Topical skin preparation
A topical skin preparation combining niacinamide, heparinoid, dipotassium glycyrrhizinate, collagen peptide, yeast extract, and glycylglycine, along with optional additives, effectively addresses the limitations of conventional preparations by enhancing collagen production, stratum corneum moisture, and user experience.
Patent Information
- Application Number
- JP2024076353
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-05-09
- Publication Date
- 2025-11-20
AI Technical Summary
Conventional topical skin preparations are insufficient in promoting collagen production, improving the feel of use, and increasing the moisture content of the stratum corneum.
A topical skin preparation containing niacinamide, heparinoid, dipotassium glycyrrhizinate, collagen peptide, yeast extract, and glycylglycine, optionally with hydrogenated soybean phospholipids and phytosterols, and further enhanced with arnica or plantago major extracts, to promote collagen production, enhance stratum corneum moisture, and improve usability.
The formulation achieves excellent collagen production, increased stratum corneum moisture, and improved skin compatibility and feel upon application.
Smart Images

Figure 2025171233000001_ABST
Abstract
Description
[Technical Field]
[0001] The present invention relates to an external preparation for skin. [Background technology]
[0002] Conventionally, various active ingredients have been proposed for topical skin preparations, and cosmetics and pharmaceuticals containing these active ingredients have been marketed. For example, Patent Document 1 describes oligopeptides and their derivatives that have collagen gel contraction promoting action or fibroblast activation action, and describes glycylglycine, dipotassium glycyrrhizinate, and heparinoids as ingredients that improve skin firmness, and niacinamide as a physiologically or pharmacologically active ingredient. [Prior art documents] [Patent documents]
[0003] [Patent Document 1] Japanese Patent Publication No. 2023-010555 Summary of the Invention [Problem to be solved by the invention]
[0004] However, conventional topical skin preparations have not been sufficient in terms of the collagen production promoting effect, the effect of improving the feeling of use, and the effect of increasing the moisture content of the stratum corneum. [Means for solving the problem]
[0005] The present invention provides the following [1] to [4]. [1] A topical skin preparation containing niacinamide, a heparinoid, dipotassium glycyrrhizinate, collagen peptide, yeast extract, and glycylglycine. [2] The topical skin preparation according to [1], further comprising hydrogenated soybean phospholipids and phytosterols. [3] The topical skin preparation according to [1] or [2], wherein the niacinamide content is 5% by mass or more. [4] The external skin preparation according to any one of [1] to [3], further comprising an extract of at least one plant selected from arnica extract and plantago major. [Effects of the Invention]
[0006] According to the present invention, it is possible to provide an external skin preparation that has an excellent collagen production promoting effect, an excellent feel when used, and an excellent effect of increasing the moisture content of the stratum corneum. [Brief explanation of the drawings]
[0007] [Figure 1] FIG. 1 is a graph showing the relative expression levels of COL1A1 in Examples and Comparative Examples. DETAILED DESCRIPTION OF THE INVENTION
[0008] A preferred embodiment of the present invention is described below. In this specification, the collagen production-promoting effect includes the collagen gene expression-promoting effect. Furthermore, the usability includes the skin compatibility of the topical skin preparation and the moist feeling after application. Furthermore, the stratum corneum moisture-enhancing effect includes a rapid-response improving effect, such as 15 minutes after application. The inventors have surprisingly discovered that by combining components expected to promote collagen production, such as (A) niacinamide, (D) collagen peptide, and (E) yeast extract, and components believed to have a fibroblast proliferation-promoting effect and prevent rough skin, such as (C) dipotassium glycyrrhizinate, with (B) heparinoids believed to be effective in promoting blood circulation and moisturizing, and (F) glycylglycine believed to have moisturizing, parakeratosis-inhibiting, and anti-inflammatory effects, it is possible to obtain an excellent collagen production-promoting effect, effectively increase the stratum corneum moisture content, and improve the usability of cosmetics.
[0009] (A) Niacinamide The topical skin preparation of the present invention contains (A) niacinamide, which effectively enhances the collagen production promoting effect and is also thought to contribute to improving the moisture content of the stratum corneum due to its excellent moisturizing effect. Niacinamide is also known as nicotinamide. Niacinamide may be an extract extracted from natural products such as rice bran, a synthetic product synthesized by a known manufacturing method, or a commercially available product. Specifically, nicotinamide listed in the 17th edition of the Japanese Pharmacopoeia can be used.
[0010] Niacinamide is preferably contained in the topical skin preparation of the present invention at 1% by mass or more, more preferably 2% by mass or more, and even more preferably 3% by mass or more. From the viewpoint of further enhancing the effects of promoting collagen production, improving stratum corneum moisture content, and providing an excellent feel when used, (A) niacinamide is preferably contained in the topical skin preparation of the present invention at 4% by mass or more, particularly preferably 5% by mass or more. The upper limit of the amount of (A) niacinamide in the topical skin preparation is preferably 15% by mass or less, from the viewpoint of obtaining an external skin preparation with an excellent feel when used, more preferably 12% by mass or less, and most preferably 10% by mass or less.
[0011] In the topical skin preparation of the present invention, the proportion of (A) niacinamide in the total solid content of components (A) to (F) is preferably 30% by mass or more, more preferably 40% by mass or more, even more preferably 50% by mass or more, even more preferably 60% by mass or more, and particularly preferably 70% by mass or more. The proportion of (A) niacinamide in the total solid content of components (A) to (F) is preferably 99.5% by mass or less, more preferably 99% by mass or less, and even more preferably 97% by mass or less.
[0012] (B) Heparinoids As mentioned above, heparinoids are believed to be effective in promoting blood circulation and moisturizing. By containing (B) heparinoid, the topical skin preparation of the present invention is expected to have an excellent effect of increasing stratum corneum moisture content and a pleasant feel when used. Heparinoids are also known as mucopolysaccharide polysulfates or heparinoids, and are polysulfated mucopolysaccharides such as chondroitin polysulfate. Examples of heparinoids include heparin; chondroitin polysulfates such as chondroitin sulfate D and chondroitin sulfate E; and the like. The origin of the heparinoid used in the present invention is not particularly limited, and examples include those obtained by polysulfating mucopolysaccharides and those extracted from tissues of edible animals (e.g., lungs containing tracheal cartilage from pigs, etc.). Heparinoids listed in the Japanese Pharmacopoeia's Non-Drug Standards are preferred.
[0013] The heparinoid may be in the form of a physiologically acceptable salt, such as a hydroxide or carbonate of an alkali metal such as sodium or potassium, or a salt obtained by a salt-forming reaction using an amine or the like.
[0014] In the topical skin preparation of the present invention, the amount of (B) heparinoid in the topical skin preparation is preferably 0.001% by mass or more in order to enhance the effects of the present invention achieved by using (B) heparinoid. From this perspective, the amount of (B) heparinoid in the topical skin preparation is even more preferably 0.01% by mass or more, and particularly preferably 0.05% by mass or more. From the same perspective, the amount of (B) heparinoid in the topical skin preparation is preferably 20% by mass or less, even more preferably 10% by mass or less, and particularly preferably 5% by mass or less.
[0015] In the topical skin preparation of the present invention, the amount of (B) heparinoid is preferably 0.01 parts by mass or more relative to 100 parts by mass of (A) niacinamide, in order to further improve the effects of the present invention. From this perspective, the amount of (B) heparinoid is even more preferably 0.1 parts by mass or more, and particularly preferably 0.5 parts by mass or more, relative to 100 parts by mass of (A) niacinamide. In order to further improve the effects of the present invention, the amount of (B) heparinoid is even more preferably 30 parts by mass or less, even more preferably 15 parts by mass or less, and particularly preferably 10 parts by mass or less, relative to 100 parts by mass of (A) niacinamide.
