Topical components containing ascorbic acid and / or its salts

Abstract

This invention provides an external composition that, although containing ascorbic acid or a salt thereof and an amino acid or a low-molecular-weight peptide as a primary or secondary amine, exhibits inhibited color development during storage. The invention prepares an external composition comprising: (A) ascorbic acid or a salt thereof; (B) one or more amino acids selected from the group consisting of primary or secondary amines, peptides with 10 or fewer amino acid residues, and salts of these substances; (C) one or more amino acids selected from the group consisting of 1,3-propanediol, 1,2-propanediol, ethoxyethylene glycol, and polyethylene glycol; and (D) water.

Description

Technical Field

[0001] This invention relates to a topical composition containing ascorbic acid and / or its salts. Prior Technology

[0002] Ascorbic acid is known to react chemically with amino acids or low-molecular-weight peptides that are primary or secondary amines, producing a brown substance (melanoidin) and causing coloration. This reaction is known as the amino-carbonyl reaction or the Maillard reaction. Therefore, ascorbic acid or its salts are known to have poor compatibility with amino acids or low-molecular-weight peptides that are primary or secondary amines.

[0003] Therefore, in topical formulations, it is generally avoided to combine ascorbic acid with this type of amino acid or low molecular weight peptide, or ascorbic acid derivatives that are less likely to cause the Meniere's reaction are used instead of ascorbic acid. As such as ascorbic acid derivatives, ascorbic acid 2-glucoside has been discovered, for example, as disclosed in Patent Document 1. [Previous Technical Documents] [Patent Literature]

[0004] [Patent Document 1] International Publication No. 2006 / 022174. Summary of the Invention

[0005] [The problem that the invention aims to solve]

[0006] The present invention provides an external composition that contains ascorbic acid or its salt and amino acids or low molecular weight peptides as primary or secondary amines, but whose coloring is inhibited during storage. [Methods used to solve problems]

[0007] Through diligent research, the inventors discovered that by adding one or more of the following substances to the group consisting of (A) ascorbic acid or its salts, (B) amino acids selected as primary or secondary amines, peptides with 10 or fewer amino acid residues, and salts of these substances, and (C) one or more of the following substances selected from the group consisting of 1,3-propanediol, 1,2-propanediol, ethoxyethylene glycol, and polyethylene glycol, an external composition that inhibits time-related staining caused by components (A) and (B) can be obtained, thus completing the present invention.

[0008] That is, the present invention provides the following external components. Item 1. A topical composition comprising: (A) ascorbic acid or a salt thereof; (B) one or more amino acids selected from the group consisting of primary or secondary amines, peptides having 10 or fewer amino acid residues, and salts of these substances; (C) one or more amino acids selected from the group consisting of 1,3-propanediol, 1,2-propanediol, ethoxyethylene glycol, and polyethylene glycol; and (D) water. Item 2. As described in item 1, component (B) is selected from one or more of the group consisting of α-amino acids that are primary or secondary amines, peptides with fewer than 10 amino acid residues, and salts of these substances. Item 3. As described in item 1 or 2, wherein component (B) is selected from one or more of 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 of these substances. Item 4. As described in any of items 1 to 3, the content of component (A) is from 1% to 50% by mass. Item 5. As described in any of items 1 to 4, the content of component (B) is from 0.0001% to 1% by mass. Item 6. If any of the external components described in items 1 to 5, the content of component (C) is 25% by mass or more. Item 7. As described in any of items 1 to 6, the external composition is such that, relative to the total content of component (A) is 1 part by mass, component (D) is 0.01 to 20 parts by mass. Item 8. The external composition described in any of items 1 to 7 further contains lower alcohols, butanediol, or combinations of these alcohols. [Invention Benefits]

[0009] The external composition of this invention can suppress time-dependent staining and has excellent stability. Implementation

[0010] In this instruction manual, the unit "mass%" and "g / 100g" have the same meaning.

[0011] The external composition of the present invention contains (A) ascorbic acid or a salt thereof, (B) one or more amino acids selected from the group consisting of primary or secondary amines, peptides having 10 or fewer amino acid residues, and salts of these substances, (C) one or more amino acids selected from the group consisting of 1,3-propanediol, 1,2-propanediol, ethoxyethylene glycol, and polyethylene glycol, and (D) water.

[0012] [(A) Ascorbic acid or its salt] In this invention, commercially available ascorbic acid can be used as an ingredient in pharmaceuticals, quasi-pharmaceuticals, or cosmetics as a topical skin agent. These generally refer to L-form ascorbic acid.

[0013] Salts of ascorbic acid may also be used. Here, "salts of ascorbic acid" refers to pharmaceutically permissible salts. There are no limitations; examples include salts with organic bases (e.g., salts of trimethylamine, triethylamine, monoethanolamine, triethanolamine, pyridine, etc., and salts of tertiary amines, basic ammonium salts such as arginine), and salts with inorganic bases (e.g., alkali metal salts such as ammonium, sodium, and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, aluminum salts, etc.). Sodium and potassium salts of ascorbic acid are particularly preferred. Specifically, examples include sodium ascorbate, magnesium ascorbate, and calcium ascorbate. Among these, sodium ascorbate is preferred as a salt of ascorbic acid.

[0014] As a component (A) of the present invention, one or more compounds selected from the group consisting of ascorbic acid and its salts may be used alone or in combination.

