Agent for improving dermal thickness, agent for improving skin texture, and cosmetic for improving dermal thickness or skin texture

Abstract

To provide a novel agent for improving dermal thickness and a novel agent for improving skin texture.SOLUTION: Provided is an agent for improving dermal thickness and an agent for improving skin texture, comprising enzyme-treated royal jelly as an active ingredient.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a dermis thickness improving agent, a skin texture improving agent, and a cosmetic product for improving dermis thickness or skin texture. [Background technology]

[0002] The skin is composed of the epidermis and dermis. Skin texture is the unevenness of the skin surface created by skin ridges and skin furrows.

[0003] Patent Document 1 discloses a skin collagen production promoter that contains apisin as an active ingredient. Apisin is a protein contained in royal jelly. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2012-56890 A [Non-patent literature]

[0005] [Non-Patent Document 1] Fragrance Journal, June 2017, Vol.45, No.6, p66-70 [Non-Patent Document 2] Fragrance Journal, August 2020, Vol.48, No.8, p22-26 Summary of the Invention [Problem to be solved by the invention]

[0006] The thickness of the dermis becomes thinner when collagen in the dermis decreases. Furthermore, as the skin thins, wrinkles appear. On the other hand, it is known that when collagen production is promoted, thinning of the skin improves and wrinkles are improved.

[0007] It is believed that the condition of the epidermis mainly affects the texture of the skin, but the condition of the dermis also has an effect on the texture of the skin.

[0008] An object of one aspect of the present invention is to provide a novel agent for improving dermis thickness.An object of another aspect of the present invention is to provide a novel agent for improving skin texture. [Means for solving the problem]

[0009] The present inventors have found that enzyme-treated royal jelly has an excellent effect of improving the thickness of the dermis and the texture of the skin. That is, the present invention relates to the following [1] to [7]. [1] A dermis thickness improving agent whose active ingredient is enzyme-treated royal jelly. [2] A dermis thickness improving agent described in [1], which is used to improve skin wrinkles. [3] A dermal thickness improving agent described in [1], for improving sagging skin. [4] A dermis thickness improving agent described in [1] for improving skin firmness. [5] A skin texture improving agent whose active ingredient is enzyme-treated royal jelly. [6] The improving agent according to any one of [1] to [5], wherein the enzyme-treated royal jelly is royal jelly treated with a peptidase having endopeptidase activity and exopeptidase activity. [7] A cosmetic for improving dermis thickness or skin texture, comprising the improving agent according to any one of [1] to [6]. Effect of the Invention

[0010] According to one aspect of the present invention, there is provided a novel agent for improving dermis thickness. Also, according to another aspect of the present invention, there is provided a novel agent for improving skin texture. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] Hereinafter, the embodiment for carrying out the present invention will be described in detail, however, the present invention is not limited to the following embodiment.

[0012] In this specification, the term "comprise" includes the meanings of "essentially consist of" and "consist of only." In addition, in this specification, "skin" and "skin" are synonymous.

[0013] The dermis thickness improving agent of the present invention contains enzymatically decomposed royal jelly as an active ingredient. The dermis thickness improving agent of the present invention contains enzymatically decomposed royal jelly as an active ingredient, and is thereby capable of improving the thickness of the dermis.

[0014] Improving the thickness of the dermis includes, for example, increasing the thickness of the dermis within an appropriate range and inhibiting a decrease in the thickness of the dermis.

[0015] Elastic fibers are an extracellular matrix that provides elasticity. Dermal elastic fibers present in the dermis are mainly composed of tropoelastin (TE) and fibrillin (FBN). The mechanism of elastic fiber formation is said to be that self-assembled TE is deposited on the fine fibers of FBN constructed outside the cells, and strong crosslinks are formed by enzymes, resulting in an elastic fibrous structure. Among the components of elastic fibers, the association between FBN fibers, which serve as a scaffold for fiber formation, and wrinkles and sagging has been pointed out (Non-Patent Document 1). In addition, the relationship between collagen production in the dermis and wrinkles and firmness of the skin has been reported (Non-Patent Document 2). By improving the thickness of the dermis with the dermal thickness improving agent of the present invention, it is expected that wrinkles, sagging, and firmness of the skin will be improved. Therefore, the dermal thickness improving agent of the present invention can also be used for improving wrinkles, sagging, and firmness of the skin.

[0016] The skin texture improving agent of the present invention contains enzymatically decomposed royal jelly as an active ingredient. The skin texture improving agent of the present invention contains enzymatically decomposed royal jelly as an active ingredient, and thus can improve skin texture.

