JP6284303B2 - O / W emulsion composition and external preparation for skin - Google Patents

Description

  The present invention relates to an O / W emulsion composition excellent in storage stability and transdermal absorbability of an oil-soluble active substance, and a skin external preparation containing the emulsion composition.

  The O / W type emulsion composition is widely used as a dosage form of many preparations including an external preparation for skin because it has an emollient effect and a fresh feeling of use. In the production of an emulsion, it is necessary to use a surfactant or an emulsifier in order to uniformly disperse production water and oil.

  In recent years, as a method for producing such an O / W emulsion composition, a method of emulsifying using an alkyl-modified carboxyvinyl polymer has been widely used. For example, in a composition in which ascorbic acid and a derivative thereof are blended as an active ingredient, a composition is known in which an alkyl-modified carboxyvinyl polymer is added for the purpose of improving the emulsion stability (see Patent Documents 1 and 2). These compositions are compositions containing ascorbic acid, which is a water-soluble substance, or a derivative thereof as an active ingredient, and an alkyl-modified carboxyvinyl polymer is added to increase the emulsion stability of the composition. In fact, in these compositions, various surfactants are added in addition to the alkyl-modified carboxyvinyl polymer.

  Moreover, in skin external preparations containing vitamin A or a derivative thereof as an active ingredient, tetraisopalmitate L-ascorbyl, a chelating agent and a polyhydric alcohol were added for the purpose of enhancing the stability of vitamin A or a derivative thereof. A skin external preparation is known (Patent Document 3). Patent Document 3 discloses a total of 19 compositions of Examples 1-1 to 4, Examples 2-1 to 4, Examples 3-1 to 5, and Examples 4 to 9. Among them, 18 types have surfactants added (partially fatty acid reacts with alkali to produce a surfactant after adjustment). In Example 6 of Patent Document 3, no surfactant is added, but the composition of this example is not an O / W emulsion.

  Further, an ascorbic acid derivative composition for skin containing at least one of esters and ethers of ascorbic acid as an active ingredient and at least one of phospholipid and polyalkylene glycol-diisocyanate copolymer is known (Patent Document). 4). The composition of the composition is employed for enhancing the sustainability and transdermal absorbability of the active ingredient ascorbic acid (vitamin C). The phospholipid in the composition is a surfactant. It is a substance that acts as

  Further, the emulsion contains an oil-soluble ascorbic acid derivative, which contains a water-soluble polymer such as carboxyvinyl polymer together with the oil-soluble ascorbic acid derivative, and the emulsion has a volume-based average particle size of 8 to 100 μm. A composition is known (Patent Document 5). The said composition employ | adopts the said prescription in order to improve the skin permeability of an oil-soluble ascorbic acid derivative. In practice, a surfactant is added to the emulsified composition for efficient emulsification.

JP 2003-12498 A JP 2004-91360 A JP 2001-122735 A JP 11-79930 A JP 2006-8620 A

As described above, in the O / W emulsion composition, a surfactant is generally used to uniformly disperse the aqueous phase and the oil phase. However, in the application of the O / W emulsion composition to an external preparation for skin, the addition of a surfactant is effective for ensuring the emulsification stability of the composition, but the storage stability of the oil-soluble active substance. Can be a factor that decreases the sexuality and transdermal absorbability.
Therefore, in the prior art as described above, the O / W type has high storage stability and transdermal absorbability of the oil-soluble active substance while maintaining the emulsion stability as a preparation without using a surfactant. It was almost impossible to provide an emulsion composition.

  Accordingly, an object of the present invention is an O / W type emulsion composition containing an oil-soluble active substance, which maintains the high emulsification stability as a preparation, while maintaining the storage stability and transdermal absorption of the oil-soluble active substance. The object is to provide an O / W emulsion composition that is excellent in safety and safety.

As a result of intensive studies, the present inventors have found that the above-mentioned problems can be solved by adopting the following conditions (1) to (4) in an O / W emulsion containing an oil-soluble active substance. The present invention has been completed based on such knowledge.
(1) The composition contains an alkyl-modified carboxyvinyl polymer and / or a salt thereof.
(2) Adjusting the pH of the composition to 4.0 to 8.0.
(3) The average particle diameter of the emulsion particles in the composition is 2 to 30 μm.
(4) The composition does not substantially contain a surfactant.

