Cosmetics for improving dermal thickness or skin texture

Abstract

To provide a novel agent for improving dermal thickness and skin texture. [Solution] A cosmetic for improving the thickness of the dermis or the texture of the skin, comprising enzyme-treated royal jelly, (acrylates / alkyl acrylate (C10-30)) crosspolymer, 1,3-butylene glycol, pentylene glycol, phenoxyethanol, carbomer, potassium hydroxide, caprylic / capric triglyceride, and water.

Description

Technical Field

[0001] The present invention relates to an agent for improving the thickness of the dermis, an agent for improving the texture of the skin, and a cosmetic for improving the thickness of the dermis or the texture of the skin.

Background Art

[0002] The skin is composed of the epidermis and the dermis. The texture of the skin is the unevenness of the skin surface formed by skin bumps and grooves.

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

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] When the collagen in the dermis decreases, the thickness of the dermis becomes thinner. In addition, when the thinning of the skin progresses, wrinkles appear. On the other hand, it is known that when the production of collagen is promoted, the thinning is improved and the wrinkles are improved.

[0007] While the condition of the epidermis is thought to be the primary factor influencing skin texture, the condition of the dermis is also believed to have an impact on skin texture.

[0008] One aspect of the present invention aims to provide a novel agent for improving the thickness of the dermis. Another aspect of the present invention aims to provide a novel agent for improving the texture of the skin. [Means for solving the problem]

[0009] The inventors have discovered that enzyme-treated royal jelly has excellent effects in improving dermal thickness and skin texture. In other words, the present invention relates to the following [1] to [7]. [1] A dermal thickness improving agent containing enzyme-treated royal jelly as the active ingredient. [2] A dermal thickness improving agent described in [1], for the improvement of wrinkles in the skin. [3] A dermal thickness improving agent described in [1], for improving skin sagging. [4] A dermal thickness improving agent described in [1], for improving skin firmness. [5] A skin texture improving agent containing enzyme-treated royal jelly as an active ingredient. [6] The improvement agent according to any one of [1] to [5], wherein the enzyme-treated royal jelly is royal jelly treated with a peptidase having both endopeptidase activity and exopeptidase activity. A cosmetic product for improving the thickness of the dermis or the texture of the skin, containing any of the improving agents described in [7][1] to [6]. [Effects of the Invention]

[0010] One aspect of the present invention provides a novel agent for improving the thickness of the dermis. Another aspect of the present invention provides a novel agent for improving the texture of the skin. [Modes for carrying out the invention]

[0011] The following describes in detail embodiments for carrying out the present invention, but the present invention is not limited to the following embodiments.

[0012] In this specification, "comprise" encompasses both the meanings of "essentially consist of" and "consist of only." Furthermore, in this specification, "skin" and "flesh" are synonymous.

[0013] The dermal thickness improving agent of the present invention contains enzymatically hydrolyzed royal jelly as an active ingredient. By containing enzymatically hydrolyzed royal jelly as an active ingredient, the dermal thickness improving agent of the present invention can improve the thickness of the dermis.

[0014] Improving dermal thickness includes, for example, increasing dermal thickness within an appropriate range and suppressing the decrease in dermal thickness.

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

[0016] The skin texture improving agent of the present invention contains enzyme-hydrolyzed royal jelly as an active ingredient. By containing enzyme-hydrolyzed royal jelly as an active ingredient, the skin texture improving agent of the present invention can improve skin texture.

[0017] Improving the texture of the skin 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 improver and skin texture improver of the present invention each also include the meaning for an additive that imparts the action of improving the dermis thickness or improving the skin texture.

[0019] Royal jelly is a milky jelly-like substance made by mixing the secretions secreted from the hypopharyngeal gland and the large parotid gland of worker bees aged 3 to 12 days among bees. The main bioactive components in royal jelly include, for example, saturated fatty acids unique to royal jelly, organic acids such as unsaturated fatty acids, as well as proteins, amino acids, peptides, lipids, saccharides, vitamins B, folic acid, nicotinic acid, pantothenic acid and other vitamins, various minerals, etc. The production area of royal jelly may be any of European countries, Oceania countries, the United States, Brazil, Japan, China, and other Asian countries, etc.

