JP7537871B2 - Skin preparations - Google Patents

Description

The present invention relates to a skin preparation for external use that contains pullulan and tranexamic acid or a salt thereof.

The barrier function of the stratum corneum is evaluated using the amount of water evaporation from the skin (transepidermal water loss: TEWL) as an indicator (Non-Patent Document 1).
Tranexamic acid has been used as an active ingredient in cosmetics because of its moisturizing and whitening effects (Patent Document 1).

However, there was an issue that tranexamic acid was only slightly effective in improving the stratum corneum barrier function.

JP 2017-109972 A

New Cosmetics Handbook, published October 30, 2006, 505 pages New Cosmetics Handbook, published October 30, 2006, 118 pages

The objective of the present invention is to provide an external skin preparation that improves TEWL by blending pullulan with an external skin preparation that contains tranexamic acid or a salt thereof.

The present invention provides a skin preparation for external use that contains tranexamic acid or a salt thereof and pullulan.

The topical skin preparation of the present invention has a TEWL improving effect.

The following describes the form for implementing the present invention.

The topical skin preparation of the present invention can be used for any application, such as cosmetics, quasi-drugs, and pharmaceuticals.

The tranexamic acid or its salt may be any that is generally used in cosmetics, etc. The content is preferably 0.01 to 5% by mass, more preferably 1 to 2.5% by mass, and most preferably 2% by mass, based on the total amount of the topical skin preparation.

The pullulan used in the present invention is not particularly limited as long as it can be incorporated into topical skin preparations, but it is preferable to use one with a molecular weight of 100,000 to 100,000. Commercially available pullulan products include "Pullulan for cosmetics" and "Pullulan as a food additive" (both manufactured by Hayashibara Biochemical Laboratories, Inc.).

The content of pullulan in 100% by mass of the topical skin preparation of the present invention is preferably 0.01% by mass or more, more preferably 0.03% by mass or more, and preferably 1.0% by mass or less, more preferably 0.5% by mass or less, and even more preferably 0.2% by mass or less, from the viewpoints of moisturizing effect and non-sticky feel when used.

Next, we will describe optional ingredients that can be incorporated into the topical skin preparation of the present invention.

The skin topical preparation of the present invention may contain one or more anti-inflammatory agents selected from glycyrrhizinic acid, glycyrrhetinic acid, azulene, salicylic acid, allantoin, derivatives thereof, and salts thereof.

Glycyrrhizic acid, its derivatives and their salts are not particularly limited as long as they can be incorporated into topical skin preparations, but specific examples include glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc. Among these, it is preferable to use dipotassium glycyrrhizinate. Commercially available products include glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate (all manufactured by Alps Pharmaceutical Co., Ltd.), dipotassium glycyrrhizinate, monoammonium glycyrrhizinate (all manufactured by Maruzen Pharmaceutical Co., Ltd.), dipotassium glycyrrhizinate "Kouki", monoammonium glycyrrhizinate "Kouki" (all manufactured by Koukisha), etc.

When glycyrrhizinic acid, its derivatives, and their salts are blended, the blending amount is preferably 0.0001% by mass or more based on the total amount of the topical skin preparation. Also, 2% by mass or less is preferable, 0.8% by mass or less for those that are washed off, and 0.5% by mass or less for those that are not washed off is more preferable.

Glycyrrhetinic acid, its derivatives and their salts are not particularly limited as long as they can be incorporated into topical skin preparations, but specific examples include glycyrrhetinic acid, stearyl glycyrrhetinate, glycerin glycyrrhetinate, etc. Among these, it is preferable to use glycyrrhetinic acid and stearyl glycyrrhetinate. Commercially available products include β-glycyrrhetinic acid, stearyl glycyrrhetinate (both manufactured by Alps Pharmaceutical Co., Ltd.), glycyrrhetinic acid, C-O-Grettinol (registered trademark) (both manufactured by Maruzen Pharmaceutical Co., Ltd.), Agritinone, Agritinone Stearyl (both manufactured by Tokiwa Phytochemical Research Institute), Glycyrrhetinic Acid "Kouki", Stearyl Glycyrrhetinate "Kouki" (both manufactured by Koukisha), etc.