That is, the present invention relates to the following.
[1]
An O / W emulsion composition containing an oil-soluble active substance and an alkyl-modified carboxyvinyl polymer and / or a salt thereof,
The pH of the composition is 4.0 to 8.0;
The average particle size of the emulsion particles in the composition is from 2 μm to 30 μm, and the composition contains substantially no surfactant,
The above composition.
[2]
The composition according to [1], which contains, as the oil-soluble active substance, at least one selected from the group consisting of oil-soluble vitamins, derivatives thereof or salts thereof; and oil-soluble derivatives of water-soluble vitamins or salts thereof. object.
[3]
As said oil-soluble active substance, vitamin A, its derivatives or salts thereof; vitamin E, its derivatives or salts thereof; vitamin D, its derivatives or salts thereof; vitamin K, its derivatives or salts thereof; oil-soluble ascorbine The composition according to [1] or [2], comprising at least one selected from the group consisting of an acid derivative or a salt thereof; and an oil-soluble pyridoxine derivative or a salt thereof.
[4]
Vitamin A, its derivatives or salts thereof; vitamin E, its derivatives or salts thereof; vitamin D, its derivatives or salts thereof; oil-soluble ascorbic acid derivatives or salts thereof; and oil-soluble pyridoxine The composition according to any one of [1] to [3], which contains one or more selected from the group consisting of derivatives or salts thereof.
[5]
The oil-soluble active substance contains at least one selected from the group consisting of vitamin A, derivatives thereof or salts thereof; vitamin E, derivatives or salts thereof; and oil-soluble ascorbic acid derivatives or salts thereof; The composition according to any one of [1] to [4].
[6]
The oil-soluble active substance contains two or more selected from the group consisting of vitamin A, derivatives thereof or salts thereof; vitamin E, derivatives or salts thereof; and oil-soluble ascorbic acid derivatives or salts thereof; The composition according to any one of [1] to [5].
[7]
The composition according to any one of [1] to [6], which contains vitamin A, a derivative thereof or a salt thereof; and an oil-soluble ascorbic acid derivative or a salt thereof as the oil-soluble active substance.
[8]
The composition according to any one of [1] to [7], wherein the pH is 4.5 to 7.5.
[9]
The composition according to any one of [1] to [8], wherein the pH is 4.5 to 7.0.
[10]
[1] A skin external preparation containing the composition according to any one of [9].
[11]
The external preparation for skin according to [10], which is a cosmetic composition, a skin care composition, or a pharmaceutical composition.

  According to the present invention, there is provided an O / W emulsion composition in which the storage stability and transdermal absorbability of an oil-soluble active substance are remarkably improved while maintaining high emulsification stability as an O / W emulsion formulation. be able to. Furthermore, since the O / W emulsion composition of the present invention does not substantially contain a surfactant, it is possible to provide an extremely safe O / W emulsion formulation.

FIG. 1 shows the results of comparing the transdermal absorbability of vitamin A oil (retinol palmitate) for each composition of Example 2 and Comparative Example 3. FIG. 2 shows the results of comparison of the transdermal absorbability of ascorbyl tetra-2-hexyldecanoate for each composition of Example 2 and Comparative Example 3. FIG. 3 shows the results of comparing the transdermal absorbability of dl-α-tocopherol acetate for each of the compositions of Example 3 and Comparative Examples 4 to 6.

  The present invention is an O / W emulsion composition containing an oil-soluble active substance and an alkyl-modified carboxyvinyl polymer and / or a salt thereof, and the pH of the composition is 4.0 to 8.0, The average particle diameter of the emulsion particles in the composition is from 2 μm to 30 μm, and the composition is substantially free from a surfactant.

  In the present invention, the oil-soluble active substance may be appropriately selected in consideration of the desired use and efficacy, and is not particularly limited. Examples of the oil-soluble active substance of the present invention include the following.

Oil-soluble vitamins:
Vitamin A such as carotene, lycopene (provitamin A), astaxanthin, lutein, crocetin, retinoid, retinal (vitamin A1), dehydroretinal (vitamin A2), retinoic acid, retinol, retinol acetate, retinol palmitate (vitamin A oil) And its derivatives and salts thereof; tocopherol (d-α-tocopherol), tocopherol acetate (dl-α-tocopherol acetate, d-α-tocopherol acetate), tocopherol nicotinate, (linoleic acid / oleic acid) tocopherol, linoleic acid Vitamin E such as tocopherol and its derivatives and their salts; Vitamin D such as ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), 1,2,5-dihydroxy-cholecalciferol Beauty derivatives and their salts; phytonadione (vitamin K1), menaquinone (vitamin K2), menadione (vitamin K3), vitamin K and derivatives and salts thereof thereof such menadiol (vitamin K4).

Oil-soluble derivatives of water-soluble vitamins:
Oil-soluble pyridoxine derivatives (oil-soluble derivatives of vitamin B ₆ ) such as pyridoxine dicaprylate, pyridoxine dipalmitate, pyridoxine tripalmitate, pyridoxine trishexyldecanoate, pyridoxine tri-2-hexyldecanoate and the like; ascorbyl dipalmitate, stearin Oil-soluble ascorbic acid derivatives (oil-soluble derivatives of vitamin C) such as ascorbyl acid, ascorbyl tetra-2-hexyldecanoate, and ascorbyl palmitate, and salts thereof.

