Composition for external use containing ascorbic acid and / or its salt

Abstract

The present invention relates to providing an external composition which contains an ascorbic acid or a salt thereof, and a low-molecular peptide or an amino acid that is a primary amine or a secondary amine, and in which coloring is suppressed during storage.　Prepared is an external composition which contains: (A) an ascorbic acid or a salt thereof; (B) at least one or at least two selected from the group consisting of an amino acid that is a primary amine or a secondary amine, a peptide having at most 10 amino acid residues and salts thereof; (C) at least one or at least two selected from the group consisting of 1,3-propanediol, propylene glycol, ethoxydiglycol, and polyethyleneglycol; and (D) water.

Description

[Technical field]

[0001] The present invention relates to a composition for external use containing ascorbic acid and / or a salt thereof. [Background technology]

[0002] It is known that ascorbic acid reacts chemically with primary or secondary amine amino acids and low molecular weight peptides to produce brown substances (melanoidins) and cause coloration. This reaction is called the aminocarbonyl reaction or Maillard reaction. For this reason, it is known that ascorbic acid or its salts are incompatible with primary or secondary amine amino acids and low molecular weight peptides.

[0003] Therefore, in the case of a composition for external use, it is common to avoid combining ascorbic acid with such amino acids or low molecular weight peptides, or to use an ascorbic acid derivative that is less likely to cause the Maillard reaction instead of ascorbic acid. For example, Patent Document 1 discloses that ascorbic acid 2-glucoside has been found as such an ascorbic acid derivative. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2006 / 022174 Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention relates to providing a composition for external use which contains ascorbic acid or a salt thereof and an amino acid or a low-molecular-weight peptide which is a primary amine or a secondary amine, and yet which is suppressed from discoloring during storage. [Means for solving the problem]

[0006] As a result of intensive research, the inventors have found that by adding (A) one or more members selected from the group consisting of ascorbic acid or a salt thereof, (B) amino acids which are primary amines or secondary amines, peptides having 10 or fewer amino acid residues, and salts thereof, to (C) one or more members selected from the group consisting of 1,3-propanediol, propylene glycol, ethoxydiglycol, and polyethylene glycol, a composition for external use which is suppressed in discoloration over time due to components (A) and (B) can be obtained, thereby completing the present invention.

[0007] That is, the present invention provides the following topical composition. Section 1. (A) ascorbic acid or its salts; (B) one or more selected from the group consisting of primary amine or secondary amine amino acids, peptides having 10 or less amino acid residues, and salts thereof; (C) one or more selected from the group consisting of 1,3-propanediol, propylene glycol, ethoxydiglycol, and polyethylene glycol; and (D)Water A topical composition comprising: Section 2. Item 2. The composition for external use according to Item 1, wherein component (B) is one or more members selected from the group consisting of α-amino acids which are primary amines or secondary amines, peptides having 10 or fewer amino acid residues, and salts thereof. Section 3. Item 3. The composition for external use according to Item 1 or 2, wherein component (B) is one or more selected from the group consisting of glycine, serine, threonine, alanine, valine, cysteine, methionine, citrulline, arginine, lysine, histidine, ornithine, aspartic acid, glutamic acid, proline, 4-hydroxyproline, N-methylglycine, N-acetylserine, N-acetylcysteine, glutathione, tetrapeptide-5, and salts thereof. Section 4. Item 4. The composition for external use according to any one of Items 1 to 3, wherein the content of component (A) is 1 to 50% by mass. Section 5. Item 5. The composition for external use according to any one of items 1 to 4, wherein the content of component (B) is 0.0001 to 1% by mass. Section 6. Item 6. The composition for external use according to any one of items 1 to 5, wherein the content of component (C) is 25% by mass or more. Section 7. Item 7. The composition for external use according to any one of items 1 to 6, wherein the amount of the component (D) is 0.01 to 20 parts by mass per part by mass of the total amount of the component (A). Section 8. Item 8. The composition for external use according to any one of Items 1 to 7, further comprising a lower alcohol, butylene glycol, or a combination thereof. Effect of the Invention

[0008] The topical composition of the present invention is inhibited from discoloring over time and has excellent stability. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] In this specification, the unit of content "mass%" is synonymous with "g / 100 g".

[0010] The topical composition of the present invention contains (A) ascorbic acid or a salt thereof, (B) one or more types selected from the group consisting of amino acids which are primary amines or secondary amines, peptides having 10 or fewer amino acid residues, and salts thereof, (C) one or more types selected from the group consisting of 1,3-propanediol, propylene glycol, ethoxydiglycol, and polyethylene glycol, and (D) water.