When glycyrrhetinic acid, its derivatives, and their salts are blended, the amount is preferably 0.0001% by mass or more of the total amount of the topical skin preparation. Also, 2% by mass or less is preferable, 0.8% by mass or less for those that are to be washed off, and 0.5% by mass or less for those that are not to be washed off is more preferable.

There are no particular limitations on azulene, its derivatives and their salts as long as they can be incorporated into topical skin preparations, but specific examples include azulene, guaiazulene, ethyl guaiazulene sulfonate, sodium guaiazulene sulfonate, chamazulene, etc. Among these, sodium guaiazulene sulfonate is preferably used. Commercially available products include guaiazulene, water-soluble azulene (both manufactured by Konan Kako Co., Ltd.), etc.

When azulene, its derivatives, and their salts are blended, the blending amount is preferably 0.0001% by mass or more of the total amount of the topical skin preparation. Also, the blending amount is preferably 1% by mass or less, and more preferably 0.1% by mass or less.

There are no particular limitations on the salicylic acid, its derivatives and their salts as long as they can be incorporated into topical skin preparations, but specific examples include salicylic acid, methyl salicylate, glycol salicylate, sodium salicylate, ethylhexyl salicylate, etc. Among these, it is preferable to use ethylhexyl salicylate and sodium salicylate. Commercially available products include SALICYLIC ACID (manufactured by Solvay), methyl salicylate (manufactured by API Corporation), sodium salicylate (manufactured by Yoshitomi Fine Chemicals), Escarol Salicylate 587 (manufactured by Ashland Japan), Parsol EHS (manufactured by DSM), etc.

When salicylic acid, its derivatives, and their salts are blended, the blending amount is preferably 0.0001% by mass or more of the total amount of the topical skin preparation. Also, the blending amount is preferably 1% by mass or less, and more preferably 0.2% by mass or less.

Allantoin, its derivatives and their salts are not particularly limited as long as they can be incorporated into topical skin preparations, but specific examples include allantoin, aluminum chlorhydroxyl allantoin, aluminum dihydroxyl allantoin, etc. Among these, it is preferable to use allantoin. Commercially available products include allantoin (manufactured by Ashland Japan), allantoin, ALCA (both manufactured by Kawaken Fine Chemicals), RonaCare (registered trademark) Allantoin (manufactured by Meeck), etc.

When allantoin, its derivatives, and salts thereof are used, the amount is preferably 0.0001% by mass or more of the total amount of the topical skin preparation. Also, 1% by mass or less is preferable, 0.5% by mass or less for those that are washed off, and 0.3% by mass or less for those that are not washed off is more preferable.

The skin topical preparation of the present invention may contain one or more whitening agents selected from ascorbic acid, its derivatives and their salts, hydroquinone, its derivatives and their salts, and nicotinic acid, its derivatives and their salts.

Ascorbic acid, its derivatives and their salts are not particularly limited as long as they can be incorporated into topical skin preparations, but specifically, ascorbic acid includes L-ascorbic acid, and ascorbic acid derivatives include L-ascorbic acid monoesters such as L-ascorbic acid glucoside, L-ascorbic acid 2-phosphate, L-ascorbic acid 3-phosphate, L-ascorbic acid 6-phosphate, L-ascorbic acid 2-polyphosphate, and L-ascorbic acid 2-sulfate, as well as L-ascorbic acid monoalkyl esters such as L-ascorbic acid 2-palmitate, L-ascorbic acid 6-palmitate, L-ascorbic acid 2-stearate, and L-ascorbic acid 6-stearate, Examples of salts of ascorbic acid and ascorbic acid derivatives include sodium salts, potassium salts, magnesium salts, calcium salts, barium salts, ammonium salts, monoethanolamine salts, diethanolamine salts, triethanolamine salts, monoisopropanolamine salts, triisopropanolamine salts, etc. Among these, ascorbic acid 2-glucoside and magnesium ascorbyl phosphate are preferred. Commercially available products include AA2G (Hayashibara Biochemical Laboratories), C-mate (BASF Japan), and NIKKOL VC-PMG (Nikko Chemicals).