[0016] Furthermore, in the topical skin preparation of the present invention, the proportion of the heparinoid (B) relative to 100 parts by mass of the total solid content of the components (A) to (F) is preferably 0.005 parts by mass or more, in order to further improve the effects of the present invention. From this perspective, the amount of the heparinoid (B) relative to 100 parts by mass of the total solid content of the components (A) to (F) is even more preferably 0.01 parts by mass or more, particularly preferably 0.05 parts by mass or more, even more preferably 0.1 parts by mass or more, and particularly preferably 0.5 parts by mass or more. From the viewpoint of further improving the effects of the present invention, the amount of the heparinoid (B) relative to 100 parts by mass of the total solid content of the components (A) to (F) is even more preferably 30 parts by mass or less, even more preferably 15 parts by mass or less, and particularly preferably 10 parts by mass or less.
[0017] (C) Dipotassium glycyrrhizinate As mentioned above, dipotassium glycyrrhizinate is said to have a fibroblast proliferation promoting effect and acts to prevent rough skin. The inclusion of dipotassium glycyrrhizinate in the topical skin preparation of the present invention is thought to contribute to its excellent collagen production promoting effect.
[0018] Dipotassium glycyrrhizinate is not particularly limited as long as it is used as an ingredient in pharmaceuticals, quasi-drugs, or cosmetics for external skin preparations. Dipotassium glycyrrhizinate can be obtained by reacting glycyrrhizic acid with potassium hydroxide (KOH) or the like, and glycyrrhizic acid can be obtained by isolating and purifying it from a plant extract containing glycyrrhizinic acid.
[0019] In the topical skin preparation of the present invention, the amount of (C) dipotassium glycyrrhizinate in the topical skin preparation is preferably 0.0005% by mass or more, in order to enhance the effects of the present invention by using (C) dipotassium glycyrrhizinate. From this viewpoint, the amount of (C) dipotassium glycyrrhizinate in the topical skin preparation is even more preferably 0.005% by mass or more, and particularly preferably 0.01% by mass or more. From the same viewpoint, the amount of (C) dipotassium glycyrrhizinate in the topical skin preparation is preferably 5% by mass or less, even more preferably 2% by mass or less, and particularly preferably 0.6% by mass or less.
[0020] In the topical skin preparation of the present invention, the amount of (C) dipotassium glycyrrhizinate is preferably 0.005 parts by mass or more relative to 100 parts by mass of (A) niacinamide, in order to further improve the effects of the present invention. From this viewpoint, the amount of (C) dipotassium glycyrrhizinate is even more preferably 0.05 parts by mass or more, and particularly preferably 0.2 parts by mass or more, relative to 100 parts by mass of (A) niacinamide. In order to further improve the effects of the present invention, the amount of (C) dipotassium glycyrrhizinate is preferably 30 parts by mass or less, even more preferably 15 parts by mass or less, and particularly preferably 5 parts by mass or less, relative to 100 parts by mass of (A) niacinamide.
[0021] Furthermore, in the topical skin preparation of the present invention, the proportion of (C) dipotassium glycyrrhizinate is preferably 0.001 parts by mass or more per 100 parts by mass of the total solid content of components (A) to (F), in order to further improve the effects of the present invention. From this perspective, the amount of (C) dipotassium glycyrrhizinate is even more preferably 0.01 parts by mass or more, particularly preferably 0.05 parts by mass or more, even more preferably 0.1 parts by mass or more, and particularly preferably 0.3 parts by mass or more, per 100 parts by mass of the total solid content of components (A) to (F). In order to further improve the effects of the present invention, the amount of (C) dipotassium glycyrrhizinate is even more preferably 30 parts by mass or less, even more preferably 15 parts by mass or less, and particularly preferably 10 parts by mass or less, per 100 parts by mass of the total solid content of components (A) to (F).
[0022] (D) Collagen peptide As described above, collagen peptides are said to have a collagen production-promoting effect, but also have a moisturizing effect. As will be seen from a comparison between Comparative Example 3 and Example 2 described below, by incorporating (D) collagen peptide in combination with (A) to (C) and (E) and (F) in the topical skin preparation of the present invention, highly effective collagen production promotion, improvement of stratum corneum moisture content, and improvement of usability can be achieved.
[0023] Collagen is one of the proteins that make up the dermis, ligaments, tendons, bones, cartilage, etc. of animals, and in the present invention, collagen peptides are used that are obtained by hydrolyzing collagen (including its denatured form, gelatin) collected from any collagen-rich tissue using a proteolytic enzyme or an acid or base catalyst. The collagen or gelatin that is the raw material for collagen peptides may be derived from pigs, chickens, fish, etc., and one or more of these can be used as raw materials.
[0024] In order to enhance the effects of the present invention, the weight-average molecular weight (Mw) of the collagen peptide used in the present invention is preferably 50 or more, more preferably 70 or more, even more preferably 100 or more, and particularly preferably 200 or more. In order to enhance the effects of the present invention, the upper limit of the weight-average molecular weight (Mw) of the collagen peptide is, for example, preferably 10,000 or less, more preferably 8,000 or less, even more preferably 6,000 or less, and particularly preferably 4,000 or less.
[0025] The weight-average molecular weight of collagen peptides can be calculated according to the method described in "20-2 Average Molecular Weight" of the Photographic Gelatin Test Method (PAGI Method) 10th Edition of the Japan Gelatin and Collagen Peptide Industry Association. The PAGI method estimates the molecular weight distribution of collagen peptides by obtaining a chromatogram using gel filtration with high-performance liquid chromatography. When using commercially available collagen peptides, the weight-average molecular weight (Mw) can be determined based on the product information provided by the supplier.
[0026] In the present invention, commercially available collagen peptides can be used, and suitable examples of commercially available collagen peptides include "FCP" and "FCP-AH" manufactured by Nippi Co., Ltd., "GBB-50SP" manufactured by Nitta Gelatin Co., Ltd., "F5000HD" and "P5000HD" manufactured by Unitec Foods Co., Ltd., "Promois W-32", "Promois W-32LS", "Promois W-32NO", and "Promois W-32R" (all weight average molecular weight 400), "Promois W-52", "Promois W-52P", and "Promois W-52Q" (all weight average molecular weight 2000) manufactured by Seiwa Kasei Co., Ltd., and "Falconix CTP-F (BG)" (weight average molecular weight 5000) manufactured by Ichimaru Falcos Co., Ltd.
[0027] In the topical skin preparation of the present invention, the amount of (D) collagen peptide in terms of solid content in the topical skin preparation is preferably 0.000001% by mass or more, in order to enhance the effects of the present invention by using (D) collagen peptide. From this perspective, the amount of (D) collagen peptide in terms of solid content in the topical skin preparation is even more preferably 0.00001% by mass or more, and particularly preferably 0.0001% by mass or more. From the same perspective, the amount of (D) collagen peptide in terms of solid content in the topical skin preparation is preferably 1% by mass or less, even more preferably 0.1% by mass or less, and particularly preferably 0.01% by mass or less.
[0028] In the external skin preparation of the present invention, the amount of (D) collagen peptide, as solid content, is preferably 0.00002 parts by mass or more relative to 100 parts by mass of (A) niacinamide, in order to further improve the effects of the present invention.From this point of view, the amount of (D) collagen peptide, as solid content, is more preferably 0.0002 parts by mass or more relative to 100 parts by mass of (A) niacinamide, and particularly preferably 0.002 parts by mass or more.In order to further improve the effects of the present invention, the amount of (D) collagen peptide is preferably 20 parts by mass or less relative to 100 parts by mass of (A) niacinamide, more preferably 2 parts by mass or less, and particularly preferably 0.2 parts by mass or less.
