Collagen production promoter

Abstract

To provide a collagen production promoter that is combined with a specific extract as an active ingredient to exhibit a synergistic collagen production promoting effect.SOLUTION: A collagen production promoter contains the following (A) and (B) as active ingredients. (A) Angelica acutiloba extract and (B) placenta extract.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a collagen production promoter containing a specific extract as an active ingredient. [Background technology]

[0002] Placenta extract is an extract extracted from the placenta of animals and plants, and is widely used in the fields of beauty, health, and medicine. Non-Patent Document 1 describes the effectiveness of placenta extract as a topical agent as follows: In the dermis, it promotes the proliferation of skin fibroblasts and stimulates the expression of type I collagen and fibroblast growth factor, which is expected to have a beneficial effect on skin turnover. In the epidermis, it stimulates the expression of type I collagen, keratin 10, and filaggrin by skin keratinocytes, thereby effectively strengthening the skin barrier. Placenta extract is also known to contain various antioxidant components, and is expected to have anti-aging effects by weakening the action of reactive oxygen species generated by ultraviolet rays, etc.

[0003] In addition, Angelica acutiloba, a type of herbal medicine, is included in the middle section of the Shennong Materia Medica and has been used as a feminine medicine since ancient times. It is often used in traditional Chinese medicine to treat gynecological disorders such as sensitivity to cold, anemia, and circulatory disorders. It is also expected to have medicinal effects on pain, inflammation, and skin diseases. In Japan, two types of Angelica sinensis are cultivated: Yamato Angelica sinensis and Hokkai Angelica sinensis. Patent Document 1 describes collagen production promoters, heat shock protein production promoters, and decorin production promoters that contain Hokkai Angelica sinensis extract as an active ingredient.

[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] Yasuhiko Komatsu et al., Fragrance Journal, Vol. 44 No. 6, 47-54 (2016) [Patent documents]

[0006] [Patent Document 1] JP 2019-1751 A Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to provide a collagen production promoter that exerts a synergistic collagen production promoting effect by using a specific extract in combination as an active ingredient. [Means for solving the problem]

[0008] The means for solving the problems of the present invention is to provide a collagen production promoter containing the following (A) and (B) as active ingredients: (A) Angelica acutiloba extract (B) Placenta extract [Effects of the Invention]

[0009] The collagen production promoter of the present invention exhibits a synergistic collagen production promoting effect when used in combination with a specific extract as an active ingredient. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, an embodiment of the present invention will be described.

[0011] COL1A1 is an abbreviation for Collagen Type I Alpha 1 Chain, and is a factor that constitutes type I collagen.

[0012] [Angelica extract] Angelica acutiloba is a plant belonging to the Apiaceae family and the Angelica genus.

[0013] The Angelica acutiloba extract used in the present invention can be any extract commonly used in cosmetics, topical skin preparations, etc., and is not particularly limited, but it is preferable to use Hokkai Touki (Angelica acutiloba var. sugiyamae) in view of its effectiveness. In addition, an extract obtained from Hokkai Touki organically grown in Yunosawa, Mashike-cho, Hokkaido, can also be used in the present invention.

[0014] The part of Angelica sinensis used in the present invention for extraction 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.

[0015] The amount of the Angelica acutiloba extract in the collagen production promoter 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 collagen production promoter.

[0016] [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.

[0017] [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.

[0018] 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.

[0019] 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.

[0020] [Planting] In the spring, the raised Hokkai Touki seedlings are planted. It is preferable to use Hokkai Touki seedlings that have been raised for one year. From the standpoint of cultivation efficiency, it is preferable to plant them 20 to 50 cm apart and 30 to 100 cm apart.

[0021] [Development] Applying additional fertilizer in late June and around September will help the roots to grow larger. Remove weeds as needed and water the plant as needed depending on the dryness.

[0022] [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, keep the moisture content below 20% and store under dry conditions.

[0023] [extraction] When preparing the extract of the above-mentioned plant, the plant is used as it is or after drying. From the viewpoint of extraction efficiency, it is preferable to perform extraction after processing such as chopping, drying, or crushing. 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.

[0024] [Placenta extract] The origin of the placenta from which the placenta extract used in the present invention is obtained is not particularly limited, and examples include animals such as humans, horses, pigs, salmon, herring, and sturgeon, and plants such as roses, melons, camellias, and tulips. Among these origins, from the viewpoint of commercial use, it is preferable to use those derived from salmon, pigs, or plants, and it is particularly preferable to use those derived from salmon. Commercially available products such as Falconix PC-1 (Ichimaru Falcos Co., Ltd.), Placenta Extract H-VSF-D (Horus Co., Ltd.), Nichirei Water-Soluble Placenta Extract BF (Nichirei Foods Co., Ltd.), and Marine Placenta (Japan Barrier Free Co., Ltd.) can also be used.

