topical skin preparations

Abstract

To provide new means to improve an ECM cycle.SOLUTION: A topical skin preparation comprises a hydrolyzed Pinctada fucata byssus.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to topical skin preparations, and more particularly to topical skin preparations, agents for improving wrinkles and / or sagging skin, eye drops, corneal wound healing agents, extracellular matrix (ECM) cycle improving agents, and Endo180 expression enhancers. [Background technology]

[0002] In the dermis of the skin, ECM, which is composed of proteins such as collagen and elastin, surrounds fibroblasts. ECM components such as collagen and elastin are responsible for important skin functions such as firmness and elasticity. To maintain the homeostasis of these functions, it is known that the ECM components are produced by fibroblasts and then degraded, and the degradation products are taken up by fibroblasts, resulting in the production of new ECM components, in a cycle known as the "homeostasis of the ECM." It has also been discovered that natural aging due to aging and photoaging due to ultraviolet rays slows down the uptake of degradation products and the production of ECM components, disrupting the ECM cycle, and that when the ECM cycle is disrupted, wrinkles and sagging skin become more likely to form. Therefore, for example, lycoperoside A has been proposed as an ECM cycle improver (Patent Documents 1 and 2). Genes involved in the ECM cycle include Endo180, Smad2, Neurainidase-1, and Fibulin-4, as well as LAMP-1. Endo180 is known to be involved in the uptake of fragmented collagen by fibroblasts, Smad2 in collagen production by fibroblasts, Neurainidase-1 in the uptake of fragmented elastin by fibroblasts, and Fibulin-4 in elastin production by fibroblasts. LAMP-1 is also known to be involved in the intracellular digestion of fibroblasts and the clearance of ECM components.

[0003] Furthermore, it has been reported that Endo180 heals corneal wounds when expressed in keratocytes (for example, Non-Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 2020-65539 [Patent Document 2] Patent Publication No. 2021-6043 [Non-patent literature]

[0005] [Non-Patent Document 1] Aya Takahashi, "The role of Endo180 in collagen contractility in corneal stromal cells (Kindai University Grant-in-Aid for Scientific Research, 20K18401)" (https: / / kaken.nii.ac.jp / ja / grant / KAKENHI-PROJECT-20K18401 / ) Summary of the Invention [Problem to be solved by the invention]

[0006] On the other hand, although the byssus of the pearl oyster (Pinctada fucata) is known to be adhesive and rich in protein, there have been no reports examining whether pearl oyster byssus hydrolysate has an effect on improving the ECM cycle, such as by enhancing the expression of Endo180, Smad2, Neurainidase-1, Fibulin-4, and LAMP-1.Furthermore, there have been no reports examining whether pearl oyster byssus hydrolysate has an effect on improving skin wrinkles and sagging, or on corneal wound healing.

[0007] An object of the present invention is to provide a new means for improving the ECM cycle. [Means for solving the problem]

[0008] The object of the present invention is to provide the following <1> ~ <26> was resolved by the following means. <1> An external skin preparation (hereinafter also referred to as the external skin preparation of the present invention) containing a pearl oyster byssus hydrolysate. <2> The pearl oyster byssus hydrolysate is one or more selected from the group consisting of an acid hydrolysate of pearl oyster byssus, an alkaline hydrolysate of pearl oyster byssus, and an enzymatic hydrolysate of pearl oyster byssus. <1> The topical skin preparation according to claim 1. <3> An agent for improving wrinkles and / or sagging skin (hereinafter also referred to as the agent for improving wrinkles and / or sagging skin of the present invention) containing a pearl oyster byssus hydrolysate as an active ingredient. <4> An eye drop containing a pearl oyster byssus hydrolysate (hereinafter also referred to as the eye drop of the present invention). <5> A corneal wound healing agent (hereinafter also referred to as the corneal wound healing agent of the present invention) containing a pearl oyster byssus hydrolysate as an active ingredient. <6> An ECM cycle improver (hereinafter also referred to as the ECM cycle improver of the present invention) containing a pearl oyster byssus hydrolysate as an active ingredient. <7> An Endo180 expression enhancer (hereinafter also referred to as the Endo180 expression enhancer of the present invention) containing a pearl oyster byssus hydrolysate as an active ingredient.