[0029] Furthermore, in the topical skin preparation of the present invention, the proportion of (D) collagen peptide, as solid content, relative to 100 parts by mass of the total solid content of the (A) to (F) components is preferably 0.00002 parts by mass or more, in terms of improving the effects of the present invention. From this perspective, the amount of (D) collagen peptide, as solid content, relative to 100 parts by mass of the total solid content of the (A) to (F) components is even more preferably 0.0002 parts by mass or more, particularly preferably 0.002 parts by mass or more, even more preferably 0.001 parts by mass or more, and particularly preferably 0.01 parts by mass or more. From the viewpoint of improving the effects of the present invention, the amount of (D) collagen peptide, as solid content, relative to 100 parts by mass of the total solid content of the (A) to (F) components is even more preferably 2 parts by mass or less, even more preferably 1 part by mass or less, and particularly preferably 0.5 parts by mass or less.
[0030] (E) Yeast extract Yeast extract is known to be effective in promoting collagen production and moisturizing. As will be seen from a comparison with Comparative Example 3 and Example 2 described below, by incorporating yeast extract (E) in combination with ingredients (A) to (D) and (F) in the topical skin preparation of the present invention, highly effective collagen production promotion, improvement of stratum corneum moisture content, and improvement of usability can be achieved.
[0031] (E) The yeast extract used in the present invention may be an extract of yeast with a polar solvent, a product obtained by lysing yeast by autolysis, acid hydrolysis, alkaline hydrolysis, enzymatic hydrolysis, or the like and then filtering, or a product obtained by drying the liquid obtained by the above-mentioned lysis and extracting it with a polar solvent. Preferably, the yeast extract used is obtained by extracting the liquid obtained by lysing yeast by autolysis or acid hydrolysis with water, propylene glycol, 1,3-butylene glycol, or a mixture thereof, after drying.
[0032] Yeasts include yeasts belonging to the Endomycetaceae family such as the genus Eremascus and the genus Endomyces, the genus Candida, the genus Schizosaccharomyces, the genus Nadsonia, the genus Saccharomycodes, and the genus Hansenias. pora, Wickerhamia, Saccharomyces, Kluyveromyces, Lodderomyces, Wingea, Endomycopsis, Pichia, Hansenula, Pachysolen, Cit Examples of ascomycete yeasts include yeasts belonging to the family Saccharomycoideae, such as the genera Spermomyces, Debaryomyces, Schwanniomyces, Dekkera, Saccharomycopsis, and Lipomyces, and yeasts belonging to the family Spermophthoraceae, such as the genera Spermophthora, Eremothecium, Crebrothecium, Ashbya, Nematospora, Metschnikowia, and Coccidiascus. The genus Saccharomycopsis is preferred.
[0033] When the topical skin preparation of the present invention contains yeast extract (E), the amount thereof is preferably 0.00001% by mass or more in terms of solid content in the topical skin preparation, in order to enhance the effects of the present invention achieved by using the yeast extract. From this perspective, the amount of yeast extract in the topical skin preparation is even more preferably 0.0001% by mass or more in terms of solid content, and particularly preferably 0.001% by mass or more. From the same perspective, the amount of yeast extract in the topical skin preparation is preferably 1% by mass or less in terms of solid content, even more preferably 0.1% by mass or less, and particularly preferably 0.02% by mass or less.
[0034] When the topical skin preparation of the present invention contains (E) yeast extract, the amount thereof is preferably 0.0002 parts by mass or more in terms of solid content relative to 100 parts by mass of (A) niacinamide, in order to further improve the effects of the present invention. From this perspective, the amount of (E) yeast extract is even more preferably 0.002 parts by mass or more, and particularly preferably 0.02 parts by mass or more, relative to 100 parts by mass of (A) niacinamide. In order to further improve the effects of the present invention, the amount of (E) yeast extract is even more preferably 2 parts by mass or less, and particularly preferably 0.4 parts by mass or less, in terms of solid content relative to 100 parts by mass of (A) niacinamide.
[0035] Furthermore, in the topical skin preparation of the present invention, the proportion of (E) yeast extract, as solids, relative to 100 parts by mass of the total solids of components (A) to (F) is preferably 0.0001 parts by mass or more, in terms of improving the effects of the present invention. From this perspective, the amount of (E) yeast extract, as solids, relative to 100 parts by mass of the total solids of components (A) to (F), is even more preferably 0.001 parts by mass or more, particularly preferably 0.005 parts by mass or more, even more preferably 0.01 parts by mass or more, and particularly preferably 0.05 parts by mass or more. From the viewpoint of improving the effects of the present invention, the amount of (E) yeast extract is even more preferably 5 parts by mass or less, even more preferably 3 parts by mass or less, and particularly preferably 1.5 parts by mass or less, in terms of 100 parts by mass of the total solids of components (A) to (F).
[0036] (F) Glycylglycine Glycylglycine, the component (F), is known to have an inhibitory effect on parakeratosis. As shown in Examples 1 and 2 and Comparative Examples 1 and 2 described below, it was surprisingly found that by adding glycylglycine to components (A) to (E), it was possible to obtain excellent effects such as excellent collagen production promotion effects, excellent stratum corneum moisture content improvement effects, good skin compatibility, and excellent moisturizing feeling after application.
[0037] When the topical skin preparation of the present invention contains (F) glycylglycine, its amount in the topical skin preparation is preferably 0.0001% by mass or more, in order to enhance the effects of the present invention achieved by using (F) glycylglycine. From this perspective, the amount of glycylglycine in the topical skin preparation is even more preferably 0.001% by mass or more, and particularly preferably 0.005% by mass or more. From the same perspective, the amount of (F) glycylglycine in the topical skin preparation is preferably 3% by mass or less, more preferably 1% by mass or less, even more preferably 0.5% by mass or less, even more preferably 0.1% by mass or less, and particularly preferably 0.05% by mass or less.
[0038] When the topical skin preparation of the present invention contains (F) glycylglycine, the amount thereof is preferably 0.001 parts by mass or more relative to 100 parts by mass of (A) niacinamide, in order to further improve the effects of the present invention. From this viewpoint, the amount of (F) glycylglycine is more preferably 0.01 parts by mass or more, and particularly preferably 0.05 parts by mass or more, relative to 100 parts by mass of (A) niacinamide. In order to further improve the effects of the present invention, the amount of (F) glycylglycine is preferably 3 parts by mass or less, more preferably 1.5 parts by mass or less, and even more preferably 1 part by mass or less, relative to 100 parts by mass of (A) niacinamide.
[0039] Furthermore, in the topical skin preparation of the present invention, the proportion of glycylglycine (F) is preferably 0.0001 parts by mass or more per 100 parts by mass of the total solid content of components (A) to (F), in order to further improve the effects of the present invention. From this perspective, the amount of glycylglycine (F) is more preferably 0.001 parts by mass or more, particularly preferably 0.005 parts by mass or more, even more preferably 0.01 parts by mass or more, and particularly preferably 0.05 parts by mass or more, per 100 parts by mass of the total solid content of components (A) to (F). In order to further improve the effects of the present invention, the amount of glycylglycine (F) is more preferably 3 parts by mass or less, even more preferably 1.5 parts by mass or less, and particularly preferably 1 part by mass or less, per 100 parts by mass of the total solid content of components (A) to (F).
[0040] (G) Hydrogenated soybean phospholipid In the present invention, the topical skin preparation preferably contains (G) hydrogenated soybean phospholipid. In particular, by including (G) hydrogenated soybean phospholipid and (H) phytosterol, an emulsion can be obtained in which an oil phase using this is dispersed in an aqueous phase containing (A) niacinamide, (B) a heparinoid, (C) dipotassium glycyrrhizinate, (D) collagen peptide, and (E) yeast extract (F) glycylglycine. In this emulsion, the amphiphilic component (G) improves the penetration of the composition, and the emollient component (H) improves skin softness, facilitating penetration of the components (A) to (F), thereby achieving the excellent effects of the present invention.
[0041] As the (G) hydrogenated soybean phospholipid used in the present invention, hydrogenated soybean lecithin or the like can be used, in which the unsaturated carbon chains in soybean phospholipids such as soybean lecithin are converted to saturated bonds by hydrogenation.
