JP7584945B2 - Skin preparations - Google Patents

Description

The present invention relates to a skin preparation for external use.

As humans age, various aging phenomena such as age spots, wrinkles, and sagging skin appear. Known causes of these include a decline in the skin's barrier function, a decrease in moisture content, disruptions to cell turnover, and a decrease in the production or decomposition or alteration of collagen and elastin. A wide variety of proposals have been made to prevent and improve these conditions (Patent Document 1, Patent Document 2, Patent Document 3).

Niacinamide is a water-soluble vitamin in the vitamin B group, and is also known as nicotinamide. It is known to have skin-soothing, whitening, and anti-aging effects, and many cosmetics containing niacinamide are on the market.

Edelweiss (Leontopodium alpinum) is an alpine plant classified in the Asteraceae family, and its extract has already been disclosed as being incorporated into topical skin preparations (Patent Document 4). Lamium album (Lamium album) is a perennial plant classified in the Lamiaceae family, and its extract has already been disclosed as being incorporated into topical skin preparations (Patent Document 5).

There are also many studies being conducted on the use of plant extracts in combination with other plant extracts in cosmetics. However, the effects of plant extracts are not synergistically improved when simply used in combination; some extracts have additive effects, while others cancel each other out, making the effects of these combinations unpredictable. There is therefore a great need for plant extract combinations that provide greater effects with smaller amounts.

Patent No. 4780817 JP 2001-261568 A JP 2005-8571 A JP 2001-288032 A Japanese Patent Application Publication No. 10-330221

The objective of the present invention is to provide a skin care product that contains niacinamide and a specific plant extract and has a high anti-aging effect.

The present invention provides an external skin preparation containing the following (A) to (C):
(A) Niacinamide (B) Edelweiss extract (C) Lamium extract

The topical skin preparation of the present invention exhibits a high anti-aging effect by combining niacinamide with a specific plant extract.

The following describes how to implement the present invention.

[Niacinamide]
Niacinamide is a water-soluble vitamin belonging to the vitamin B group, and is also called nicotinamide.

The niacinamide used in the present invention is not particularly limited in terms of its raw materials, manufacturing method, purification method, etc., so long as it is one that is normally used in external skin preparations.

The amount of the compound in the topical skin preparation used in the present invention is 0.001% to 20% by mass, preferably 0.01% to 15% by mass, and more preferably 0.1% to 10% by mass, based on the total amount of the topical skin preparation.

[Edelweiss]
Edelweiss (scientific name: Leontopodium alpinum) is an alpine plant belonging to the genus Leontopodium in the family Asteraceae.

The edelweiss extract used in the present invention may be one that is usually incorporated into topical skin preparations. Edelweiss extracts extracted directly from plants or commercially available edelweiss extracts may be used. Examples of commercially available edelweiss extracts include EDELWEISS GC (Albaflor), EDELWEISS EP, and EDELWEISS B (all from DSM Nutrition Japan).

The amount of the compound in the topical skin preparation used in the present invention is preferably 0.00001% to 5% by mass, and more preferably 0.00001% to 1% by mass, based on the total amount of the topical skin preparation.

Constituent parts of edelweiss that can be used include, for example, leaves, stems, flowers, buds, and the whole plant above ground, with the whole plant above ground being preferred.

[Lamb's Lamium]
Lamium (scientific name: Lamium album) is a perennial plant classified in the genus Lamium in the family Lamiaceae.

The dead nettle extract used in the present invention may be one that is usually incorporated into topical skin preparations. Either one extracted directly from the plant or a commercially available dead nettle extract may be used. Examples of commercially available dead nettle extracts include Falcorex dead nettle B (Ichimaru Falcos Co., Ltd.).

The amount of the compound in the topical skin preparation used in the present invention is preferably 0.00001% to 5% by mass, and more preferably 0.00001% to 1% by mass, based on the total amount of the topical skin preparation.

Usable parts of Lamium include, for example, leaves, stems, flowers, buds, and the whole plant above ground, with the whole plant above ground being preferred.

