Composition for external use

Abstract

To provide a composition for external use which reduces an odor of a polyhydric alcohol or phenoxyethanol and / or to provide a composition for external use having excellent safety.SOLUTION: It was found that an odor derived from a polyhydric alcohol or phenoxyethanol can be reduced when a heparinoid, niacinamide or tranexamic acid and ectoine are blended in a composition for external use blended with a polyhydric alcohol or phenoxyethanol. Further, it was found that when ectoine is blended in a composition for external use blended with a polyhydric alcohol or phenoxyethanol, a heparinoid, niacinamide or tranexamic acid, safety of a preparation can be improved. That is, there is provided a composition for external use which comprises (a) at least one selected from a group consisting of a heparinoid, niacinamide and tranexamic acid, (b) a polyhydric alcohol or phenoxyethanol and (c) ectoine.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to topical compositions containing heparinoids, niacinamide, or tranexamic acid. [Background technology]

[0002] Heparinoids are a type of acidic mucopolysaccharides, and are known to have a wide range of effects on the skin, including moisturizing, anti-inflammatory, blood flow promotion, and scar and keloid treatment and prevention. Niacinamide is a type of water-soluble vitamin B, and is known to have effects on the skin such as improving rough skin, whitening, blood flow promotion, and anti-wrinkle. Tranexamic acid has anti-inflammatory and whitening effects. These ingredients are incorporated into external preparations such as cosmetics, quasi-drugs, and pharmaceuticals as active ingredients expected to have their own effects on the skin.

[0003] Preservatives are usually blended into topical compositions to inhibit the growth of microorganisms contaminating from the outside and improve the shelf life of the product. Parabens (paraoxybenzoic acid esters) are commonly used as preservatives for such purposes, but because parabens are skin irritants, polyhydric alcohols and phenoxyethanol are often used in combination in topical preparations such as cosmetics and medicines. Polyhydric alcohols with multiple hydroxyl groups in the molecule are widely used as moisturizing agents because they penetrate the stratum corneum and act as an intermediary between keratin and water molecules, thereby exerting moisturizing properties, while dihydric polyhydric alcohols such as pentylene glycol and hexanediol have been reported to inhibit the growth of microorganisms (Non-Patent Document 1). Phenoxyethanol is an aromatic alcohol with one hydroxyl group in the molecule, and has a wide range of antibacterial activity and has been widely used as a relatively safe preservative (Non-Patent Document 2). However, eye irritation caused by 1,2-pentanediol (Non-Patent Document 3) and slight sensory irritation caused by phenoxyethanol (Non-Patent Document 4) have been reported. In addition, since these polyhydric alcohols and phenoxyethanol have an odor, the odor becomes an issue in external preparations such as cosmetics that are applied to the skin. In response to this, Patent Document 1 identifies the components that cause the odor contained in alkanediol, and by reducing the content of the specific compound to a certain level or less, alkanediol with less odor is produced. In addition, Patent Document 2 shows that the amount of 1,2-alkanediol and phenoxyethanol used can be reduced by blending a salt of lanolin fatty acid, which also has an emollient effect.

[0004] On the other hand, ectoine is a cyclic amino acid that is abundant in alkaliphilic bacteria that live in salt lakes in Egypt. Ectoine has the ability to retain moisture by forming hydration nuclei and protects cells from dryness, ultraviolet rays, air pollutants, temperature, and chemicals (Non-Patent Document 5), so it is said to have moisturizing and skin barrier function improving effects, and is incorporated as a moisturizing agent in external preparations such as cosmetics and quasi-drugs. [Prior art documents] [Patent documents]

[0005] [Non-Patent Document 1] Fragrance Journal (2006) Vol. 34, No. 4, 34-38 [Non-Patent Document 2] J Eur Acad Dermatol Venereol (2019) 33, Suppl. 7, 15-24 [Non-Patent Document 3] International Journal of Toxicology (2012) Vol. 31(Supplement 2) 147S-168S [Non-Patent Document 4] Koshokai Journal (1988) Vol. 12, No. 4, 238-247 [Non-Patent Document 5] Clinics in Dermatology (2008) 26, 326-333 [Patent Document 1] WO2006 / 118111 [Patent Document 2] JP 2020-83771 A Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a composition for external use which reduces the odor of polyhydric alcohol or phenoxyethanol and / or a composition for external use which is excellent in safety. [Means for solving the problem]

[0007] The present inventors have found that when a composition for external use containing polyhydric alcohol or phenoxyethanol is combined with a heparinoid, niacinamide, or tranexamic acid, and ectoine, the odor derived from the polyhydric alcohol or phenoxyethanol can be reduced.Furthermore, the present inventors have found that when ectoine is combined with a preparation for external use containing polyhydric alcohol or phenoxyethanol, a heparinoid, niacinamide, or tranexamic acid, the safety of the preparation can be improved.