[0009] <8> An Smad2 expression enhancer whose active ingredient is pearl oyster byssus hydrolysate. <9> A neurinidase-1 expression enhancer whose active ingredient is pearl oyster byssus hydrolysate. <10> A fibulin-4 expression enhancer whose active ingredient is hydrolyzed pearl oyster byssus. <11> A LAMP-1 expression enhancer whose active ingredient is pearl oyster byssus hydrolysate.

[0010] <12> A collagen production cycle enhancer whose active ingredient is Akoya oyster byssus hydrolysate. <13> An elastin production cycle enhancer whose active ingredient is hydrolyzed pearl oyster byssus. <14> An ECM component clearance enhancer (hereinafter referred to as <1> and <3> ~ <14> These agents are collectively referred to as the agent of the present invention).

[0011] <15> Use of a pearl oyster byssus hydrolysate for the manufacture of an agent for improving wrinkles and / or sagging skin. <16> Use of pearl oyster byssus hydrolysate for improving wrinkles and / or sagging skin. <17> A method for improving wrinkles and / or sagging skin, comprising a step of using a pearl oyster byssus hydrolysate.

[0012] <18> Use of a pearl oyster byssus hydrolysate for the manufacture of a corneal wound healing agent. <19> Use of pearl oyster byssus hydrolysate for corneal wound healing. <20> A method for healing corneal wounds, comprising a step of using a pearl oyster byssus hydrolysate.

[0013] <21> Use of pearl oyster byssus hydrolysate for the production of an ECM cycle improving agent. <22> Use of pearl oyster byssus hydrolysate to improve the ECM cycle. <23> A method for improving the ECM cycle, comprising a step of using pearl oyster byssus hydrolysate.

[0014] <24> Use of a pearl oyster byssus hydrolysate for the production of an Endo180 expression enhancer. <25> Use of pearl oyster byssus hydrolysate to enhance Endo180 expression. <26> A method for enhancing Endo180 expression, comprising a step of using a pearl oyster byssus hydrolysate. [Effects of the Invention]

[0015] The topical skin preparation, skin wrinkle and / or sagging improving agent, eye drop, corneal wound healing agent, and ECM cycle improving agent of the present invention have an excellent ECM cycle improving effect. The Endo180 expression enhancer of the present invention has an excellent effect of enhancing Endo180 expression. [Brief explanation of the drawings]

[0016] [Figure 1] Graph showing the effect of pearl oyster byssus hydrolysate on improving the ECM cycle. [Figure 2] Graph showing the effect of pearl oyster byssus hydrolysate on enhancing Endo180 expression. [Figure 3] A diagram showing that pearl oyster byssus hydrolysate alleviates the decrease in Endo180 expression. [Figure 4] A diagram showing that pearl oyster byssus hydrolysate alleviates the decrease in Endo180 production. DETAILED DESCRIPTION OF THE INVENTION

[0017] The agent of the present invention is characterized by using a pearl oyster byssus hydrolysate. First, the pearl oyster byssus hydrolysate will be described in detail.

[0018] (Hydrolyzed pearl oyster byssus) The term "Akoya oyster byssus hydrolysate" refers to the hydrolysis of the byssus of the pearl oyster (Pinctada fucata). The byssus of the pearl oyster is rich in protein, and hydrolysis produces protein hydrolysates including various amino acids. After the byssus of the pearl oyster is recovered from the pearl oyster, one or two steps selected from a cutting step in which the byssus is cut into small pieces, and an attachment removal step in which attachments are removed from the byssus using running water or the like may be carried out as necessary prior to hydrolysis.

