topical skin preparations

Abstract

To provide a topical preparation for skin that contains specific components in combination, thus synergistically exhibiting a barrier function improving effect and an anti-aging effect.SOLUTION: A topical preparation for skin contains the following (A)-(C). (A) Rose extract, (B) Terminalia extract and (C) pyridoxine hydrochloride.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an external skin preparation containing specific ingredients. [Background technology]

[0002] Factors that contribute to the worsening of skin conditions such as wrinkles, sagging skin, loss of skin elasticity, and disturbances in skin surface morphology include the decline in the function of dermal fibroblasts due to aging and the accompanying decrease and degeneration of dermal matrix such as collagen and elastin. Furthermore, in recent years, the skin barrier function has been attracting attention. Human skin, which comes into contact with the external environment, is constantly exposed to ultraviolet rays, dryness, and allergens such as pollen. These external environments cause various skin problems, such as dryness, blemishes, wrinkles, sagging, and inflammation. To solve these problems, various research and development efforts have been made on anti-aging agents and barrier function enhancers (Patent Document 1, Patent Document 2).

[0003] Many studies have been conducted on the incorporation of various ingredients, either alone or in combination, into topical skin preparations. However, when ingredients are used in combination, the effects are not necessarily synergistically improved by simply combining them; some ingredients may have additive effects, while others may cancel each other out, making the effects of the combination unpredictable. In particular, there is a great need for ingredients that can be used in smaller amounts to provide greater effects in topical skin preparations. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-195534

[0005] [Patent Document 2] Japanese Patent Application Laid-Open No. 2015-205853 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide an external skin preparation that exerts a synergistic barrier function improving effect and anti-aging effect by using specific ingredients in combination. [Means for solving the problem]

[0007] The means for solving the problems of the present invention is to provide an external skin preparation containing the following (A) to (C): (A) Rose extract (B) Terminalia extract (C) Pyridoxine hydrochloride [Effects of the Invention]

[0008] By using specific ingredients in combination, the topical skin preparation of the present invention synergistically exhibits the effects of promoting and inhibiting the production of barrier function-related factors in human neonatal epidermal keratinocytes, as well as the effect of promoting the production of anti-aging-related factors in human neonatal skin fibroblasts. DETAILED DESCRIPTION OF THE INVENTION

[0009] Hereinafter, an embodiment of the present invention will be described.

[0010] FLG is an abbreviation for filaggrin, a natural moisturizing factor that plays an important role in the skin's barrier function.

[0011] TJP1 is an abbreviation for tight junction protein 1, and is a factor involved in the formation of tight junctions, which are important for skin barrier function.

[0012] COX2 stands for cyclooxygenase 2, an enzyme involved in the production of prostaglandins, which cause inflammation.

[0013] COL3A1 is an abbreviation for collagen type III alpha 1 chain, and is a factor involved in the production of type III collagen present in dermal tissue.

[0014] SOD2 is an abbreviation for superoxide dismutase 2, an enzyme present in mitochondria that breaks down reactive oxygen species generated within cells.

[0015] [Rose] Rose is a plant belonging to the genus Rosa in the family Rosaceae. The rose extract used in the present invention is not particularly limited as long as it is typically used in pharmaceuticals, quasi-drugs, cosmetics, foods and beverages, etc., but it is preferable to use an extract extracted from Rosa damascena Mill. or Rosa Centifolia L., and more preferably an extract from Bulgaria.

[0016] Examples of rose parts that can be used include leaves, stems, flowers, buds, and the entire above-ground plant, but it is preferable to use the flowers, and it is further preferable to use the aqueous layer component obtained by steam distillation of the flowers as the extract.

[0017] The amount of the compound in the external skin preparation of the present invention is preferably 0.0000001 to 5% by mass, more preferably 0.0000001 to 3% by mass, based on the total amount of the external skin preparation.

[0018] [Terminaria] Terminalia is a plant belonging to the genus Terminalia in the family Combretaceae.

[0019] The Terminalia extract used in the present invention is not particularly limited as long as it is one that is normally used in pharmaceuticals, quasi-drugs, cosmetics, food and beverages, etc., but it is preferable to use an extract extracted from Terminalia sericea Burch.