[0011] [(A) Ascorbic acid or its salt] In the present invention, ascorbic acid that is commercially available as a component of pharmaceuticals, quasi-drugs, or skin care products in the field of cosmetics can be used, and these generally refer to the L-isomer.

[0012] Salts of ascorbic acid can also be used. Here, the salts of ascorbic acid are pharma- ceutical acceptable salts. Examples of the salts include, but are not limited to, salts with organic bases (e.g., salts with tertiary amines such as trimethylamine salts, triethylamine salts, monoethanolamine salts, triethanolamine salts, and pyridine salts, and basic ammonium salts such as arginine), salts with inorganic bases (e.g., alkali metal salts such as ammonium salts, sodium salts, and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, and aluminum salts). Particularly preferred salts of ascorbic acid are sodium salts and potassium salts. Specific examples include sodium ascorbate, magnesium ascorbate, and calcium ascorbate. Among these, sodium ascorbate is preferred as the salt of ascorbic acid.

[0013] As the component (A) of the present invention, one compound selected from the group consisting of ascorbic acid and its salts can be used alone, or two or more compounds can be used in combination.

[0014] The total content of the component (A) relative to the total amount of the topical composition of the present invention is appropriately set depending on the balance with other components. The total content of the component (A) relative to the total amount of the topical composition is not particularly limited, but is preferably 1% by mass or more, more preferably 3% by mass or more, and even more preferably 5% by mass or more, from the viewpoint of imparting functions such as whitening, anti-inflammation, anti-aging, and anti-oxidation. From the viewpoint of prominently exhibiting the effects of the present invention, the total content of the component (A) relative to the total amount of the topical composition is preferably 50% by mass or less, more preferably 40% by mass or less, and even more preferably 30% by mass or less. The total content of the component (A) relative to the total amount of the topical composition is preferably 1 to 50 mass %, more preferably 3 to 40 mass %, and even more preferably 5 to 30 mass %.

[0015] [(B) one or more selected from the group consisting of primary amine or secondary amine amino acids, peptides having 10 or less amino acid residues, and salts thereof] The amino acids which are primary amines or secondary amines and peptides having 10 or less amino acid residues used in component (B) of the present invention each contain a primary amino group (-NH2), a secondary amino group (>NH), or both of these groups. In the present invention, compounds selected from the group consisting of amino acids, peptides having 10 or less amino acid residues, and salts thereof may be used alone or in combination of two or more.

[0016] The amino acid used in the component (B) of the present invention is not particularly limited as long as it is used as a component of a skin external preparation in the fields of medicines, quasi-drugs, or cosmetics. The amino acid is not particularly limited, and examples thereof include α-amino acids, β-amino acids, γ-amino acids, δ-amino acids, etc., or salts thereof, among which α-amino acids or salts thereof are preferred.

[0017] The α-amino acid of the component (B) of the present invention is not particularly limited, but is preferably L-amino acid. Examples of α-amino acids include neutral amino acids such as glycine, serine, threonine, alanine, valine, leucine, isoleucine, asparagine, glutamine, cysteine, methionine, phenylalanine, tyrosine, tryptophan, citrulline, azaserine, cystathionine, homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, ε-N-acetyllysine, proline, 4-hydroxyproline, N-methylglycine, N-acetylserine, and N-acetylcysteine; basic amino acids and salts thereof such as arginine, lysine, histidine, ornithine, ω-N-methylarginine, ε-N,N,N-trimethyllysine, 5-hydroxylysine, and 3-methylhistidine; and acidic amino acids and salts thereof such as aspartic acid, glutamic acid, γ-carboxyglutamic acid, and O-phosphoserine. Among these, the α-amino acids used in the component (B) of the present invention are preferably one or more selected from glycine, serine, threonine, alanine, valine, cysteine, methionine, citrulline, arginine, lysine, histidine, ornithine, aspartic acid, glutamic acid, proline, 4-hydroxyproline, N-methylglycine, N-acetylserine, N-acetylcysteine, and salts thereof, from the viewpoint of solubility in water; glycine, serine, threonine, alanine, valine, cysteine, methionine More preferably, one or more selected from glycine, serine, threonine, N-acetylcysteine, arginine, lysine, 4-hydroxyproline, N-acetylcysteine, and salts thereof are used; even more preferably, one or more selected from glycine, serine, threonine, N-acetylcysteine, arginine, lysine, 4-hydroxyproline, N-acetylcysteine, and salts thereof are used; and particularly preferably, one or more selected from glycine, serine, arginine, N-acetylcysteine, and salts thereof are used.