[0019] Examples of the pearl oyster byssus hydrolysate include one or more selected from the group consisting of an acid hydrolysate of pearl oyster byssus, an alkaline hydrolysate of pearl oyster byssus, and an enzymatic hydrolysate of pearl oyster byssus. Among these, one or more selected from the group consisting of an acid hydrolysate of pearl oyster byssus and an enzymatic hydrolysate of pearl oyster byssus are preferred, and an acid hydrolysate of pearl oyster byssus is more preferred.

[0020] Examples of acids used in acid hydrolysis include inorganic acids such as hydrochloric acid, nitric acid, sulfuric acid, boric acid, and phosphoric acid; and organic acids such as acetic acid and citric acid. These acids may be used singly or in combination of two or more. Acids can be broadly classified into strong acids and weak acids, with strong acids being preferred. The pH of the acid hydrolysis is preferably 0.001 to 3.0, more preferably 0.1 to 2.0. The reaction temperature for acid hydrolysis is usually 70 to 140°C, and the reaction time is usually 6 to 72 hours, preferably 12 to 36 hours. After completion of the acid hydrolysis reaction and cooling as necessary, it is preferable to carry out a step selected from a neutralization step, a solid-liquid separation step in which precipitates and / or suspended matter are removed by a solid-liquid separation operation (e.g., decantation, centrifugation, filtration, etc.), and a drying step (e.g., one or more steps selected from reduced pressure, heating, and freeze-drying). Note that the solid-liquid separation operation may be carried out singly or in combination of two or more steps.

[0021] The neutralization step may be carried out, for example, by gradually adding hydroxide to the reaction product of the acid hydrolysis and stirring the mixture. Examples of hydroxides include alkali metal hydroxides such as lithium hydroxide, potassium hydroxide, and sodium hydroxide; and alkaline earth metal hydroxides such as calcium hydroxide, strontium hydroxide, and barium hydroxide. When a solid-liquid separation step is carried out after the neutralization step, a hydrophilic organic solvent may be added and allowed to stand at 0 to 30°C prior to solid-liquid separation. This allows the solubilized neutralized salt to precipitate. Examples of hydrophilic organic solvents include methanol, ethanol, n-propyl alcohol, isopropyl alcohol, butyl alcohol, ethylene glycol, propylene glycol, diethylene glycol, glycerin, trimethylolpropane, 1,3-butylene glycol, acetone, and methyl ethyl ketone.

[0022] Examples of alkalis used in alkaline hydrolysis include alkali metal hydroxides such as lithium hydroxide, potassium hydroxide, and sodium hydroxide. These may be used alone or in combination of two or more. Alkalis can be broadly classified into strong alkalis and weak alkalis, with strong alkalis being preferred. The pH of the alkaline hydrolysis is preferably 11.0 to 14.0, more preferably 12.0 to 14.0. The reaction temperature and reaction time for alkaline hydrolysis are preferably in the same ranges as those for acid hydrolysis. After completion of the alkaline hydrolysis reaction, the reaction mixture is cooled as necessary, and then a step selected from a neutralization step, a solid-liquid separation step, and a drying step is preferably carried out. The solid-liquid separation step and the drying step may be carried out in the same manner as the solid-liquid separation step and the drying step after completion of the acid hydrolysis reaction. When the solid-liquid separation step is carried out after the neutralization step, a hydrophilic organic solvent may be added and allowed to stand at 0 to 30°C prior to the solid-liquid separation. Examples of the hydrophilic organic solvent include those similar to those mentioned above.

[0023] The neutralization step may be carried out, for example, by gradually adding an acid to the reaction product of alkaline hydrolysis and stirring the mixture. Examples of the acid include inorganic salts such as hydrochloric acid, nitric acid, and sulfuric acid; and organic acids such as acetic acid and citric acid.