[0020] Usable parts of Terminalia include, for example, bark, roots, fruits, etc., with bark and roots being preferred.

[0021] The amount of the compound in the external skin preparation of the present invention is preferably 0.0000001 to 5% by mass, more preferably 0.0000001 to 3% by mass, based on the total amount of the external skin preparation.

[0022] When preparing the extract of the above plant, the plant is used as it is or after drying. 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.

[0023] [Pyridoxine hydrochloride] The pyridoxine hydrochloride used in the present invention is the hydrochloride salt of pyridoxine (vitamin B6), and its raw materials, production method, purification method, etc. are not particularly limited as long as it is normally used in pharmaceuticals, quasi-drugs, cosmetics, foods and beverages, etc.

[0024] The amount of the compound in the topical skin preparation of the present invention is preferably 0.0000001 to 5% by mass, more preferably 0.00001 to 3% by mass, and most preferably 0.0001 to 1% by mass, based on the total amount of the topical skin preparation.

[0025] 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.

[0026] 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.

[0027] The topical skin preparation of the present invention can be prepared by a conventional method.

[0028] The external skin preparation of the present invention can be used in the dosage form of, for example, a lotion, emulsion, or ointment. [Example]

[0029] 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.

[0030] First, the method for preparing the plant extracts used in the examples will be described.

[0031] [Rose extract] The aqueous layer obtained by steam distillation of Bulgarian Rosa damascena flowers was used as the rose extract.

[0032] [Terminaria extract] The dried bark and roots of Terminalia sericea were crushed and immersed in 9 times the mass of methanol, filtered, the filtrate was collected, and the solvent was distilled off. The obtained extract was dried, and the resulting powder was dissolved in 1,3-butylene glycol to a concentration of 1.75 mass% as pure extract to obtain Terminalia extract.

[0033] [Test using human neonatal epidermal keratinocytes] 3 x 10 human neonatal epidermal keratinocytes 5 The cells were seeded onto a 6-well plate at 100 cells / well and cultured overnight in Humedia-KG2 medium. The medium was replaced with Humedia-KG2 medium supplemented with a predetermined amount of each plant extract, and the cells were incubated at 37°C, 5% CO 2 The cells were cultured in an incubator for 24 hours. RNA was extracted from the collected cells using a commercially available RNA extraction kit (QuickGene RNA Cultured Cell Kits). 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. The mRNA expression level was expressed relative to the expression level without the addition of each component, which was set at 1. The effects of each component are shown in Table 2.

[0034] [Test using human newborn skin fibroblasts] 6 × 10 human neonatal skin fibroblasts 5 The cells were seeded onto a 6-well plate at 100 cells / well and cultured overnight in DMEM medium containing 0.5% FBS. The medium was replaced with DMEM medium containing 0.5% FBS containing each component at an arbitrary concentration, and incubated at 37°C, 5% CO 2 The cells were cultured in an incubator for 24 hours. RNA was extracted from the collected 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 shown as relative values, with the expression level without each component set at 1. The effects of each component are shown in Table 3.

[0035] The primer sequences used are shown in Table 1.

[0036] [Table 1]

[0037] In the examples and comparative examples, each component was dissolved in the medium so that the concentration of each component was as shown in Tables 2 and 3. The rose extract and Terminalia extract were v / v %, and pyridoxine hydrochloride was w / v %.

[0038] [Table 2]

[0039] As shown in Table 2, in human neonatal epidermal keratinocytes, in Example 1, in which rose extract, Terminalia extract, and pyridoxine hydrochloride were used in combination at 1 / 3 the amount of each, the expression of FLG and TJP1 increased synergistically and the expression of COX2 decreased synergistically compared to Comparative Examples 1 to 3, in which each component was used alone. Therefore, the topical skin preparation of the present invention exhibits a high barrier function improving effect.

[0040] [Table 3]

[0041] As shown in Table 3, in human neonatal skin fibroblasts, the expression of COL3A1 and SOD2 was synergistically increased in Example 2, which used a combination of rose extract, Terminalia extract, and pyridoxine hydrochloride in 1 / 3 amounts each, compared to Comparative Examples 4 to 6, which used each ingredient alone. Therefore, the topical skin preparation of the present invention exhibits a high anti-aging effect.