[0042] The content of (G) hydrogenated soybean phospholipid in the topical skin preparation is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, particularly preferably 0.05% by mass or more, and particularly preferably 0.1% by mass or more, in order to improve the skin permeability of the topical skin preparation and to enhance the effects of the present invention. Also, the content of (G) hydrogenated soybean phospholipid in the topical skin preparation is preferably 20% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, and particularly preferably 2% by mass or less, in order to enhance the feel during use.
[0043] In the topical skin preparation of the present invention, the amount of (G) hydrogenated soybean phospholipid is preferably 0.01 parts by mass or more per 100 parts by mass of (A) niacinamide, in order to enhance the skin penetration of the topical skin preparation and to enhance the effects of the present invention. From this perspective, the amount of (G) hydrogenated soybean phospholipid is even more preferably 0.1 parts by mass or more, and particularly preferably 0.5 parts by mass or more, per 100 parts by mass of (A) niacinamide. In order to further enhance the effects of the present invention, the amount of (G) hydrogenated soybean phospholipid is even more preferably 30 parts by mass or less per 100 parts by mass of (A) niacinamide, in order to provide an excellent feel during use, and even more preferably 15 parts by mass or less, and particularly preferably 10 parts by mass or less.
[0044] The content of (G) hydrogenated soybean phospholipid in the topical skin preparation is preferably 0.01 parts by mass or more per 100 parts by mass of the total solid content of components (A) to (F), in order to enhance the skin penetration of the topical skin preparation and to enhance the effects of the present invention. From this perspective, the content is more preferably 0.05 parts by mass or more, even more preferably 0.1 parts by mass or more, and particularly preferably 0.5 parts by mass or more. Furthermore, the content of (G) hydrogenated soybean phospholipid in the topical skin preparation is preferably 20 parts by mass or less per 100 parts by mass of the total solid content of components (A) to (F), in order to obtain a topical skin preparation that is smooth to the touch and has excellent skin penetration, and is more preferably 15 parts by mass or less, and even more preferably 10 parts by mass or less.
[0045] (H) Phytosterols Phytosterol is a general term for phytosterols contained in plants, and known major components include β-sitophytosterol, stigmaphytosterol, campephytosterol, and brassicaphytosterol. The phytosterol may be a mixture of multiple phytosterols. The topical skin preparation of the present invention preferably contains (H) phytosterol in addition to (G) hydrogenated soybean phospholipid, as this provides excellent emulsion stability and is particularly excellent in terms of feel during use and skin penetration. As can be seen from a comparison between Examples 2 and 3 described below, the topical skin preparation of the present invention can further improve the collagen production-promoting effect, stratum corneum moisture-increasing effect, and feel during use.
[0046] When phytosterol is contained, the content thereof in the topical skin preparation is preferably 0.001% by mass or more from the above viewpoint, more preferably 0.005% by mass or more, and particularly preferably 0.01% by mass or more. Furthermore, when phytosterol is contained, the content thereof in the topical skin preparation is preferably 10% by mass or less from the viewpoint of easily obtaining a topical skin preparation that is smooth in use and has excellent skin permeability, and from the viewpoint of obtaining a stable composition, more preferably 5% by mass or less, even more preferably 3% by mass or less, and particularly preferably 1% by mass or less.
[0047] In the topical skin preparation of the present invention, the amount of (H) phytosterol is preferably 0.001 parts by mass or more relative to 100 parts by mass of (A) niacinamide, in order to enhance the skin permeability of the topical skin preparation and to achieve excellent effects of the present invention. From this perspective, the amount of (H) phytosterol is even more preferably 0.05 parts by mass or more, and particularly preferably 0.1 parts by mass or more, relative to 100 parts by mass of (A) niacinamide. In order to further improve the effects of the present invention, the amount of (H) phytosterol is even more preferably 15 parts by mass or less relative to 100 parts by mass of (A) niacinamide, in order to easily obtain a topical skin preparation that is smooth to use and has excellent skin permeability, and is even more preferably 10 parts by mass or less, and particularly preferably 5 parts by mass or less.
[0048] The content of (H) phytosterol in the topical skin preparation is preferably 0.001 parts by mass or more per 100 parts by mass of the total solid content of components (A) to (F), in order to enhance the skin permeability of the topical skin preparation and to achieve excellent effects of the present invention. From this perspective, the amount of (H) phytosterol is more preferably 0.05 parts by mass or more, and even more preferably 0.1 parts by mass or more, per 100 parts by mass of the total solid content of components (A) to (F). Furthermore, the content of (H) phytosterol in the topical skin preparation is preferably 15 parts by mass or less, more preferably 10 parts by mass or less, and even more preferably 5 parts by mass or less, per 100 parts by mass of the total solid content of components (A) to (F), in order to obtain a topical skin preparation that is smooth to the touch and has excellent skin permeability.
[0049] (I) Arnica extract The topical skin preparation of the present invention may further contain (I) arnica extract as a component different from components (A) to (F), (G), and (H). As shown in Examples 3 and 4 described below, in this case, the topical skin preparation of the present invention is particularly effective in promoting collagen production and increasing the moisture content of the stratum corneum, and also provides an excellent feel when used.
[0050] Arnica is a plant of the Asteraceae family, genus Arnica (Asteroideae), and its scientific name is Arnica montana. Arnica has been known to be used as an agent for suppressing UV damage and contained in compositions for preventing skin aging, but its effects of promoting collagen production, etc., are not known. Arnica may be used from any of flowers, leaves, stems, roots, and fruits, or the whole plant (including flowers, leaves, stems, roots, and fruits). In the present invention, when using an arnica extract, an arnica flower extract is particularly preferred because it has excellent collagen production promoting effects, stratum corneum moisture content improving effects, good skin compatibility, and a moist feeling after application. In addition to arnica flower extract, arnica flower extract also includes extracts using other parts of arnica (stems, leaves, etc.) as the extracted parts.
[0051] The arnica extract may be obtained by squeezing an extract containing the plant body either directly or after crushing, or by extracting the plant body with a solvent either directly or after crushing. The extraction solvent may be water, a hydrophilic organic solvent, or a water-containing hydrophilic organic solvent. Examples of hydrophilic organic solvents include lower aliphatic alcohols having 1 to 3 carbon atoms, such as methanol, ethanol, propanol, and isopropanol, and polyhydric alcohols having 2 to 4 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin.
[0052] When the topical skin preparation of the present invention contains (I) arnica extract, its amount in the topical skin preparation is preferably 0.0000001% by mass or more as solid content, in order to ensure the above-mentioned effects of using (I) arnica extract.From this viewpoint, the amount of (I) arnica extract in the topical skin preparation is more preferably 0.00001% by mass or more as solid content, and particularly preferably 0.0001% by mass or more.Furthermore, from the same viewpoint, the amount of (I) arnica extract in the topical skin preparation is preferably 0.1% by mass or less as solid content, more preferably 0.05% by mass or less, and particularly preferably 0.01% by mass or less.
[0053] In the external preparation for skin of the present invention, the amount of (I) arnica extract is preferably 0.000002 parts by mass or more in terms of solid content relative to 100 parts by mass of (A) niacinamide, in order to enhance the skin permeability of the external preparation for skin and to enhance the effects of the present invention.From this viewpoint, the amount of (I) arnica extract is more preferably 0.0002 parts by mass or more in terms of solid content relative to 100 parts by mass of (A) niacinamide, and particularly preferably 0.002 parts by mass or more.In order to further improve the effects of the present invention, the amount of (I) arnica extract is preferably 2 parts by mass or less in terms of solid content relative to 100 parts by mass of (A) niacinamide, more preferably 1 part by mass or less, and particularly preferably 0.2 parts by mass or less.
