronic acid oligomer methylsilanol ester and a heparinoid.

5. A cosmetic comprising a mannuronic acid oligomer methylsilanol ester and a heparinoid.

6. A pharmaceutical comprising a mannuronic acid oligomer methylsilanol ester and a heparinoid.

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