[0042] [Example 3] 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 (total amount: 100) (11) Arginine (1% by mass aqueous solution) 20.0 (12) Rose extract 0.00001 (13) Terminalia extract 0.0000001 (14) Pyridoxine hydrochloride 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 (14) are added in order and mixed uniformly.

[0043] [Example 4] Lotion (1) Ethanol 15.0 (mass%) (2) Polyoxyethylene (40E.O.) hydrogenated castor oil 0.3 (3)Fragrance 0.1 (4) Purified water (total amount: 100) (5) Citric acid 0.02 (6) Sodium citrate 0.1 (7) Glycerin 1.0 (8) Hydroxyethyl cellulose 0.1 (9) Rose extract 0.0001 (10) Terminalia extract 0.00001 (11) Pyridoxine hydrochloride 0.00001 Manufacturing method: Dissolve (2) and (3) in (1). Then add (4) to (11) in order, and stir thoroughly to mix evenly.

[0044] [Example 5] 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 (total amount: 100) (11) Carboxyvinyl polymer (1% by mass aqueous solution) 15.0 (12) Rose extract 0.000001 (13) Terminalia extract 0.001 (14) Pyridoxine hydrochloride 0.005 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) to (14) are added at 40°C and mixed uniformly.

[0045] [Example 6] Beauty serum (1) Purified water, the amount (mass%) of which the total amount is 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) Rose extract 0.000002 (17) Terminalia extract 0.00001 (18) Pyridoxine hydrochloride 0.0003 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) to (18) are added at 40°C, and mixed uniformly.

[0046] [Example 7] Water-based gel (1) Carboxyvinyl polymer 0.5 (mass%) (2) Purified water (total volume: 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) Rose extract 0.0001 (10) Terminalia extract 0.0005 (11) Pyridoxine hydrochloride 0.000001 Manufacturing method: (1) is added to (2) and stirred uniformly, and then (3) is added. After stirring uniformly, (5) that has been pre-dissolved in (4) is added. After stirring uniformly, (6) to (11) that have been pre-mixed are added and stirred uniformly.

[0047] [Example 8] Cleansing agent (1) Squalane 81.0 (mass%) (2) Polyoxyethylene glyceryl isostearate 15.0 (3) Purified water (total amount: 100) (4) Rose extract 0.00001 (5) Terminalia extract 0.00001 (6) Pyridoxine hydrochloride 0.000005 Preparation: (1) and (2) are dissolved uniformly. To this, (3) to (6) are added in order and mixed uniformly.

[0048] [Example 9] Facial cleanser (1) Stearic acid 16.0 (mass%) (2) Myristic acid 16.0 (3) Lipophilic Glyceryl Monostearate 2.0 (4) Glycerin 20.0 (5) Sodium hydroxide 7.5 (6) Coconut oil fatty acid amidopropyl betaine 1.0 (7) Purified water (total amount: 100) (8) Rose extract 0.00002 (9) Terminalia extract 0.00002 (10) Pyridoxine hydrochloride 0.000001 Manufacturing method: Heat and dissolve oil phase ingredients (1) to (4) at 80°C. Meanwhile, heat and dissolve water phase ingredients (5) to (7) at 80°C, and mix and stir uniformly with the oil phase ingredients. Start cooling, and add ingredients (8) to (10) at 40°C and mix uniformly.

[0049] [Example 10] Makeup base cream (1) Squalane 10.0 (mass%) (2) Cetyl alcohol 2.0 (3) Glycerin tri-2-ethylhexanoate 2.5 (4) Lipophilic glyceryl monostearate 1.0 (5) Propylene glycol 11.0 (6) Sucrose fatty acid ester 1.3 (7) Arbutin 3.0 (8) L-Ascorbic acid 2-glucoside 2.5 (9) Purified water (total amount: 100) (10) Titanium dioxide 1.0 (11) Bengala 0.1 (12) Yellow iron oxide 0.4 (13) Rose extract 0.00001 (14) Terminalia extract 0.00001 (15) Pyridoxine hydrochloride 0.0001 (16)Fragrance 0.1 Manufacturing method: The oil phase components (1) to (4) are mixed and heated to 75°C to dissolve. Meanwhile, the water phase components (5) to (9) are mixed and heated to dissolve at 75°C, to which the pigments (11) and (12) are added and uniformly dispersed using a homomixer. The oil phase components are added to the water phase components and emulsified using a homomixer. After emulsification, cooling is initiated, and at 40°C, (13) to (16) are added and mixed uniformly.