When preparing the above extract, the raw plant is used as it is or after drying. As the extraction solvent, water, lower alcohols such as methanol, ethanol, propanol, isopropanol, etc., polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc., ethers such as ethyl ether, propyl ether, etc., esters such as ethyl acetate, butyl acetate, etc., ketones such as acetone, ethyl methyl ketone, etc., and polar organic solvents can be used, and one or more of these can be selected and used. In addition, physiological saline, phosphate buffer, phosphate buffered physiological saline, etc. may also be used. The extracts obtained by the above solvents can be used as they are, but they may also be concentrated, dried, and then dissolved again in water or a polar solvent, or may be used after purification treatment such as bleaching, deodorization, and desalting to the extent that the skin physiological function improving effect is not impaired, or after fractionation treatment by column chromatography. In addition, the extracts may be hydrolyzed using acids, alkalis, enzymes, etc., and used. For storage, the extracts may be freeze-dried after purification treatment and dissolved in a solvent when used. They can also be used by being encapsulated in vesicles such as liposomes or microcapsules. The extraction process is not particularly limited as long as the soluble components contained in the extraction raw material can be dissolved in the extraction solvent, and can be carried out according to a conventional method. For example, an extract can be obtained by immersing the extraction raw material in an extraction solvent in an amount 5 to 30 times (by mass) the amount of the extraction raw material, extracting the soluble components at room temperature or under reflux heating, and then filtering to remove the extraction residue. A paste-like concentrate can be obtained by distilling off the solvent from the obtained extract, and a dry product can be obtained by further drying this concentrate.

In addition to the above-mentioned ingredients, optional ingredients used in ordinary cosmetics and quasi-drugs can be blended into the topical skin preparation used in the present invention to the extent that they do not inhibit the effects of the present invention. Specific examples include oils, surfactants, thickeners, preservatives, fragrances, moisturizers, antioxidants, anti-inflammatory agents, antibacterial agents, etc.

The formulation of the topical skin preparation used in the present invention is not particularly limited, and may be any formulation, such as water-based, oil-based, or emulsion-based.

The topical skin preparation used in the present invention can be prepared by standard methods.

The topical skin preparations used in the present invention can be in the form of, for example, lotions, emulsions, and ointments.

The present invention will be explained in detail below with reference to examples, but the scope of the present invention is not limited thereto. The blend amounts are in mass % unless otherwise specified.

First, we will show how to prepare the plant extracts used in the examples.

[Edelweiss extract]
The dried aerial parts of edelweiss were immersed in a 70% by volume aqueous solution of ethanol, filtered, and the solvent was removed by distillation. The product was freeze-dried to obtain an edelweiss extract.

[Lamb's Lamium Extract]
The dried above-ground parts of Lamium were soaked in water, filtered, and the solvent was removed by distillation. The resultant was freeze-dried to give Lamium extract.

[Test using human epidermal keratinocytes]
Human epidermal keratinocytes were seeded in a 6-well plate at a cell density of 3 x ¹⁰⁵ cells/well and cultured overnight in Humedia-KG2 medium. The medium was replaced with fresh medium in which the plant extract dry powder was dissolved at an arbitrary concentration, and cultured for 24 hours in a 37°C, 5% _CO2 incubator. RNA was extracted from the collected cells using a commercially available RNA extraction kit (Quick Gene RNA Cultured Cell HC Kit S), and gene expression was confirmed by real-time PCR using the Cyber Green method after cDNA synthesis using the following primers. GAPDH was used as an internal standard. The mRNA expression level was shown as a relative value, with the expression level in the absence of each plant extract set to 1. Each effect is shown in Tables 3 to 5.

[Test using human skin fibroblasts]
Human dermal fibroblasts were seeded in a 6-well plate at a cell density of 5 x ¹⁰⁵ cells/well and cultured overnight in DMEM medium containing 5% FBS. The medium was replaced with DMEM medium containing 0.5% FBS in which the plant extract dry powder was dissolved at any concentration, and cultured for 24 hours in a 37°C, 5% _CO2 incubator. RNA was extracted from the collected cells using a commercially available RNA extraction kit (Quick Gene RNA Cultured Cell HC Kit S), and gene expression was confirmed by real-time PCR using the Cyber Green method after cDNA synthesis using the following primers. GAPDH was used as an internal standard. The mRNA expression level was shown as a relative value with the expression level in the absence of each plant extract set to 1. Each effect is shown in Table 6.

The primer sequences used are shown in Table 1.

In the examples, each extract was dissolved in the medium so that the concentration (w/v%) was the amount shown in Table 2.