[0017] Improvement of skin texture includes, for example, an increase in the texture volume ratio, an increase in the texture area ratio, an increase in the maximum texture depth, an increase in the number of textures, etc. The shape and number of textures, such as the texture volume ratio, can be measured, for example, by a reflection replica analysis system ASA-03RXD (Nippon Ash Co., Ltd.).

[0018] The dermis thickness improving agent and skin texture improving agent of the present invention each also include the meaning of an additive that imparts an effect of improving the dermis thickness or improving the skin texture.

[0019] Royal jelly is a milky white jelly-like substance made by mixing secretions secreted from the hypopharyngeal gland and mandibular gland by 3-12-day-old worker bees among honeybees. The main physiologically active components in royal jelly include, for example, organic acids such as saturated fatty acids and unsaturated fatty acids that are specific to royal jelly, proteins, amino acids, peptides, lipids, sugars, vitamin B, vitamins such as folic acid, nicotinic acid, and pantothenic acid, and various minerals. Royal jelly may be produced in any of European countries, Oceanian countries, America, Brazil, Japan, China, and other Asian countries.

[0020] The enzyme-treated royal jelly is royal jelly treated with a proteolytic enzyme (protease). Preferably, the enzyme-treated royal jelly is hypoallergenic, in which allergic reactions caused by proteins contained in royal jelly are suppressed by protease treatment. Therefore, the enzyme-treated royal jelly may contain organic acids such as the above-mentioned saturated fatty acids and unsaturated fatty acids, lipids, sugars, vitamins, and various minerals, in addition to the protease decomposition products of proteins contained in royal jelly.

[0021] The royal jelly used to produce the enzyme-treated royal jelly is not particularly limited, and examples thereof include raw royal jelly, royal jelly powder obtained by drying and powdering raw royal jelly, and raw royal jelly extracted with water or aqueous ethanol, etc.

[0022] Enzyme-treated royal jelly can be produced by treating royal jelly raw material with an enzyme having at least endopeptidase activity, an enzyme having at least exopeptidase activity, and / or an enzyme having both endopeptidase activity and exopeptidase activity.

[0023] Examples of proteolytic enzymes having at least endopeptidase activity include endopeptidases derived from animals (e.g., trypsin, chymotrypsin, etc.), plants (e.g., papain, etc.), and microorganisms (e.g., lactic acid bacteria, yeast, mold, Bacillus subtilis, actinomycetes, etc.).

[0024] Examples of proteolytic enzymes having at least exopeptidase activity include carboxypeptidase, aminopeptidase, exopeptidases derived from microorganisms (e.g., lactic acid bacteria, Aspergillus bacteria, Rhizopus bacteria, etc.), and pancreatin and pepsin which also have endopeptidase activity.

[0025] Among these various enzymes, preferred examples of enzymes having both exopeptidase activity and endopeptidase activity include peptidase produced by Streptomyces griseus (trade name: Actinase AS), peptidase produced by Aspergillus oryzae (trade name: Protease A, Flavorzyme, Proteax), and peptidase produced by Aspergillus melleus (trade name: Protease P). Preferred examples of enzymes having exoprotease activity include peptidase produced by Aspergillus oryzae (trade name: Umamizyme G, Promod 192P, Promod 194P, Sumizyme FLAP), peptidase produced by Aspergillus sojae (trade name: Sternzyme B15024), peptidase produced by the genus Aspergillus (trade name: Coclase P), and peptidase produced by Rhizopus oryzae (trade name: Peptidase R). Further preferred examples of enzymes having endoprotease activity include peptidase produced by Bacillus subtilis (trade name: Orientase 22BF, Nucleisin), peptidase produced by Bacillus licheniformis (trade name: Alcalase), peptidase produced by Bacillus stearothermophilus (trade name: Protease S), peptidase produced by Bacillus amyloliquefaciens (trade name: Neutrase), and peptidase produced by the genus Bacillus (trade name: Protamex).

[0026] Enzyme treatment to reduce the allergenicity of royal jelly can be carried out, for example, according to the description in JP-A-2007-295919 and JP-A-2007-295920.

[0027] The enzyme-treated royal jelly may be a filtrate obtained by filtering an enzyme-treated royal jelly solution. Filtration can be performed, for example, by suction filtration or a filter press with a particle pore size of less than 10 μm.

[0028] Commercially available enzyme-treated royal jelly may be used. A specific example of commercially available enzyme-treated royal jelly is Enzymatic Decomposition Royal Jelly King (manufactured by Yamada Bee Farm).