[0018] A peptide is a polymer in which amino acids, which are monomers, are condensed through amide bonds (peptide bonds). The peptide of component (B) of the present invention has 10 or less amino acid residues (monomer unit number). From the viewpoint of significantly exhibiting the effects of the present invention, the number of amino acid residues is preferably 8 or less, more preferably 5 or less, even more preferably 4 or less, and particularly preferably 2 or 3.

[0019] As such peptides, known natural or synthetic peptides that are incorporated in cosmetics and quasi-drugs can be used. The peptides of component (B) of the present invention are not particularly limited, but specifically include dipeptides (dipeptide-4, etc.); tripeptides (glutathione, tripeptide-3, etc.); tetrapeptides (tetrapeptide-5, etc.); oligopeptides (oligopeptide-6, decapeptide-2, etc.); legume plant protein hydrolysates (hydrolyzed soy protein); silk protein hydrolysates; pearl protein hydrolysates; collagen hydrolysates (water-soluble collagen), low molecular weight collagen, collagen peptides, hydrolyzed collagen, hydrolyzed elastin, atelocollagen, collagen derivatives such as succinyl atelocollagen, peptides containing chemical modifications (acetylation, palmitoylation, myristoylation, nicotinoylation, ursolylation, azelaylation, biotinylation, etc.), and salts thereof. Of these, the peptide of component (B) more preferably contains at least one or more selected from the group consisting of glutathione, tetrapeptide-5, and salts thereof, with glutathione or a salt thereof being even more preferred.

[0020] In the topical composition of the present invention, the total content of component (B) relative to the total amount of the topical composition is preferably 0.0001% by mass or more, more preferably 0.0005% by mass or more, and even more preferably 0.001% by mass or more. The total content of the component (B) relative to the total amount of the topical composition is preferably 1 mass % or less, more preferably 0.8 mass % or less, and even more preferably 0.5 mass % or less, from the viewpoint of prominently exhibiting the effects of the present invention. The total content of component (B) relative to the total amount of the topical composition of the present invention is preferably 0.0001 to 1 mass %, more preferably 0.0005 to 0.8 mass %, and even more preferably 0.001 to 0.5 mass %.

[0021] [(C) one or more selected from the group consisting of 1,3-propanediol, propylene glycol, ethoxydiglycol, and polyethylene glycol] 1,3-propanediol is a compound with the CAS number 504-63-2. Propylene glycol is another name for 1,2-propanediol, a chemical compound with the CAS number 57-55-6. Ethoxydiglycol, also known as diethylene glycol monoethyl ether, is a compound with the CAS number 111-90-0.

[0022] The polyethylene glycol (PEG) used in the present invention preferably has a degree of polymerization of 4 or more and is used as a base in ordinary medicines, quasi-drugs, and cosmetics. In the present invention, a relatively low molecular weight polyethylene glycol is preferably used. Although not limited, specifically, polyethylene glycols having an average molecular weight of about 150 to 1000 are preferred, and more preferably, polyethylene glycols having an average molecular weight of about 170 to 800 are more preferred. Specific examples of such polyethylene glycols include polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 500, polyethylene glycol 600, polyethylene glycol 700, and polyethylene glycol 800. These are commercially available, and therefore, these commercially available products can be obtained and used. Specific examples of commercially available products include polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, and polyethylene glycol 600 sold by NOF Corporation, and polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, and polyethylene glycol 600 sold by Sanyo Chemical Industries, Ltd.

[0023] Here, the average molecular weight can be determined, for example, in accordance with the average molecular weight test described in the section on polyethylene glycol in the "Standards for Quasi-Drug Raw Materials 2006" in Japan.

[0024] <Method for measuring the average molecular weight of polyethylene glycol with an average molecular weight of 190 to 210> Weigh out approximately 0.8g of polyethylene glycol accurately and place it in a 200mL pressure-resistant stoppered bottle. Add approximately 25mL of pyridine, heat to dissolve, and allow to cool. Separately, take 42g of phthalic anhydride and add it to a 1L light-shielded stoppered bottle containing 300mL of freshly distilled pyridine. Shake vigorously to dissolve, then leave to stand for 16 hours or more. Weigh out 25mL of this liquid accurately and add it to the pressure-resistant stoppered bottle, seal it, wrap it in a strong cloth, and place it in a water bath that has been preheated to 98℃±2℃. At this time, make sure that the liquid in the bottle is immersed in the water in the water bath. Heat at 98℃±2℃ for 30 minutes, then allow to cool to room temperature. Next, add exactly 50mL of 0.5mol / L sodium hydroxide solution, and titrate this solution with 0.5mol / L sodium hydroxide solution. Use 5 drops of phenolphthalein-pyridine solution (1→100) as an indicator. The end point of the titration shall be when the solution turns a pale red color that lasts for 15 seconds. Perform a blank test in the same manner. The obtained value is applied to the following formula to calculate the average molecular weight. Average molecular weight = [amount of sample (g) × 4000] / (ab) a: Amount of 0.5 mol / L sodium hydroxide solution consumed in the blank test (mL) b: Amount of 0.5 mol / L sodium hydroxide solution consumed in the test of the sample (mL)