[0008] That is, the present invention provides: (1) A composition for external use, comprising (a) at least one selected from the group consisting of heparinoids, niacinamide, and tranexamic acid, (b) a polyhydric alcohol or phenoxyethanol, and (c) ectoine; (2) (b) The composition for external use according to (1), wherein the polyhydric alcohol is an alkanediol; (3) The composition for external use according to (2), wherein the alkanediol is 1,2-pentanediol or 1,2-hexanediol. (4) The composition for external use according to (1) or (2), which is a cosmetic, a quasi-drug, or a pharmaceutical product; It is. Effect of the Invention

[0009] According to the present invention, it is possible to provide a composition for external use which reduces the odor derived from polyhydric alcohols or phenoxyethanol and / or is excellent in safety. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The components used in the topical composition of the present invention may be of the same quality as those normally used in pharmaceuticals, quasi-drugs, or cosmetics.

[0011] The amount of the heparinoid of the present invention to be incorporated in the composition for external use of the present invention is preferably 0.01 to 5 w / w%, and more preferably 0.1 to 0.5 w / w%.

[0012] The amount of niacinamide in the present invention is preferably 0.1 to 20 w / w %, and more preferably 1 to 10 w / w %, in the topical composition of the present invention.

[0013] The amount of tranexamic acid in the present invention is preferably 0.1 to 5 w / w%, and more preferably 1 to 5 w / w%, in the topical composition of the present invention.

[0014] The polyhydric alcohol of the present invention is not particularly limited as long as it is one that is normally used in pharmaceuticals, quasi-drugs, or cosmetics, but is preferably an alkanediol, such as 1,3-butylene glycol, propylene glycol, propanediol, 1,2-pentanediol, 1,2-hexanediol, dipropylene glycol, caprylyl glycol, glycerin, and diglycerin. These may be used alone or in combination of two or more. The amount of the polyhydric alcohol of the present invention is preferably 0.1 to 30 w / w%, more preferably 1 to 15 w / w%, in the topical composition of the present invention.

[0015] The blending amount of phenoxyethanol in the topical composition of the present invention is preferably 0.01 to 2 w / w%, more preferably 0.05 to 1 w / w%.

[0016] The amount of ectoine in the present invention is preferably 0.1 to 10 w / w%, more preferably 1 to 5 w / w%, and most preferably 2 to 3 w / w% in the topical composition of the present invention. Also, it is preferably 0.3 to 100 parts by mass, more preferably 3 to 50 parts by mass, relative to 1 part by mass of heparinoid. Also, it is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, relative to 1 part by mass of niacinamide. Also, it is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, relative to 1 part by mass of tranexamic acid.

