JP2024060463A - Composition for topical application to the skin - Google Patents

Abstract

[Problem] To provide a composition for external use on the skin, preferably a moisturizer, containing a heparinoid, which has a higher skin moisturizing effect than conventional compositions while preferably causing less irritation to sensitive skin. [Solution] To provide a composition for external use on the skin containing a heparinoid, an extract of a plant of the genus Artemisia or peach, and a liquid carrier. The content of the extract is preferably in the range of 0.0001% by mass to 1% by mass of the composition for external use on the skin. In addition, the content of the heparinoid is preferably in the range of 0.005% by mass to 5% by mass of the composition for external use on the skin. [Selected Figures] None

Description

The present invention relates to a composition for topical use on the skin and a method for enhancing moisturizing effect.

It is known that when a composition containing a heparinoid is applied to the skin as a topical preparation, it provides skin moisturizing effects, anti-inflammatory effects, and blood circulation promoting effects (Non-Patent Document 1). For this reason, several topical compositions containing heparinoids have been proposed. For example, Patent Document 1 describes a topical composition containing a heparinoid and an amino acid component, and Patent Document 2 describes a topical skin preparation containing a heparinoid, tocopherol, an anti-inflammatory agent, and an antipruritic agent.

Also known are skin external preparations containing plant extracts: for example, a cosmetic containing cucumber juice and carrot extract, peach leaf extract, chamomile flower extract, or beech bud extract (Patent Document 3); a cosmetic containing peach extract and having a protein glycation inhibitory effect (Patent Document 4); a moisturizer containing an extract of immature peach fruit (Patent Document 5); a skin external preparation containing an extract of a plant of the genus Artemisia and midkine, retinoid, estrogen, or vitamin D1 (Patent Document 6); a cosmetic composition containing a plant extract of a plant of the Asteraceae family and having an ultraviolet protection effect (Patent Document 7); and a cosmetic containing a genus herb extract, Japanese pepper extract, peony extract, artemisia extract, lemon balm extract, or rosehip extract and having a kinesin inhibitory effect (Patent Document 8).

Peach leaves are sometimes used as bath additives and are said to be effective against heat rash, eczema, rashes, and rough skin; mugwort leaves are said to have an antipruritic effect and are used for dialysis patients and those with atopic dermatitis (Non-Patent Document 2). It is also known that mugwort leaf extracts contain 1,8-cineol, α-thujone, β-thujone, and the like (Non-Patent Documents 2 and 3). It has also been reported that peach leaf extracts contain tannins, amino acids, flavonoids, phenols, nitrile glycosides, chlorogenic acid, and the like (Non-Patent Documents 2 and 4).

JP 2021-59524 A JP 2016-196419 A JP 2006-219431 A JP 2016-124827 A JP 2015-151390 A Japanese Patent Application Laid-Open No. 10-251133 JP 2002-128630 A JP 2013-166712 A

Product name: Hillmild Package insert URL: https://www.info.pmda.go.jp/downfiles/otc/PDF/J2001000156_02_A.pdf 2nd Edition Color Edition Chinese Medicine Encyclopedia - Raw Medicines, Herbs, and Folk Medicines (Ishiyaku Publishing Co., Ltd.) Traditional medicine and pharmacognosy (Nankodo) Research J. Pharm. and Tech. 12(7): July 2019, Study of Biologically Active Compounds in Prunus persica Leaves Extract

As mentioned above, conventional skin topical compositions containing heparinoids have moisturizing, anti-inflammatory and blood circulation promoting effects, but these topical compositions are sometimes required to have even stronger effects, particularly a stronger moisturizing effect. In addition, extracts of peaches and Artemisia plants are known to have therapeutic effects against skin diseases, but it was not clear whether they had moisturizing effects as topical skin preparations, and in particular whether they showed immediate moisturizing effects.

The inventor first confirmed that extracts of peaches and Artemisia plants have a moisturizing effect as an external preparation for the skin, and in particular, that they exhibit an immediate moisturizing effect within one hour of application to the skin. Furthermore, the inventor discovered that by combining a heparinoid with an extract of peaches and Artemisia plants, the moisturizing effect of the heparinoid is synergistically enhanced, and that this synergistic effect is immediate. Based on this finding, the present invention provides an external composition for the skin that contains a heparinoid and has a high moisturizing effect on the skin, and is preferably less irritating to sensitive skin.

That is, the present invention relates to the following composition for external use on the skin.
[1] A composition for external application to the skin, comprising a heparinoid, an extract of a plant of the genus Artemisia or a peach, and a liquid carrier.
[2] The topical skin composition described in [1], wherein the extract is contained in an amount of 0.0001% by mass to 1% by mass as an active ingredient in the topical skin composition.
[3] The composition for topical skin application described in [1] or [2], wherein the content of the heparinoid is 0.005% by mass to 5% by mass relative to the composition for topical skin application.
[4] The composition for external use on the skin according to any one of [1] to [3], which is a moisturizer.