[0015] The total content of component (A) relative to the total amount of the topical composition of this invention can be appropriately set by balancing it with other components. The total content of component (A) relative to the total amount of the topical composition is not particularly limited, but from the viewpoint of imparting functions such as whitening, anti-inflammatory, anti-aging, and antioxidant properties, it 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 that the invention can be significantly effective relative to the total amount of the external components, the total content of component (A) 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 component (A) relative to the total amount of the topical composition is preferably 1% to 50% by mass, more preferably 3% to 40% by mass, and even more preferably 5% to 30% by mass.

[0016] [(B) Selected from one or more of the group consisting of amino acids that are primary or secondary amines, peptides with 10 or fewer amino acid residues, and salts of these substances] The amino acids used as primary or secondary amines, and peptides with 10 or fewer amino acid residues used in component (B) of this invention, all contain a primary amino group (-NH2), a secondary amino group (>NH), or both. In this invention, compounds selected from the group consisting of amino acids, peptides with 10 or fewer amino acid residues, and salts of these substances may be used alone or in combination of two or more.

[0017] The amino acid used in component (B) of this invention is not particularly limited as long as it is used as an ingredient in a topical skin preparation in the fields of pharmaceuticals, quasi-pharmaceuticals, or cosmetics. There is no particular limitation on the amino acid; examples include α-amino acids, β-amino acids, γ-amino acids, δ-amino acids, or salts of these substances, with α-amino acids or their salts being preferred.

[0018] The α-amino acid used as component (B) of this invention is not particularly limited, but is preferably L-form. Examples of α-amino acids include: glycine, serine, threonine, alanine, valine, leucine, isoleucine, aspartic acid, glutamine, cysteine, methionine, phenylalanine, tyrosine, tryptophan, citrulline, nifedipine, cystathionine, cysteine, S-adenosylcysteine, S-adenosylmethionine, ε-N-acetylsamine, proline, and 4-hydroxyproline. Neutral amino acids such as amino acids, N-methylglycine, N-acetyserine, and N-acetycysteine; basic amino acids and their salts such as arginine, lysine, histamine, ornithine, ω-N-methylarginine, ε-N,N,N-trimethyllysine, 5-hydroxylysine, and 3-methylhistamine; and acidic amino acids and their salts such as aspartic acid, glutamic acid, γ-carboxyglutamic acid, and O-phosphoserine. Of which, the α-amino acid used in component (B) of the present invention, from the viewpoint of solubility in water, is preferably selected from one or more of glycine, serine, threonine, alanine, valine, cysteine, methionine, citrulline, arginine, lysine, histidine, ornithine, aspartic acid, glutamic acid, proline, 4-hydroxyproline, N-methylglycine, N-acetylsermine, N-acetylscysteine, and salts of these substances; more preferably selected from glycine, serine, threonine, alanine, valine, ... Cysteine, methionine, arginine, lysine, histidine, 4-hydroxyproline, N-methylglycine, N-acetylserine, N-acetylcysteine, and salts thereof; more preferably, it is selected from glycine, serine, threonine, N-acetylcysteine, arginine, lysine, 4-hydroxyproline, N-acetylcysteine, and salts thereof; particularly preferably, it is selected from glycine, serine, arginine, N-acetylcysteine, and salts thereof.

[0019] A peptide is a polymer formed by the condensation of amino acids as monomers through amide bonds (peptide bonds). In the present invention, the peptide component (B) has 10 or fewer amino acid residues (monomer units). From the viewpoint of significantly maximizing the effects of the present invention, the number of amino acid residues is preferably 8 or fewer, more preferably 5 or fewer, and even more preferably 4 or fewer, and particularly preferably 2 or 3.

[0020] Such peptides can be known natural or synthetic peptides formulated in cosmetics and quasi-pharmaceuticals. The peptides used as component (B) of this invention are not particularly limited, but specifically include: dipeptides (such as dipeptide-4); tripeptides (such as glutathione and tripeptide-3); tetrapeptides (such as tetrapeptide-5); oligopeptides (such as oligopeptide-6 and decapeptide-2); legume protein hydrolysates (hydrolyzed soybean protein); silk protein hydrolysates; pearl protein hydrolysates; collagen hydrolysates (water-soluble collagen), low molecular weight collagen, collagen peptides, hydrolyzed collagen, hydrolyzed elastin, determinated collagen (atelocollagen), succinyl determinated collagen, and other collagen derivatives; peptides containing chemical modifications (acetylation, palmitylation, myristylation, nicotinic acidation, arbutinization, azelaication, biotinylation, etc.), or salts of these substances. The peptide that is component (B) is preferably one or more of the group consisting of glutathione, tetrapeptide-5 and salts of these substances, and more preferably glutathione or a salt thereof.

[0021] In the external composition of the present invention, the total content of component (B) relative to the total amount of the external 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. From the viewpoint of significantly exerting the effects of the present invention, the total content of component (B) is preferably 1% by mass or less, more preferably 0.8% by mass or less, and even more preferably 0.5% by mass or less, relative to the total amount of the external components. The total content of component (B) relative to the total amount of the external components of the present invention is preferably 0.0001% by mass to 1% by mass, more preferably 0.0005% by mass to 0.8% by mass, and even more preferably 0.001% by mass to 0.5% by mass.