Hydroquinone, its derivatives, and salts thereof are not particularly limited as long as they can be incorporated into topical skin preparations, and hydroquinone glycosides are a suitable example. Examples of the sugar chain portion of hydroquinone glycosides include pentoses such as L-arabinose, D-xylose, D-ribose, D-xylulose, D-lyxose, and D-ribulose, hexoses such as D-glucose, D-galactose, D-mannose, D-tagalose, D-fructose, and L-sorbose, and amino acid sugars such as D-glucosamine, D-galactosamine, sialic acid, and muramic acid. Examples of hydroquinone derivatives and salts thereof include uronic acids such as D-glucuronic acid, D-galacturonic acid, D-mannuronic acid, and L-iduronic acid, or methyl compounds and acetyl compounds thereof. Examples of the salts include sodium salts, potassium salts, magnesium salts, calcium salts, barium salts, ammonium salts, monoethanolamine salts, diethanolamine salts, triethanolamine salts, monoisopropanolamine salts, and triisopropanolamine salts. Of the hydroquinone derivatives, it is preferable to use arbutin and/or its salts, which have a chemical structure in which hydroquinone and glucose are bonded. Commercially available products include arbutin (manufactured by Nippon Fine Chemicals Co., Ltd.) and ARUBTIN (manufactured by SK Bioland Co., Ltd.).

Nicotinic acid, its derivatives and their salts are not particularly limited as long as they can be incorporated into topical skin preparations. Specifically, nicotinic acid derivatives include nicotinamide and nicotinic acid esters, and esters include tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, and ethyl nicotinate. Of these, nicotinamide is preferably used. Commercially available products include niacinamide USP PC (manufactured by Lonza Japan), nicotinamide (manufactured by DSM Nutrition Japan), etc.

The skin external preparation of the present invention may contain one or more types selected from the above-mentioned whitening agents.
When a whitening agent is added, the amount of the whitening agent is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, and even more preferably 0.1% by mass or more, based on the total amount of the skin topical preparation. This allows a whitening effect to be obtained. The amount of the whitening agent is preferably 5% by mass or less, more preferably 3% by mass or less, and even more preferably 1% by mass or less, based on the total amount of the skin topical preparation.
For example, when a whitening agent is added, the amount of the whitening agent is preferably 0.0001% by mass to 5% by mass, more preferably 0.001% by mass to 3% by mass, and even more preferably 0.1 to 1% by mass, based on the total amount of the topical skin preparation.

The skin topical agent of the present invention can be used as a sunscreen cosmetic by incorporating metal oxide microparticles and organic UV absorbers.

There are no particular limitations on the metal oxide microparticles, but it is common to use one or two selected from fine titanium oxide microparticles and fine zinc oxide microparticles. The metal oxide microparticles can be directly incorporated into the skin topical preparation of the present invention, but they can also be used after being pre-dispersed in silicone oil, ester oil, or an aqueous component. In addition, powders in which metal oxide microparticles are coated on the surface of plate-shaped powders and powders in which such powders have been modified with a surface modifier can also be used.

The type of organic UV absorber is not particularly limited, and known organic UV absorbers can be used without restriction. Examples of such known organic UV absorbers include cinnamic acid derivatives such as 2-ethylhexyl paramethoxycinnamate, isopropyl methoxycinnamate, and isoamyl methoxycinnamate; PABA derivatives such as paraaminobenzoic acid (hereinafter abbreviated as "PABA"), ethyl PABA, ethyl-dihydroxypropyl PABA, ethylhexyl-dimethyl PABA, and glyceryl PABA; salicylic acid derivatives such as homosalate, ethylhexyl salicylate, dipropylene glycol salicylate, and TEA salicylate; benzophenone-1, benzophenone-2, benzophenone- 3 or oxybenzone, benzophenone-4, benzophenone-5, benzophenone-6, benzophenone-8, benzophenone-9, benzophenone-12 and other benzophenone derivatives; 3-benzylidene camphor, 4-methylbenzylidene camphor, benzylidene camphorsulfonic acid, camphor benzalkonium methosulfate, terephthalidene discamphorsulfonic acid, polyacrylamide methyl benzylidene camphor, and other benzylidene camphor derivatives; anisotriazine, diethylhexylbutamido triazone, 2,4,6-tris(diisobutyl-4'- aminobenzalmalonate)-s-triazine, 2,4-bis-[{4-(2-ethylhexyloxy)-2-hydroxy}-phenyl]-6-(4-methoxyphenyl)-1,3,5-triazine, 2,4,6-tris[4-(2-ethylhexyloxycarbonyl)anilino]-1,3,5-triazine and other triazine derivatives; phenylbenzimidazole derivatives such as phenyldibenzimidazole tetrasulfonate disodium; phenylbenzotriazoles such as drometrizole trisiloxane and methylenebis(benzotriazolyltetramethylbutylphenol) Derivatives; anthranil derivatives such as menthyl anthranilate; imidazoline derivatives such as 2-ethylhexyl dimethoxybenzylideneoxoimidazolidinepropionate; benzalmalonate derivatives such as polyorganosiloxanes having benzalmalonate functional groups; 4,4-diarylbutadiene derivatives such as 1,1-dicarboxy(2,2'-dimethylpropyl)-4,4-diphenylbutadiene; octocrylene, 2-[4-(diethylamino)-2-hydroxybenzoyl]hexyl benzoate, 4-tert-butyl-4'-methoxydibenzoylmethane, etc. The organic UV absorbers can be used alone or in combination of two or more.