[0054] The content of the arnica extract (I) in the topical skin preparation is preferably 0.00002 parts by mass or more in terms of solid content per 100 parts by mass of the total solid content of the components (A) to (F), in order to enhance the skin penetration of the topical skin preparation and to enhance the effects of the present invention. From this perspective, the amount of the arnica extract (I) is more preferably 0.0002 parts by mass or more, and even more preferably 0.002 parts by mass or more, in terms of solid content per 100 parts by mass of the total solid content of the components (A) to (F). Furthermore, in order to further enhance the effects of the present invention, the content of the arnica extract (I) in the topical skin preparation is preferably 1 part by mass or less, even more preferably 0.5 parts by mass or less, and particularly preferably 0.2 parts by mass or less, in terms of solid content per 100 parts by mass of the total solid content of the components (A) to (F).
[0055] (J) Plantago major extract The topical skin preparation of the present invention may further contain (J) psyllium extract instead of or in addition to (I) arnica extract as a component different from components (A) to (F), (G), and (H). As shown in Examples 4 and 5 described below, in this case, the topical skin preparation of the present invention can achieve particularly excellent effects of promoting collagen production and increasing the moisture content of the stratum corneum, as well as an excellent feel when used.
[0056] Plantago major is a plant of the genus Plantago in the family Plantaginaceae, and its scientific name is Plantago major. Plantago major extracts are known to have singlet oxygen quenching and anti-glycation properties, but their collagen production-promoting effects are unknown. Plantago major may be used in any form selected from the group consisting of flowers, leaves, stems, roots, and fruits, or the entire plant (including flowers, leaves, stems, roots, and fruits). In the present invention, when using plantago major extract, plantago major seed extract is particularly preferred because of its excellent collagen production-promoting effects, stratum corneum moisture-enhancing effects, and excellent usability. Plantago major seed extract also includes extracts obtained from other parts of plantago major in addition to plantago major seeds.
[0057] The plantago major extract may be obtained by squeezing the juice from an extract containing the plant body either directly or after crushing, or by extracting the plant body directly or after crushing with a solvent. The extraction solvent may be water, a hydrophilic organic solvent, or a water-containing hydrophilic organic solvent. Examples of hydrophilic organic solvents include lower aliphatic alcohols having 1 to 3 carbon atoms, such as methanol, ethanol, propanol, and isopropanol, and polyhydric alcohols having 2 to 4 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin.
[0058] When the topical skin preparation of the present invention contains (J) psyllium major extract, the amount thereof is preferably 0.0000001% by mass or more in terms of solid content in the topical skin preparation, in order to ensure the effects of using the psyllium major extract. From this perspective, the amount of (J) psyllium major extract in the topical skin preparation is even more preferably 0.0001% by mass or more, and particularly preferably 0.001% by mass or more, in terms of solid content in the topical skin preparation. From the same perspective, the amount of (J) psyllium major extract in the topical skin preparation is preferably 0.005% by mass or less, even more preferably 0.003% by mass or less, and particularly preferably 0.001% by mass or less, in terms of solid content.
[0059] In the topical skin preparation of the present invention, the amount of (J) psyllium extract is preferably 0.000002 parts by mass or more in terms of solid content relative to 100 parts by mass of (A) niacinamide, in order to enhance the skin permeability of the topical skin preparation and to enhance the effects of the present invention. From this perspective, the amount of (J) psyllium extract is even more preferably 0.002 parts by mass or more, and particularly preferably 0.02 parts by mass or more, in terms of solid content relative to 100 parts by mass of (A) niacinamide. In order to further improve the effects of the present invention, the amount of (J) psyllium extract is preferably 0.1 parts by mass or less, even more preferably 0.06 parts by mass or less, and particularly preferably 0.02 parts by mass or less, in terms of solid content relative to 100 parts by mass of (A) niacinamide.
[0060] The content of (J) psyllium extract in the topical skin preparation is preferably 0.000002 parts by mass or more in terms of solid content per 100 parts by mass of the total solid content of components (A) to (F), in order to enhance the skin penetration of the topical skin preparation and to enhance the effects of the present invention. From this perspective, the amount of (J) psyllium extract is more preferably 0.002 parts by mass or more, and even more preferably 0.02 parts by mass or more, in terms of solid content per 100 parts by mass of the total solid content of components (A) to (F). Furthermore, in order to further enhance the effects of the present invention, the content of (J) psyllium extract in the topical skin preparation is preferably 0.2 parts by mass or less, even more preferably 0.09 parts by mass or less, and particularly preferably 0.04 parts by mass or less, in terms of solid content per 100 parts by mass of the total solid content of components (A) to (F).
[0061] In addition to the above-mentioned components, other ingredients may be used in the topical skin preparation, such as organic solvents, oils other than phytosterols, emulsifiers other than hydrogenated phospholipids, thickeners, chelating agents, pH adjusters, fragrances, surfactants, and preservatives, which are generally used in topical skin preparations. Examples of organic solvents include, or in addition to, the organic solvents used to prepare the phospholipid solution listed above: monohydric alcohols having 4 or less carbon atoms, such as ethanol, 2-propanol (isopropyl alcohol), butanol, and isobutyl alcohol; dihydric alcohols having 5 to 12 carbon atoms, such as propylene glycol, 1,3-butylene glycol, pentylene glycol, isopentyl diol, diethylene glycol, dipropylene glycol, ethylhexylglycerin, 1,3-propanediol, 1,5-pentanediol, 1,2-hexanediol, 1,2-octanediol, and 1,2-decanediol; diethylene glycol monoethyl ether; glycol ethers such as ethylene glycol monoethyl ether (ethoxydiglycol), ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, triethylene glycol monoethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, propylene glycol monoethyl ether, and dipropylene glycol monoethyl ether; glycol ether esters such as ethylene glycol monoethyl ether acetate, diethylene glycol monoethyl ether acetate, and propylene glycol monoethyl ether acetate; and glycol esters such as diethoxyethyl succinate and ethylene glycol disuccinate. Among these, it is preferable to use a dihydric alcohol having 5 to 12 carbon atoms in terms of moisturizing properties, feeling in use, and bacteriostasis, and it is particularly preferable to use 1,3-butylene glycol and / or pentylene glycol.
[0062] From the viewpoints of smoothness during use, moisturizing properties, and bacteriostasis, the amount of the organic solvent in the external skin preparation is preferably 1 to 35% by mass, and more preferably 3 to 25% by mass.
[0063] Oils include vegetable oils such as safflower oil, soybean oil, evening primrose oil, grape seed oil, rosehip oil, kukui nut oil, almond oil, sesame oil, wheat germ oil, corn oil, cottonseed oil, avocado oil, olive oil, camellia oil, persic oil, castor oil, peanut oil, hazelnut oil, macadamia nut oil, and medfoam oil; animal oils such as squalane; hydrocarbon oils such as liquid paraffin, liquid isoparaffin, and petrolatum; ethyl oleate, ethyl linoleate, and myristyl alcohol. Isopropyl palmitate, isopropyl isostearate, isopropyl lanolinate, hexyl laurate, myristyl myristate, cetyl myristate, octyldodecyl myristate, decyl oleate, octyldodecyl oleate, hexyldecyl dimethyl octanoate, cetyl octanoate, isocetyl octanoate, cetostearyl octanoate, stearyl octanoate, isostearyl octanoate, cetyl palmitate, cetyl lactate, Examples of oils that can be used include ester oils such as diisostearyl malate, dioctyl succinate, glyceryl tricaprylate, glyceryl tri-2-ethylhexanoate (triethylhexanoin), glyceryl trilaurate, glyceryl tripalmitate, glyceryl tristearate, glyceryl trioxystearate, glyceryl triisostearate, glyceryl trioleate, glyceryl triundecylenate, glyceryl tribehenate, glycerin trimyristate, tri(caprylic / capric)glycerin, propylene glycol dicaprylate, propylene glycol dicaprate, propylene glycol dinonanoate, propylene glycol di(caprylic / capric)ate, propylene glycol distearate, propylene glycol diisodistearate, and propylene glycol dioleate; and silicone oils such as cyclic silicone, methylphenyl silicone, and dimethicone. One or more of these can be selected and used.