Other oil-soluble active substances:
Other examples include oil-soluble active substances such as gamma oryzanol, hinokitiol, ethinyl estradiol, stearyl glycyrrhetinate, glycyrrhetinyl stearate, ceramide, sterols, and oil-soluble licorice extract.

  According to the O / W emulsion composition of the present invention, both the storage stability and transdermal absorbability of the oil-soluble active substance can be improved while maintaining the emulsion stability as a preparation. In particular, when an oil-soluble substance having a problem of storage stability is used, those disadvantages can be solved. Furthermore, in the O / W type emulsion composition of the present invention, the transdermal absorbability of the oil-soluble active ingredient can also be improved. This is an advantage of the present invention. Substances in which the superiority of the present invention stands out include oil-soluble vitamins and / or oil-soluble derivatives of water-soluble vitamins.

  Therefore, the composition of the present invention contains at least one selected from the group consisting of oil-soluble vitamins, derivatives thereof or salts thereof, and oil-soluble derivatives of water-soluble vitamins or salts thereof as the oil-soluble active substance. It is preferable to do. Further, the composition of the present invention comprises vitamin A, a derivative thereof or a salt thereof; vitamin E, a derivative thereof or a salt thereof; vitamin D, a derivative thereof or a salt thereof; One or more selected from the group consisting of oil-soluble ascorbic acid derivatives (oil-soluble derivatives of vitamin C) or salts thereof; and oil-soluble pyridoxine derivatives (oil-soluble derivatives of vitamin B6) or salts thereof; It is preferable to contain. More preferably, the composition of the present invention contains vitamin A, a derivative thereof or a salt thereof; vitamin E, a derivative thereof or a salt thereof; vitamin D, a derivative thereof or a salt thereof; One or more selected from the group consisting of ascorbic acid derivatives (oil-soluble derivatives of vitamin C) or salts thereof; and oil-soluble pyridoxine derivatives (oil-soluble derivatives of vitamin B6) or salts thereof may be contained. In particular, among the oil-soluble compounds, components that have been conventionally considered to have a problem in storage stability, such as vitamin A and oil-soluble ascorbic acid derivatives, are formulated into the O / W emulsion of the present invention. Without impairing the emulsion stability, it is possible not only to improve the storage stability of the active substance but also to improve the transdermal absorbability as compared with conventional O / W emulsions. Therefore, the composition of the present invention comprises vitamin A, a derivative thereof or a salt thereof; vitamin E, a derivative thereof or a salt thereof; and an oil-soluble ascorbic acid derivative (an oil-soluble derivative of vitamin C). Or it is especially preferable to contain 1 or more types selected from the group which consists of the salt.

As a more specific embodiment, the composition of the present invention may contain the following substances as the oil-soluble active substance.
(1) Vitamin E, derivatives thereof or salts thereof.
(2) Vitamin A, a derivative thereof or a salt thereof; and an oil-soluble ascorbic acid derivative or a salt thereof.
(3) Vitamin A, its derivatives or salts thereof; Vitamin E, its derivatives or salts thereof; Vitamin D, its derivatives or salts thereof; oil-soluble ascorbic acid derivatives or salts thereof; and oil-soluble pyridoxine derivatives or salts thereof .

  Among the above oil-soluble active substances, oil-soluble vitamin A such as carotene, lycopene, astaxanthin, lutein, crocetin, retinoid, retinal, retinoic acid, retinol, retinol acetate, retinol palmitate, etc. Vitamin E such as tocopherol (d-α-tocopherol), tocopherol acetate (dl-α-tocopherol acetate, d-α-tocopherol acetate), tocopherol nicotinate, (linoleic acid / oleic acid) tocopherol, tocopherol linoleate, etc. (Including derivatives thereof or salts thereof); and / or oil-soluble ascorbic acid derivatives (including salts thereof) such as ascorbyl dipalmitate, ascorbyl stearate, ascorbyl tetra-2-hexyldecanoate, ascorbyl palmitate Free) when incorporated into the compositions of the present invention, the storage stability of those substances and percutaneous absorption property can be particularly improved. In addition, two or more kinds selected from the group consisting of vitamin A, derivatives thereof or salts thereof; vitamin E, derivatives thereof or salts thereof; and oil-soluble ascorbic acid derivatives (oil-soluble derivatives of vitamin C) or salts thereof When formulated, the storage stability and transdermal absorbability of these oil-soluble active substances are remarkably increased, so that the O / W emulsion composition is extremely useful as a cosmetic composition, skin care composition, or pharmaceutical composition. high. In a particularly preferred embodiment, the composition of the present invention contains, as the oil-soluble active substance, vitamin A oil (retinol palmitate), natural vitamin E (d-α-tocopherol), dl-α-tocopherol acetate, trishexyldecane. One or more selected from the group consisting of acid pyridoxine, cholecalciferol and ascorbyl tetra-2-hexyldecanoate, preferably two or more.