[0024] The enzymatic hydrolysis may be carried out using a protease. Examples of proteolytic enzymes of plant origin include papain, bromelain, and ficin. Examples of proteolytic enzymes of animal origin include trypsin, chymotrypsin, kallikrein, and pancreatin. These proteolytic enzymes may be used alone or in combination of two or more. Among these, trypsin and α-chymotrypsin are preferred. Proteolytic enzymes produced by Aspergillus, Bacillus subtilis, actinomycetes, etc. may also be used. After enzymatic hydrolysis, a step selected from an enzyme inactivation step, a solid-liquid separation step (e.g., decantation, centrifugation, filtration, etc.), and a drying step (e.g., reduced pressure, heating, freeze-drying, etc.) may be carried out.

[0025] The weight-average molecular weight of the pearl oyster byssus hydrolysate is preferably 75-800, more preferably 100-500. The weight average molecular weight can be calculated, for example, from the content ratio of each amino acid in the pearl oyster byssus hydrolysate and the average degree of polymerization.

[0026] (External skin preparation) The topical skin preparation of the present invention is characterized by containing the above-mentioned pearl oyster byssus hydrolysate. The content of the pearl oyster byssus hydrolysate in the external skin preparation of the present invention is preferably 0.001% by mass or more and 5% by mass or less, and more preferably 0.002% by mass or more and 1% by mass or less. In addition to the pearl oyster byssus hydrolysate, the topical skin preparation of the present invention may contain water, a lower alcohol, an oil, a surfactant, a water-soluble polymer, a powder, a disinfectant, a moisturizer, a fragrance, a preservative, a colorant, a chelating agent, an ultraviolet protection agent, an antioxidant, a pH adjuster, etc. These may be used alone or in combination of two or more.

[0027] The topical skin preparation of the present invention can be an emulsion composition (oil-in-water emulsion composition, water-in-oil emulsion composition), an aqueous composition, or an oily composition depending on the intended use, etc. The dosage form may be any of solid, semi-solid, and liquid. The application site of the external skin preparation of the present invention is preferably the skin excluding the scalp, more preferably the face, body, hands, feet, etc. The external skin preparation of the present invention can be produced by a conventional method.

[0028] Furthermore, the topical skin preparation of the present invention has an excellent effect of improving the ECM cycle. As used herein, "ECM cycle improvement" refers to the improvement of disruption of a series of cycles, including the production of extracellular matrix (ECM) components by fibroblasts, the degradation of ECM components, the uptake of the degradation products into fibroblasts, and the production of new ECM components. Examples of ECM cycle improvement include enhancement of the collagen production cycle, such as increased Endo180 expression and Smad2 expression; enhancement of the elastin production cycle, such as increased Neurainidase-1 expression and Fibulin-4 expression; and enhancement of ECM component clearance, such as increased LAMP-1 expression. As shown in the examples below, the topical skin preparation of the present invention has excellent effects of increasing Endo180 expression in dermal fibroblasts, Smad2 expression in dermal fibroblasts, Neurainidase-1 expression in dermal fibroblasts, Fibulin-4 expression in dermal fibroblasts, and LAMP-1 expression in dermal fibroblasts. Therefore, the topical skin preparation of the present invention is useful for improving wrinkles and / or sagging skin. As used herein, "improving wrinkles and / or sagging skin" is a concept that encompasses not only improving either or both of wrinkles and sagging skin formed on the skin, but also inhibiting either or both of wrinkles and sagging skin from forming on the skin. The topical skin preparation of the present invention can be in the form of various cosmetics, quasi-drugs, or pharmaceuticals. More specifically, the cosmetic form can be skin care cosmetics such as lotions, serums, packs, emulsions, creams, and sunscreens (e.g., sunscreen emulsions and sunscreen creams); makeup cosmetics such as powders, foundations, eye shadows, mascaras, eyeliners, lipsticks, and lip balms; bath additives; and skin cleansers. The pharmaceutical or quasi-drug form can be ointments, creams, topical liquids, patches, and the like.