[0025] Examples of salmon from which salmon-derived placenta extract can be obtained include white salmon, sockeye salmon, silver salmon, rainbow trout, cherry salmon, and Chinook salmon. The placenta obtained from salmon is made from ovarian membrane, which is the outer skin of the roe of the fish belonging to the above-mentioned salmonidae, and can be obtained by washing only the outer skin after the roe is collected from the ovary. For the composition of the present invention, the ovarian membrane after washing can be crushed in a mixer, mortar, emulsifier, etc., and used as is, or components extracted by treating the ovarian membrane with a protease can be used.

[0026] The placenta extract derived from pigs can be obtained, for example, by extracting it from pig placenta in a sterile environment using water after freezing and thawing. Furthermore, components extracted by treating with protease may also be used.

[0027] The amount of placenta extract in the collagen production promoter of the present invention is not particularly limited, but is, for example, 0.000001 to 5% by mass, and preferably 0.000001 to 3% by mass, relative to the total amount of the collagen production promoter. If the amount is less than 0.000001% by mass, the effect may not be exerted.

[0028] The collagen production promoter of the present invention can be prepared by adding the extract to an aqueous carrier such as purified water, an aqueous solution of a lower alcohol, or a buffer solution, an emulsion carrier, a gel carrier, a paste carrier such as a cream, or a powder carrier, etc.

[0029] The collagen production promoter of the present invention can be used alone, but can also be used as an external skin preparation by blending optional ingredients used in ordinary cosmetics and quasi-drugs to an extent that does not inhibit the effects of the present invention. Specific examples of optional ingredients include oils, surfactants, thickeners, preservatives, fragrances, moisturizers, antioxidants, anti-inflammatory agents, and antibacterial agents.

[0030] The formulation of the collagen production promoter of the present invention or the topical skin preparation containing the collagen production promoter is not particularly limited, and may be any formulation such as water-based, oil-based, or emulsion-type, and can be used in the formulation of, for example, a lotion, emulsion, or ointment.

[0031] The collagen production promoter of the present invention or an external skin preparation containing the collagen production promoter can be prepared by a standard method. [Example]

[0032] 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.

[0033] First, the method for preparing the extract used in the examples will be described.

[0034] [Hokkaido Angelica Extract] (1) From cultivation to harvest Hokkai touki 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 30cm apart and furrows 50cm apart. In late June and early September, organic chicken manure and organic rice bran were added as top dressing. Weeds were removed as needed, and the soil 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 Angelica sinensis extract The roots of Angelica sinensis obtained in (1) were pulverized in a mill mixer. After immersion in a 50% by volume aqueous ethanol solution, the solvent was distilled off, and the roots were added to a 45% by volume aqueous ethanol solution so that the pure extract content was 1% by mass, thereby preparing a Angelica sinensis extract.

[0035] [Placenta extract] A placenta extract was prepared by adding a placenta extract obtained by enzymatically treating salmon ovarian membrane to a 0.8% by volume aqueous ethanol solution so that the pure extract content was 0.4% by mass.

[0036] [Test using human newborn skin fibroblasts] 1 x 10 human neonatal skin fibroblasts 5 Cells were seeded onto 12-well plates at 1000 cells / well and cultured overnight in DMEM medium containing 5% FBS. The medium was replaced with commercially available maintenance medium (Fibroblast Homeostasis Medium) containing each component at the desired concentration and cultured for 24 hours in a 37°C, 5% CO2 incubator. RNA was extracted from the harvested cells using a commercially available RNA extraction kit (QuickGene RNA Cultured Cell HCKitS). After cDNA synthesis, gene expression was confirmed by real-time PCR using the Cyber ​​Green method with the following primers. GAPDH was used as an internal standard. mRNA expression levels are expressed relative to the expression level without each component, which is set to 1. The effects of each component are shown in Table 2.

[0037] The primer sequences used are shown in Table 1.

[0038] [Table 1]

[0039] 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.

[0040] [Table 2]

[0041] As shown in Table 2, the expression level of COL1A1 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 level of COL1A1 increased synergistically. Therefore, the collagen production-promoting agent of the present invention showed a synergistic improvement in the collagen production-promoting effect when used in combination with Angelica acutiloba extract and placenta extract.

[0042] Examples of formulations for external skin preparations containing the collagen production promoter of the present invention are shown below.

[0043] [Formulation Example 1] 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) Angelica sinensis extract 0.1 (13) Placenta extract 0.0001 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.

[0044] [Formulation example 2] 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) Angelica acutiloba extract 0.1 (10) Placenta extract 0.0001 Manufacturing method: Dissolve (2) and (3) in (1). Then add (4) to (10) in order, and stir thoroughly to mix evenly.

[0045] [Prescription Example 3] 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) Angelica acutiloba extract 0.001 (13) Placenta extract 0.01 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.

[0046] [Prescription Example 4] 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) Angelica sinensis extract 0.005 (17) Placenta extract 0.01 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.

[0047] [Formulation example 5] 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) Angelica acutiloba extract 0.001 (10) Placenta extract 0.05 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.

[0048] All of Formulation Examples 1 to 5 exhibit the effect of promoting collagen production.

Claims

[Claim 1] A collagen production promoter containing the following (A) and (B) as active ingredients: (A) Angelica acutiloba extract (B) Placenta extract

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