[0064] Examples of emulsifiers include glycerin fatty acid esters such as glyceryl stearate (SE); polyglycerin fatty acid esters such as polyglyceryl-6 laurate, polyglyceryl-10 myristate, polyglyceryl-10 stearate, and polyglyceryl-10 isostearate; and polyoxyethylene esters such as PEG-5 glyceryl stearate, PEG-15 glyceryl stearate, PEG-15 glyceryl isostearate, PEG-20 glyceryl triisostearate, and PEG-5 glyceryl oleate. Glycerin fatty acid esters; sorbitan fatty acid esters such as sorbitan coconutate, sorbitan oleate, sorbitan sesquioleate, and sorbitan palmitate; polyoxyethylene sorbitan fatty acid esters such as polysorbate 40, polysorbate 60, polysorbate 80, and PEG-20 sorbitan isostearate; polyoxyethylene sorbitan fats such as sorbeth-6 laurate, sorbeth-6 tetraoleate, sorbeth-30 tetraoleate, and sorbeth-60 tetraoleate Fatty acid esters; polyoxyethylene hydrogenated castor oils such as PEG-20 hydrogenated castor oil, PEG-30 hydrogenated castor oil, PEG-60 hydrogenated castor oil, and PEG-50 hydrogenated castor oil triisostearate; polyoxyethylene alkyl ethers such as polyoxyethylene cetyl ether (ceteth-20), polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, and polyoxyethylene behenyl ether; PPG-4 ceteth-1, PPG-8 ceteth-20, and PPG-6 decyltetradeceth-12 and polyoxyethylene polyoxypropylene alkyl ethers such as PPG-6-decyltetradeceth-20; and polyethylene glycol fatty acid esters such as PEG-10 laurate, PEG-10 stearate, PEG-25 stearate, PEG-40 stearate, PEG-45 stearate, PEG-55 stearate, PEG-10 oleate, PEG-150 distearate, and PEG-8 diisostearate; and the like. These may be used alone or in combination of two or more.
[0065] Examples of thickeners include various types that can be used in the fields of cosmetics and pharmaceuticals. For example, natural polysaccharides, cellulose-based polymers, synthetic polymers, clay minerals, etc. can be used.
[0066] Examples of natural polysaccharides include polysaccharides derived from animals and plants or from microbial fermentation, such as xanthan gum, succinoglycan, carrageenan, guar gum, locust bean gum, galactan, gum arabic, tragacanth gum, tamarind gum, agar, agarose, mannan, curdlan, alginic acid or a salt thereof, gum arabic, pectin, quince seed, starch, algae colloid, chondroitin sulfate or a salt thereof, chitosan and its derivatives, nucleic acids or a salt thereof, ribonucleic acid or a salt thereof, water-soluble proteins such as casein, collagen, gelatin, albumin, fibroin, elastin, keratin, and sericin, and mucopolysaccharides such as hyaluronic acid or a salt thereof and chondroitin sulfate. Among these, xanthan gum is preferred in terms of usability.
[0067] Cellulose-based polymers are polymers composed of units of cellulose or its derivatives. Specific examples include carboxymethyl cellulose or its salts, methyl cellulose, ethyl cellulose, propyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and sulfonated cellulose derivatives.
[0068] Synthetic polymers are polymers artificially synthesized using monomers as structural units. Specific examples include vinyl polymers such as carboxyvinyl polymers and polyvinyl alcohol, acrylic acid-based polymers such as acrylic acid / alkyl methacrylate copolymers, acrylates / alkyl acrylate crosspolymers, and polyacrylic acid, acrylamide-based polymers such as polyacrylamide and polyalkylacrylamide / polyacrylamide copolymers, and (PEG-240 / decyltetradeceth-20 / HDI) copolymers. Among these, carboxyvinyl polymers and acrylic acid / alkyl methacrylate copolymers are preferred from the viewpoint of usability.
[0069] Clay minerals are substances commonly known as the main component minerals that make up clay, such as laponite, bentonite, smectite kaolinite, and montmorillonite.
[0070] Antibacterial and antiseptic agents include parabens (hydroxybenzoic acid esters) such as methylparaben, ethylparaben, propylparaben, and butylparaben; phenoxyethanol; alkyl glyceryl ethers such as 2-ethylhexylglyceryl ether (ethylhexylglycerin); salicylic acid; lanolin fatty acids and their salts; sodium benzoate; isothiazolinone derivatives such as methylchloroisothiazolinone and methylisothiazolinone; imidazolinium urea; dehydroacetic acid and its salts; phenols; and haloesters such as triclosan. Examples of the antibacterial agents include fluorinated bisphenols, acid amides, quaternary ammonium salts; trichlorocarbanide, zinc pyrithione, benzalkonium chloride, benzethonium chloride, sorbic acid, chlorhexidine, chlorhexidine gluconate, halocarban, hexachlorophene, hinokitiol; other phenols such as phenol, isopropylphenol, cresol, thymol, parachlorophenol, phenylphenol, and phenylphenol sodium; phenylethyl alcohol, photosensitizers, antibacterial zeolites, and silver ions.
[0071] The amount of the antibacterial / antiseptic agent in the external preparation for skin is preferably 0.01 to 1% by mass, more preferably 0.05 to 0.5% by mass.
[0072] Examples of chelating agents include edetates (ethylenediaminetetraacetates) such as EDTA, EDTA2Na, EDTA3Na, and EDTA4Na; hydroxyethylethylenediaminetriacetates such as HEDTA3Na; pentetates (diethylenetriaminepentaacetate); phytic acid; phosphonic acids such as etidronic acid and salts thereof such as sodium salts; sodium oxalate; polyamino acids such as polyaspartic acid and polyglutamic acid; sodium polyphosphate, sodium metaphosphate, phosphoric acid; sodium citrate, and citric acid.
[0073] Preferred examples of the pH adjuster, acid, or alkali include acetic acid, sodium acetate, hydrochloric acid, sulfuric acid, monoethanolamine, diethanolamine, triethanolamine, isopropanolamine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-hydroxymethyl-1,3-propanediol, arginine, sodium hydroxide, potassium hydroxide, aqueous ammonia, guanidine carbonate, and ammonium carbonate.
[0074] Although not limited thereto, the amount of water is preferably 40 to 90% by mass in the external preparation for skin.
[0075] The method for producing the external skin preparation of the present invention is not particularly limited, and it can be produced in accordance with known methods. For example, the topical skin preparation of the present invention can be prepared by mixing the components (A) to (F) and, if necessary, the components (G) to (J). The topical skin preparation of the present invention may or may not contain an emulsifier, and may or may not be an emulsion. For example, when the topical skin preparation of the present invention contains an emulsifier, it can be an emulsion obtained by mixing and emulsifying an aqueous phase and an oily phase. In the latter case, the components (A) to (J) may be added to either the oily phase or the aqueous phase. It is preferable that the topical skin preparation of the present invention is a composition in which water is the continuous phase, since this facilitates penetration of the components (A) to (F) into the skin. "Water as the continuous phase" means that the total amount of oil is very small, at 10% by mass or less, or that the emulsion is one in which water is the continuous phase. Examples of emulsions in which water is the continuous phase include oil-in-water emulsions and water-in-oil-in-water emulsions.
[0076] The types of the external skin preparation of the present invention include hair cosmetics, skin cosmetics, makeup cosmetics, fragrance cosmetics, body cosmetics, etc. The external skin preparation of the present invention can be produced according to a conventional method.
[0077] To explain the types of topical skin preparations of the present invention in more detail, preferred examples of hair cosmetics include shampoos such as oil shampoo, cream shampoo, conditioning shampoo, anti-dandruff shampoo, hair color shampoo, and rinse-in-one shampoo; hair care agents such as rinse, conditioner, treatment, hair pack, hair mist, and hair oil; hair styling products such as hair foam, hair mousse, hair spray, hair wax, hair gel, hair cream, water grease, setting lotion, pomade, and tic; hair dyes such as color lotion, hair color treatment, hair manicure, and oxidation hair dye; hair tonic, hair liquid, hair blow dryer, split end coat, permanent wave agent, straight perm agent, hair bleach, hair color pre-treatment, hair color after-treatment, perm pre-treatment, perm after-treatment, and hair growth agent.