[0022] [(C) Select one or more from the group consisting of 1,3-propanediol, 1,2-propanediol, ethoxyethylene glycol and polyethylene glycol] 1,3-Propanediol is a compound with CAS (Chemical Abstracts Service) number 504-63-2. 1,2-Propylene glycol is another name for 1,2-propanediol, a compound with CAS number 57-55-6. Ethoxyethylene glycol, also known as diethylene glycol monoethyl ether, is a compound with CAS number 111-90-0.

[0023] The polyethylene glycol (PEG) used in this invention preferably has a degree of polymerization of 4 or higher, and is commonly used as a base agent in pharmaceuticals, quasi-pharmaceuticals, and cosmetics. In this invention, polyethylene glycol with relatively low molecular weight is preferably used. There is no limitation, but specifically, polyethylene glycol with an average molecular weight of approximately 150 to 1000 is preferred, and more preferably, polyethylene glycol with an average molecular weight of approximately 170 to 800. Examples of such polyethylene glycols include: polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 500, polyethylene glycol 600, polyethylene glycol 700, polyethylene glycol 800, etc. Commercially available products are available for these, and therefore, these commercially available products can also be obtained and used. Specifically, examples of commercially available products include polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, and polyethylene glycol 600 sold by Nippon Oil Co., Ltd., and polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, and polyethylene glycol 600 sold by Sanyo Chemical Industries Co., Ltd.

[0024] Here, the average molecular weight can be determined, for example, by means of the average molecular weight test described in the section on polyethylene glycol in Japan's "Standard Specifications for Pharmaceutical Raw Materials 2006".

[0025] [Method for determining the average molecular weight of polyethylene glycol with an average molecular weight of 190 to 210] Accurately weigh approximately 0.8 g of polyethylene glycol and place it in a pressure-resistant co-stoppered bottle of approximately 200 mL. Add approximately 25 mL of pyridine, heat to dissolve, and allow to cool. Separately, measure 42 g of phthalic anhydride and add it to an accurately weighed 1 L light-proof co-stoppered bottle containing 300 mL of freshly distilled pyridine. Vigorously shake to mix and dissolve, then let stand for at least 16 hours. Accurately weigh 25 mL of this solution and add it to the pressure-resistant co-stoppered bottle, then seal it tightly, wrap it with a sturdy cloth, and place it in a water bath preheated to 98℃±2℃. Immerse the liquid in the bottle in the water bath. Heat at 98℃±2℃ for 30 minutes, then allow to cool to room temperature. Next, accurately add 50 mL of 0.5 mol / L sodium hydroxide solution and titrate the solution using this solution. The indicator used here is 5 drops of phenolphthalein-pyridine solution (1→100). The titration endpoint was set when the liquid turned a pale pink color for 15 seconds. A blank test was performed using the same method. Substitute the obtained value into the following formula to calculate the average molecular weight. Average molecular weight = [sample amount (g) × 4000] / (ab) a: The volume (mL) of 0.5 mol / L sodium hydroxide solution consumed in the blank test. b: The volume (mL) of 0.5 mol / L sodium hydroxide solution consumed in the test of the sample.

[0026] In addition, when the average molecular weight of polyethylene glycol is outside the range of 190 to 210, the weighing amount may be appropriately changed, but the weighing amount is based on the test method for polyethylene glycol with an average molecular weight of 190 to 210.

[0027] These polyethylene glycols can also be used in one type or in combination of two or more types.

[0028] From the viewpoint of significantly exerting the effects of the present invention, the total content of component (C) relative to the total amount of the external composition is preferably 25% by mass or more, more preferably 27% by mass or more, further preferably 28% by mass or more, and even more preferably 30% by mass or more. The total content of component (C) relative to the total amount of the external components can be appropriately adjusted by the content of component (A), preferably 75% by mass or less, more preferably 70% by mass or less, and even more preferably 65% ​​by mass or less. The total content of component (C) relative to the total amount of the external components of the present invention is preferably 25% to 75% by mass, more preferably 27% to 70% by mass, and even more preferably 28% to 65% by mass.

[0029] In the external composition of the present invention, the ratio of the total content of component (C) to component (A) is not particularly limited. It is more preferably 0.5 to 75 parts by mass relative to 1 part by mass of the total content of component (A), more preferably 0.75 to 50 parts by mass, and even more preferably 1 to 25 parts by mass.

[0030] [(D) Water] The topical composition of this invention is a liquid composition comprising water. The water content is not limited, but is preferably 0.1% by mass or more relative to the total amount of the topical composition, more preferably 1% by mass or more, and even more preferably exceeding 1% by mass (e.g., 3% by mass or more). The term "exceeding 1% by mass" is not limited; for example, it can be 1.01% by mass or more, or 1.1% by mass or more. By including such a small amount of water, a topical composition that inhibits the precipitation of ascorbic acid or its salts and exhibits excellent stability can be produced. In addition, the water content relative to the total amount of the external components is, for example, 50% by mass or less, preferably 40% by mass or less, and more preferably 35% by mass or less.

[0031] The total content of component (D) relative to the total amount of the external components of the present invention is preferably from 0.1% by mass to 50% by mass, more preferably from more than 1% by mass to 40% by mass, and even more preferably from 3% by mass to 35% by mass.

[0032] In the external composition of the present invention, the ratio of the content of component (D) to component (A) is not particularly limited, but the content of component (D) to component (A) 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, relative to 1 part by mass of the total content of component (A).