As a more specific embodiment, the composition of the present invention may contain the following substances as the oil-soluble active substance.
(1) Natural vitamin E (d-α-tocopherol) and / or dl-α-tocopherol acetate.
(2) Vitamin A oil (retinol palmitate); and ascorbyl tetra-2-hexyldecanoate.
(3) Vitamin A oil (retinol palmitate); natural vitamin E (d-α-tocopherol) and / or dl-α-tocopherol acetate; cholecalciferol; ascorbyl tetra-2-hexyldecanoate; and pyridoxine trishexyldecanoate.

  However, the description relating to the effective substance is not intended to limit the oil-soluble active substance of the present invention to a specific substance.

  The amount of the oil-soluble active substance in the composition of the present invention is not particularly limited as long as it is determined in consideration of the desired use and efficacy, and is, for example, about 0.1% relative to the total weight of the composition. From 001 wt% to about 30 wt%, preferably from about 0.01 wt% to about 20 wt%.

  The composition of the present invention contains an alkyl-modified carboxyvinyl polymer and / or a salt thereof. The alkyl group of the alkyl-modified carboxyvinyl polymer may be linear or branched. The number of carbon atoms of the alkyl group is not particularly limited as long as it exhibits an emulsifying function, but is, for example, 8 to 35, and preferably 10 to 30. Examples of such an alkyl-modified carboxyvinyl polymer include a copolymer obtained by copolymerizing a long-chain alkyl acrylate monomer having 8 to 35 carbon atoms (preferably 10 to 30 carbon atoms) and an olefinically unsaturated carboxylic acid monomer. It is possible to use. More specifically, it is possible to use a copolymer obtained by copolymerizing 1 to 50% by weight of a long-chain alkyl acrylate monomer and 50 to 99% by weight of an olefinically unsaturated carboxylic acid monomer. In order to adjust the properties of the copolymer, a copolymer having a crosslinked structure obtained by blending and polymerizing an olefinic polyfunctional monomer can also be used (for example, see JP-A-2002-193731).

  Specifically, as the alkyl-modified carboxyvinyl polymer in the present invention, a copolymer of a long-chain alkyl acrylate monomer represented by the following general formula (1) and an olefinically unsaturated carboxylic acid monomer can be used.

(However, R is a linear or branched alkyl group having 8 to 35 carbon atoms, preferably 10 to 30 carbon atoms, and R ′ is hydrogen or a methyl group.)

  Examples of the long-chain alkyl acrylate monomer include alkyl acrylates having 8 to 35 carbon atoms, preferably 10 to 30 carbon atoms such as decyl acrylate, lauryl acrylate, palmityl acrylate, stearyl acrylate, and behenyl acrylate, and methacrylates corresponding thereto. One or more selected monomers, and examples of the olefinically unsaturated carboxylic acid monomer include acrylic acid, methacrylic acid, α-chloro-acrylic acid, α-phenylacrylic acid, sorbic acid, cinnamic acid, and maleic acid. One or more monomers selected from the group of polymerizable compounds containing an olefinic double bond such as acid, fumaric acid or maleic anhydride and at least one carboxyl group, and preferably an excellent polymer which is easily available Acrylic with ability Examples include acids. As a copolymer from a long-chain alkyl acrylate and an olefinically unsaturated carboxylic acid monomer, in addition to the above-mentioned essential components of the long-chain alkyl acrylate and the olefinically unsaturated carboxylic acid monomer, In order to adjust the properties, olefinic polyfunctional monomers such as methylene bisacrylamide, allyl acrylate, methallyl methacrylate, divinyl ether, allyl sucrose, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, glyceryl triacrylate are blended. A copolymer having a crosslinked structure obtained by polymerization can also be used in the present invention. The blending amount of the olefin polyfunctional monomer is preferably about 0.01 to about 4% by weight, more preferably 0.2 to 1 based on the total amount of the long-chain alkyl acrylate monomer and the olefin polyfunctional monomer. 0.0% by weight. These copolymers can be produced by the methods described in, for example, JP-A Nos. 51-6190 and 2-39312.

  The average molecular weight of the alkyl-modified carboxyvinyl polymer of the present invention is not particularly limited, but is preferably about 500,000 to 5,000,000.

  Such alkyl-modified carboxyvinyl polymers include Pemlen TR-1 or Pemlen TR-2 ((Acrylates / alkyl acrylate (C10-30)) crosspolymer) (Noveon), Carbopol 1342 (Noveon). ), Carbopol ETD2020 (manufactured by Noveon), Allianz OPT (manufactured by International Specialty Products), and the like, these commercial products may be used.

  The blending amount of the alkyl-modified carboxyvinyl polymer in the composition of the present invention varies greatly depending on the type of alkyl-modified carboxyvinyl polymer, other blends, the amount of oil phase, emulsification conditions, etc., but it is usually the total weight of the composition. On the other hand, about 0.01 wt% to about 4.0 wt% can be blended, and preferably about 0.1 wt% to about 2.0 wt% can be blended.