[0029] The content of the above-mentioned active ingredient in the dermis thickness improving agent and skin texture improving agent of the present invention, in terms of solid content relative to the total amount of the dermis thickness improving agent or skin texture improving agent, may be, for example, 0.1% by mass or more, 1% by mass or more, 3% by mass or more, 3.5% by mass or more, 5% by mass or more, 7% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, 45% by mass or more, 50% by mass or more, 55% by mass or more, 60% by mass or more, 65% by mass or more, 70% by mass or more, 75% by mass or more, 80% by mass or more, 85% by mass or more, 90% by mass or more, 93% by mass or more, 95% by mass or more, 98% by mass or more, 99% by mass or more, or 100% by mass. The content of the above-mentioned active ingredient in the dermis thickness improving agent and skin texture improving agent, in terms of solid content relative to the total amount of the dermis thickness improving agent or skin texture improving agent, may be, for example, 100% by mass or less, 99% by mass or less, 98% by mass or less, 95% by mass or less, 93% by mass or less, 90% by mass or less, 85% by mass or less, 80% by mass or less, 75% by mass or less, 70% by mass or less, 65% by mass or less, 60% by mass or less, 55% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, 8% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less.

[0030] The dermis thickness improving agent and skin texture improving agent of the present invention can be applied to the skin. The amount of the dermis thickness improving agent and skin texture improving agent of the present invention administered to the skin may vary depending on the application site and application range, but for example, the amount of the active ingredient applied to the skin may be 0.01 mg to 50 mg, preferably 0.02 mg to 40 mg, or 0.02 mg to 35 mg, or 0.025 mg to 30 mg, calculated as a dry solid content.

[0031] The dermis thickness improving agent and skin texture improving agent of the present invention can be used as an ingredient in cosmetics. A cosmetic containing the dermis thickness improving agent or skin texture improving agent of the present invention as an ingredient can be a cosmetic for improving dermis thickness or improving skin texture. The cosmetic of the present invention also includes quasi-drugs. The content of the active ingredient in the cosmetic containing the dermis thickness improving agent or skin texture improving agent of the present invention is not particularly limited, and may be an effective amount that can achieve the dosage of parenteral administration of the agent.

[0032] A cosmetic product containing the dermis thickness improving agent or skin texture improving agent of the present invention as an ingredient can be produced, for example, by adding the dermis thickness improving agent or skin texture improving agent of the present invention to an intermediate product in the production process of the cosmetic product.

[0033] The pH of the dermis thickness improving agent and skin texture improving agent of the present invention, or the cosmetic product containing the dermis thickness improving agent and skin texture improving agent of the present invention, may be, for example, 4.5 to 6.5, or 5.0 to 6.5.

[0034] The cosmetic product may be in any form, such as a solid, liquid, or paste. The cosmetic product may be a medicated cosmetic product (i.e., a quasi-drug). The cosmetic product includes any cosmetic product that can be applied to the skin, mucous membranes, body hair, head hair, scalp, nails, teeth, facial skin, lips, and other parts of animals (including humans).

[0035] Cosmetics can take a wide variety of formulations, including aqueous solutions, solubilized solutions, emulsions, powders, oils, gels, ointments, aerosols, water-oil two-layer systems, and water-oil-powder three-layer systems.

[0036] The use of the cosmetics is arbitrary, and examples of basic cosmetics include facial cleanser, lotion, milky lotion, cream, gel, essence, beauty serum, pack, mask, mist, UV protection cosmetics, etc.; makeup cosmetics include foundation, lipstick, blusher, eye shadow, eyeliner, mascara, etc.; nail cosmetics include nail polish, base coat, top coat, nail polish remover, etc.; and other examples include facial cleanser, (paste or liquid) dentifrice, mouth rinse, oral cosmetics, massage agents, cleansing agents, aftershave lotion, preshave lotion, shaving cream, body soap, soap, shampoo, rinse, hair treatment, hair styling agent, hair tonic agent, hair mist, hair foam, hair liquid, hair gel, hair spray, hand cream, hand soap, hair growth agent, antiperspirant, bath agent, etc.

[0037] In addition to the above-mentioned enzyme-treated royal jelly, the cosmetic product may contain, as needed, ingredients that are typically used in cosmetics, such as alcohol, disinfectants, preservatives, surfactants, aqueous components, water, colorants, pH adjusters, solubilizers, abrasives, foaming agents, enzymes, flavorings, chelating agents, excipients, thickeners, bases, emulsifiers, solvents, stabilizers, oils, cleaning agents (lactic acid bacteria), whitening agents, moisturizers, antioxidants, UV absorbers, powder components, colorants, and various skin nutrients.

