topical skin preparations

Abstract

To provide a topical skin preparation that is combined with a specific extract to exhibit a synergistic anti-aging effect.SOLUTION: A topical skin preparation contains the following (A) and (B): (A) rhubarb extract and (B) plant worm extract.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an external skin preparation containing a specific extract and having anti-aging effects. [Background technology]

[0002] Factors that contribute to the worsening of skin conditions such as wrinkles, sagging skin, loss of skin elasticity, inflammation, and disturbances in the skin surface morphology include, for example, a decline in the function of dermal fibroblasts due to aging and the accompanying decrease and degeneration of dermal matrix such as collagen. Furthermore, external stresses such as ultraviolet rays, dryness, and allergens such as pollen also contribute to the worsening of skin conditions. Various studies have been conducted to prevent and improve these skin conditions. For example, extracts from Camphor tree (Patent Document 1) are known to have the effect of promoting collagen production. Furthermore, topical skin preparations containing quince seed extract and specific plant extracts are known to have the effect of improving the skin's barrier function (Patent Document 2).

[0003] Langerhans cells, which are present specifically in the epidermis of the skin, transduce stimuli such as bacteria, viruses, chemicals, pollen, and ultraviolet rays that enter from the outside, and are responsible for maintaining skin homeostasis. RANKL (Receptor Activator of Nuclear factor-Kappa B Ligand) is known to act on Langerhans cells and to increase the survival rate of Langerhans cells (Non-Patent Document 1). RANKL is abundant in the epidermis, and epidermal cells that express high levels of RANKL are known to express large amounts of proteins important for the epidermal barrier function (Non-Patent Document 2).

[0004] Many studies have been conducted on the use of various extracts, either alone or in combination. However, when using extracts in combination, the effects are not synergistically improved by simply combining them, but rather the effects of the combination are unpredictable, with some extracts having additive effects and others canceling out others. There is a great need for extract combinations that can achieve greater effects with smaller doses. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Jean-Baptiste O.Barbaroux.et al.J Immunol July 15, 2008, 181(2)1103-1108 [Non-patent document 2] Noevir Group, Press Release, June 21, 2021, https: / / www.noevir.co.jp / new / ir_info / pdf / per51 / 210621c.pdf [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2003-146837 [Patent Document 2] Japanese Patent Application Publication No. 2019-019095 Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to provide an external skin preparation that exhibits a synergistic anti-aging effect by using specific extracts in combination. [Means for solving the problem]

[0008] The means for solving the problems of the present invention is to provide an external skin preparation containing the following (A) and (B): (A) Rhubarb extract (B) Cordyceps sinensis extract [Effects of the Invention]

[0009] The external skin preparation of the present invention exhibits a synergistic anti-aging effect when used in combination with a specific extract.

[0010] The external skin preparation of the present invention, when used in combination with a specific extract, exhibits a synergistic effect of promoting RANKL production and COL4A1 production. DETAILED DESCRIPTION OF THE INVENTION

[0011] Hereinafter, an embodiment of the present invention will be described.

[0012] RANKL, an abbreviation for Receptor Activator of Nuclear factor-Kappa B Ligand, is a cytokine required for osteoclast differentiation and immune tissue formation. It is abundant in the epidermis, and epidermal cells with high RANKL expression also express proteins important for the epidermal barrier function.

[0013] COL4A1 is an abbreviation for Collagen Type IV Alpha 1 Chain, and is a factor that constitutes type IV collagen, a major component of basement membranes.

[0014] [Rhubarb extract] Rhubarb (Rheum rhaponticum, Rheum rhabarbarum or Rheum palmatum), also known as tiger rhubarb, is a plant of the Polygonaceae family, genus Rheum.

[0015] The rhubarb extract used in the present invention is not particularly limited and may be one that is commonly incorporated into cosmetics, topical skin preparations, etc. In addition, in the present invention, an extract obtained from rhubarb organically grown in Yunosawa, Mashike-cho, Hokkaido, may also be used.