[0033] [pH] From the viewpoint of the stability of component (A), low irritation to the skin or mucous membranes, and good skin feel, the topical composition of the present invention is preferably in the acidic range of pH 1.5 to 4.5, and more preferably in the acidic range of pH 2 to 4.

[0034] [lower alcohols] In view of improving user experience, stability, and promoting transdermal absorption, the topical composition of this invention may contain lower alcohols in addition to components (A) to (D) as described above, provided it does not impair the effectiveness of the invention. The lower alcohols used in this invention are not particularly limited to those used as ingredients in topical skin preparations in the pharmaceutical, quasi-pharmaceutical, or cosmetic fields. When "lower alcohol" is mentioned in this specification, it refers to alcohols with 1 to 6 carbon atoms (C1-C6). C1-C3 alcohols are particularly preferred in the topical composition of this invention. Ethanol is particularly preferred; methanol, n-propanol, isopropanol, etc., may also be used.

[0035] In the external composition of the present invention, when lower alcohols are present, the total content of lower alcohols relative to the total amount of the external composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, further preferably 0.5% by mass or more, further 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, further preferably 40% by mass or less, and further preferably 35% by mass or less.

[0036] The total content of lower alcohols contained in the topical composition of the present invention relative to the total amount of the topical composition is preferably from 0.01% to 50% by mass, more preferably from 0.1% to 45% by mass, even more preferably from 0.5% to 40% by mass, even more preferably from 1% to 35% by mass, and particularly preferably from 3% to 35% by mass.

[0037] Butanediol In terms of improving user experience, stability and promoting transdermal absorption, the external composition of this invention may contain butylene glycol (also known as 1,3-butanediol or 1,3-butanediol) in addition to the components (A) to (D) above, as long as it does not impair the effect of this invention.

[0038] In the topical composition of the present invention, when butylene glycol is present, from the viewpoint of improving user experience, stability and promoting transdermal absorption, the content of butylene glycol relative to the total amount of the topical composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and even more preferably 0.3% by mass or more. The content of butanediol is preferably below 40% by mass, more preferably below 35% by mass, and even more preferably below 30% by mass.

[0039] The content of butanediol in the external composition of the present invention is preferably from 0.01% to 40% by mass, more preferably from 0.1% to 35% by mass, and even more preferably from 0.3% to 30% by mass.

[0040] pH adjuster In terms of improving user experience, stability and promoting transdermal absorption, the external composition of this invention may contain a pH adjuster in addition to components (A) to (D) above, as long as it does not impair the effect of this invention.

[0041] As a pH adjuster used in this invention, it can be a compound commonly used as an ingredient in topical skin preparations in the pharmaceutical, quasi-pharmaceutical, or cosmetic fields. There are no particular limitations, but examples include: pH adjusters containing amines (e.g., aminoethylsulfonic acid or its salts, monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, L-carnitine, low molecular weight betaine (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 metabisulfite, potassium metabisulfite, sodium phosphate, potassium nitrate, sodium borate, preferably sodium metabisulfite), 3-O-ethyl ascorbic acid or its salts, etc.

[0042] In the external composition of this invention, the total content of the pH adjuster relative to the total amount of the external 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 external composition is preferably 10% by mass or less, more preferably 5% by mass or less. The content of the pH adjuster containing an amine relative to the total amount of the external composition is preferably 0.01% by mass to 10% by mass, more preferably 0.05% by mass to 5% by mass.

[0043] In the external composition of this invention, the ratio of the pH adjuster content to component (A) is not particularly limited. The ratio is preferably 0.00001 to 20 parts by mass relative to 1 part by mass of the total content of component (A), more preferably 0.0001 to 20 parts by mass, further preferably 0.0005 to 10 parts by mass, further preferably 0.005 to 5 parts by mass, and even more preferably 0.01 to 1 part by mass.

[0044] [Other ingredients] In addition to components (A) to (D) mentioned above, the external composition of this invention aims to enhance or supplement the various effects of ascorbic acid. Furthermore, in order to add other useful effects, one or more of the following components may be formulated: whitening components, anti-inflammatory components, antibacterial components, cell activating components, astringent components, antioxidant components, acne-improving components, anti-aging components, collagen and other biological component synthesis promoting components, blood circulation promoting components, moisturizing components, etc.

[0045] In addition to components (A) to (D) mentioned above, the external formulations of this invention may also include surfactants, soluble components, oils, sugars, or transdermal absorption enhancers. In particular, by incorporating surfactants, soluble components, or oils, the stability, effectiveness, and user experience of ascorbic acid in aqueous solvents can be further improved.

[0046] In the external formulations of this invention, various ingredients commonly used as ingredients in topical preparations in the pharmaceutical, quasi-pharmaceutical, or cosmetic fields can be formulated as needed, within a range that does not impair appearance stability or viscosity, and does not affect the effectiveness of this invention. These include, for example, irritant reducers, thickeners, preservatives, UV protectants, colorants, dispersants, added pH adjusters, fragrances, etc. Furthermore, these ingredients can be formulated individually or in combination of two or more.

[0047] The external composition of this invention can be prepared into various desired forms, such as paste, mousse, gel, liquid, emulsion, cream, sheet (substrate-supported), aerosol, and spray, by mixing any of the above-mentioned components (A) to (D) as needed, and further by adding other solvents or base agents of commonly used external agents as needed, and adjusting the pH as needed. These can be manufactured using conventional methods in the industry.