[0050] [Example 11] Emulsion foundation (1) Methylpolysiloxane 2.0 (mass%) (2) Squalane 5.0 (3) Octyldodecyl myristate 5.0 (4) Cetyl alcohol 1.0 (5) Polyoxyethylene (20E.O.) Sorbitan monostearate 1.3 (6) Sorbitan monostearate 0.7 (7) 1,3-butylene glycol 8.0 (8) Xanthan gum 0.1 (9) Methyl parahydroxybenzoate 0.1 (10) Arbutin 3.0 (11) L-Ascorbic acid 2-glucoside 2.5 (12) Purified water (total amount: 100) (13) Titanium dioxide 9.0 (14) Talc 7.4 (15) Bengala 0.5 (16) Yellow iron oxide 1.1 (17) Black iron oxide 0.1 (18) Rose extract 0.0005 (19) Terminalia extract 0.003 (20) Pyridoxine hydrochloride 0.01 (21)Fragrance 0.01 Manufacturing method: Mix oil phase ingredients (1) to (6) and heat to dissolve at 75°C. Meanwhile, mix water phase ingredients (7) to (12) and heat to dissolve, then add pigments (13) to (17) and disperse uniformly using a homomixer. Add oil phase ingredients and emulsify. After emulsification, start cooling, and add ingredients (18) to (21) sequentially at 40°C and mix uniformly.

[0051] [Example 12] Water-in-oil emollient cream (1) Liquid paraffin 30.0 (mass%) (2) Microcrystalline Wax 2.0 (3) Vaseline 5.0 (4) Diglycerin oleate 5.0 (5) Sodium chloride 1.3 (6) Potassium chloride 0.1 (7) Propylene glycol 3.0 (8) 1,3-butylene glycol 5.0 (9) Methyl parahydroxybenzoate 0.1 (10) Arbutin 3.0 (11) L-Ascorbic acid 2-glucoside 2.5 (12) Purified water (total amount: 100) (13) Rose extract 0.00001 (14) Terminalia extract 0.00001 (15) Pyridoxine hydrochloride 0.01 (16)Fragrance 0.2 Manufacturing method: (5) and (6) are dissolved in a portion of (12) and brought to 50°C, and gradually added to (4) heated to 50°C while stirring. After mixing, the mixture is uniformly dispersed in (1) to (3) which have been heated and dissolved at 70°C. To this, (7) to (11) are dissolved in the remainder of (12) at 70°C and added while stirring, and emulsified using a homomixer. After emulsification, cooling is started, and (13) to (16) are added at 40°C and mixed uniformly.

[0052] [Example 13] Pack (1) Purified water (total volume: 100) (2) Polyvinyl alcohol 12.0 (mass%) (3) Ethanol 17.0 (4) Glycerin 5.0 (5) Polyethylene glycol (average molecular weight 1000) 2.0 (6) Arbutin 3.0 (7) L-Ascorbic acid 2-glucoside 2.5 (8) Rose extract 0.01 (9) Terminalia extract 0.001 (10) Pyridoxine hydrochloride 0.001 (11)Fragrance 0.001 Manufacturing method: (2) and (3) are mixed and heated to 80°C, and then dissolved in (1) that has also been heated to 80°C. After uniform dissolution, (4) to (7) are added and cooling is initiated while stirring. Cool to 40°C, and (8) to (11) are added and mixed uniformly.

Claims

[Claim 1] A topical skin preparation containing the following (A) to (C): (A) Rose extract (B) Terminalia extract (C) Pyridoxine hydrochloride

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