[0025] In the case of polyethylene glycol having an average molecular weight other than 190 to 210, the weighed amount may be changed as appropriate, but otherwise the test method is similar to that for polyethylene glycol having an average molecular weight of 190 to 210.

[0026] These polyethylene glycols can be used alone or in combination of two or more.

[0027] In the topical composition of the present invention, the total content of component (C) relative to the total amount of the topical composition is, from the viewpoint of prominently exhibiting the effects of the present invention, preferably 25% by mass or more, more preferably 27% by mass or more, even more preferably 28% by mass or more, and particularly preferably 30% by mass or more. The total content of the (C) component relative to the total amount of the topical composition can be appropriately adjusted depending on the content of the (A) component, but is preferably 75 mass% or less, more preferably 70 mass% or less, and even more preferably 65 mass% or less. The total content of component (C) relative to the total amount of the topical composition of the present invention is preferably 25 to 75 mass %, more preferably 27 to 70 mass %, and even more preferably 28 to 65 mass %.

[0028] In the topical composition of the present invention, the ratio of the total content of component (C) to component (A) is not particularly limited, but is preferably 0.5 to 75 parts by mass, more preferably 0.75 to 50 parts by mass, and even more preferably 1 to 25 parts by mass, per 1 part by mass of the total content of component (A).

[0029] [(D)Water] The topical composition of the present invention is a liquid composition containing water. The content of water is not limited, but is preferably 0.1% by mass or more, more preferably 1% by mass or more, and even more preferably more than 1% by mass (e.g., 3% by mass or more) based on the total amount of the topical composition. The content of more than 1% by mass is not limited, but may be, for example, 1.01% by mass or more or 1.1% by mass or more. By including such a small amount of water, the precipitation of ascorbic acid or a salt thereof can be suppressed, and the topical composition can be excellent in stability. The water content is, for example, 50% by mass or less, preferably 40% by mass or less, and more preferably 35% by mass or less, based on the total amount of the composition for external use.

[0030] The total content of the component (D) relative to the total amount of the topical composition of the present invention is preferably 0.1 to 50 mass %, more preferably more than 1 mass % to 40 mass %, and even more preferably 3 to 35 mass %.

[0031] In the topical composition of the present invention, the ratio of the content of component (D) to the content of component (A) is not particularly limited, but is preferably 0.01 to 20 parts by mass, more preferably 0.05 to 15 parts by mass, and even more preferably 0.2 to 10 parts by mass, per part by mass of the total content of component (A).

[0032] [pH] The topical composition of the present invention preferably has an acidic pH range of 1.5 to 4.5, more preferably 2 to 4, from the viewpoints of the stability of component (A), low irritation to the skin and mucous membranes, and good feel on the skin when used.

[0033] [Lower alcohol] The topical composition of the present invention may contain a lower alcohol in addition to the above components (A) to (D) in terms of improving the feeling of use, stability, and promoting percutaneous absorption, as long as the effects of the present invention are not hindered. The lower alcohol used in the present invention is not particularly limited as long as it is used as a component of a skin topical agent in the fields of medicines, quasi-drugs, or cosmetics. In this specification, the term "lower alcohol" refers to an alcohol having 1 to 6 carbon atoms (C1-C6). Among these, the topical composition of the present invention can preferably use alcohols having C1 to C3. As such an example, ethanol is preferable, but methanol, n-propanol, isopropanol, etc. can also be used.

[0034] In the topical composition of the present invention, the total content of lower alcohols relative to the total amount of the topical composition, if any, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.5% by mass or more, even more preferably 1% by mass or more, and particularly preferably 3% by mass or more. The content of ethanol is preferably 50% by mass or less, more preferably 45% by mass or less, even more preferably 40% by mass or less, and even more preferably 35% by mass or less.