Furthermore, the present invention relates to a method for enhancing the moisturizing effect described below.
[5] A method for enhancing the moisturizing effect of a topical skin composition containing a heparinoid, comprising blending an extract of an Artemisia plant or peach into the topical skin composition.

When applied to the skin, the topical skin composition of the present invention can enhance the skin's moisturizing properties more than conventional compositions containing heparinoids.

1. Skin topical composition
The skin topical preparation of the present invention contains 1) a heparinoid, 2) an extract of a plant of the genus Artemisia or peach, and 3) a liquid carrier, and may further contain other compounded ingredients.

[1-1. Heparinoids]
The heparinoid is a polysulfurized ester of mucopolysaccharide. Mucopolysaccharide is a complex polysaccharide containing amino sugar widely distributed in animal tissues and body fluids, such as chondroitin sulfate. The heparinoid may be obtained by polysulfating mucopolysaccharide, or may be obtained by extraction from tissues of edible animals (e.g., bovine lungs containing tracheal cartilage). The heparinoid contained in the skin topical composition of the present invention may be a heparinoid listed in the Japanese Pharmacopoeia Non-Drug Standards.

The topical skin composition of the present invention contains a heparinoid in an amount of 0.005% by mass or more, preferably 0.01% by mass or more, more preferably 0.05% by mass or more, and even more preferably 0.1% by mass or more, based on the composition. The topical skin composition of the present invention contains a heparinoid in an amount of 5% by mass or less, preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably 0.5% by mass or less, based on the composition. The topical skin composition of the present invention contains a heparinoid in an amount of, for example, 0.1% by mass or 0.3% by mass. The content of the heparinoid can be appropriately set so that the topical skin composition has an appropriate moisturizing effect.

[1-2. Extracts of Artemisia or Peach]
The skin external composition of the present invention contains the extract of Artemisia or peach. These extracts exert moisturizing effect in the skin external composition of the present invention, and can enhance the moisturizing effect of the skin external composition by synergistic action with heparinoid. In particular, it is shown in the examples below that the extract of Artemisia or peach enhances the immediate moisturizing effect of heparinoid.

[1-2-1. Extracts from Artemisia plants]
The Artemisia plant in the Artemisia plant extract may be any plant of the Artemisia genus in the Asteraceae family. Examples of Artemisia genus plants include Artemisia princeps Pampanini (Artemisia vulgaris L. var. indica Maxim.), Artemisia vulgaris L. var. vulgatissima Bess., Artemisia montana Pampanini, Artemisia mongolia Fischer, Artemisia feddei, Artemisia japonica Thunb., Artemisia stelleriana Bess., Artemisia keiskeana Miq., Artemisia lavandulaefolia DC., Artemisia sinanensis Yabe, Artemisia norvegica Fries., Artemisia arctica Less., and Artemisia mongolia. (Artemisia schmidtiana Maxim.), Artemisia apiacea Hance, Artemisia annua L., Artemisia fukudo Makino, Artemisia capillaris Thunb., Artemisia absinthium, Artemisia iwayomogi, Artemisia japonica f. resedifolia, Artemisia kitadakensis, Artemisia koidzumii, Artemisia cina, Artemisia lactiflora, Artemisia maritima (A. monogyna), Artemisia monophylla, Artemisia scoparia), Artemisia pedunculosa, Artemisia stolonifera, Artemisia abrotanum, Artemisia anomala, Artemisia arborescens, Artemisia argyi, Artemisia caucasica (=Artemisia assoana=Artemisia lanata=Artemisia pedemontana), Artemisia dracunculus, Artemisia eriopoda, Artemisia finita, Artemisia frigida, Artemisia gmelinii, Artemisia halodendron, Artemisia hedinii, Artemisia incana, Artemisia integrifolia, Artemisia lagocephala, Artemisia ludoviciana, Artemisia pallens, Artemisia parviflora, Artemisia pontica, Artemisia sacrorum, Artemisia sacrorum, Artemisia selengensis, Artemisia Artemisia sieversiana, Artemisia subdigitata, Artemisia tangutica, Artemisia tilesii, Artemisia tomentosa, Artemisia vulgaris, etc. The Artemisia plant is preferably Artemisia oryzae, Artemisia moniliforme, Artemisia moniliforme, or Artemisia umbellata. The Artemisia plant in the Artemisia plant extract is one of these plants or a combination of two or more of them.