[0078] Skin cosmetics include lotions such as softening lotion, astringent lotion, cleansing lotion, multi-layered lotion, and liposome lotion; emulsions such as emollient lotion, moisture lotion, milky lotion, nourishing lotion, nourishing milk, skin moisture, moisturizing emulsion, massage lotion, exfoliating smoother, elbow lotion, hand lotion, and body lotion; emollient cream, nourishing cream, nourishing cream, vanishing cream, moisture cream, night cream, massage cream, cleansing cream, makeup cream, base cream, pre-makeup cream, sunscreen cream, suntan cream, hair removal cream, deodorant cream, and shaving cream. gels such as moisturizing gels, whitening gels, and all-in-one gels; serums such as moisturizing essences, whitening essences, moisturizing serums, and whitening serums; sunscreens such as sun protectants, sun protectors, UV care milks, and sunscreens; packs and masks such as peel-off packs, powder packs, washing packs, oil packs, and cleansing masks; makeup removers such as cleansing foams, cleansing creams, cleansing milks, cleansing lotions, cleansing gels, and cleansing oils; and facial cleansers such as paste facial cleansers, gel facial cleansers, foam facial cleansers, facial cleansing powders, cosmetic soaps, transparent soaps, medicated soaps, liquid soaps, and shaving soaps.
[0079] Preferred examples of makeup cosmetics include lipstick, lip gloss, foundation, blush, face powder, concealer, eyeliner, mascara, eye shadow, eyebrow pencil, nail enamel, enamel remover, and nail treatment.
[0080] Preferred examples of the aromatic cosmetics include perfumes, perfumes, parfums, eau de parfum, eau de toilette, eau de cologne, solid perfumes, aromatic powders, perfumed soaps, body lotions, and bath oils.
[0081] Preferred examples of body cosmetics include body cleansers such as body shampoos, deodorant cosmetics such as deodorant lotions, deodorant powders, deodorant sprays and deodorant sticks, bleaches, depilatories, bath additives, and insect repellents such as insect repellent sprays.
[0082] Among these, the types of external skin preparations of the present invention are preferably lotions, emulsions, creams, gels, beauty serums, packs, makeup removers, facial cleansers, etc., in terms of their moisturizing effect and the effect of improving the feeling of use.
[0083] Preferred dosage forms of the topical skin preparation of the present invention include emulsion-type cosmetics such as oil-in-water (O / W) type, water-in-oil (W / O) type, W / O / W type, and O / W / O type, as well as oil-based cosmetics, solid cosmetics, liquid cosmetics, paste cosmetics, stick-type cosmetics, volatile oil-type cosmetics, powder cosmetics, jelly-type cosmetics, gel-type cosmetics, paste-type cosmetics, emulsified polymer-type cosmetics, sheet-type cosmetics, mist-type cosmetics, and spray-type cosmetics. When the topical skin preparation of the present invention is an emulsion, the continuous phase may be either an aqueous phase or an oil phase. In the examples described below, compositions having an aqueous phase as the continuous phase are prepared.
[0084] Furthermore, as will be shown in the examples below, the external skin preparation of the present invention is a composition having a collagen production promoting effect and can also be used as a collagen production promoter.
[0085] Collagen is a major structural protein, accounting for approximately one-third of mammalian tissues. It is an essential component of many matrix tissues, including skin, bone, cartilage, tendons, and ligaments. Therefore, decreased collagen production is known to cause various diseases. Skin is exposed daily to various physical and chemical stressors, including UV rays, dryness, cold, heat, and drugs. As a result, skin function declines, resulting in various skin aging phenomena. Skin aging phenomena include wrinkle formation, sagging skin, loss of elasticity, impaired barrier function, and decreased moisture retention of the stratum corneum. Wrinkles are known to be of two types: epidermal and dermal. Dermal wrinkles are caused by a decrease in collagen production in dermal fibroblasts due to UV exposure and aging. Decreased collagen production also leads to skin sagging and loss of elasticity. Therefore, promoting collagen production is important for preventing and improving dermal wrinkles, sagging skin, and loss of elasticity. Promoting collagen production is important for preventing and improving skin aging due to the above-mentioned effects.
[0086] Collagen is classified into types according to its function and structure, and the type of collagen used in the present invention is not particularly limited, but is preferably type I, type III, or type V collagen, more preferably type I collagen.
[0087] The topical skin preparation of the present invention is expected to suppress diseases such as wrinkle formation, sagging skin, loss of elasticity, loss of barrier function, and loss of moisture retention of the stratum corneum (horny layer) and to heal skin wounds by promoting the production of collagen, particularly collagen in the skin, and preventing and improving skin aging caused by a decrease in collagen. [Example]
[0088] The present invention will be described below based on examples, but the present invention is not limited to the following examples.
[0089] <Test substance> The test substances used are shown in Table 1. The amount of test substance is the amount of active ingredient except for collagen peptide, yeast extract, arnica extract, and psyllium extract. The heparinoids shown in Table 1 were commercially available products. As the "collagen peptide (aqueous solution)" shown in Table 1, a commercially available product (derived from shark, weight-average molecular weight 280 to 3000) (concentration 1% by mass) was used. As the "yeast extract (aqueous solution)" shown in Table 1, a commercially available yeast extract (concentration 10% by mass) obtained by extraction from a decomposition liquid of yeast belonging to the genus Saccharomycopsis was used. As the hydrogenated soybean phospholipid shown in Table 1, commercially available hydrogenated soybean lecithin was used. The phytosterols shown in Table 1 were commercially available products. As the "Arnica extract (aqueous solution)" shown in Table 1, an aqueous solution of an extract (active ingredient 0.5% by mass) obtained by extracting arnica flowers using an aqueous 1,3-butylene glycol solution as an extraction solvent was used. As the "Plantago major (aqueous solution)" shown in Table 1, an aqueous solution of an extract (active ingredient 0.1% by mass) obtained by extracting seeds of Plantago major using ethanol as an extraction solvent was used.
[0090] BG in Table 1 is an abbreviation for 1,3-butylene glycol.
[0091] <Comparative Examples 1 to 3, Examples 1 and 2> All of the ingredients shown in Table 1 were mixed and stirred using a three-one motor until a uniform, transparent solution was obtained, to prepare a skin topical preparation.
[0092] <Examples 3 to 5> Phase A was prepared by pre-heating BG, hydrogenated soybean phospholipids, and phytosterols to 70°C and homogenizing them, while Phase B was prepared by pre-heating water and other ingredients to 70°C and homogenizing them. Phase A was added to Phase B, and the mixture was homogenized using a homomixer, after which it was cooled to prepare the topical skin preparation.
[0093] <Test method 1: Collagen production promotion effect> In a 37°C, 5% CO2 incubator, 75 cm 2 Normal human dermal fibroblasts (NHDF) were cultured in 10% FBS-DMEM flasks. The cells were suspended by trypsinization and placed in each well of a collagen-coated 96-well plate at a concentration of 1.0 × 10 4 The cells were seeded at a density of 100 cells / well and pre-cultured for 24 hours in a 5% CO2 incubator at 37°C. After removing the medium from each well, 100 μL / well of medium containing the test substance was added, and the cells were cultured for 24 hours in a 5% CO2 incubator at 37°C. Serum-free DMEM was used as the medium for preparing the test substance, and the total concentration of the test substance (the external skin preparation itself) in the medium was 0.005% by mass. After 24 hours of culture, the medium was removed and the cells were washed twice with PBS. RNA was recovered using an Rneasy Mini Kit (QIAGEN), and real-time PCR was performed on the obtained RNA using the One Step TBGreen® PrimeScript™ RT-PCR Kit II (Perfect Real Time) (TaKaRa). PCR was performed under conditions based on the kit's instructions. COL1A1 gene expression levels were measured using COL1A1 primers (QIAGEN). Here, RRN18S gene expression levels were measured using RRN18S primers (QIAGEN) as an endogenous control. The ratio of COL1A1 gene expression levels to RRN18S gene expression levels is shown below as a relative value, with the value for Comparative Example 1 set to 1. The results are shown in Figure 1.