[0035] The total content of lower alcohols contained in the topical composition of the present invention is preferably 0.01 to 50 mass%, more preferably 0.1 to 45 mass%, even more preferably 0.5 to 40 mass%, even more preferably 1 to 35 mass%, and particularly preferably 3 to 35 mass%, relative to the total amount of the topical composition.

[0036] [Butylene glycol] From the viewpoints of improving the sensation of use, stability, and promotion of transdermal absorption, the topical composition of the present invention may contain butylene glycol (also called 1,3-butylene glycol or 1,3-butanediol) in addition to the above components (A) to (D), as long as the effects of the present invention are not impaired.

[0037] In the topical composition of the present invention, the content of butylene glycol relative to the total amount of the topical composition, if contained, is preferably 0.01 mass% or more, more preferably 0.1 mass% or more, and even more preferably 0.3 mass% or more, from the viewpoints of improving the feel in use, stability, and promoting transdermal absorption. The butylene glycol content is preferably 40% by mass or less, more preferably 35% by mass or less, and even more preferably 30% by mass or less.

[0038] The content of butylene glycol in the topical composition of the present invention is preferably 0.01 to 40 mass %, more preferably 0.1 to 35 mass %, and even more preferably 0.3 to 30 mass %.

[0039] [pH adjuster] From the viewpoints of improving the feeling of use, stability, and promotion of transdermal absorption, the topical composition of the present invention may contain a pH adjuster in addition to the above components (A) to (D), as long as the effects of the present invention are not impaired.

[0040] The pH adjuster used in the present invention can be a compound that is generally used as a component of skin external preparations in the fields of medicines, quasi-drugs, or cosmetics.Not particularly limited, examples of pH adjusters include amine-containing pH adjusters (e.g., aminoethylsulfonic acid or its salt, monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, L-carnitine, low molecular weight betaine (more preferably trimethylglycine)), organic acid salts (e.g., sodium lactate, sodium acetate, sodium citrate, sodium succinate, sodium oxalate, calcium gluconate, sodium pyrrolidone carboxylate, etc.), inorganic acid salts (e.g., sodium pyrosulfite, potassium pyrosulfite, sodium phosphate, potassium nitrate, sodium borate, preferably sodium pyrosulfite), 3-O-ethyl ascorbic acid or its salt, etc.

[0041] In the topical composition of the present invention, the total content of the pH adjuster relative to the total amount of the topical composition is not particularly limited, but is preferably 0.01% by mass or more, more preferably 0.05% by mass or more. The total content of the pH adjuster relative to the total amount of the topical composition is preferably 10% by mass or less, more preferably 5% by mass or less. The content of the pH adjuster having an amine relative to the total amount of the topical composition is preferably 0.01% by mass to 10% by mass, more preferably 0.05% by mass to 5% by mass.

[0042] In the topical composition of the present invention, the content ratio of the pH adjuster relative to the component (A) is not particularly limited, but is preferably 0.00001 to 20 parts by mass, more preferably 0.0001 to 20 parts by mass, even more preferably 0.0005 to 10 parts by mass, even more preferably 0.005 to 5 parts by mass, and particularly preferably 0.01 to 1 part by mass, relative to 1 part by mass of the total content of the component (A).

[0043] [Other ingredients] In addition to the above components (A) to (D), the topical composition of the present invention may further contain one or more combinations of various components, such as whitening components, anti-inflammatory components, antibacterial components, cell activating components, astringent components, antioxidant components, acne treatment components, anti-aging components, components promoting the synthesis of biological components such as collagen, blood circulation promoting components, moisturizing components, and anti-aging components, for the purpose of enhancing or supplementing the various effects of ascorbic acid or for the purpose of imparting other useful effects.

[0044] The topical composition of the present invention may further contain, in addition to the above-mentioned components (A) to (D), a surfactant, a solubilizing component, oils and fats, sugars, or a component that enhances transdermal absorption. In particular, by adding a surfactant, a solubilizing component, or oils and fats, the stability, efficacy, and usability of ascorbic acid in an aqueous solvent can be further improved.

[0045] The topical composition of the present invention may contain various components that are generally used as components of topical preparations in the fields of medicines, quasi-drugs, or cosmetics, such as irritation reducers, thickeners, preservatives, UV protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc., as necessary, within quantitative and qualitative ranges that do not impair the qualities such as appearance stability and viscosity, and do not impair the effects of the present invention. These components may be used alone or in any combination of two or more.