The extract of Artemisia genus plants can be obtained by extracting Artemisia genus plants; each part of Artemisia genus plants, such as flowers, stems, leaves, roots, and the whole plant can be extracted, and it is preferable to extract Artemisia genus plants by extracting leaves. Artemisia genus plants may be subjected to the extraction procedure in their raw form, but considering the extraction efficiency, it is preferable to perform the extraction after processing such as chopping, drying, and crushing.

Extraction of Artemisia plants can be performed using an extraction solvent; examples of the extraction solvent include water, lower alcohols such as methanol, ethanol, propanol, and isopropanol, polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol, and glycerin, ethers such as ethyl ether and propyl ether, esters such as ethyl acetate and butyl acetate, and polar organic solvents such as ketones such as acetone and ethyl methyl ketone; the extraction solvent is preferably water, ethanol, propylene glycol, or 1,3-butylene glycol, and one or more of the extraction solvents may be used in combination. In addition, phosphate buffer or physiological saline may be used in consideration of the incorporation into external skin preparations. The appropriate extraction temperature is about 5 to 50°C.

The extract of Artemisia plants extracted with an extraction solvent may be blended directly into the skin topical composition of the present invention; however, the extract with the extraction solvent may be blended into the skin topical composition of the present invention after 1) concentration, drying, and then redissolving in water or a polar solvent, 2) purification such as bleaching, deodorization, and desalting, or 3) water layer component obtained by steam distillation. For storage, the extract with the extraction solvent may be freeze-dried after purification, and then dissolved in a solvent when used.

The extract of Artemisia plants is not particularly limited, but preferably contains active ingredients such as terpenoids (such as sionale), monoterpenes (Thujopsis niger), and phenylpropanoids (chlorogenic acid) (see Non-Patent Documents 2 and 3).

The content of the extract of Artemisia plant in the topical skin preparation is preferably 0.0001% by mass or more, more preferably 0.0005% by mass or more, as the content of the active ingredient (extract (i.e., not including the solvent)) of the extract of Artemisia plant; and preferably 1% by mass or less, more preferably 0.5% by mass or less. The content of the active ingredient of the extract of Artemisia plant may be a concentration that can impart a moisturizing effect to the topical skin preparation of the present invention, and is preferably a concentration that can enhance the moisturizing effect through a synergistic effect with the heparinoid.

Extracts of plants of the genus Artemisia may be commercially available. For example, extracts of leaves of Artemisia princeps include Waism (registered trademark) Gaiyo (Maruzen Pharmaceuticals), Artemisia Liquid (Ichimaru Falcos), Artemisia Extract-ET(J), Artemisia Extract-BG(K), Artemisia Extract-BG(J) (all Yamada Yaken), Gaiyo Extract BG (Maruzen Pharmaceuticals), Gaiyo Extract BG-50 (Koei Kogyo), NEWAPLE (HYUNDAI BIOLAND), AOF Artemisia Extract-HBG (Yamada Yaken), etc.; and Artemisia water includes Artemisia Water K (Koei Kogyo), Artemisia Water K/EPH (Koei Kogyo), etc.

[1-2-2. Peach extract]
The peach in the peach extract may be any peach (Prunus persica) belonging to the Rosaceae family, including Hakuho, Hakuto, and Ogonto peaches. The peach extract can be obtained by extracting peach leaves, fruit, stone (endocarp), flowers, whole plant, etc.; preferably, peach leaves, fruit, stone (endocarp), more preferably peach leaves. The peach extract in the present invention may also be a "concentrate" of fruit juice obtained by squeezing peach fruits.

The peaches to be extracted are washed with water to remove foreign matter if necessary, and then either left as is or dried, and then chopped or crushed as necessary, and then contacted with an extraction solvent for extraction. Extraction of peaches can be performed using an extraction solvent (such as the immersion method), or using supercritical extraction or steam distillation. Examples of extraction solvents for extracting peaches include water; lower alcohols such as methanol, ethanol, and propanol; polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and glycerin; esters such as ethyl acetate, butyl acetate, and methyl propionate; ketones such as acetone and methyl ethyl ketone; ethers such as ethyl ether and isopropyl ether; and hydrocarbon solvents such as n-hexane, toluene, and chloroform. The extraction solvent is preferably water, ethanol, propylene glycol, 1,3-butylene glycol, absolute ethanol, or the like. The extraction solvent is a single solvent or a mixture of two or more solvents.

The extract of peach leaves is not particularly limited, but preferably contains tannins, amino acids, flavonoids, phenols, nitrile glycosides, etc. as active ingredients. The extract of peach fruit is not particularly limited, but preferably contains organic acids, vitamins, pectin, etc. as active ingredients (see Non-Patent Documents 2 and 4). The extract of peach seeds is not particularly limited, but preferably contains peach kernel extract.