[0094] As shown in Figure 1, in each Example in which niacinamide, heparinoid, dipotassium glycyrrhizinate, collagen peptide, yeast extract, and glycylglycine were combined, the relative expression level of the collagen gene COL1A1 was higher than in each Comparative Example. For example, as can be seen from a comparison of Comparative Examples 1 and 2 with Examples 1 and 2, the addition of glycylglycine to the six components (niacinamide, heparinoid, dipotassium glycyrrhizinate, collagen peptide, and yeast extract) increased the relative expression level of COL1A1 by more than 5%. Furthermore, as can be seen from a comparison of Comparative Example 3 with Example 2, the addition of collagen peptide and yeast extract to the four components (niacinamide, heparinoid, dipotassium glycyrrhizinate, and glycylglycine) increased the relative expression level of COL1A1 by 7% (=(1.08-1.01) / 1.01(%)). Furthermore, a comparison of Examples 2 and 3 showed that the relative expression level of COL1A1 was further improved by 4% (=(1.12-1.08) / 1.08(%)) by combining the combination of niacinamide, heparinoid, dipotassium glycyrrhizinate, collagen peptide, yeast extract, and glycylglycine with hydrogenated soybean phospholipids and phytosterols to make an eight-component mixture; a comparison of Examples 3 and 4 showed that the relative expression level of COL1A1 was further improved by 5% (=(1.18-1.12) / 1.12(%)) by combining arnica extract with the eight components; and a comparison of Examples 4 and 5 showed that the relative expression level of COL1A1 was further improved by 6% (=(1.25-1.18) / 1.25(%)) by combining psyllium spp. with the nine components. From the above, it is clear that the external skin preparation of the present invention can effectively enhance collagen gene expression.
[0095] [Table 1]
[0096] <Test Method 2: Evaluation of topical skin preparations> (1) Evaluation of usability The resulting topical skin preparation was evaluated for usability. Five subjects in their 20s and 30s were randomly selected as subjects. After washing the inner arm of each subject and allowing it to acclimate for 15 minutes, 0.03 g of the topical skin preparation was applied to a 3 cm x 3 cm area. Evaluation items included usability (ease of application, moisturizing sensation), and a comprehensive assessment was conducted based on a five-point scale. The average values of the five subjects for each item in the questionnaire are shown in Table 2.
[0097] (Familiarity) 5: Very familiar and very good. 4: Somewhat familiar, good. 3: Neither good nor bad, usability is average. 2: Somewhat difficult to get used to, bad. 1: Unfamiliar, unsuitable for use, very bad;
[0098] (Moisturizing feeling after application) 5: It feels very moisturizing after application, which is great. 4: It leaves the skin moist after application, which is good. 3: I feel a slight moist feeling after application. 2: There is almost no moist feeling after application, which is bad. 1: There is no moist feeling after application, and it is unsuitable for use and very bad.
[0099] (2) Measurement of stratum corneum moisture content Three subjects in their 20s and 30s were randomly selected as subjects. After washing the inside of the subject's forearm and allowing it to acclimate for 15 minutes, the moisture content of the stratum corneum was measured in a 3 x 3 cm area. 0.03 ml (one dropper) of the topical skin preparation was then applied to the area and left for 15 minutes, after which a second measurement of the moisture content of the stratum corneum was performed. The equipment used was a Corneometer (Courage+Khazaka). The measurement environment was a temperature of 26.8°C and humidity of 37%. The unit of moisture content of the stratum corneum was arbitrary units (AU).
[0100] [Table 2]
[0101] As shown in Table 2, in each Example in which niacinamide, heparinoid, dipotassium glycyrrhizinate, collagen peptide, yeast extract, and glycylglycine were combined, the feel during use (good absorption, moist feeling after application) and stratum corneum moisture content after application were greater than those of each Comparative Example. For example, as can be seen from a comparison of Comparative Examples 1 and 2 with Examples 1 and 2, adding glycylglycine to the six components of niacinamide, heparinoid, dipotassium glycyrrhizinate, collagen peptide, and yeast extract improved absorption by 0.6 points or more, moist feeling after application by 0.6 points or more, and stratum corneum moisture content by 14.4 points or more. Furthermore, as can be seen from a comparison of Comparative Example 3 with Example 1, adding collagen peptide and yeast extract to the four components of niacinamide, heparinoid, dipotassium glycyrrhizinate, and glycylglycine improved absorption by 0.2 points or more, moist feeling after application by 0.2 points or more, and stratum corneum moisture content by 7.9 points. Furthermore, a comparison of Examples 2 and 3 showed that combining niacinamide, heparinoids, dipotassium glycyrrhizinate, collagen peptide, yeast extract, and glycylglycine with hydrogenated soybean phospholipids and phytosterols to make a total of eight ingredients further improved the absorption, moist feeling after application, and stratum corneum moisture content; a comparison of Examples 3 and 4 showed that combining arnica extract with the above eight ingredients further improved the absorption, moist feeling after application, and stratum corneum moisture content; and a comparison of Examples 4 and 5 showed that combining psyllium with the above nine ingredients further improved the absorption, moist feeling after application, and stratum corneum moisture content. From the above, it is clear that the topical skin preparation of the present invention can effectively enhance the feeling of use and the moisture content of the skin.
[0102] Below, we will show prescription examples using the external skin preparation of the present invention. These prescription examples are merely illustrative of the present invention, and the present invention is not limited to these prescription examples. In the prescription examples below, the solid content of the collagen peptide aqueous solution, the solid content of the yeast extract, the solid content of the allonica extract, and the solid content of the plantago major were the same as in Examples 1 to 5.
[0103] [Formulation example 1: Lotion] [Table 3]
[0104] (Manufacturing method) A: Ingredients 7, 8, and 11 to 14 were preheated and homogenized. B: Ingredients 1 to 6, 9, 10, 15 to 17, 20, and 21 were preheated and homogenized. C: A was added to B and emulsified uniformly, then cooled and the pH was adjusted with 18 and 19 to obtain a lotion.
[0105] [Formulation example 2: Beauty serum] [Table 4]
[0106] (Manufacturing method) A: Ingredients 7, 8, and 11 to 16 were preheated and homogenized. B: Ingredients 1 to 6, 9, 10, 17 to 24, and 26 to 28 were preheated and homogenized. C: A was added to B, and after uniform emulsification, it was cooled and the pH was adjusted to 25 to obtain a beauty serum.
[0107] [Formulation example 3: Cream] [Table 5]
[0108] (Manufacturing method) A: Ingredients 7, 8, and 11-22 were preheated and homogenized. B: Ingredients 1-6, 9, 10 and 23-30, 32, 33 were preheated and homogenized. C: A was added to B and emulsified uniformly, then cooled and the pH was adjusted to 31 to obtain a cream. [Industrial Applicability]
[0109] The topical skin preparation of the present invention is industrially useful because it has an excellent collagen-enhancing effect, an effect of improving the feeling of use, and an effect of increasing the moisture content of the stratum corneum of the skin after use.
Claims
1. A topical skin preparation comprising niacinamide, a heparinoid, dipotassium glycyrrhizinate, collagen peptide, yeast extract, and glycylglycine.
2. 2. The external skin preparation according to claim 1, further comprising hydrogenated soybean phospholipids and phytosterols.
3. 3. The external skin preparation according to claim 1, wherein the content of niacinamide is 5% by mass or more.
4. The external skin preparation according to claim 1 or 2, further comprising an extract of at least one plant selected from arnica extract and plantago major.
Citation Information
Patent Citations
Oligopeptides with collagen gel contraction promoting effect and their use
JP2023010555A
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