[0029] (eye drops) The eye drops of the present invention are characterized by containing the above-mentioned pearl oyster byssus hydrolysate. The content of the pearl oyster byssus hydrolysate in the eye drops of the present invention is preferably 0.001% by mass or more and 5% by mass or less, and more preferably 0.001% by mass or more and 1% by mass or less. In addition to the pearl oyster byssus hydrolysate, the eye drops of the present invention may contain additives that are incorporated into pharmaceuticals and quasi-drugs. Examples of such additives include isotonicity agents, chelating agents, preservatives, antioxidants, thickening agents, and various bases (e.g., water). These additives may be used alone or in combination of two or more.

[0030] The dosage form of the eye drops of the present invention may be any of solid, semi-solid and liquid, but is preferably semi-solid or liquid. The eye drops of the present invention can be produced by a conventional method.

[0031] The eye drops of the present invention are excellent in the effect of increasing Endo180 expression in corneal stromal cells. Therefore, the eye drops of the present invention are useful for corneal wound healing.

[0032] (Agent for improving wrinkles and / or sagging skin, corneal wound healing agent, ECM cycle improver, and Endo180 expression enhancer) The agent for improving wrinkles and / or sagging of skin, the agent for healing corneal wounds, the agent for improving the ECM cycle, and the agent for enhancing Endo180 expression of the present invention contain the above-mentioned pearl oyster byssus hydrolysate as an active ingredient.

[0033] As shown in the Examples below, pearl oyster byssus hydrolysate has excellent effects of improving the ECM cycle and enhancing Endo180 expression. Examples of ECM cycle improvement include, as described above, enhancing the collagen production cycle through enhanced Endo180 expression and Smad2 expression; enhancing the elastin production cycle through enhanced Neurainidase-1 expression and Fibulin-4 expression; and enhancing the clearance of ECM components through enhanced LAMP-1 expression. Among these, pearl oyster byssus hydrolysate is suitable for enhancing the collagen production cycle and is particularly suitable for enhancing Endo180 expression. The pearl oyster byssus hydrolysate can enhance the expression of Endo180 in skin fibroblasts or corneal stromal cells, the expression of Smad2 in skin fibroblasts, the expression of Neurainidase-1 in skin fibroblasts, the expression of Fibulin-4 in skin fibroblasts, and the expression of LAMP-1 in skin fibroblasts, and is therefore useful as an agent for improving skin wrinkles and / or sagging and as an agent for healing corneal wounds. Examples of sites where Endo180, Smad2, Neurainidase-1, Fibulin-4, and LAMP-1 are expressed include skin and eye tissue.

[0034] In addition, the pearl oyster byssus hydrolysate can be used as an agent for improving skin wrinkles and / or sagging, an agent for healing corneal wounds, an agent for improving ECM cycle, and an agent for enhancing Endo180 expression, and can be used for improving skin wrinkles and / or sagging, healing corneal wounds, improving the ECM cycle, and enhancing Endo180 expression, and can also be used to produce an agent for improving skin wrinkles and / or sagging, an agent for healing corneal wounds, an agent for improving ECM cycle, and an agent for enhancing Endo180 expression. Here, the above-mentioned "use" may be administration or ingestion to a human or a non-human animal, and may be therapeutic or non-therapeutic use. Note that "non-therapeutic" is a concept that does not include medical procedures, i.e., a concept that does not include methods of surgery, therapy, or diagnosis on humans, more specifically, a concept that does not include methods of surgery, therapy, or diagnosis on humans by a physician or a person under the direction of a physician.

[0035] The agents for improving wrinkles and / or sagging skin, corneal wound healing agents, ECM cycle improvers, and Endo180 expression enhancers of the present invention can be used as pharmaceuticals, quasi-drugs, cosmetics, or foods that are effective in improving wrinkles and / or sagging skin, healing corneal wounds, improving the ECM cycle, and enhancing Endo180 expression, or as ingredients to be incorporated into pharmaceuticals, quasi-drugs, cosmetics, or foods. The food products are based on the concept of improving wrinkles and / or sagging skin, healing corneal wounds, improving the ECM cycle, and increasing Endo180 expression, and can be labeled as such as health functional foods (e.g., functional foods, foods for specified health uses, foods with nutrient functions, etc.) as needed.