[0048] From the viewpoint of significantly exerting the effects of the present invention, the external composition of the present invention is preferably a transparent or translucent composition that makes ascorbic acid and / or its salts soluble. Here, "soluble" is defined as follows: That is, it refers to the transmittance at a wavelength of 700 nm, for example, using a spectrophotometer or photophotometer UV-2450 (manufactured by Shimadzu Corporation) for ultraviolet-visible absorbance measurement, where the transmittance is within the range of 80% to 100%, preferably 85% to 100%, and even more preferably 90% to 100%. Here, the transmittance of water is set to 100%. More specifically, the transmittance measurement method is based on the method described in the 16th Revision of the Japanese Pharmacopoeia [B] General Test Method 2. Physical Test Method Spectroscopic Measurement Method 2.24 Ultraviolet-Visible Absorbance Measurement Method. Furthermore, the term "transparent or translucent" refers to an L value of 85 or higher, ideally 90 or higher, which is an indicator of transparency. The L value is a lightness parameter used in the CIELAB colorimetric system, and can be measured using spectrophotometers such as the CM-5 spectrophotometer (manufactured by Konica Minolta Corporation).

[0049] [Viscosity] The topical composition of the present invention can be prepared to have a suitable viscosity, particularly desirable for use in topical skin applications. The viscosity of the topical composition of the present invention is not particularly limited; for example, the viscosity measured using an E-type viscometer at 25°C is typically around 1 mPa·s to 300 mPa·s, preferably around 1 mPa·s to 200 mPa·s, more preferably around 1 mPa·s to 100 mPa·s, and even more preferably around 1 mPa·s to 50 mPa·s. More specifically, the viscosity measurement method is based on the method described in the 16th Revision of the Japanese Pharmacopoeia [B] General Test Method 2. Physical Test Method Other Physical Test Methods 2.53 Viscosity Measurement Method 2.2 Rotational Viscometer Method 2.1.3 Conical-Plate Type Rotational Viscometer (Conical-Plate Type Viscometer).

[0050] [use] The external components of this invention can be used in particular as whitening agents, anti-inflammatory agents, and anti-aging agents, for example, they can have the effects of acne prevention or treatment, and antioxidant effects. Furthermore, by applying it to the skin, it can improve skin transparency, maintain moisture, improve complexion, and inhibit roughness. Furthermore, it can have the effects of skin conditioning and moisturizing, making pores less noticeable. In addition, it can also be used for the prevention or treatment of insect larvae.

[0051] The external components of this invention can be formulated as basic cosmetics such as beauty serums, lotions, sunscreen creams, emulsions, creams, lotions, oils, and dressings; makeup cosmetics such as powder, lipstick, lip gloss, mascara, eyeshadow, eyeliner, eyebrow pencil, and nail polish; detergents such as washcloths, facial cleansers, and body washes; and various external components belonging to the fields of cosmetics, topical medicines, or quasi-topical pharmaceuticals, such as anti-underarm odor agents, athlete's foot treatment agents, antipruritic agents, wound healing agents, wipes, cleansers, anti-inflammatory and analgesic agents, acne treatment agents, hemorrhoid treatment agents, bactericides, disinfectants, whitening agents, and UV protection agents. Regarding its effects on the skin, this invention is preferably used in topical skin preparations (epidermal formulations) and other products applied to the skin.

[0052] The external components of this invention can be used once a day or several times a day, according to known or customary usage and dosage, depending on the intended use.

[0053] Regarding the above-described embodiments, the present invention further discloses the following components. [1] A topical composition comprising: (A) ascorbic acid or a salt thereof; (B) one or more amino acids selected from the group consisting of primary or secondary amines, peptides having 10 or fewer amino acid residues, and salts of these substances; (C) one or more amino acids selected from the group consisting of 1,3-propanediol, 1,2-propanediol, ethoxyethylene glycol, and polyethylene glycol; and (D) water. [2] As described in [1], component (B) is selected from one or more of the group consisting of α-amino acids that are primary or secondary amines, peptides with fewer than 10 amino acid residues, and salts of these substances. [3] As described in [1] or [2], wherein component (B) is selected from one or more of 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 of these substances. [4] The external composition described in any of [1] to [3] contains (A) in a quantity of 1% to 50% by mass. [5] The external composition described in any of [1] to [4] contains (B) in a quantity of 0.0001% to 1% by mass. [6] The external composition described in any of [1] to [5] contains (C) component at a content of 25% by mass or more. [7] As described in any of [1] to [6], the content of component (D) is from 0.1% to 50% by mass. [8] As described in any of [1] to [7], the external composition is such that, relative to the total content of component (A) is 1 part by mass, component (C) is 0.5 to 75 parts by mass. [9] As described in any of [1] to [8], the external composition is 0.01 to 20 parts by mass relative to the total content of component (A).

[10] External components as described in any of [1] to [9], wherein the pH is 1.5 to 4.5.

[11] The external composition described in any of [1] to

[10] further contains a lower alcohol, butanediol or a combination of these alcohols.

[12] As described in

[11] , the external composition contains 0.01% to 50% by mass of lower alcohols.

[13] External components as described in

[11] or

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

[14] The external composition described in any of [1] to

[13] further contains 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] As described in

[14] , the external composition contains the aforementioned pH adjuster in an amount of 0.01% to 10% by mass.