[0038] The alcohol may be, for example, 1,3-butylene glycol, pentylene glycol, or phenoxyethanol. The total content of the alcohol in the cosmetic product may be, for example, 5% by weight or more, 7% by weight or more, 10% by weight or more, or 12% by weight or more, and may be 20% by weight or less, 18% by weight or less, or 15% by weight or less, based on the total amount of the cosmetic product.

[0039] The oil may be, for example, caprylic / capric triglyceride, etc. The content of the oil in the cosmetic product may be, for example, 0.5% by weight or more, 0.8% by weight or more, 1.0% by weight or more, 1.3% by weight or more, and 5% by weight or less, 3% by weight or less, 2% by weight or less, based on the total amount of the cosmetic product.

[0040] The thickener may be, for example, a hydrophilic thickener. The thickener may be, for example, a carbomer. The content of the thickener in the cosmetic product may be, for example, 0.05% by weight or more, 0.1% by weight or more, 0.15% by weight or more, 0.2% by weight or more, and 3% by weight or less, 1% by weight or less, 0.5% by weight or less, or 0.3% by weight or less, based on the total amount of the cosmetic product.

[0041] The cosmetic product containing the dermis thickness improving agent and skin texture improving agent of the present invention may further contain (acrylates / alkyl acrylate (C10-30)) crosspolymer. These are cosmetic ingredients known as thickeners and emulsion stabilizers, and are preferred because they have the effect of promoting the penetration of royal jelly into the skin.

[0042] The (acrylates / alkyl acrylate (C10-30)) crosspolymer is a copolymer of one or more monomers consisting of acrylic acid, methacrylic acid or simple esters thereof and an alkyl acrylate crosslinked with an allyl ether of sucrose or an allyl ether of pentaerythritol. Specifically, the alkyl acrylate is an alkyl acrylate having an alkyl group having 10 to 30 carbon atoms. As the (acrylates / alkyl acrylate (C10-30)) crosspolymer, a commercially available (acrylates / alkyl acrylate (C10-30)) crosspolymer (e.g., Pemulen (trademark) TR-1) may be used.

[0043] The content of the (acrylates / alkyl acrylate (C10-30)) crosspolymer in the cosmetic product may be, for example, 0.01% by mass or more, 0.1% by mass or more, 0.3% by mass or more, 0.4% by mass or more, 0.5% by mass or more, 1% by mass or more, 2% by mass or more, 3% by mass or more, 5% by mass or more, and may be 20% by mass or less, 15% by mass or less, 10% by mass or less, 8% by mass or less, 5% by mass or less, 3% by mass or less, 2% by mass or less, 1% by mass or less, 0.5% by mass or less, relative to the total amount of the cosmetic product.

[0044] The dermis thickness improving agent and skin texture improving agent of the present invention described above are intended to be applied to mammals including humans (preferably humans). EXAMPLES

[0045] The present disclosure will be described in more detail below with reference to examples, although the present invention is not limited to these examples.

[0046] [Preparation of enzyme-treated royal jelly extract] Royal jelly was subjected to enzyme treatment according to the method described in WO2020 / 196065A1. Specifically, 400 mL of ion-exchanged water was added to 474 g of raw royal jelly and stirred until homogenous to prepare a royal jelly dilution. The pH of the royal jelly dilution was adjusted to 7.8 by adding a 2N NaOH aqueous solution. Next, a solution of 4.75 g of Proteax (Amano Enzyme Co., Ltd.), which has both endopeptidase and exopeptidase activities, dissolved in 20 mL of ion-exchanged water was added to the royal jelly dilution, and ion-exchanged water was further added so that the total amount was 980 g. The reaction mixture was reacted at 50 ° C (constant temperature water bath) for 2 hours while stirring with a propeller to perform hydrolysis. The temperature of the constant temperature water bath was raised to 80 ° C and stirred for 15 minutes to inactivate the protease. The obtained royal jelly enzyme-treated solution was filtered to a particle pore size of 3 μm using suction filtration or a filter press to obtain a royal jelly enzyme-treated filtrate. Butylene glycol, pentylene glycol, phenoxyethanol, and purified water were added to the royal jelly enzyme-treated filtrate so that the concentration of the royal jelly enzyme-treated filtrate was 2.5% by weight, and an enzyme-treated royal jelly extract was obtained.