[0046] The topical composition of the present invention can be prepared in various desired forms such as paste, mousse, gel, liquid, milky lotion, cream, sheet (supported by a substrate), aerosol, spray, etc. by mixing the above-mentioned optional components with the above-mentioned components (A) to (D) as necessary, further mixing with other solvents and bases for topical agents commonly used as necessary, and adjusting the pH as necessary. These can be produced by methods commonly used in the art.

[0047] From the viewpoint of prominently exhibiting the effects of the present invention, the composition for external use of the present invention is particularly preferably a transparent or translucent composition in which ascorbic acid and / or a salt thereof is solubilized. Here, "solubilized" is defined as follows. That is, for example, it refers to a transmittance of 80 to 100%, preferably 85 to 100%, more preferably 90 to 100%, as measured at a wavelength of 700 nm using a spectrophotometer or photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation) by ultraviolet-visible absorbance measurement. Here, the transmittance of water is taken as 100%. More specifically, the method of measuring the transmittance is in accordance with the method described in the 16th revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Spectroscopic Measurement Methods 2.24 Ultraviolet-Visible Absorbance Measurement Method. Moreover, "transparent or translucent" refers to an L value, which is an index of transparency, of 85 or more, and preferably 90 or more. The L value is a parameter of lightness used in the CIELAB color system, and can be measured using a spectrophotometer such as the CM-5 spectrophotometer (manufactured by Konica Minolta, Inc.).

[0048] [viscosity] The topical composition of the present invention can be prepared as a composition having a suitable viscosity, which is particularly desirable when the topical composition is applied to the skin. The viscosity of the topical composition of the present invention is not particularly limited, but for example, the viscosity measured at 25°C using an E-type viscometer is usually about 1 to 300 mPa·s, preferably about 1 to 200 mPa·s, more preferably about 1 to 100 mPa·s, and even more preferably about 1 to 50 mPa·s. The viscosity measurement method is more specifically in accordance with the method described in the 16th revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Other Physical Test Methods 2.53 Viscosity Measurement Method 2. Method 2 Rotational Viscometer Method 2.1.3 Cone-Plate Type Rotational Viscometer (Cone-Plate Type Viscometer).

[0049] [Application] The composition for external use of the present invention can be used as a whitening agent, an anti-inflammatory agent, an anti-aging agent, and can have, for example, acne prevention and treatment, and antioxidant effects.Furthermore, by applying to the skin, it may have the effect of increasing the transparency of the skin, maintaining moisture, improving the skin texture, and suppressing roughness.Furthermore, it may have the effect of making pores less noticeable, conditioning and moisturizing the skin, and can also be used to prevent and treat blemishes.

[0050] The topical composition of the present invention may be, for example, a basic cosmetic product such as a beauty essence, a skin lotion, a sunscreen cream, a milky lotion, a cream, a lotion, an oil, or a pack; a makeup cosmetic product such as a foundation, a lipstick, a lip cream, a mascara, an eyeshadow, an eyeliner, an eyebrow pencil, or a nail polish; a cleanser such as a face wash, a cleanser, or a body wash; an anti-arm odor agent, athlete's foot treatment agent, an antipruritic agent, a wound healing agent, a cleaning agent, a cleaning agent, an anti-inflammatory analgesic agent, an acne treatment agent, an agent for hemorrhoids, a germicide, a disinfectant, a skin whitening agent, an ultraviolet protection agent, or any other composition belonging to the field of cosmetics, topical medicine, or topical quasi-drug. In view of the effect on the skin, the present invention is preferably used in a product applied to the skin, such as a skin topical agent (a preparation for the skin).

[0051] The topical composition of the present invention can be used in a known or commonly used dosage form, from once to several times a day, depending on the application.