[16] As described in

[14] or

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

[17] The external composition described in any of [1] to

[16] is in the form of paste, mousse, gel, liquid, emulsion, cream, sheet, aerosol, or spray.

[18] As described in any of [1] to

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

[19] The external components described in any of [1] to

[18] have a viscosity of 1 mPa·s to 300 mPa·s when measured at 25°C.

[0054] Furthermore, regarding the above-described embodiments, the present invention further discloses the following method.

[20] A method for inhibiting time-dependent staining of a topical composition, comprising: (A) ascorbic acid or a salt thereof, (B) one or more amino acids selected from the group consisting of primary or secondary amines, peptides with 10 or fewer amino acid residues, and salts of these substances, and (D) water containing one or more amino acids selected from the group consisting of 1,3-propanediol, 1,2-propanediol, ethoxyethylene glycol, and polyethylene glycol. [Example]

[0055] Secondly, the present invention is specifically illustrated by means of embodiments, but the present invention is not limited to the following embodiments. Furthermore, the units of the component amounts in the table are by mass%.

[0056] [Ascorbic acid staining inhibition confirmation test] The embodiments and comparative examples of the present invention were evaluated to determine whether the topical composition exhibited color inhibition after storage at 50°C. Specifically, according to the formulations listed in various formulation sheets, ascorbic acid was added to a mixed solution of various components, and the solution was heated at 60°C and mixed for 10 minutes to dissolve it, thereby preparing the topical composition. The prepared topical composition was filled into a transparent glass bottle and kept at 50°C for 1 week under light protection.

[0057] Then, the colorimetric properties of each topical component were evaluated using a CM-5 spectrophotometer (manufactured by Konica Minolta, Inc.). Measurements using the spectrophotometer involved adding 1 mL of the test solution to a glass bath (CM-A97, 2 mm thick) and measuring the b-value in the CIELAB colorimetric system at 25°C. The measured values ​​were obtained using purified water as a blank sample. The change in color difference Δb before and after incubation at 50°C for one week was calculated using the following formula. (Change in color difference (Δb)) = (Measured value of the test solution after heat preservation (b value after heat preservation)) - (Measured value of the test solution before heat preservation (b value before heat preservation)) The b-value is used as an indicator of transparency. The smaller the Δb value, the less coloring. In addition, the Δb (ratio of Δb) of each sample when the control Δb is normalized to 1 is calculated as follows. (Δb ratio) = (Δb value of each sample) / (Δb value of the control) It can be seen that if the Δb ratio of the sample is below 0.75, less staining can be visually observed compared to the control. Therefore, in each table, the presence or absence of staining can be determined by whether the Δb ratio of the topical component relative to the comparative example used as the control is below 0.75.

[0058] [Experimental Example 1] As a formulation containing 25% by mass of ascorbic acid and 0.01% by mass of L-serine, the external formulations of the compositions shown in Table 1 were prepared according to conventional methods.

[0059] The results of the ascorbic acid staining inhibition confirmation test of the components 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 the control.

[0060] [Table 1] Ingredient Name Example 1-1 Example 1-2 Example 1-3 Example 1-4 Comparative example 1-1 Comparative example 1-2 ascorbic acid 25 25 25 25 25 25 L-Serine 0.01 0.01 0.01 0.01 0.01 0.01 Purified water 30 30 30 30 30 30 Trimethylglycine 5 5 5 5 5 5 1,3-Propanediol 39.99 1,2-Propanediol 39.99 ethoxyethylene glycol 39.99 PEG400 39.99 dipropylene glycol 39.99 ethanol 39.99 Total 100 100 100 100 100 100 The ratio of Δb 0.59 0.57 0.75 0.58 1.00 Unable to prepare (Formulas are expressed in parts by weight)

[0061] The Δb ratios of the components in the examples were all below 0.75. Therefore, even though ascorbic acid and L-serine were present, the coloring was significantly suppressed compared to Comparative Example 1-1 after heat treatment. In addition, in Comparative Example 1-2, ascorbic acid could not be prepared because it was not completely dissolved.

[0062] [Experimental Examples 2 to 8] External compositions of the embodiments and comparative examples prepared according to conventional methods, as shown in Tables 2 and 3.

[0063] The results of the ascorbic acid staining inhibition confirmation test of the components of the Examples and Comparative Examples are shown in Tables 2 and 3. The Δb ratios in the tables represent the Δb ratios relative to Examples 2-1 to 2-3 when Comparative Example 2 is the control, the Δb ratios relative to Examples 3-1 to 3-3 when Comparative Example 3 is the control, the Δb ratios relative to Examples 4-1 to 4-3 when Comparative Example 4 is the control, the Δb ratios relative to Example 5 when Comparative Example 5 is the control, the Δb ratios relative to Examples 6-1 to 6-2 when Comparative Example 6 is the control, the Δb ratios relative to Examples 7-1 to 7-4 when Comparative Example 7 is the control, and the Δb ratios relative to Example 8 when Comparative Example 8 is the control.