[0016] The part of rhubarb used for extraction in the present invention is not particularly limited, and one or more parts selected from the whole plant, leaves, stems, flowers, fruits, and roots can be used, but it is preferable to use the roots.

[0017] The amount of rhubarb extract to be incorporated into the topical skin preparation of the present invention is not particularly limited, but is preferably 0.0000001 to 5% by mass, more preferably 0.0000001 to 1% by mass, based on the total amount of the topical skin preparation.

[0018] [Yunosawa, Mashike Town, Hokkaido] The area is located in the northwest of Hokkaido, in the southern part of the Rumoi Regional Development Bureau, and includes Mount Shokanbetsu, which is 1,492 m above sea level. In the present invention, it is preferable to cultivate it in the Yunosawa district of Mashike town, which has a high altitude.

[0019] [Field preparation] Before planting, organic fertilizer is applied to improve the soil quality of the field. Specifically, one or more of the following organic fertilizers are used in combination: fermented chicken manure, oil cake, fermented oil cake, bone meal, fish meal, rice bran, fermented rice bran, leaf mold, bark compost, magnesium lime, slaked lime, and iodine phosphate fertilizer.

[0020] Fermented chicken manure, oil cake, fermented oil cake, bone meal, fish meal, rice bran, fermented rice bran, leaf mold, bark compost, and iodized phosphate fertilizer are mainly used to replenish the three major nutrients: nitrogen, phosphorus, and potassium. These fertilizers can be used alone or in combination of two or more. The amount of these fertilizers applied can be increased or decreased depending on the condition of the original soil.

[0021] Fertilization should be carried out at least seven days before planting. If fertilization is carried out within six days of planting, the soil improvement effect of the fertilizer will be insufficient, causing fertilizer burn and poor initial growth. Organic fertilizer can be applied in furrows or over the entire surface, but over-the-surface application is preferred for work efficiency.

[0022] [Planting] The raised rhubarb seedlings are planted in March to June. It is preferable to use rhubarb seedlings that have been raised for one year. From the viewpoint of cultivation efficiency, it is preferable to plant them with a spacing of 50 to 100 cm between plants and a spacing of 30 to 100 cm between furrows.

[0023] [Development] By applying additional fertilizer as needed, the roots can be expected to grow larger. Remove weeds as needed and water the plant as needed depending on the dryness.

[0024] [harvest] Harvest in late autumn when the leaves begin to yellow and die. Dig up on a sunny day, taking care not to damage the roots. Wash with water or hot water immediately after harvesting, or after air-drying for several months. It is also possible to remove the soil by air-drying without washing. When storing, store under dry conditions with a moisture content of less than 20%.

[0025] [Cordyceps sinensis extract] Cordyceps is a type of ascomycete mushroom that parasitizes insects or their larvae of the Lepidoptera and Coleoptera orders, forming sclerotia inside the insect's body, and then producing fruiting bodies on the surface of the host insect's or its larvae in the summer.

[0026] The Cordyceps used in the present invention can be those typically incorporated into cosmetics, topical skin preparations, etc., and are not particularly limited, but it is preferable to use Cordyceps sinensis, which parasitizes the larvae of the bat moth family (Hepialus armoricanus Ober.), forms sclerotia within the body, and produces root-like fruiting bodies from the head in summer. Other known Cordyceps species besides Cordyceps sinensis include the semi-mushroom (Cordyceps sobolifera B.), the pupa (Cordyceps militaris Link), and the mimikaki-take (Cordyceps nutans Pat.), and these may also be used in the present invention.

[0027] The part of Cordyceps used in the present invention can be extracted from either the fruiting body or the angiosperm, but it is preferable to use the fruiting body.