[0052] In relation to the above-mentioned embodiment, the present invention further discloses the following composition. [1] (A) ascorbic acid or its salts; (B) one or more selected from the group consisting of primary amine or secondary amine amino acids, peptides having 10 or less amino acid residues, and salts thereof; (C) one or more selected from the group consisting of 1,3-propanediol, propylene glycol, ethoxydiglycol, and polyethylene glycol; and (D) water. A topical composition comprising: [2] The topical composition described in [1], wherein component (B) is one or more selected from the group consisting of α-amino acids which are primary amines or secondary amines, peptides having 10 or fewer amino acid residues, and salts thereof. [3] The composition for external use according to [1] or [2], wherein component (B) is one or more selected from the group consisting of glycine, serine, threonine, alanine, valine, cysteine, methionine, citrulline, arginine, lysine, histidine, ornithine, aspartic acid, glutamic acid, proline, 4-hydroxyproline, N-methylglycine, N-acetylserine, N-acetylcysteine, glutathione, tetrapeptide-5, and salts thereof. [4] The composition for external use according to any one of [1] to [3], wherein the content of component (A) is 1 to 50 mass %. [5] The composition for external use according to any one of [1] to [4], wherein the content of component (B) is 0.0001 to 1 mass %. [6] The composition for external use according to any one of [1] to [5], wherein the content of component (C) is 25% by mass or more. [7] The composition for external use according to any one of [1] to [6], wherein the content of component (D) is 0.1 to 50 mass %. [8] The composition for external use according to any one of [1] to [7], wherein the amount of the component (C) is 0.5 to 75 parts by mass per 1 part by mass of the total amount of the component (A). [9] The composition for external use according to any one of [1] to [8], wherein the amount of the component (D) is 0.01 to 20 parts by mass per 1 part by mass of the total amount of the component (A).

[10] The composition for external use according to any one of [1] to [9], which has a pH of 1.5 to 4.5.

[11] The composition for external use according to any one of [1] to

[10] , further comprising a lower alcohol, butylene glycol, or a combination thereof.

[12] The composition for external use according to

[11] , wherein the content of the lower alcohol is 0.01 to 50% by mass.

[13] The composition for external use according to

[11] or

[12] , wherein the content of butylene glycol is 0.01 to 40% by mass.

[14] The composition for external use according to any one of [1] to

[13] , further comprising one or more pH adjusters selected from the group consisting of a pH adjuster having an amine, an organic acid salt, an inorganic acid salt, and 3-O-ethyl ascorbic acid and its salts.

[15] The composition for external use according to

[14] , wherein the content of the pH adjuster is 0.01 to 10% by mass.

[16] The composition for external use according to

[14] or

[15] , wherein the content of the pH adjuster is 0.00001 to 20 parts by mass per 1 part by mass of the total content of the component (A).

[17] The composition for external use according to any one of [1] to

[16] , which is in the form of a paste, a mousse, a gel, a liquid, a milky lotion, a cream, a sheet, an aerosol, or a spray.

[18] The composition for external use according to any one of [1] to

[17] , wherein the component (A) is solubilized and transparent or translucent.

[19] The composition for external use according to any one of [1] to

[18] , which has a viscosity measured at 25°C of 1 to 300 mPa s.

[0053] In addition, in relation to the above-mentioned embodiment, the present invention further discloses the following method.

[20] (A) ascorbic acid or its salts; (B) one or more selected from the group consisting of primary amine or secondary amine amino acids, peptides having 10 or less amino acid residues, and salts thereof; and (D) In ​​water, (C) one or more selected from the group consisting of 1,3-propanediol, propylene glycol, ethoxydiglycol, and polyethylene glycol A method for suppressing coloration over time in a topical composition, comprising incorporating EXAMPLES

[0054] EXAMPLES Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to the following examples. In the tables, the unit of the amount of each component is % by mass.

[0055] [Ascorbic acid color inhibition confirmation test] For the examples and comparative examples of the present invention, the presence or absence of inhibition of coloring of the topical compositions after storage at 50° C. was evaluated. Specifically, according to the prescriptions listed in the various prescription tables, ascorbic acid was added to a mixed solution of various components, which was then heated and mixed at 60° C. for 10 minutes to dissolve, to prepare a topical composition. The prepared topical composition was filled into a transparent glass bottle and kept at 50° C. for 1 week in the dark.

[0056] Thereafter, the coloring of each external composition was evaluated using a spectrophotometer CM-5 (Konica Minolta, Inc.). For the measurement using the spectrophotometer, 1 mL of the test solution was placed in a glass cell (CM-A97, thickness 2 mm) and the b value in the CIELAB color system was measured at 25°C. The measured value was the b value obtained using purified water as a blank. The change in color difference Δb before and after keeping at 50°C for 1 week was calculated using the following formula. (Change in color difference (Δb)) = (Measurement value of test liquid after keeping warm (b value after keeping warm)) - (Measurement value of test liquid before keeping warm (b value before keeping warm)) The b value is used as an index of transparency. The smaller the Δb value, the less coloring there is. When the Δb value of the control is standardized to 1, the Δb (Δb ratio) of each sample can be calculated as follows: (Δb ratio) = (Δb value of each sample) / (Δb value of control) It was found that if the Δb ratio of the sample was 0.75 or less, the coloring was clearly less than that of the control. Therefore, in each table, the presence or absence of coloring can be determined based on whether the Δb ratio of the topical composition to the comparative example is 0.75 or less.