[0020] Enzyme-treated royal jelly is obtained by treating royal jelly with a proteolytic enzyme (protease). Preferably, it is a low-allergen enzyme-treated royal jelly in which the allergic reaction caused by the protein contained in royal jelly is suppressed by protease treatment. Therefore, in addition to the protease degradation products of the proteins contained in royal jelly, enzyme-treated royal jelly may contain the organic acids such as the saturated fatty acids and unsaturated fatty acids described above, lipids, saccharides, vitamins, and various minerals.

[0021] The royal jelly used for the production of enzyme-treated royal jelly is not particularly limited, and examples include raw royal jelly, royal jelly powder obtained by drying raw royal jelly into powder, or an extract obtained by extracting raw royal jelly with water or hydrous 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 and exopeptidase activity.

[0023] Examples of proteolytic enzymes that possess 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 that possess at least exopeptidase activity include carboxypeptidases, aminopeptidases, exopeptidases derived from microorganisms (e.g., lactic acid bacteria, Aspergillus species, Rhizopus species, etc.), and pancreatin and pepsin, which also possess endopeptidase activity.

[0025] Among these various enzymes, preferred examples of enzymes possessing both exopeptidase and endopeptidase activity include Streptomyces griseus-produced peptidase (product name: Actinase AS), Aspergillus oryzae-produced peptidase (product names: Protease A, Flavorzyme, Proteax), and Aspergillus melleus-produced peptidase (product name: Protease P). Preferred examples of enzymes possessing exoprotease activity include Aspergillus oryzae-produced peptidase (product names: Umamizyme G, Promod 192P, Promod 194P, Sumizyme FLAP), and Aspergillus sojae-produced peptidase (product name: Sternzyme). Examples include peptidases produced by Aspergillus species (product name: Cocrase P) and peptidases produced by Rhizopus oryzae (product name: Peptidase R). Furthermore, preferred examples of enzymes possessing endoprotease activity include peptidase produced by Bacillus subtilis (trade names: Orientase 22BF, Nucleicin), peptidase produced by Bacillus licheniformis (trade name: Alcalase), peptidase produced by Bacillus stearothermophilus (trade name: Protease S), peptidase produced by Bacillus amyloliquefaciens (trade name: Neutralase), and peptidase produced by Bacillus species (trade name: Protamex).

[0026] Enzymatic treatment to reduce the allergenicity of royal jelly can be carried out, for example, in accordance with the descriptions in Japanese Patent Publication No. 2007-295919 and Japanese Patent Publication No. 2007-295920.

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

[0028] Commercially available enzyme-treated royal jelly may be used. Specific examples of commercially available enzyme-treated royal jelly include, for example, Enzyme-Decomposed Royal Jelly King (manufactured by Yamada Bee Farm Co., Ltd.).

[0029] The amount of the above-mentioned active ingredient in the dermal thickness improving agent and skin texture improving agent of the present invention 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, relative to the total amount of the dermal thickness improving agent or skin texture improving agent. The amount of the above-mentioned active ingredient in the dermal thickness improving agent and the 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, relative to the total amount of the dermal thickness improving agent or the skin texture improving agent.

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

[0031] The dermal thickness improving agent and skin texture improving agent of the present invention can be used as an ingredient in cosmetics. Cosmetics containing the dermal thickness improving agent or skin texture improving agent of the present invention as an ingredient can be cosmetics for improving dermal thickness or skin texture. The cosmetics of the present invention also include quasi-drugs. The amount of the above active ingredient in cosmetics containing the dermal thickness improving agent or skin texture improving agent of the present invention is not particularly limited, and is sufficient as long as it is an effective amount that can achieve the parenteral administration dose of the above agent.