When an organic UV absorber is used, the amount is preferably 1 to 20% by mass. If the amount is less than 1% by mass, sufficient sunscreen effect cannot be obtained, and if the amount is more than 20% by mass, it will have a negative effect on the feeling of use, such as stickiness and increased primary irritation to the skin.

The topical skin preparation of the present invention may contain solid spherical borosilicate particles.
The average particle size of the solid spherical borosilicate particles is preferably 0.1 μm or more, more preferably 1 μm or more, even more preferably 5 μm or more, and even more preferably 7 μm or more. The average particle size of the solid spherical borosilicate particles is preferably 20 μm or less, more preferably 15 μm or less, and even more preferably 13 μm or less. For example, from the viewpoint of the stickiness reduction effect, the average particle size of the solid spherical borosilicate particles is preferably 1 to 20 μm, more preferably 5 to 15 μm, and even more preferably 7 to 13 μm. The average particle size of the solid spherical borosilicate particles can be measured as the number-average average particle size according to the principle of microscopy in accordance with the shape of the powder particles.

In the solid spherical borosilicate particles, the borosilicate may be an alkali metal salt such as Na or K, an alkaline earth metal salt such as Mg or Ca, an Al salt, or a combination of these salts. Preferred are Na borosilicate, Ca borosilicate, Al borosilicate, Ca/Na borosilicate, and Ca/Al borosilicate, and more preferably Ca/Na borosilicate.
The solid spherical borosilicate particles are indicated by the cosmetic name (INCI name) as borosilicate (Ca/Na) (CALCIUM SODIUM BOROSILICATE), borosilicate (Ca/Al) (CALCIUM ALUMINUM BOROSILICATE), etc., and in the present invention, solid spherical borosilicate particles having any name may be used, with the use of borosilicate (Ca/Na) being more preferable.

When solid spherical borosilicate particles are mixed, the amount of solid spherical borosilicate particles is not particularly limited, but is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and even more preferably 1% by mass or more, based on the total amount of skin external preparation.In addition, the amount of solid spherical borosilicate particles is not particularly limited, but is preferably 30% by mass or less, more preferably 20% by mass or less, and even more preferably 10% by mass or less, based on the total amount of skin external preparation.
For example, the amount of the solid spherical borosilicate particles is preferably 0.01 to 30% by mass, more preferably 0.1 to 20% by mass, and even more preferably 1 to 10% by mass, based on the total amount of the topical skin preparation. For example, in a topical skin preparation in the form of an aqueous or oil medium, the amount of the solid spherical borosilicate particles is more preferably 0.01 to 10% by mass, based on the total amount of the topical skin preparation. Furthermore, in a topical skin preparation in the form of a powder or solid, the amount of the solid spherical borosilicate particles is more preferably 0.1 to 20% by mass, based on the total amount of the topical skin preparation.

The solid spherical borosilicate particles may be untreated or may be hydrophilically or hydrophobically treated.

The topical skin preparation of the present invention can contain zinc oxide-coated spherical powder. Zinc oxide-coated spherical powder has the ability to solidify sebum, and is expected to have the effect of improving the durability of makeup.