The content of peach extract in the topical skin preparation is, for example, preferably 0.0001% by mass or more, expressed as the content of the active ingredient (extract (i.e., not including the solvent)) of the peach extract; on the other hand, it is preferably 1% by mass or less, more preferably 0.1% by mass or less, and even more preferably 0.05% by mass or less. The content of the active ingredient of the peach extract may be at a concentration that can impart a moisturizing effect to the topical skin preparation of the present invention, and is preferably at a concentration that can enhance the moisturizing effect through a synergistic effect with the heparinoid.

Peach extracts available on the market may be used. For example, peach leaf extracts include Yamanashi Peach Leaf Extract BG30 (Maruzen Pharmaceuticals), Peach Hydroglycerin Extract (Berkem), Peach Leaf Liquid B (Ichimaru Falcos), Peach Leaf Extract-BG, Peach Leaf Extract-ET (Yamada Yaken), Peach Leaf Extract (3), Peach Leaf Extract BG-100, Oil-Soluble Peach Leaf Extract, Mixed Plant Extract (33) (Koei Kogyo), etc.; peach juices include Baby Peach Extract, Baby Fruit Mix (Katakura Coop Agri), Hormo Fruit Peach, Hormo Fruit Peach/N (Koei Kogyo), Mixed Fruit Extract (1), Mixed Fruit Extract P (Koei Kogyo), etc.

[1-3. Liquid carrier]
The skin topical composition of the present invention can contain a suitable liquid carrier depending on the properties of the composition. For example, if the skin topical composition of the present invention is an aqueous solution (e.g., lotion or serum) or gel, the main carrier can be water, if it is an emulsion, the main carrier can be water and oil (e.g., petrolatum, etc.), and if it is an ointment or oily cream, the main carrier can be oil.

The topical skin composition of the present invention may contain a polyhydric alcohol such as glycerin, propylene glycol, or 1,3-butylene glycol as a liquid carrier. Furthermore, the topical skin composition of the present invention may contain a lower alcohol such as ethanol or propanol as a liquid carrier. However, when it is desired to reduce skin irritation when the topical skin composition of the present invention is applied to sensitive skin, it is preferable that the topical skin composition does not contain or substantially does not contain a lower alcohol, particularly ethanol.

[1-4. Other ingredients]
In addition to the heparinoid, the extract of a plant of the genus Artemisia or peach, and the liquid carrier, the topical skin composition of the present invention may contain other compounding ingredients depending on the effect desired for the topical skin composition or the desired dosage form of the preparation.

The skin topical composition of the present invention may contain other active ingredients, such as anti-aging agents, anti-inflammatory agents, acne care agents, antihistamines, etc. Examples of anti-aging agents include niacinamide (also called nicotinamide), arbutin, tranexamic acid, vitamins (e.g., tocopherol derivatives, vitamin C derivatives, retinol palmitate, etc.), ellagic acid, linoleic acid, etc.; examples of anti-inflammatory agents include allantoin, glycyrrhizic acid or its salts (e.g., dipotassium glycyrrhizinate), ε-aminocaproic acid, etc.; examples of acne care agents include isopropylmethylphenol, salicylic acid, etc.; examples of antihistamines include diphenhydramine or its salts, etc.

The topical skin composition of the present invention may further contain a moisturizing agent. The above-mentioned extract of a plant of the genus Artemisia or peach can also function as a moisturizing agent; however, other moisturizing agents may also be included, such as 1) ceramide or a ceramide-like component, 2) phospholipid polymer, 3) plant extract (other than peach extract and extract of a plant of the genus Artemisia), 4) amino acid moisturizing agent, 5) squalane, 6) polyhydric alcohol, 7) isomerized sugar, or 8) protein hydrolyzate. The amount of these to be added can be set according to the moisturizing effect required for the topical skin composition.

1) Ceramide is a type of sphingolipid, a compound in which a fatty acid is amide-bonded to a sphingoid. The ceramide-like component may be a sugar ceramide such as glucosylceramide or galactosylceramide, or a synthetic ceramide such as SOFCARE (registered trademark) ceramide SL-E (Kao Corporation, N-(hexadecyloxyhydroxypropyl)-N-(hydroxyethylhexadecanamide)) or CERACUTE (registered trademark)-L (NOF Corporation, glyceryl-N-(2-methacryloyloxyethyl)carbamate-stearyl methacrylate copolymer). The content of ceramide and/or ceramide-like component in the topical skin composition of the present invention may be set according to the purpose, and is not particularly limited.