[0028] The amount of Cordyceps extract blended in the external skin preparation of the present invention is not particularly limited, but is preferably 0.00000001 to 5% by mass, more preferably 0.00000001 to 1% by mass, based on the total amount of the external skin preparation.

[0029] [extraction] When preparing the extract, the raw material is used as is or after drying. From the viewpoint of extraction efficiency, it is preferable to perform processing such as chopping, drying, or crushing before extraction. The extraction solvent may be selected from polar organic solvents such as water, lower alcohols (e.g., methanol, ethanol, propanol, isopropanol), polyhydric alcohols (e.g., 1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin), ethers (e.g., ethyl ether, propyl ether), esters (e.g., ethyl acetate, butyl acetate), ketones (e.g., acetone, ethyl methyl ketone), etc. Alternatively, physiological saline, phosphate buffer, phosphate-buffered physiological saline, etc. may be used. The extracts obtained with the above solvents can be used as they are, or they can be concentrated, dried, and then redissolved in water or a polar solvent, or they can be purified by bleaching, deodorizing, desalting, or other methods without impairing their skin physiological function-improving effects, or fractionated by column chromatography before use. The extracts can also be hydrolyzed using acids, alkalis, enzymes, or the like. For storage, the extracts can be lyophilized after purification and dissolved in a solvent before use. They can also be encapsulated in vesicles such as liposomes or microcapsules. The extraction process is not particularly limited as long as it can dissolve the soluble components contained in the extraction raw material into the extraction solvent, and can be carried out according to conventional methods. For example, the extraction raw material is immersed in an extraction solvent in an amount (mass ratio) 5 to 30 times the amount of the extraction raw material, and the soluble components are extracted at room temperature or under reflux heating, followed by filtration to remove the extraction residue, thereby obtaining an extract. The solvent is distilled off from the obtained extract to obtain a paste-like concentrate, which is then further dried to obtain a dried product.

[0030] In addition to the above-mentioned components, the topical skin preparation of the present invention may contain optional components used in ordinary cosmetics and quasi-drugs to the extent that the effects of the present invention are not impaired. Specific examples include oils, surfactants, thickeners, preservatives, fragrances, moisturizers, antioxidants, anti-inflammatory agents, antibacterial agents, etc.

[0031] The formulation of the external skin preparation of the present invention is not particularly limited, and may be any of aqueous, oil-based, emulsion-type, and the like.

[0032] The topical skin preparation of the present invention can be prepared by a conventional method.

[0033] The external skin preparation of the present invention can be used in the dosage form of, for example, a lotion, emulsion, or ointment. [Example]

[0034] The present invention will be specifically described below with reference to examples, but the scope of the present invention is not limited to these examples.

[0035] First, the method for preparing the extract used in the examples will be described.

[0036] [Rhubarb extract] (1) From cultivation to harvest Rhubarb was cultivated in an organic JAS-certified field in Yunosawa, Mashike-cho, Hokkaido. In mid-April, one week before planting, the field was prepared by applying organic chicken manure, organic rice bran, organic lime, and organic molten phosphorus. Planting was carried out with roots that had been raised for one year, spaced 50cm apart between plants and 50cm apart between furrows. In late June and early September, additional fertilization with organic chicken manure and organic rice bran was carried out. Weeds were removed as needed, and the field was watered according to dryness. On a sunny day in late November, the plants were dug up, taking care not to damage the roots, and allowed to air-dry. After air-drying, they were washed with hot water and water, and then stored in a dehydrated state. (2) Preparation of rhubarb extract The rhubarb roots obtained in (1) were crushed in a mill mixer. After immersion in an 80% by volume aqueous solution of ethanol, the solvent was distilled off, and the roots were added to a 50% by volume aqueous solution of 1,3-butylene glycol so that the pure extract content was 0.5% by mass, thereby preparing a rhubarb extract.