  The pH of the composition of the present invention is from about 4.0 to about 8.0. This is because, if the pH value of the composition deviates from the above range, emulsification of the composition becomes difficult and emulsification stability cannot be ensured, and sufficient storage stability of the oil-soluble active substance cannot be ensured. In particular, when the pH value of the composition exceeds 8.0, the storage stability of an oil-soluble ascorbic acid derivative (for example, ascorbyl tetra-2-hexyldecanoate) among oil-soluble active substances is lowered. Furthermore, if the pH value of the composition is less than 4.0, the emulsifiability and emulsification stability of the composition will decrease. The pH of the composition of the present invention is not particularly limited as long as the pH of the composition of the present invention is adjusted within this range according to the desired purpose and application. However, the oil-soluble active substance is further maintained while maintaining high emulsification stability of the composition. From the viewpoint of remarkably improving the storage stability, it is preferably about 4.5 to about 7.5, more preferably about 4.5 to about 7.0.

  The substance used for adjusting the pH of the composition of the present invention is not particularly limited, but hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide, monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine , Alkanolamines such as diisopropanolamine and triisopropanolamine, citric acid, malic acid, tartaric acid, lactic acid, fumaric acid, succinic acid, maleic acid, acetic acid and other organic acids and their salts, hydrochloric acid, sodium carbonate, sodium bicarbonate, Inorganic acids such as sodium hydroxide, potassium hydroxide, phosphoric acid, trisodium phosphate, sodium hydrogen phosphate, dipotassium phosphate, potassium dihydrogen phosphate and their salts, etc., guanidine carbonate, ammonium carbonate, 2 -Amino-2-methyl-1,3-pro Examples thereof include pandiol, 2-amino-2-hydroxymethyl-1,3-propanediol, and L-arginine. In the present invention, when the alkyl-modified carboxyvinyl polymer is acidic, an alkaline substance is often added.

  In addition to the above-mentioned components, the composition of the present invention includes oils, powders, pigments, polymers, preservatives, fragrances, ultraviolet absorbers, solvents, natural substances that can be used in cosmetic preparations and pharmaceutical external preparations for skin. Arbitrary components such as plant extract components, seaweed extract components, herbal medicine components, moisturizers, salts, antioxidants, sequestering agents and the like can be appropriately blended.

  Examples of the oil include volatile and non-volatile oils that can be used in skin external preparations such as cosmetics and pharmaceuticals, solvents, resins, and the like, and may be liquid, paste, or solid at room temperature. . Examples of oils include higher alcohols such as cetyl alcohol, isostearyl alcohol, lauryl alcohol, hexadecyl alcohol, octyldodecanol, fatty acids such as isostearic acid, undecylenic acid, oleic acid, isononyl isononanoate, isotridecyl isononanoate, myristine Such as myristyl acid, hexyl laurate, decyl oleate, isopropyl myristate, hexyl decyl dimethyloctanoate, glyceryl trioctanoate, glyceryl tri-2-heptylundecanoate, diethyl phthalate, octyl oxystearate, diisostearyl malate, etc. Esters, hydrocarbons such as liquid paraffin, paraffin, petrolatum, squalane, lanolin, reduced lanolin, liquid lanolin, carnauba wax, candelilla wax Wax such as ceresin, ozokerite, microcrystalline wax, mink oil, cacao butter, palm oil, palm kernel oil, camellia oil, sesame oil, soybean oil, argania spinosa kernel oil, castor oil, olive oil, hydrogenated palm oil, bird 2 -Glyceryl ethylhexanoate, glyceryl tri (capryl / capric acid), pentaerythritol tetra-2-ethylhexanoate, dipentaerythritol hexaoxystearate, cholesteryl hydroxystearate, di (N-lauroyl-L-glutamate) Oils such as behenyl, 2-octyldodecyl), polyethylene wax, ethylene / α-olefin / co-oligomer, and the like.

  Other forms of oil include, for example, dimethylpolysiloxane, methylhydrogenpolysiloxane, methylphenylpolysiloxane, polyether-modified organopolysiloxane, fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane, and alkyl-modified organopolysiloxane. , Terminal-modified organopolysiloxane, fluorine-modified organopolysiloxane, amodimethicone, amino-modified organopolysiloxane, silicone gel, acrylic silicone, trimethylsiloxysilicic acid, dimethylsilylated silica and other silicone compounds, perfluoropolyether, fluorinated pitch, Examples thereof include fluorine compounds such as fluorocarbon and fluoroalcohol.