2) Phospholipid polymers are methacryloyloxyethyl phosphorylcholine polymers, which are biocompatible polymers similar to phospholipids, the main components of biological membranes. Examples of phospholipid polymers include Lipidure (registered trademark) (NOF Corporation, 2-methacryloyloxyethyl phosphorylcholine-butyl methacrylate copolymer), NIKKOL (registered trademark), and Resinol S-10 (Nikko Chemicals Co., Ltd., hydrogenated soybean phospholipid). The content of the phospholipid polymer in the topical skin composition of the present invention may be set according to the purpose and is not particularly limited.

3) Plant extracts include amacha extract, althea root extract, arnica flower extract, aloe extract, aloe vera extract, ginkgo extract, fennel extract, uva ursi extract, pea extract, Scutellaria root extract, Dutch mustard extract, orange extract, pueraria root extract, chamomile extract, oat extract, carrot extract, artemisia capillaris extract, raspberry extract, aloe arborescens extract, cucumber extract, quince seed extract, cumin extract, clematis extract, and gentian extract. Ana extract, Geranium extract, Burdock extract, Wheat germ extract, Condorus crispus extract, Meadowsweet extract, Peony root extract, Ophiopogon root extract, Honeysuckle flower extract, Spirulina maxima extract, Hypericum perforatum extract, Valeriana officinalis root extract, Hedera helix extract, Elderberry extract, Juniper extract, Achillea millefolium extract, Mentha piperita extract, Sage extract, Thyme extract, Thymus vulgaris extract, These include: goat leaf extract, centella extract, terminalia extract, capsicum fruit extract, calendula extract, tomato extract, tormentilla extract, garlic extract, wild rose extract, burdock extract, burdock root extract, parsley extract, witch hazel extract, rose extract, parietaria extract, bitter orange peel extract, hibamata extract, bilberry extract, poria columbine extract, butcher's broom extract, grape extract, tilia cordata flower extract, placenta extract, prune extract, hayflower extract, safflower extract, hop extract, mulberry root bark extract, milk thistle extract, horse chestnut extract, melissa extract, melilot extract, mugwort extract, peach extract, cornflower extract, mountain mugwort extract, eucalyptus extract, lily extract, European white birch extract, mugwort extract, lavender extract, laminaria digitata extract, apple extract, lettuce extract, lemon extract, rosemary extract, and Roman chamomile extract. The skin topical composition of the present invention may contain any plant extract, and suitable examples include aloe extract and Centella asiatica extract. Aloe extract is an extract from the leaf pulp of aloe (Cape aloe, Aloe vera, Aloe aloe, etc.), a medicinal plant of the lily family. Aloe extract is said to contain uronic acid, lipids, proteins, amino acids, and anthraquinone compounds (aloin, aloe emodin, etc.). The content of aloe extract in the skin topical composition of the present invention may be set according to the purpose, and is not particularly limited.

4) An amino acid moisturizer is a moisturizer derived from an amino acid such as glutamic acid. Examples of amino acid moisturizers include pyrrolidone carboxylic acid or its salts (e.g., sodium salt), pyrrolidine carboxylic acid or its salts, acyl pyrrolidine carboxylic acid or its salts, and acyl basic amino acid alkyl esters or its salts. The amino acid in the amino acid moisturizer may be racemic or optically active. Amino acid moisturizers are available on the market as AJIDEW (registered trademark) (Ajinomoto Co., Inc.), PRODEW (registered trademark) (Ajinomoto Co., Inc.), Aquadew (registered trademark) (Ajinomoto Co., Inc.), CAE (registered trademark) (Ajinomoto Healthy Supply Co., Inc.), etc. The content of the amino acid moisturizer in the skin topical composition of the present invention may be set according to the purpose and is not particularly limited.

5) Squalane is a saturated hydrocarbon obtained by reducing (hydrogenating) squalene, a hydrocarbon obtained from the liver oil of deep-sea sharks such as the borax shark, and is a colorless liquid. The content of the amino acid moisturizer in the topical skin composition of the present invention can be set according to the purpose and is not particularly limited.

6) Examples of polyhydric alcohols as humectants include glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol, etc.

7) Isomerized sugar is a mixture of sugars made by mixing dilute alkali-treated "glucose" and dilute alkali-treated "lactose" in a ratio of 19:1, and is composed mainly of glucose and fructose. Isomerized sugar is available on the market as PENTAVITIN (DSM).

8) Protein hydrolysates include, but are not limited to, hydrolyzed elastin, hydrolyzed casein, hydrolyzed keratin, hydrolyzed wheat, hydrolyzed collagen, hydrolyzed conchiolin, hydrolyzed silk, hydrolyzed gelatin, hydrolyzed soy protein, hydrolyzed corn protein, hydrolyzed comb, hydrolyzed potato protein, hydrolyzed fibronectin, etc.