[0017] In addition to the above-mentioned components, the composition for external use of the present invention may be appropriately blended with various components used in ordinary cosmetics, quasi-drugs, pharmaceuticals, etc., within the scope of not impairing the effects of the present invention. For example, pH adjusters (potassium hydroxide, sodium hydroxide, citric acid, sodium citrate, etc.), fragrances, refreshing agents (menthol, peppermint oil, camphor, etc.), anti-inflammatory agents (salicylic acid, glycyrrhetinic acid, allantoin, indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, etc.), disinfectants (chlorhexidine gluconate, isopropylmethylphenol, etc.), preservatives (parabens (methylparaben, butylparaben, propylparaben, etc.), benzoic acid or its salts, etc.), etc. , moisturizers (hyaluronic acid or its salts, chondroitin sulfate, amino acids (L-serine, L-proline, L-hydroxyproline, glycine, etc.), lipidure, sorbitol, maltitol, etc.), thickeners (polyvinylpyrrolidone, sodium alginate, ethyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, xanthan gum, carrageenan, etc.), extracts of various animals and plants (courgettes, Phellodendron bark, seaweed, moutan pi, licorice, rosemary, sage, etc.), vitamins (retinol palmitate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, riboflavin, etc.), antioxidants (dibutylhydroxytoluene, tocopherol, sodium edetate, ascorbic acid, isopropyl gallate, etc.), solubilizing agents (various vegetable oils, various animal oils, alkyl glyceryl ethers, hydrocarbons, etc.), oily gelling agents (inulin stearate, dextrin palmitate, etc.), metabolic activators, adhesives, antihistamines (chlorpheniramine maleate, etc.), local anesthetics Examples of such agents include procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, proparacaine, meprylcaine or salts thereof, orthocaine, oxethazaine, oxypolyethyleneoxydecane, Scotch extract, percaminpase, tesitdesitin, etc.), skin protective agents (collodion, castor oil, etc.), blood circulation promoting ingredients (γ-oryzanol, nonylic acid vanillylamide, nicotinic acid benzyl ester, capsaicin, chili pepper extract, etc.), mucopolysaccharides (glucosamine, hyaluronic acid, etc.). These ingredients may be used alone or in combination of two or more. The amount of these ingredients added is not particularly limited and can be appropriately determined while taking into consideration the feeling of use, etc. When a pharmacological ingredient is contained, the content may be appropriately determined depending on the type of pharmacological ingredient used, the expected effect, etc.

[0018] The form of the topical composition of the present invention is not particularly limited as long as it is a formulation that can be applied to the skin.Specific formulations include lotions, creams, milky lotions, gels, packs, etc.The topical composition of the present invention may be a W / O or O / W type emulsion formulation.

[0019] The composition for external use of the present invention can be used for applications such as cosmetics, quasi-drugs, pharmaceuticals, etc. The composition for external use of the present invention can be produced by a conventional method depending on the dosage form.

[0020] The effect of reducing the odor of polyhydric alcohol or phenoxyethanol of the present invention can be confirmed by performing the analysis of these using a gas chromatograph. In the present invention, when heparinoid, niacinamide, or tranexamic acid is combined with ectoine, the amount of polyhydric alcohol or phenoxyethanol in the gas phase is reduced, so that the effect of reducing the odor derived from polyhydric alcohol or phenoxyethanol can be confirmed. EXAMPLES

[0021] The present invention will be described in detail below with reference to examples and comparative examples, but the present invention is not limited to the following examples. In the examples and comparative examples, all numerical values ​​mean mass %.

[0022] (Method of preparing a composition for external use) According to the formulations shown in Tables 1 to 5 below, each component was uniformly mixed with purified water to obtain compositions of the examples and comparative examples.

[0023] (Test Example 1: Analysis of polyhydric alcohol or phenoxyethanol in the gas phase) 2 mL of each solution from Examples 1 to 8 and Comparative Examples 1 to 13 was filled into a 20 mL vial and sealed, and the polyhydric alcohol or phenoxyethanol in the gas phase was measured by headspace gas chromatography under the following test conditions, and the peak area was calculated. The peak area of ​​the polyhydric alcohol or phenoxyethanol in each sample was calculated as a percentage, assuming that the peak area of ​​the sample containing only the polyhydric alcohol or phenoxyethanol (Comparative Examples 1, 6, 8, and 12) was 100. The results are shown in Tables 1 to 4.

[0024] <Gas chromatograph test conditions> Column: DB-WAX (inner diameter 0.53 mm, length 30 m, film thickness 1 μm) Column temperature: 50℃ (5 min) → 170℃ (10 min) → 220℃ (5 min), temperature increase 50℃ / min Sample injection temperature: 150℃ Detector temperature: 230℃ Carrier gas: Helium Flow rate: 9mL / min Detection: FID Split ratio: 1:2

[0025] <Headspace autosampler test conditions> Oven temperature: 40℃ Loop temperature: 110℃ Transfer line temperature: 130℃ Vial equilibration time: 20 min Injection time: 1min

[0026] [Table 1]

[0027] [Table 2]

[0028] [Table 3]

[0029] [Table 4]