[0032] Cosmetics containing the dermal thickness improving agent or skin texture improving agent of the present invention as one component can be manufactured, for example, by adding the dermal thickness improving agent or skin texture improving agent of the present invention to an intermediate product in the manufacturing process of cosmetics.

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

[0034] Cosmetics may be in any form, such as solid, liquid, or paste. Cosmetics may be medicated cosmetics (i.e., quasi-drugs). Cosmetics include all cosmetics that can be applied to parts of animals (including humans), such as skin, mucous membranes, body hair, hair, scalp, nails, teeth, facial skin, and lips.

[0035] Cosmetic formulations can take a wide range of forms, including aqueous solutions, solubilized solutions, emulsified solutions, powders, oil-based solutions, gels, ointments, aerosols, two-layer water-oil systems, and three-layer water-oil-powder systems.

[0036] The uses of cosmetics are arbitrary. For example, basic cosmetics include facial cleansers, toners, lotions, creams, gels, essences, serums, packs, masks, mists, and UV protection cosmetics. Makeup cosmetics include foundations, lipsticks, blushes, eyeshadows, eyeliners, and mascaras. Nail cosmetics include nail polish, base coats, top coats, and nail polish removers. Other products include facial cleansers, (paste or liquid) toothpaste, mouthwash, oral cosmetics, massage agents, cleansing agents, aftershave lotions, pre-shave lotions, shaving creams, body soaps, soaps, shampoos, conditioners, hair treatments, hair styling products, hair tonics, hair mists, hair foams, hair liquids, hair gels, hair sprays, hand creams, hand soaps, hair growth products, antiperspirants, and bath additives.

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

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

[0039] The oily agent may be, for example, caprylic / capric triglyceride. The amount of oily agent in the cosmetic product may be, for example, 0.5% or more by weight, 0.8% or more by weight, 1.0% or more by weight, 1.3% or more by weight, 5% or less by weight, 3% or less by weight, or 2% or less by weight, relative to the total amount of the cosmetic product.

[0040] The thickening agent may be, for example, a hydrophilic thickening agent. The thickening agent may be, for example, carbomer. The amount of thickening agent in the cosmetic product may be, for example, 0.05% or more by weight, 0.1% or more by weight, 0.15% or more by weight, 0.2% or more by weight, 3% or less by weight, 1% or less by weight, 0.5% or less by weight, or 0.3% or less by weight, relative to the total amount of the cosmetic product.

[0041] The cosmetic product comprising the dermal 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 emulsifying stabilizers, and are preferred because they have the effect of promoting the penetration of royal jelly into the skin.

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

[0043] The content of (acrylates / alkyl acrylate (C10-30)) crosspolymer in cosmetics 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 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, or 0.5% by mass or less, based on the total amount of cosmetics.

[0044] The dermal thickness improving agent and skin texture improving agent of the present invention described above are applicable to mammals, including humans (preferably humans). [Examples]

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

[0046] [Preparation of enzyme-treated royal jelly extract] Enzymatic treatment of royal jelly was performed according to the method described in WO2020 / 196065A1. Specifically, 474 g of raw royal jelly was mixed with 400 mL of deionized water and stirred until homogeneous to prepare a royal jelly dilution. The pH of the royal jelly dilution was adjusted to 7.8 by adding 2N NaOH aqueous solution. Next, a solution of 4.75 g of Proteax (Amano Enzyme Co., Ltd.), which has both endopeptidase and exopeptidase activity, dissolved in 20 mL of deionized water was added to the royal jelly dilution, and then more deionized water was added until the total volume reached 980 g. The reaction mixture was stirred with a propeller and reacted at 50°C (constant temperature water bath) for 2 hours 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 enzyme-treated royal jelly solution was filtered to a particle pore size of 3 μm by suction filtration or filter press to obtain an enzyme-treated royal jelly filtrate. Butylene glycol, pentylene glycol, phenoxyethanol, and purified water were added to the enzyme-treated royal jelly filtrate to a concentration of 2.5% by weight to obtain an enzyme-treated royal jelly extract.