The skin topical composition of the present invention may contain a thickening agent. The thickening agent is not particularly limited as long as it is pharma- ceutical acceptable, but examples thereof include water-soluble polymers such as carboxyvinyl polymer, polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, xanthan gum, sodium chondroitin sulfate, and sodium hyaluronate; and celluloses such as hydroxyethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and sodium carboxymethyl cellulose. These thickening agents may be used alone or in combination of two or more.

The skin topical composition of the present invention may contain a pH adjuster for adjusting the pH of the composition to a desired value. Examples of pH adjusters include inorganic acids (phosphoric acid, pyrophosphoric acid, metaphosphoric acid, polyphosphoric acid, sulfuric acid, nitric acid, hydrochloric acid, etc.) and their salts; organic acids (monocarboxylic acids (e.g., acetic acid, sorbic acid), polycarboxylic acids (e.g., oxalic acid, succinic acid, maleic acid, fumaric acid), oxycarboxylic acids (e.g., hydroxymonocarboxylic acids (e.g., glycolic acid, lactic acid, gluconic acid), hydroxypolycarboxylic acids (e.g., tartaric acid, malic acid, citric acid, etc.)), etc. and their salts; inorganic bases (metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), etc.); organic bases (amines (e.g., alkanolamines (e.g., monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, N-methylethanolamine, N-aminoethylethanolamine, N-methyldiethanolamine, etc.), etc.), amino acids (e.g., glycine, etc.), etc.). The topical skin composition of the present invention may contain a combination of multiple types of pH adjusters.

The skin topical composition of the present invention may contain a preservative. Examples of preservatives include paraoxybenzoic acid esters, commonly known as "parabens". Specifically, examples of preservatives include methylparaben (methyl paraoxybenzoate), ethylparaben (ethyl paraoxybenzoate), propylparaben, isopropylparaben, butylparaben, isobutylparaben, and salts thereof. The skin topical composition of the present invention may contain a combination of multiple types of parabens, for example, a combination of methylparaben with ethylparaben or propylparaben. When the skin topical composition of the present invention contains paraben, the content of paraben in the composition may be 1 w/v% or less, preferably 0.5 w/v% or less, and more preferably 0.25 w/v% or less.

When the topical skin composition of the present invention is in the form of an emulsion, it contains an emulsifier. The emulsifier may be any of anionic, cationic, amphoteric, and nonionic surfactants. Examples of emulsifiers include, but are not limited to, glyceryl monostearate, polyoxyl stearate, glycol distearate, lecithin, sorbitan sesquioleate, sorbitan trioleate, steareth-2, and coconut oil fatty acid PEG-7 glyceryl.

The topical skin composition of the present invention may contain softeners, colorants, fragrances, etc.

[1-5. Dosage form of topical skin composition]
The skin topical composition of the present invention is preferably a liquid preparation, but the formulation is not particularly limited, and may be an aqueous preparation, an oily preparation, an emulsion preparation (either an oil-in-water emulsion or a water-in-oil emulsion), a suspension preparation, an aerosol preparation, a gel preparation, etc. The skin topical composition of the present invention may be in the form of a cosmetic, such as a solid, pressed, oil, liquid, gel, balm, mud, cream, milk, lotion, foam, film, powder, water, pencil, spray (mist), stick, sheet, etc.

The pH of the topical composition for skin of the present invention is preferably adjusted to a range of 5 to 7. This is because it is easier to increase the permeability of the topical composition for skin into the skin.

The viscosity of the topical skin composition of the present invention can be adjusted as appropriate depending on the dosage form of the preparation and the desired feel when the composition is applied to the skin. For example, a composition with a lower viscosity is more likely to wet and spread easily when applied to the skin; a composition with a higher viscosity is more likely to be easily absorbed when applied to the skin. For example, as a guideline, if the topical skin composition of the present invention is an aqueous solution, the viscosity may be in the range of 400 to 1300 mPa·s, and if it is an emulsion, the viscosity may be in the range of 2000 to 12000 mPa·s. The viscosity is measured under rheometer conditions of 25°C, 0.33 rpm, and the viscosity after 90 seconds.

The skin topical composition of the present invention is filled in a container, for example, a light-shielding container. The skin topical composition of the present invention can also be filled in a pump or spray type container to facilitate application to the skin.

2. Uses of topical skin composition
The skin topical composition of the present invention is used by applying to the skin, for example, by coating on the skin. For example, the skin topical composition can be directly rubbed into the skin, or gauze soaked in the skin topical composition can be applied to the skin. The affected area to which the skin topical composition of the present invention is applied is not particularly limited as long as it is skin, and examples thereof include, but are not limited to, affected areas that particularly require moisturization, such as the face, flaky knees and heels, and the back. The frequency of application to the skin is not particularly limited, but may be about once to several times a day.