[0064] [Table 2] Ingredient Name Experimental Example 2 Experimental Example 3 Test Example 4 Experimental Example 5 Example 2-1 Example 2-2 Example 2-3 Comparative example 2 Example 3-1 Example 3-2 Example 3-3 Comparative example 3 Example 4-1 Example 4-2 Example 4-3 Comparative example 4 Example 5 Comparative example 5 ascorbic acid 20 20 20 20 5 5 5 5 10 10 10 10 10 10 L-Serine 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 L-arginine 0.1 0.1 0.1 0.1 Glycine 0.001 0.001 Purified water 25 25 25 25 20 20 20 20 20 20 20 20 20 20 Trimethylglycine 3.5 3.5 3.5 3.5 1,3-Propanediol 51.49 74.99 69.9 69.999 1,2-Propanediol 74.99 ethoxyethylene glycol 51.49 74.99 69.9 PEG400 51.49 69.9 dipropylene glycol 51.49 74.99 69.9 69.999 Total 100 100 100 100 100 100 100 100 100 100 100 100 100 100 The ratio of Δb 0.50 0.54 0.47 1.00 0.45 0.42 0.45 1.00 0.32 0.39 0.45 1.00 0.56 1.00

[0065] [Table 3] Ingredient Name Experimental Example 6 Experimental Example 7 Example 6-1 Example 6-2 Comparative example 6 Example 7-1 Example 7-2 Example 7-3 Example 7-4 Comparative example 7 ascorbic acid 10 10 10 10 10 10 10 10 N-acetyl-L-cysteine 0.1 0.1 0.1 Glutathione 0.1 0.1 0.1 0.1 0.1 Purified water 20 20 20 20 20 20 20 20 1,3-Propanediol 69.9 69.9 1,2-Propanediol 69.9 69.9 ethoxyethylene glycol 69.9 PEG400 69.9 dipropylene glycol 69.9 69.9 Total 100 100 100 100 100 100 100 100 The ratio of Δb 0.39 0.47 1.00 0.56 0.62 0.58 0.55 1.00 (Formulas are expressed in parts by weight)

[0066] [Table 4] Ingredient Name Experimental Example 8 Example 8 Comparative Example 8 ascorbic acid 10 10 Tetrapeptide-5 0.001 0.001 Purified water 19.999 19.999 1,3-Propanediol 70 dipropylene glycol 70 Total 100 100 The ratio of Δb 0.22 1.00 (Formulas are expressed in parts by weight)

[0067] The Δb ratios of Examples 2-1 to 2-3 and Examples 3-1 to 3-3 were all below 0.75, thus demonstrating that even under conditions of low ascorbic acid concentration, coloring was significantly inhibited compared to the comparative examples. Furthermore, in cases where L-arginine, glycine, N-acetyl-L-cysteine, glutathione, or tetrapeptide-5 (β-Ala-His-Ser-His) was used instead of L-serine, as in Examples 4-1 to 4-3, 5, 6-1 to 6-2, 7-1 to 7-4, and 8, coloring was significantly inhibited compared to the comparative examples even after heat treatment.

[0068] [Formulation Example] Based on Formulation Examples 1 to 28 in Tables 5 and 6 below, the external application composition (cosmetic serum) of the present invention was prepared. The amounts in Tables 5 and 6 are expressed as mass %

[0069] [Table 5] Ingredient Name Formula Example 1 Formula Example 2 Formula Example 3 formula example 4 formula example 5 Formula Example 6 Formula Example 7 Formula Example 8 Formula Example 9 Formula Example 10 Formula Example 11 formula example 12 Formula Example 13 Formula Example 14 Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing quantity (%) Mixing quantity (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing quantity (%) Mixing amount (%) Mixing amount (%) ascorbic acid 30 30 30 25 25 25 25 25 20 20 20 20 20 20 1,2-Propanediol 1.949 5.03 16.07 10.23 5.13 38.2299 21.038 ethoxyethylene glycol 35.279 30 7.03 33 10 5 PEG400 30 43.7299 10 50 0.74 10 5 1,3-Propanediol 30 35.2399 40.14 20 45 4 28.13 20 1,3-Butanediol 0.5 2 11 10 dipropylene glycol 3 1 5 1 8 5 2 concentrated glycerin 3 4 0.5 Anhydrous ethanol 2 4 4 3 3 10 3 12 5 Glutathione 0.001 0.01 0.2 L-Serine 0.001 0.1 0.0001 0.001 L-arginine 0.2 0.2 0.05 Glycine 0.0001 0.5 0.001 N-acetylcysteine 0.0001 0.05 Purified water 35 30 30 35 18 20 20 25 18 15 30 28 25 20 Polyoxyethylene hydrogenated castor oil 40 0.2 Polyoxyethylene (20) Polyoxypropylene (4) Cetyl ether 0.2 0.2 0.4 0.2 0.2 0.4 0.2 0.2 0.4 Polyoxyethylene polyoxypropylene decyl Tetradecyl ether 0.2 0.2 0.2 0.5 2-Methacryloxyethylphosphocholine-butyl methacrylate copolymer solution (BG) 0.1 1 0.1 Jojoba oil 0.1 0.05 0.05 d-δ-tocopherol 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 dl-α-tocopherol acetate 0.1 0.1 Grapefruit extract 0.5 0.5 0.1 0.1 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Lemon extract 0.1 0.5 0.5 0.1 0.1 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Kiwi extract 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 spices 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Dipotassium glycyrrhizate 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Hydrolyzed hyaluronic acid 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 Sodium hyaluronate 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 Total 100 100 100 100 100 100 100 100 100 100 100 100 100 100