  Examples of powders or pigments include pigments such as Red No. 104, Red No. 102, Red No. 226, Red No. 201, Red No. 202, Yellow No. 4, Black No. 401, Blue No. 1 aluminum lake, Yellow No. 4 aluminum Lake, yellow No. 5 aluminum lake, yellow No. 203 barium lake and other lake dyes, nylon powder, silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, silicone elastomer spherical powder Body, polymers such as polyethylene powder, yellow iron oxide, bengara, black iron oxide, chromium oxide, carbon black, colored pigments such as ultramarine and bitumen, white pigments such as zinc oxide, titanium oxide, cerium oxide, talc, mica, Extender pigments such as sericite, kaolin, and plate-like barium sulfate Pearl pigments such as titanium mica, metal salts such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate and magnesium silicate, inorganic powders such as silica and alumina, bentonite, smectite, boron nitride, fine particle titanium oxide, fine particle zinc oxide, etc. In addition, these materials may be subjected to any surface treatment such as N-acylated lysine treatment, amino acid treatment, hydrophilic polymer treatment, oil agent treatment, silicone treatment, metal soap treatment, inorganic compound treatment, plasma treatment, mechanochemical. It is also possible to use a material that has been treated. Moreover, it is also possible to process what adjusted the color of the mixture to skin color etc. Furthermore, it is possible to obtain a powder having an ultraviolet protection function by using an ultraviolet scattering component such as fine particle titanium oxide or fine particle zinc oxide.

  Examples of the polymer include carboxyvinyl polymers other than the above alkyl-modified carboxyvinyl polymer, sodium polyacrylate, cellulose ether, calcium alginate, ethylene / acrylic acid copolymer, vinylpyrrolidone polymer, vinyl alcohol / vinylpyrrolidone copolymer Polymers, cationic polymers such as nitrogen-substituted acrylamide polymers, cationized guar gum, dimethylacrylammonium polymers, polyvinyl alcohol, pullulan, deoxyribonucleic acid and salts thereof, acidic mucopolysaccharides and salts thereof such as chondroitin sulfate, tamarind seed polysaccharides , Agar, xanthan gum, quince seed gum, hydroxyethyl cellulose, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic Crystalline cellulose, arabinogalactan, karaya gum, tragacanth gum, alginic acid, hyaluronic acid and its salts, albumin, casein, curdlan, gellan gum, dextran, cellulose, polyethyleneimine, highly polymerized polyethylene glycol, (glyceryl amidoethyl methacrylate / stearyl methacrylate) ) Copolymers and the like.

  Examples of the preservative include benzoic acid, sodium benzoate, undecylenic acid, salicylic acid, sorbic acid or a salt thereof, dehydroacetic acid or a salt thereof, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, isopropyl paraoxybenzoate, Organic acids such as butyl paraoxybenzoate, isobutyl paraoxybenzoate, benzyl paraoxybenzoate and their derivatives, isopropylmethylphenol, chlorhexidine gluconate, cresol, thymol, parachlorophenol, phenylethyl alcohol, phenylphenol, sodium phenylphenol, phenoxyethanol , Phenols such as phenoxydiglycol, phenol, benzyl alcohol, cetylpyridinium chloride, benzalkonium chloride, salt Quaternary ammonium salts such as benzethonium, methylbenzethonium chloride, lauryltrimethylammonium chloride, alkylisoquinolium bromide and domifenone bromide, tea extracts, hinokitiol, apple extract and other plant extracts, chloramine T, chlorhexidine, zinc pyrithione, etc. Can be mentioned.

  Examples of organic ultraviolet absorbers include 2-methoxyhexyl paramethoxycinnamate, 2-ethylhexyl paradimethylaminobenzoate, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfate, 2,2′-dihydroxy-4-methoxybenzophenone, p-methoxyhydrocinnamic acid diethanolamine salt, paraaminobenzoic acid (hereinafter abbreviated as PABA), homomenthyl salicylate, methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano -3,3-diphenyl acrylate, octyl dimethyl PABA, octyl salicylate, 2-phenyl-benzimidazole-5-sulfuric acid, triethanolamine salicylate, 3- (4-methylbenzylidene) camphor, 2,4-dihydroxybenzene Zophenine, 2,2 ′, 4,4′-tetrahydroxybenzophenone, 2,2′-dihydroxy-4,4′-dimethoxybenzophenone, 2-hydroxy-4-N-octoxybenzophenone, 4-isopropyldibenzoylmethane, Examples include butylmethoxydibenzoylmethane, 4- (3,4-dimethoxyphenylmethylene) -2,5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and the like.

  Examples of the solvent include purified water, normal water, ethanol, hot spring water, deep ocean water and the like.