[0037] [Cordyceps sinensis extract] The fruiting bodies of Cordyceps sinensis were dried, crushed, immersed in a 70% by volume aqueous ethanol solution, and then filtered. A Cordyceps extract was prepared by adding the dried fruiting bodies to the 70% by volume aqueous ethanol solution to a concentration of 0.24% by mass as the pure extract.

[0038] [Test using 3D cultured epidermis] Commercially available 3D cultured human epidermis (LabCyte EPI-MODEL) was cultured overnight in a dedicated assay medium at 37°C in a 5% CO2 incubator. A PBS solution containing a designated amount of each extract was added to the epidermal tissue surface and incubated for 2 hours in a 37°C, 5% CO2 incubator. After rinsing with PBS, the tissue was cultured for 24 hours in a 37°C, 5% CO2 incubator. A PBS solution containing a designated amount of each extract was again added to the epidermal tissue surface and incubated for 2 hours in a 37°C, 5% CO2 incubator. After rinsing with PBS, the tissue was cultured for 4 hours in a 37°C, 5% CO2 incubator. RNA was extracted from the harvested 3D cultured human epidermis using a commercially available RNA extraction kit (ReliaPrep RNA Miniprep Systems). cDNA was synthesized, and gene expression was confirmed by real-time PCR using the CyberGreen method with the following primers. GAPDH was used as an internal standard. mRNA expression levels were expressed relative to the expression level without each component. The effects of each component are shown in Table 2.

[0039] The primer sequences used are shown in Table 1.

[0040] [Table 1]

[0041] In the examples and comparative examples, each extract was dissolved in the medium so that the extract concentration (w / v%) was as shown in Table 2.

[0042] [Table 2]

[0043] As shown in Table 2, the expression levels of RANKL and COL4A1 increased in Example 1 compared to Comparative Examples 1 and 2, in which each extract was added alone. Furthermore, since the concentration of each extract added in Example 1 was half that of Comparative Examples 1 and 2, it can be seen that the expression levels of RANKL and COL4A1 increased synergistically. Therefore, the external skin preparation of the present invention showed a synergistically improved anti-aging effect when used in combination with rhubarb extract and cordyceps extract.

[0044] [Example 2] Emulsion (1) Squalane 10.0 (mass%) (2) Methylphenylpolysiloxane 4.0 (3) Hydrogenated palm kernel oil 0.5 (4) Hydrogenated soybean phospholipid 0.1 (5) Polyoxyethylene monostearate Sorbitan (20E.O.) 1.3 (6) Sorbitan monostearate 1.0 (7) Glycerin 4.0 (8) Methyl parahydroxybenzoate 0.1 (9) Carboxyvinyl polymer 0.15 (10) Purified water (balance to make 100) (11) Arginine (1% by mass aqueous solution) 20.0 (12) Rhubarb extract 0.001 (13) Cordyceps sinensis extract 0.00001 Manufacturing method: The oil phase ingredients (1) to (6) are heated and dissolved at 80°C. Meanwhile, the water phase ingredients (7) to (10) are heated and dissolved at 80°C. The oil phase ingredients are added to this while stirring, and the mixture is uniformly emulsified using a homogenizer. After cooling to 40°C, the ingredients (11) to (13) are added in order and mixed uniformly.

[0045] [Example 3] Lotion (1) Ethanol 15.0 (mass%) (2) Polyoxyethylene (40E.O.) hydrogenated castor oil 0.3 (3)Fragrance 0.1 (4) Purified water (balance to make 100%) (5) Citric acid 0.02 (6) Sodium citrate 0.1 (7) Glycerin 1.0 (8) Hydroxyethyl cellulose 0.1 (9) Rhubarb extract 0.01 (10) Cordyceps sinensis extract 0.000001 Manufacturing method: Dissolve (2) and (3) in (1). Then add (4) to (10) in order, and stir thoroughly to mix evenly.