[0036] The application means of the skin wrinkle and / or sagging improving agent and ECM cycle improving agent of the present invention is preferably oral or transdermal, more preferably transdermal. The application means of the corneal wound healing agent of the present invention is preferably eye drop. The application means of the Endo180 expression enhancer of the present invention is preferably oral, transdermal, or eye drop, more preferably oral or eye drop. Note that "skin" is a concept that encompasses the skin of the face, body, hands, feet, and scalp. Ingredients other than the pearl oyster byssus hydrolysate that can be blended when formulated for transdermal use (topical skin preparation) or eye drop use (eye drops) include the same ingredients that can be blended in the topical skin preparation and eye drops of the present invention.

[0037] When the agent for improving wrinkles and / or sagging skin, the agent for improving ECM cycle, or the agent for enhancing Endo180 expression of the present invention is used transdermally (as an external preparation for skin), its dosage form may be an ointment, cream, emulsion, gel, paste, lotion, spray, patch, etc. Furthermore, the external preparation for skin may be in the form of, for example, a lotion, serum, pack, emulsion, cream, sunscreen, sun oil, bath additive, skin cleanser, etc.

[0038] In the skin wrinkle and / or sagging improvement agent, corneal wound healing agent, ECM cycle improvement agent, and Endo180 expression enhancer of the present invention, the content of Akoya oyster byssus hydrolysate is preferably 0.001% by mass or more and 5% by mass or less, and more preferably 0.002% by mass or more and 1% by mass or less. The agent for improving skin wrinkles and / or sagging, corneal wound healing agent, ECM cycle improving agent, and Endo180 expression enhancer of the present invention is preferably ingested, applied, or instilled into the eyes in an amount of 0.2 to 100 mg, more preferably 0.4 to 20 mg, per day for an adult, as a pearl oyster byssus hydrolysate. [Example]

[0039] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[0040] [Preparation Example: Preparation of pearl oyster byssus hydrolysate] 50 g of pearl oyster byssus, after removing any extraneous matter with running water, was placed in a flask equipped with a condenser, and 500 g of sulfuric acid diluted 10 times with water was added. The mixture was hydrolyzed at 110°C for 24 hours (pH: 1.0). After cooling, calcium hydroxide was gradually added to adjust the pH to 6.5. The product was then centrifuged (6000 rpm, 15 minutes) and the supernatant was collected. Two volumes of ethanol were added to the supernatant, stirred, and allowed to stand at 4°C for 14 days. The mixture was then filtered, and the filtrate was collected. The collected filtrate was then evaporated and freeze-dried to obtain a pearl oyster byssus hydrolysate (weight-average molecular weight: 137).

[0041] [Test Example 1: ECM Cycle Improvement Effect] Normal human dermal fibroblasts (hereafter abbreviated as NHDF; cells from the second passage, manufactured by Kurabo) were pre-cultured in serum-free medium for NHDF (hereafter abbreviated as BM) at 37°C and 5% CO2 for 24 hours. Next, the pearl oyster byssus hydrolysate obtained in the preparation examples was adjusted to a concentration of 0 mg / mL (control), 5 mg / mL, or 10 mg / mL in fresh medium (BM), and added to NHDF as test medium. The medium was then post-cultured for 48 hours at 37°C and 5% CO2. After 48 hours of culture, the expression levels of five genes related to the ECM cycle improvement effect (Endo180, Smad2, Neurainidase-1, Fibulin-4, and LAMP-1) were evaluated by real-time PCR. The results are shown in Figure 1 (Mean ± SD, n = 5, *: p < 0.05, **: p < 0.01; the ECM cycle improvement effects shown in Figure 1 are relative values ​​with the expression level in the control group set at 1.0). As shown in Figure 1, improvement of the ECM cycle in normal human skin fibroblasts was confirmed when pearl oyster byssus hydrolysate was used.