[0047] [Preparation of test samples] A cosmetic containing enzyme-treated royal jelly extract (hereinafter referred to as RJ cream) and a placebo cosmetic (hereinafter referred to as placebo) were prepared with the formulations shown in Table 1. The units of values ​​are weight percent. 1,3-butylene glycol, pentylene glycol, and phenoxyethanol were contained in the enzyme-treated royal jelly extract in the same formulation ratio as the placebo.

[0048] [Table 1]

[0049] Sixty-four women were asked to apply either RJ Cream or a placebo twice a day for 12 weeks to one half of their face, and the other test product was applied to the remaining half of their face under the same conditions. The effects of RJ Cream on the skin were examined by comparing the results with the side to which the placebo was applied. Subject information is shown in Table 2. The eye corner wrinkle grade was the value at screening.

[0050] [Table 2]

[0051] [Statistical analysis] Statistical analysis was performed for each evaluation item using the following method. The significance level was set at 5% using a two-sided test. For evaluation items with missing data, the data for all observation points for the relevant subjects were treated as missing values.

[0052] (intragroup comparison) For each evaluation item, the results before use of the test product were used as a control, and the results after use were tested using paired t-test or Wilcoxon signed-rank test. The significance level was adjusted according to the number of tests using the Bonferroni method.

[0053] (Intergroup comparison) For each evaluation item, the placebo-applied side of the same subject was used as a control, and the RJ-applied side was tested using Student's t-test.

[0054] [Test sample application] Approximately 1g of the test product was applied to half of the face twice a day (morning and evening) for 12 weeks. If participants normally used lotion or cream, they were asked to use the test product instead. The order of application of the skin care cosmetics and the method of application of the test product were as follows: (1) Daily use lotion (2) Essences, serums, etc. for everyday use (3) Test specimen Take half the amount (about 0.6g, 3 pumps) into your dry palms and gently and carefully apply it to half of your face, spreading it evenly. Next, take the other half (about 0.4g, 2 pumps) into your palms and gently and carefully apply it to half of your face, then gently and carefully apply it to the corners of your eyes, and finally wrap your hands together to blend it into your skin.

[0055] [Skin condition measurement] All measurements were carried out in a testing room adjusted to maintain a room temperature of 20-22°C and humidity of 45-55%. After washing their faces with a designated cleansing agent and face wash (Kyoshinsha Co., Ltd.), subjects allowed their skin to acclimate to the testing room environment for at least 15 minutes, and then performed the following tests on both the left and right sides of their faces.

[0056] With the eyes gently closed, the skin analysis agent SKINCAST (RSI, Inc.) was applied to the wrinkles at the corner of the eye and a replica of the skin at the corner of the eye was taken. The replica was measured in three dimensions using PRIMOS CR (Canfield Scientific, Inc., USA) and a replica fixing stand, and in order to evaluate the same area for the replicas taken on each examination day, the wrinkles were aligned using the attached software and the wrinkle analysis parameters for the following items were calculated. Maximum wrinkle maximum depth: The maximum depth of the largest wrinkle within the analysis range

[0057] Dermal thickness was measured using DermaLab (Cortex Technology). The average value of three measurements taken at the same location on the cheek was used as the result.

[0058] A cheek replica was taken using the skin analyzer SKINCAST (RSI Co., Ltd.), and the texture shape (texture volume ratio) was evaluated using a reflection replica analysis system ASA-03RXD (Japan Ash Co., Ltd.). The texture volume ratio is the sum of the areas judged to be texture within a specified area, expressed as 1 mm 2It is expressed as the average value per unit area, divided by 100. A higher texture volume ratio indicates a higher skin ridge and a more regular texture.

[0059] [Table 3]

[0060] It was confirmed that the use of the test product containing enzyme-treated royal jelly extract was effective in reducing wrinkles, increasing the thickness of the dermis, and improving skin texture.

Claims

1. A dermis thickness improving agent that contains enzyme-treated royal jelly as an active ingredient.

2. The dermis thickness improving agent according to claim 1 , which is used for improving skin wrinkles.

3. The dermis thickness improving agent according to claim 1 , which is used to improve sagging skin.

4. The dermis thickness improving agent according to claim 1 , which is used to improve skin firmness.

5. A skin texture improving agent that contains enzyme-treated royal jelly as an active ingredient.

6. The improving agent according to claim 1 or 5, wherein the enzyme-treated royal jelly is royal jelly treated with a peptidase having endopeptidase activity and exopeptidase activity.

7. A cosmetic for improving dermis thickness or skin texture, comprising the improving agent according to claim 1 or 5.

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