[0070] [Table 6] Ingredient Name formula Example 15 formula Example 16 Formula Example 17 Formula Example 18 Formula Example 19 Formula Example 20 Formula Example 21 formula Example 22 Formula Example 23 Formula Example 24 Formula Example 25 Formula Example 26 Formula Example 27 Formula Example 28 Mixing quantity (%) Mixing quantity (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing quantity (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) Mixing amount (%) ascorbic acid 20 15 15 15 15 15 10 10 10 10 5 3 3 3 1,2-Propanediol 2 28.679 8.629 24.63 25.179 0.28 8.323 ethoxyethylene glycol 50.129 10 45 10 30 30 52 30 3.23 55 PEG400 10 8.23 58.53 2.724 10 9.73 3.439 2.12 1,3-Propanediol 15 50 30 5 55 60 30 55 1,3-Butanediol 8 5 5 5 8 10 11 10 10 dipropylene glycol 3 2 2 15 4 5 5 5 concentrated glycerin 2 0.5 2.5 2.5 Anhydrous ethanol 5 5 2 10 5 10 15 8 8 10 10 10 10 Glutathione 0.001 0.1 0.2 0.001 0.1 0.05 0.05 0.001 L-Serine 0.001 0.001 0.001 0.7 L-arginine 0.001 0.3 0.1 0.001 0.1 Glycine 0.05 0.005 0.05 0.4 0.3 0.005 N-acetylcysteine 0.05 0.4 0.2 0.2 purified water 18 12 18 20 18 15 10 8 19 12 10 1 10 10 Polyoxyethylene hydrogenated castor oil 40 0.2 0.2 0.2 0.2 0.2 Polyoxyethylene (20) Polyoxypropylene (4) Cetyl ether 0.2 0.2 0.3 0.2 0.2 0.4 0.2 Polyoxyethylene polyoxypropylene Decyltetradecyl ether 0.2 0.2 0.2 0.2 0.2 0.2 0.2 2-Methylpropenyloxyethyl Phosphocholine-methacrylic acid Butyl ester copolymer liquid (BG) 0.05 0.3 1 Jojoba oil 0.2 0.1 d-δ-tocopherol 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 dl-α-tocopherol acetate 0.1 0.1 0.1 Grapefruit extract 0.5 0.1 0.5 0.5 0.1 0.5 0.5 0.5 0.1 0.1 0.1 Lemon extract 0.5 0.1 0.5 0.5 0.1 0.5 0.5 0.5 0.5 0.1 0.5 0.1 0.01 Kiwi fruit extract 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 spices 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Dipotassium glycyrrhizate 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Hydrolyzed hyaluronic acid 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 Sodium hyaluronate 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 Total 100 100 100 100 100 100 100 100 100 100 100 100 100 100

Claims

1. A topical composition comprising: (A) ascorbic acid or a salt thereof; (B) one or more amino acids selected from the group consisting of primary or secondary amines, peptides having 10 or fewer amino acid residues, and salts of the aforementioned substances; (C) one or more amino acids selected from the group consisting of 1,3-propanediol, 1,2-propanediol, ethoxyethylene glycol, and polyethylene glycol; and (D) water; wherein the content of component (A) is 1% to 50% by mass; the content of component (B) is 0.0001% to 1% by mass; the content of component (D) is 0.1% to 50% by mass; and component (C) is 0.5 to 75 parts by mass relative to 1 part by mass of the total content of component (A); and component (D) is 0.01 to 20 parts by mass relative to 1 part by mass of the total content of component (A); but the aforementioned topical composition does not include: The detergent is composed of 0.5% by weight polyethylene glycol 1500, 5% by weight 1,3-butanediol, 8% by weight glycerin, 0.4% by weight maltose, 0.002% by weight hydroxyproline, 0.002% by weight serine, 0.002% by weight glycine, 0.1% by weight polymethyl methacrylate glucoyl ethyl ester, 0.3% by weight polyoxyethylene (60) hydrogenated castor oil, 0.5% by weight starch-sodium polyacrylate graft polymer, 0.2% by weight polyoxypropylene (23) polyoxyethylene (34) stearic acid, 0.3% by weight 4-isobutylresorcinol, 1% by weight sodium ascorbate, 1% by weight tranexamic acid, and 0.5% by weight sodium oxalate. Composed of 0.1% by mass of glutathione and water; and an emulsion comprising 0.2% by mass of acrylic acid-methacrylate copolymer, 0.2% by mass of carboxyethylene polymer, 5% by mass of 1,3-butanediol, 2% by mass of 1,2-hexanediol, 2% by mass of polyethylene glycol 6000, 0.3% by mass of 4-isobutylresorcinol, 1% by mass of sodium ascorbate, 1% by mass of tranexamic acid, and 0.5% by mass of sodium oxalate. It consists of 0.1% by weight of glutathione, 0.3% by weight of potassium hydroxide, 1.5% by weight of squalene, 0.5% by weight of glyceryl monostearate, 0.1% by weight of sucrose monolaurate, 5% by weight of petrolatum, and water.

2. The external composition as described in claim 1, wherein component (B) is selected from one or more of the group consisting of α-amino acids as primary or secondary amines, peptides with 10 or fewer amino acid residues, and salts of the aforementioned substances.

3. An external composition as described in claim 1 or 2, wherein component (B) is selected from one or more of 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 of the foregoing substances.

4. An external composition as described in claim 1 or 2, wherein the content of component (C) is 25% by mass or more.

5. An external composition as described in claim 1 or 2, which further comprises a lower alcohol, butanediol, or a combination of the aforementioned alcohols.