The topical skin composition of the present invention is expected to exert moisturizing, anti-inflammatory, and blood circulation promoting effects when applied to the skin; as a result, it can have effects such as improving rough and chapped skin, preventing heat rash, chilblains, cracks, chapped skin, and acne, conditioning the skin and keeping it healthy, moisturizing the skin, protecting the skin, and preventing dry skin.

The skin topical composition of the present invention is preferably used as a skin moisturizer, since it has a particularly high moisturizing effect on the skin. In particular, the skin topical composition of the present invention contains an extract of peach or Artemisia plant together with a heparinoid, and thereby enhances both the immediate moisturizing effect (e.g., within one hour of application to the skin) and the medium- to long-term moisturizing effect (e.g., one day after application to the skin). It was not previously known that an extract of peach or Artemisia plant exhibits an immediate moisturizing effect, which is itself a finding discovered in the present invention; in addition, the unexpected effect of the extract of peach or Artemisia plant synergistically enhancing the immediate moisturizing effect of the heparinoid is shown in the examples of this specification.

In addition, peach extracts are known to promote ceramide synthase (SPT) mRNA expression and profilaggrin mRNA expression; and Artemisia plant extracts are known to promote caspase-14 mRNA expression. These actions are believed to result in a moisturizing effect on the skin in the medium to long term. Therefore, the topical skin composition of the present invention is a moisturizer that not only has a short-term moisturizing effect, but also has enhanced medium to long-term moisturizing effect.

3. Method for producing topical skin composition
The method of producing the skin topical composition of the present invention is not particularly limited, and can be produced according to a conventional method depending on the dosage form. For example, it can be obtained by sequentially adding and mixing a predetermined amount of each compounding component (including at least heparinoids and extracts of Artemisia plants or peach) to a liquid carrier. The method of producing the composition of each dosage form is described in, for example, "Emulsion Preparation Technology Case Studies (Publisher: Technical Information Association, Authors: Mizuno Asako, Terada Chiharu Planning and Editing)" and can be referred to.

The present invention will be described in more detail below with reference to examples, but the present invention should not be construed as being limited to these examples.

Samples for [Example 1] and [Example 2]: A heparinoid (listed in the FDA) and a peach leaf extract (peach leaf extract from Yamanashi Prefecture BG30 (Maruzen Pharmaceuticals), 0.20% solution) were added to purified water in the amounts shown in Tables 1 and 2, and dissolved at room temperature.
Sample for [Comparative Example 1]: Heparinoids (listed products) in the amounts shown in Tables 1 to 4 were added to purified water and dissolved at room temperature.
Samples for [Comparative Example 2] and [Comparative Example 3]: Peach leaf extract (Peach leaf extract from Yamanashi Prefecture BG30 (Maruzen Pharmaceuticals), 0.20% solution) in the amounts shown in Tables 1 and 2 was added to purified water and dissolved at room temperature. The composition of Peach leaf extract from Yamanashi Prefecture BG30 (Maruzen Pharmaceuticals) is 0.20% by mass of peach leaf extract, 29.94% by mass of 1,3-butylene glycol, and 69.86% by mass of water.

Samples for [Example 3] and [Example 4]: Heparinoids (listed in the FDA) and Artemisia leaf extract (Japanese name: Gaiyo (Maruzen Pharmaceuticals), 1.00%), which is an extract of plants of the Artemisia genus, were added to purified water in the amounts shown in Tables 3 and 4, and dissolved at room temperature.
Samples for [Comparative Example 4] and [Comparative Example 5]: Artemisia leaf extract (Wa ism <Gaiyo> (Maruzen Pharmaceuticals), 1.00%), which is an extract of plants of the genus Artemisia, was added to purified water in the amounts shown in Tables 3 and 4, and dissolved at room temperature. The composition of Wa ism <Gaiyo> (Maruzen Pharmaceuticals) is 1.00% by mass of Artemisia extract, 49.50% by mass of 1,3-butylene glycol, and 49.50% by mass of water.

The moisturizing effect on the skin of subjects (two humans) was confirmed for the samples prepared in each Example and Comparative Example, and for water (control sample). First, before application of each sample, the skin moisture content of the subject's skin application site (inside of the forearm) was measured five times, and the average of the three moisture increase rates excluding the maximum and minimum values was taken as the moisture content before application X. Then, 5 μL of each sample was applied to a circular area of approximately 0.8 cm in diameter on the site. 30 minutes (Test Examples 1 and 2) or 1 hour (Test Examples 3 and 4) after application, the skin moisture content of the skin application site was measured five times, and the average of the three moisture increase rates excluding the maximum and minimum values was taken as the moisture content after application Y.