The spherical powder used in the zinc oxide-coated spherical powder is not particularly limited as long as it can be incorporated into topical skin preparations, but it is preferable to use one or more types selected from (acrylates/ethylhexyl acrylate) crosspolymer, metal salt of alkenyl succinic acid starch ester, and spherical borosilicate powder in terms of the cosmetic durability.

The zinc oxide used in the zinc oxide-coated spherical powder is not particularly limited as long as it can be incorporated into a solid powder cosmetic. The shape of the zinc oxide is not particularly limited. From the viewpoint of sebum solidification ability, the average powder diameter of the zinc oxide is preferably 10 to 200 nm, more preferably 15 to 100 nm, and even more preferably 15 to 50 nm.

The zinc oxide-coated spherical powder can be obtained, for example, by coating a spherical powder with zinc oxide.
Although untreated zinc oxide can be used as is, it is preferable to use zinc oxide that has been subjected to a hydrophobic treatment. The hydrophobic treatment agent is not particularly limited, and examples thereof include dimethicone, methyl hydrogen polysiloxane, and metal soap. Among these hydrophobic treatment agents, it is preferable to use dimethicone. The coating amount of the hydrophobic treatment agent may be an amount sufficient to hydrophobize the zinc oxide. Specifically, the mass ratio of zinc oxide to the hydrophobic treatment agent is preferably 85:15 to 99:1, and more preferably 90:10 to 98:2.

In the zinc oxide-coated spherical powder used in the skin external preparation of the present invention, the coating amount of zinc oxide is preferably 0.01 parts by mass or more, more preferably 0.05 parts by mass or more, per part by mass of the spherical powder. Also, the coating amount of zinc oxide is preferably 2 parts by mass or less, more preferably 1.5 parts by mass or less, per part by mass of the spherical powder. Within this range, the sebum solidification ability can be further improved, and sebum breakdown can be further prevented.
The coating amount of zinc oxide is preferably 0.01 to 2 parts by mass, and more preferably 0.05 to 1.5 parts by mass, per part by mass of the spherical powder.

As a method for coating the spherical powder with zinc oxide, various methods known so far can be used, such as physicochemical mixing and grinding methods (dry and wet), chemical deposition methods, etc. From the viewpoint of the sebum solidification ability of the zinc oxide-coated spherical powder, the dry mixing and grinding method is preferably used.

Commercially available zinc oxide-coated spherical powders include Pulsair ASOZ-20, Pulsair OPZ-NV, and Pulsair CBZ-NV (all manufactured by Suzuki Oil Industries Co., Ltd.).

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

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

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

The topical skin preparation of the present invention can be used in the form of, for example, a lotion, emulsion, ointment, or powder.

The present invention will be specifically explained below using examples, but the scope of the present invention is not limited thereto. The blending amounts are in mass % unless otherwise specified.

[TEWL test]
- Wash the inside of your forearm with the designated soap and wipe off any moisture from your forearm.
- Allow the subject to rest for 15 minutes in an environment of 21±0.5°C and relative humidity of 50±5% to acclimate.
Three areas of 3.0 cm x 3.0 cm were marked on the left forearm, and a total of 6.75 mg of the Examples or Comparative Examples shown in Table 1 was applied to each area. The amount of water evaporation was measured 1 hour after application, and the rate of change from before application was calculated. The measurement was performed using a TEWL measuring device (SWL4081) manufactured by Keystone Scientific.
The three subjects were instructed not to use any cosmetics on the inside of their forearms for one week prior to the test, and the average value of two measurements was recorded for each measurement area.

As shown in Table 1, tranexamic acid alone had no effect on improving TEWL, but the addition of pullulan resulted in a dramatic improvement in TEWL.

Table 2 shows the formulations for a rough skin cream, Table 3 shows the formulations for a whitening emulsion, Table 4 shows the formulations for a water-in-oil emulsion sunscreen cosmetic, and Table 5 shows the formulations for an oil-in-water emulsion sunscreen cosmetic.

Claims (1)

A skin external preparation for improving TEWL , comprising, based on the total amount, 0.01 to 0.2% by mass of pullulan and 1 to 2.5% by mass of tranexamic acid or a salt thereof.