[0057] [Test Example 1] Compositions for external use of the Examples and Comparative Examples having the compositions shown in Table 1 containing 25% by mass of ascorbic acid and 0.01% by mass of L-serine were prepared according to a conventional method.

[0058] The results of the ascorbic acid discoloration inhibition confirmation test for the compositions of the Examples and Comparative Examples are shown in Table 1. The Δb ratios in the table represent the Δb ratios when Comparative Example 1-1 is used as a control.

[0059] [Table 1]

[0060] Since the compositions of the examples all had a Δb ratio of 0.75 or less, even though they contained ascorbic acid and L-serine, coloring was significantly suppressed after the warming treatment compared to Comparative Example 1-1. Note that in Comparative Example 1-2, ascorbic acid was not completely dissolved, and preparation was impossible.

[0061] [Test Examples 2 to 8] The topical compositions of the examples and comparative examples having the compositions shown in Tables 2 and 3 were prepared according to conventional methods.

[0062] The results of the ascorbic acid discoloration inhibition confirmation test of the compositions of the Examples and Comparative Examples are shown in Tables 2 and 3. The Δb ratios in the tables represent the ratios of Δb when Comparative Example 2 is used as a control for Examples 2-1 to 3, Comparative Example 3 is used as a control for Examples 3-1 to 3, Comparative Example 4 is used as a control for Examples 4-1 to 3, Comparative Example 5 is used as a control for Example 5, Comparative Example 6 is used as a control for Examples 6-1 to 2, Comparative Example 7 is used as a control for Examples 7-1 to 4, and Comparative Example 8 is used as a control for Example 8.

[0063] [Table 2]

[0064] [Table 3]

[0065] [Table 4]

[0066] The ratios of Δb in Examples 2-1 to 3 and Examples 3-1 to 3 were all 0.75 or less, which indicates that coloring was more significantly suppressed than in the Comparative Example even under conditions of low ascorbic acid concentrations. Also, as in Examples 4-1 to 3, 5, 6-1 to 2, 7-1 to 4, and 8, even when any of L-arginine, glycine, N-acetyl-L-cysteine, glutathione, or tetrapeptide-5 (β-Ala-His-Ser-His) was contained instead of L-serine, coloring was more significantly suppressed than in the Comparative Example even after heat retention treatment.

[0067] [Formulation example] Compositions for external use (serums) of the present invention were prepared based on Formulation Examples 1 to 28 in the following Tables 5 and 6. The blending amounts in Tables 5 and 6 are all expressed in mass %.

[0068] [Table 5]

[0069] [Table 6]

Claims

1. (A) ascorbic acid or a salt thereof; (B) one or more selected from the group consisting of α-amino acids which are primary amines or secondary amines (excluding the case where the α-amino acid is cysteine), peptides having 10 or less amino acid residues, and salts thereof; (C) one or more selected from the group consisting of 1,3-propanediol, propylene glycol, ethoxydiglycol, and polyethylene glycol; and (D) Water Contains The content of the (C) component is 25% by mass or more and 69.9% by mass or less, A composition for external use, in which the total content of the component (C) is 0.5 to 25 parts by mass per part by mass of the total content of the component (A) (excluding the cases in which the composition for external use falls under any of the following (i) to (iii): (i) a liquid cosmetic composition comprising at least iron oxide, an unsaturated fatty acid, an anionic surfactant, a water-soluble organic solvent, water, ascorbic acid, and arginine; (ii) Skin preparations for external use containing 4-alkylresorcinol and / or a salt thereof; (iii) A liquid cosmetic preparation containing iron oxide.

2. The composition for external use according to claim 1, wherein component (B) is one or more selected from the group consisting of glycine, serine, threonine, alanine, valine, methionine, citrulline, arginine, lysine, histidine, ornithine, aspartic acid, glutamic acid, proline, 4-hydroxyproline, N-methylglycine, N-acetylserine, N-acetylcysteine, glutathione, tetrapeptide-5, and salts thereof.

3. The composition for external use according to claim 1 or 2, wherein the content of component (A) is 1 to 50 mass%.

4. The composition for external use according to any one of claims 1 to 3, wherein the content of component (B) is 0.0001 to 1 mass%.

5. The composition for external use according to any one of claims 1 to 4, wherein the amount of the (D) component is 0.01 to 20 parts by mass per 1 part by mass of the total content of the (A) component.

6. The composition for external use according to any one of claims 1 to 5, further comprising a lower alcohol, butylene glycol, or a combination thereof.

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