For each sample, the moisture increase rate Z (%) was calculated by (moisture content after application Y - moisture content before application X) / moisture content before application X x 100. The moisture increase rate Z (%) for each sample minus the moisture increase rate (%) for the control sample (water) is shown as the "skin moisture increase rate" in each table.

Skin moisture content was measured using a skin surface stratum corneum moisture content measuring device SKICON (registered trademark)-200EX (Yayoi Corporation). This device can measure the moisture content of the "surface" stratum corneum by measuring the conductivity (conductance μS) of a high-frequency alternating current. This is because high-frequency current flows easily on the surface of an object, and there is a close correlation between conductivity and moisture content. In this way, in this example, the moisture content of the "surface" stratum corneum is measured to appropriately evaluate the softness and smoothness of the skin.

As shown in the results of Test Example 1 in Table 1, the sample of Comparative Example 1 containing 0.1% by mass of heparinoid showed a moisture increase rate of 11%, the sample of Comparative Example 2 containing 0.0002 (2 x 10-4) mass% of Yamanashi peach leaf extract BG30 as an active ingredient showed a moisture increase rate of 17%, while the sample of Example 1 showed a moisture increase rate of 45%. Similarly, as shown in the results of Test Example 2 in Table 2, the sample of Comparative Example 1 containing 0.1% by mass of heparinoid showed a moisture increase rate of 12%, the sample of Comparative Example 3 containing 0.02 (2 x 10-2) mass% of Yamanashi peach leaf extract BG30 as an active ingredient showed a moisture increase rate of 24%, while the sample of Example 2 showed a moisture increase rate of 63%. These results indicate that the heparinoid and peach extract act synergistically to enhance the moisturizing effect of the sample, especially the immediate moisturizing effect.

The slight difference in the rate of moisture increase in the sample from Comparative Example 1 between Test Examples 1 and 2 is due to individual differences between subjects.

As shown in the results of Test Example 3 in Table 3, the sample of Comparative Example 1 containing 0.1% by mass of heparinoid showed a moisture increase rate of 13%, the sample of Comparative Example 4 containing 0.001 (1 x 10-3) mass% of active ingredient Ism <Gaiyo> showed a moisture increase rate of 4%, while the sample of Example 3 showed a moisture increase rate of 35%. Similarly, as shown in the results of Test Example 4 in Table 4, the sample of Comparative Example 1 containing 0.1% by mass of heparinoid showed a moisture increase rate of 18%, the sample of Comparative Example 5 containing 0.1 (1 x 10-1) mass% of active ingredient Ism <Gaiyo> showed a moisture increase rate of 14%, while the sample of Example 4 showed a moisture increase rate of 44%. These results indicate that the heparinoid and the extract of Artemisia genus plants act synergistically to enhance the moisturizing effect of the sample, especially the immediate moisturizing effect.

The slight difference in the rate of moisture increase in the sample from Comparative Example 1 between Test Examples 3 and 4 is due to individual differences between subjects, as in the case of Test Examples 1 and 2.

The mechanism of synergistic action between heparinoids and peach or mugwort extracts is unclear. However, it is believed that peach or mugwort extracts have a moisturizing mechanism separate from the moisturizing mechanism of heparinoids, which is assumed to be the promotion of recovery of the lamellar structure of intercellular lipids in the stratum corneum and the increase in the amount of secondary bound water, and that there is a synergistic moisturizing effect due to the difference in the mechanism of action.

Below is an example of preparing the topical skin composition of the present invention as a lotion.

According to the present invention, a composition for external use on the skin having enhanced moisturizing effect can be provided, and therefore the present invention can be used as a cosmetic or the like for moisturizing, protecting, and preventing dryness of the skin.

Claims (5)

A composition for external use on the skin containing a heparinoid, an extract of a plant of the genus Artemisia or peach, and a liquid carrier. The composition for topical application of skin according to claim 1, wherein the extract is contained in the composition for topical application of skin in an amount ranging from 0.0001% by mass to 1% by mass as an active ingredient. The composition for topical application of skin according to claim 1 or 2, wherein the content of the heparinoid is 0.005% by mass to 5% by mass relative to the composition for topical application of skin. The composition for external use on skin according to claim 1 or 2, which is a moisturizer. A method for enhancing the moisturizing effect of a topical skin composition containing a heparinoid, comprising:
A method for enhancing moisturizing effect, comprising blending an extract of an Artemisia plant or peach with the composition for external use on skin.