As shown above, in Example 1, in which niacinamide was used in combination with edelweiss extract and white lamiaceae extract, the expression of the filaggrin production-related gene FLG was synergistically increased compared to Comparative Examples 1 to 3, in which each was used alone.

As shown above, in Example 1, in which niacinamide was used in combination with edelweiss extract and lamiaceae extract, the expression of the ceramide production-related genes SMPD1, SGMS1, and GBA was synergistically increased compared to Comparative Examples 1 to 3, in which each was used alone.

As shown above, in Example 1, in which niacinamide was used in combination with edelweiss extract and lamiaceae extract, the expression of collagen production-related genes COL7A1 and COL17A1 was synergistically increased compared to Comparative Examples 1 to 3, in which each was used alone.

As shown above, in Example 1, in which niacinamide was used in combination with edelweiss extract and white lamiaceae extract, the expression of the elastin degradation-related gene MME was synergistically reduced compared to Comparative Examples 1 to 3, in which each was used alone.

These results show that the topical skin preparation of the present invention, which synergistically increases the expression of filaggrin production-related genes, ceramide production-related genes, and collagen production-related genes, and synergistically decreases the expression of elastin degradation-related genes, exerts a strong anti-aging effect.

[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 (20 E.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 100 (11) Arginine (1% by weight aqueous solution) 20.0
(12) Niacinamide 4.0
(13) Edelweiss extract 0.01
(14) Lamium extract 0.01
Manufacturing method: The oil phase components (1) to (6) are dissolved by heating at 80°C. Meanwhile, the water phase components (7) to (10) are dissolved by heating at 80°C. The oil phase components are added to this while stirring, and the mixture is uniformly emulsified using a homogenizer. After cooling, the components (11) to (14) are added in that order at 40°C, and mixed uniformly.

[Example 3] Lotion (1) Ethanol 15.0 (mass%)
(2) Polyoxyethylene (40 E.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) Niacinamide 6.0
(10) Edelweiss extract 0.005
(11) Lamium extract 0.005
Manufacturing method: (2) and (3) are dissolved in (1). Then (4) to (11) are added in order, and the mixture is thoroughly stirred to be homogeneous.

[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) Cetanol 3.6
(6) Lipophilic glyceryl monostearate 2.0
(7) Glycerin 10.0
(8) Methyl parahydroxybenzoate 0.1
(9) Arginine (20% by weight aqueous solution) 15.0
(10) Purified water Balance (total: 100) (11) Carboxyvinyl polymer (1% by weight aqueous solution) 15.0
(12) Niacinamide 0.4
(13) Edelweiss extract 0.05
(14) Lamium extract 0.05
Manufacturing method: Heat and dissolve the oil phase components (1) to (6) at 80°C. Meanwhile, heat and dissolve the water phase components (7) to (10) at 80°C. Add the oil phase components with stirring, and emulsify uniformly using a homogenizer. Add (11) and stir, then cool, add (12) to (14) at 40°C, and mix uniformly.

[Example 5] Cosmetic essence (1) Purified water Balance (% by mass) to 100
(2) Glycerin 10.0
(3) Sucrose fatty acid ester 1.3
(4) Carboxyvinyl polymer (1% by weight aqueous solution) 17.5
(5) Sodium alginate (1% by weight 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 weight aqueous solution) 2.0
(16) Niacinamide 2.0
(17) Edelweiss extract 0.1
(18) Lamium extract 0.1
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 homogeneously emulsified using a homomixer. After cooling, (15) is added at 50°C, and (16) to (18) are added at 40°C, and mixed homogeneously.

[Example 6] Aqueous gel (1) Carboxyvinyl polymer 0.5 (mass%)
(2) Purified water (balance to make up 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) Niacinamide 4.0
(10) Edelweiss extract 0.01
(11) Lamium extract 0.01
Manufacturing method: (1) is added to (2), and after stirring uniformly, (3) is added. After stirring uniformly, (5) previously dissolved in (4) is added. After stirring uniformly, (6) to (11) previously mixed are added, and stirred and mixed uniformly.

Claims (1)

One or more agents selected from FLG gene , SMPD1 gene, SGMS1 gene, GBA gene , COL7A1 gene and COL17A1 gene expression promoters and MME gene expression inhibitors, which contain the following (A) to (C):
(A) Niacinamide (B) Edelweiss extract (C) Lamium extract