[0030] It was confirmed by sensory analysis that Comparative Examples 1, 2, 6, 7, 12, and 13 had a polyhydric alcohol odor or a phenoxyethanol odor. Each odor was stronger in Comparative Example 2 than in Comparative Example 1, Comparative Example 7 than in Comparative Example 6, and Comparative Example 13 than in Comparative Example 12, and it was confirmed that the odors became stronger concentration-dependently. As is clear from the results of Tables 1 to 3, in Comparative Examples 3, 5, and 9 to 11, which further contain either a heparinoid, niacinamide, or tranexamic acid, the amount of polyhydric alcohol or phenoxyethanol in the gas phase was reduced, compared with Comparative Examples 1, 6, and 8, which contain a polyhydric alcohol or phenoxyethanol. In Examples 1, 3 to 8, which contain ectoine in Comparative Examples 3, 5 to 11, the amount of polyhydric alcohol or phenoxyethanol in the gas phase was further reduced. In Example 2, which contains tranexamic acid and ectoine, the amount of phenoxyethanol in the gas phase was reduced, compared with Comparative Example 1. Therefore, it was confirmed that the present invention clearly reduces the odor originating from polyhydric alcohols or phenoxyethanol.

[0031] (Test Example 2: Evaluation of cytotoxicity using SIRC cells) A suspension of 3.0×104 cells / mL of rabbit cornea-derived cell line (SIRC cells) was seeded in 96-well plates (MS-8096F, Sumitomo Bakelite Co., Ltd.) at 200 μL each and cultured for 4 days. Comparative Examples 1, 6, 12, 14-16 and Examples 9-11 were exposed to each well at 200 μL / well as test substances. After 10 minutes of exposure, the test substance solution was removed and the plate was washed twice with DPBS, and then 200 μL / well of a solution (MTT solution) in which methylthiazolydiphenyl-tetrazolium bromide was dissolved in cell culture medium to a concentration of 0.5 mg / mL was added. After incubation for 2 hours under 37°C and 5% CO2 conditions, the MTT solution was removed and 2-propanol (MTT extract) containing 0.04N-HCl was added at 200 μL / well and left at room temperature for 1 hour or more. Using a plate reader, measure the absorbance of the MTT extract at 570 nm, and calculate the absorbance (570 nm) as the OD. 570 The MTT extract was used as a blank when measuring absorbance. Physiological saline was used as a solvent control. The cell viability of the test substance was calculated from the average absorbance of 3 wells using the following formula. The results are shown in Table 5.

[0032]

number

[0033] [Table 5]

[0034] Since the cell viability in Comparative Examples 1, 6, and 12 was all less than 40%, it was determined that this test system can evaluate irritation caused by polyhydric alcohols or phenoxyethanol. As is clear from the results in Table 5, the cell viability was slightly decreased in Comparative Examples 14, 15, and 16, which further contained a heparinoid or niacinamide, compared to Comparative Examples 1, 6, and 12, which contained a polyhydric alcohol or phenoxyethanol. The cell viability was increased in Examples 9, 10, and 11, which contained ectoine in Comparative Examples 14, 15, and 16, compared to Comparative Examples 1, 6, 12, and 14 to 16. Therefore, it was confirmed that the present invention improves the safety of compositions containing polyhydric alcohols or phenoxyethanol.

[0035] (Prescription example) As examples of preparations according to the present invention, examples of formulations for external use are shown in Tables 6 to 9. All units are w / w%.

[0036] [Table 6]

[0037] [Table 7]

[0038] [Table 8]

[0039] [Table 9] [Industrial Applicability]

[0040] According to the present invention, it is possible to provide a composition for external use which reduces the odor of polyhydric alcohols or phenoxyethanol and / or is excellent in safety.

Claims

1. A composition for external use, comprising (a) at least one member selected from the group consisting of heparinoids, niacinamide, and tranexamic acid, (b) a polyhydric alcohol or phenoxyethanol, and (c) ectoine.

2. The composition for external use according to claim 1, wherein (b) the polyhydric alcohol is an alkanediol.

3. The composition for external use according to claim 2, wherein the alkanediol is 1,2-pentanediol or 1,2-hexanediol.

4. The composition for external use according to claim 1 or 2, which is a cosmetic, a quasi-drug, or a pharmaceutical.

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