  Examples of natural plant extract ingredients, seaweed extract ingredients, and herbal medicine ingredients are Ashitaba extract, Avocado extract, Achacha extract, Altea extract, Arnica extract, Aloe extract, Apricot extract, Apricot extract, Ginkgo biloba extract, Fennel extract, Turmeric Extract, Oolong tea extract, Ages extract, Echinacea leaf extract, Ogon extract, Oat extract, Auren extract, Barley extract, Hypericum extract, Oyster extract, Dutch mustard extract, Orange extract, Seawater dried product, Seaweed extract, Hydrolyzed elastin, Hydrolysis Wheat powder, hydrolyzed collagen, hydrolyzed conchiolin, hydrolyzed silk, chamomile extract, carrot extract, kawara mugwort extract, calcade extract, oyster extract, kiwi extract, kina extract, cucumber Extract, guanosine, gardenia extract, kumazasa extract, clara extract, chrismum maritimum callus culture, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentian extract, black tea extract, yeast extract, burdock extract, rice bran extract , Rice germ oil, Comfrey extract, Collagen, Cowberry extract, Saishin extract, Psycho extract, Saitai extract, Salvia extract, Soybean extract, Sasa extract, Hawthorn extract, Salamander extract, Shiitake extract, Giant extract, Shikon extract, Perilla extract, Linden Extract, Citrus extract, Peonies extract, Ginger root extract, Birch extract, Horsetail extract, Kizuta extract, Hawthorn extract, Elderflower Extract, Achillea millefolium extract, mint extract, sage extract, mallow extract, nematode extract, senbu extract, soybean extract, taisu extract, thyme extract, tea extract, clove extract, chigaya extract, chimpi extract, toki extract, tokisenka extract, tonin extract, spruce Extract, Dokudami Extract, Tomato Extract, Natto Extract, Carrot Extract, Garlic Extract, Novara Extract, Hibiscus Extract, Bacmond Extract, Lotus Extract, Parsley Extract, Honey, Hamamelis Extract, Parietalia Extract, Hikikoshi Extract, Bisabolol, Biwa Extract, Fukitan Popo Extract , Fukinoto extract, Bukuryo extract, Butcher bloom extract, Grape extract, Plankton extract, Propolis, Loofahae Kiss, safflower extract, peppermint extract, body extract, button extract, hop extract, pine extract, maronier extract, honeysuckle extract, mugwort extract, melissa extract, peach extract, cornflower extract, eucalyptus extract, yukinoshita extract, yuzu extract, oil-soluble carrot extract, yokuinin Examples include extract, mugwort extract, lavender extract, apple extract, lettuce extract, lemon extract, lotus extract, rose extract, rosemary extract, roman chamomile extract, royal jelly extract and the like.

  As humectants, glycerin, diglycerin, propylene glycol, dipropylene glycol, hexylene glycol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, polyethylene glycol, 1,3- Polyols such as butylene glycol, caprylyl glycol, sorbitol, glycosyl trehalose / hydrogenated starch decomposition mixed solution, sugars such as maltitol, trehalose, raffinose, valine, leucine, isoleucine, alanine, arginine, glutamine, lysine, aspartic acid, Glutamic acid, proline, cysteine, threonine, methionine, histidine, phenylalanine, tyrosine, tryptophan, asparagine, glycine, serine and other amino acids, hydroxyproline and other amino acids Bruno acid derivatives include other trimethylglycine, urea, etc. pyrrolidone carboxylic acid (salt).

The amount of the oil phase is not particularly limited as long as it is set as appropriate in consideration of the type of ingredients used, emulsification conditions, use of the composition, and the like. % By weight to about 60% by weight.
Similarly, the amount of the aqueous phase can be about 40 wt% to about 99 wt% based on the total weight of the composition.

  The O / W type emulsion composition of the present invention emulsifies the above-mentioned essential components and optional components under arbitrary conditions and methods, so that the average particle size of the emulsion particles in the composition is in the range of 2 μm to 30 μm. It is an adjusted composition. When the average particle size of the emulsion particles exceeds 30 μm, the emulsion stability of the emulsion composition is lowered. On the other hand, when the average particle size of the emulsion particles is less than 2 μm, the transdermal absorbability of the oil-soluble active substance is lowered. If the average particle diameter of the emulsion particles deviates from the above range, sufficient storage stability and transdermal absorbability of the oil-soluble active substance cannot be ensured while maintaining the emulsification stability of the composition. It is. The average particle diameter of the emulsion particles is not particularly limited as long as it is within this range, but from the viewpoint of further improving the storage stability and transdermal absorbability of the oil-soluble active substance, preferably 2 μm to 20 μm, more The thickness is preferably 2.1 (more preferably 2.2, 2.3, 2.4) μm to 10 μm, and even more preferably 2.5 μm to 10 μm.

  In the present invention, the “average particle diameter of emulsion particles” means a 50% diameter (cumulative median diameter, median diameter) obtained by a laser diffraction / scattering method based on the Mie scattering theory. Specifically, the particle size distribution of emulsion particles can be created on a volume basis by a laser diffraction particle size distribution measuring device, and the median value can be measured as the average particle size. As a measurement sample, an emulsion composition dispersed in water can be used. As the laser diffraction type particle size distribution measuring device, for example, a laser diffraction type particle size distribution measuring device “SALD2000” manufactured by Shimadzu Corporation can be used.