[0046] [Example 4] Cream (1) Squalane 10.0 (mass%) (2) Stearic acid 2.0 (3) Hydrogenated palm kernel oil 0.5 (4) Hydrogenated soybean phospholipid 0.1 (5) Cetyl alcohol 3.6 (6) Lipophilic Glyceryl Monostearate 2.0 (7) Glycerin 10.0 (8) Methyl parahydroxybenzoate 0.1 (9) Arginine (20% by mass aqueous solution) 15.0 (10) Purified water (balance to make 100) (11) Carboxyvinyl polymer (1% by mass aqueous solution) 15.0 (12) Rhubarb extract 0.01 (13) Cordyceps sinensis extract 0.001 Manufacturing method: The oil phase ingredients (1) to (6) are heated and dissolved at 80°C. Meanwhile, the water phase ingredients (7) to (10) are heated and dissolved at 80°C. The oil phase ingredients are added to this while stirring, and the mixture is uniformly emulsified using a homogenizer. After adding (11) and stirring, the mixture is cooled, and then (12) and (13) are added at 40°C and mixed uniformly.

[0047] [Example 5] Beauty serum (1) Purified water (remaining weight percent, based on 100%) (2) Glycerin 10.0 (3) Sucrose fatty acid ester 1.3 (4) Carboxyvinyl polymer (1% by mass aqueous solution) 17.5 (5) Sodium alginate (1% by mass aqueous solution) 15.0 (6) Polyglyceryl monolaurate 1.0 (7) Macadamia nut oil fatty acid phytosteryl 3.0 (8) N-Lauroyl-L-glutamic acid Di(phytosteryl-2-octyldodecyl) 2.0 (9) Hydrogenated Palm Oil 2.0 (10) Squalane (derived from olives) 1.0 (11) Behenyl alcohol 0.75 (12) Beeswax 1.0 (13) Jojoba oil 1.0 (14) 1,3-butylene glycol 10.0 (15) L-arginine (10% by mass aqueous solution) 2.0 (16) Rhubarb extract 0.03 (17) Cordyceps sinensis extract 0.00002 Manufacturing method: The aqueous phase components (1) to (6) are mixed and dissolved by heating at 75°C. Meanwhile, the oil phase components (7) to (14) are mixed and dissolved by heating at 75°C. Next, the oil phase components are added to the aqueous phase components and pre-emulsified, and then uniformly emulsified using a homomixer. After cooling, (15) is added at 50°C, and (16) and (17) are added at 40°C, and mixed uniformly.

[0048] [Example 6] Water-based gel (1) Carboxyvinyl polymer 0.5 (mass%) (2) Purified water (balance to make 100%) (3) Sodium hydroxide (10% by weight aqueous solution) 0.5 (4) Glycerin 10.0 (5) 1,3-butylene glycol 10.0 (6) Ethanol 10.0 (7) Methyl parahydroxybenzoate 0.1 (8)Fragrance 0.1 (9) Rhubarb extract 0.01 (10) Cordyceps sinensis extract 0.00002 Manufacturing method: Add (1) to (2) and stir until uniform, then add (3). After stirring uniformly, add (5) that has been pre-dissolved in (4). After stirring uniformly, add (6) to (10) that have been pre-mixed and stir until uniform.

Claims

1. Contains the following (A) and (B): The skin external preparation contains (A) in an amount of 0.0000001 to 5% by mass based on the total mass of the skin external preparation, The skin external preparation contains (B) in an amount of 0.00000001 to 5% by mass relative to the total mass of the skin external preparation, Skin topical agent. (A) Rhubarb extract extracted with an aqueous solution containing 80% or more by volume of ethanol (B) Cordyceps extract extracted with an aqueous solution containing 70% or more by volume of ethanol

2. The topical skin preparation contains 0.0000001 to 0.03% by mass of (A) relative to the total mass of the topical skin preparation, The topical skin preparation according to claim 1, wherein the (B) is contained in an amount of 0.00000001 to 0.001% by mass relative to the total mass of the topical skin preparation.

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