[0042] [Test Example 2: Endo180 Expression Enhancement Effect (1)] NHDFs were pre-cultured with BM for 24 hours at 37°C and 5% CO2. Next, the pearl oyster byssus hydrolysate obtained in the preparation example was adjusted to a concentration of 0 mg / mL (control) or 10 mg / mL in fresh medium (BM), and added to NHDF as a test medium. After incubation for 48 hours at 37°C and 5% CO, the amount of Endo180 produced was analyzed by ELISA. The results are shown in Figure 2 (Mean ± SD, n = 3, *: p < 0.05, the effect of enhancing Endo180 expression shown in Figure 2 is a relative value when the production rate in the control group was set at 100%). As shown in Figure 2, the expression of Endo180 was enhanced when the pearl oyster byssus hydrolysate was used.

[0043] [Test Example 3: Endo180 Expression Enhancement Effect (2)] NHDFs were pre-cultured with BM for 24 hours at 37°C and 5% CO2. The cultures were then divided into four groups. Group 1 contained fresh medium (BM), Group 2 contained test medium containing 10 ng / mL interleukin-1α (IL-1α) in fresh medium (BM), Group 3 contained test medium containing 10 ng / mL IL-1α and 5 mg / mL pearl oyster byssus hydrolysate in fresh medium (BM), and Group 4 contained test medium containing 10 ng / mL IL-1α and 10 mg / mL pearl oyster byssus hydrolysate in fresh medium (BM). Each group was cultured at 37°C and 5% CO for 48 hours. After 48 hours of culture, gene and protein expression of Endo180 were analyzed.

[0044] The expression levels of Endo180 mRNA are shown in Figure 3 (Mean ± SD, n = 5, *: p < 0.05, **: p < 0.01, the expression levels of Endo180 mRNA shown in Figure 3 are relative values ​​when the expression level in the control group is set to 1.0). As shown in Figure 3, the addition of IL-1α decreased the expression level of Endo180, but when IL-1α was added together with the pearl oyster byssus hydrolysate, the expression level of Endo180 increased. Thus, the pearl oyster byssus hydrolysate was found to have the effect of alleviating the IL-1α-induced decrease in Endo180 expression.

[0045] The Endo180 production rates are shown in Figure 4 (Mean ± SD, n = 3, *: p < 0.05, **: p < 0.01, the Endo180 production rates shown in Figure 4 are relative values ​​when the production rate in the control group was set at 100%). As shown in Figure 4, the addition of IL-1α reduced the amount of Endo180 produced, but when IL-1α was added together with the pearl oyster byssus hydrolysate, the amount of Endo180 produced increased. Thus, the pearl oyster byssus hydrolysate was found to have the effect of alleviating the IL-1α-induced decrease in Endo180 production. These results indicate that pearl oyster byssus hydrolysate alleviates the suppression of Endo180 expression in NHDF by IL-1α, which is secreted from epidermal keratinocytes in response to UV irradiation.

Claims

1. An external skin preparation containing a pearl oyster byssus hydrolysate, wherein the pearl oyster byssus hydrolysate has a weight average molecular weight of 75 to 800.

2. The topical skin preparation according to claim 1, wherein the Akoya oyster byssus hydrolysate is one or more selected from the group consisting of an acid hydrolysate of Akoya oyster byssus, an alkaline hydrolysate of Akoya oyster byssus, and an enzymatic hydrolysate of Akoya oyster byssus.

3. An agent for improving wrinkles and / or sagging skin, comprising a pearl oyster byssus hydrolysate as an active ingredient, wherein the pearl oyster byssus hydrolysate has a weight average molecular weight of 75 to 800.

4. An agent for improving the ECM cycle of normal human skin fibroblasts, containing pearl oyster byssus hydrolysate as an active ingredient.

5. An agent for enhancing Endo180 expression in normal human skin fibroblasts, containing a hydrolyzed product of pearl oyster byssus as an active ingredient.

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