[0047] [Preparation of test samples] Cosmetic products containing enzyme-treated royal jelly extract (hereinafter referred to as RJ Cream) and placebo cosmetics (hereinafter referred to as Placebo) were prepared according to the formulations shown in Table 1. The units of the values ​​are in weight percent. 1,3-butylene glycol, pentylene glycol, and phenoxyethanol are contained in the enzyme-treated royal jelly extract at the same concentrations as in the placebo.

[0048] [Table 1]

[0049] Sixty-four women were instructed to apply either RJ Cream or a placebo to one half of their face twice daily for 12 weeks, while the other test product was applied to the other half of their face under the same conditions. The effects of RJ Cream on the skin were examined by comparing the results to the placebo-treated side. Subject information is shown in Table 2. The crow's feet wrinkle grade is the value at the time of screening.

[0050] [Table 2]

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

[0052] (intragroup comparison) For each evaluation item, the pre-use control group was used, and the post-use group was tested using either a paired t-test or a Wilcoxon signed-rank test. The significance level was adjusted according to the number of tests performed using the Bonferroni method.

[0053] (Comparison between groups) For each evaluation item, the side treated with placebo in the same subject was used as the control, and Student's t-test was performed on the side treated with RJ.

[0054] [Application of test sample] Approximately 1g of the test product was taken and applied to half of the face twice a day (morning and evening) for 12 weeks. If participants normally use lotion or cream, they were instructed to use the test product instead. The order of application of skincare cosmetics and the method of application of the test product were as follows. (1) Everyday toner (2) Everyday essences, serums, etc. (3) Test sample Take about half the amount, approximately 0.6g (3 pumps), into your dry palm and gently and carefully apply it to half of your face, spreading it evenly. Next, take the remaining half, approximately 0.4g (2 pumps), into your palm and gently and carefully apply it to the other half of your face, then gently and carefully apply it to the corners of your eyes as well, and finally, cup your hands over your face to help it absorb into the skin.

[0055] [Skin condition measurement] Each measurement was performed in a laboratory controlled to maintain a room temperature of 20-22°C and a humidity of 45-55%. After washing their faces with the designated cleansing agent and facial wash (Gyunyu Sekken Kyoshinsha Co., Ltd.), the subjects allowed their skin to acclimate to the laboratory environment for at least 15 minutes, and then the following tests were performed on both sides of their faces.

[0056] With the eyes lightly closed, the skin analysis agent SKINCAST (R.S.I. Co., Ltd.) was applied to the crow's feet, and a skin replica of the crow's feet was taken. The replica was measured in three dimensions using PRIMOS CR (Canfield Scientific, Inc., USA) and a replica stand. To evaluate the same area for the replica taken on each examination day, the wrinkles were aligned using the included software, and the wrinkle analysis parameters for the following items were calculated. Maximum wrinkle 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 replica of the cheek was taken using the skin analysis agent SKINCAST (R.S.I. Co., Ltd.), and the texture of the skin (texture volume ratio) was evaluated using the reflection replica analysis system ASA-03RXD (Ash Japan Co., Ltd.). The texture volume ratio is the sum of what is judged to be skin texture within a specified area, measured in 1 mm². 2This represents the average value per unit area, divided by 100. A higher texture volume ratio indicates higher ridges and a more regularly arranged skin texture.

[0059] [Table 3]

[0060] Tests using a product containing enzyme-treated royal jelly extract confirmed its effectiveness in reducing wrinkles, increasing dermal thickness, and improving skin texture.

Claims

[Claim 1] A cosmetic product for improving dermal thickness, comprising enzyme-treated royal jelly, (acrylates / C10-30 alkyl acrylate) crosspolymer, 1,3-butylene glycol, pentylene glycol, phenoxyethanol, carbomer, potassium hydroxide, caprylic / capric triglyceride, and water.

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