  The method for producing the composition of the present invention is not particularly limited as long as the average particle size of the emulsion particles falls within the above range and a desired effect is obtained, but the composition of the present invention has the above-described oil-soluble effectiveness. By mixing and stirring an oil phase component containing a substance, the alkyl-modified carboxyvinyl polymer, and an aqueous phase component containing other components, an emulsion of these oil phase component and aqueous phase component can be obtained. More specifically, an oil phase component (A) containing an oil-soluble active substance and an aqueous phase component (B) containing an alkyl-modified carboxyl vinyl polymer are prepared, and these oil phase component (A) and aqueous phase component ( B) is heated to a predetermined temperature, and then the oil phase component (A) is added to the aqueous phase component (B) and emulsified with stirring the aqueous phase component (B), thereby emulsifying the composition of the present invention. Can be obtained.

  Here, in order to make the average particle diameter of the emulsion particles within the predetermined range, the type and amount of the oil phase component including the alkyl-modified carboxyvinyl polymer and the oil-soluble active substance, the type and amount of the aqueous phase component, and It is necessary to appropriately adjust the emulsification conditions such as the heating temperature, stirring conditions, and stirring time of each oil phase and water phase component. Such adjustment of the type and amount of each component and the emulsification conditions are matters that should be appropriately selected by those skilled in the art from the viewpoints of emulsification efficiency and activity retention of medicinal components according to the components contained in the composition. It is not limited. In general, the stirring operation for emulsification can be carried out by propeller stirring, and various vacuum emulsification devices specialized for emulsification treatment are commercially available. May be. Moreover, about stirring conditions, generally the heating temperature of an oil phase and a water phase component shall be 20-90 degreeC, Preferably it is 50 to 90 degreeC, More preferably, it is 60 to 85 degreeC, On other suitable conditions The composition of the present invention can be obtained by stirring the oil phase and aqueous phase components. However, the stirring conditions are not particularly limited as long as an O / W emulsion preparation showing a predetermined average particle size can be prepared as described above, and is not intended to be limited to these conditions.

  Furthermore, the composition of the present invention is characterized by substantially not containing a surfactant. Here, the “surfactant” is a substance that has both a hydrophilic group and a hydrophobic group in its molecular structure and adsorbs to the interface with a small amount of addition, and significantly reduces the surface tension. Refers to a substance that adsorbs on the oil-water interface, lowers the interface tension between oil and water, and finely disperses oil droplets in water. Specific examples of such surfactants include polyoxyethylene sterol ether (eg, polyoxyethylene (20E.O.) soybean sterol), polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil (POE (60E)). O.) hydrogenated castor oil), polyoxyethylene polyoxypropylene alkyl ether, glycerin fatty acid ester (such as glyceryl monostearate), polyoxyethylene sorbitan fatty acid ester (such as monostearic acid POE (20E.O.) sorbitan) , Nonionic surfactants such as polyethylene glycol fatty acid ester, sucrose fatty acid ester, propylene glycol fatty acid ester, sorbitan fatty acid ester, methyl glucoside fatty acid ester, fatty acid soap (sodium stearate) Ionic surfactants such as sodium oleate, sodium lauroyl sarcosine, polyoxyethylene alkyl sulfate sodium, sodium lauryl sulfate, sodium stearoyl sulfate, lecithins (soy lecithin, egg yolk phospholipid, hydrogenated lecithin (hydrogenated soybean) Phospholipids), hydroxylated lecithin, etc.) and naturally occurring surfactants such as saponins (soybean saponin, licorice saponin, enzyme-treated saponin, etc.).

  Further, in the present invention, “substantially does not contain” means that the amount of the surfactant in the composition is not such an amount as to exhibit emulsifiability, and the content is 0.1 weight of the amount of the oil phase. % Or less, preferably 0.01% or less. Since the composition of the present invention does not substantially contain a surfactant, it is extremely safe for use as a skin external preparation.

  Although the use of the composition of this invention is not specifically limited, It can utilize as a cosmetic composition, a health care composition, a skin care composition, a pharmaceutical composition etc. More specifically, basic cosmetics such as emulsions and creams, makeup cosmetics such as foundations, hair cosmetics such as hair creams, hair restorers, health care products such as bathing agents, skin care creams and sunscreen creams, etc. It can be applied as a skin care product and an external skin pharmaceutical product containing an oil-soluble pharmaceutical active ingredient. From the viewpoint that the storage stability and transdermal absorbability of oil-soluble active ingredients such as oil-soluble vitamins and oil-soluble derivatives of water-soluble vitamins can be remarkably improved, the composition of the present invention is particularly cosmetic. High utility value as a composition and skin care composition.

  EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited to a following example.

[Example 1-1A]
Using the raw materials shown in Table 1, the O / W emulsion composition of the present invention was produced. In the production method, Group A and Group B were each heated to 80 ° C., and Group A was added and emulsified while stirring Group B. Thereafter, the obtained composition was cooled to 35 ° C. The emulsifying device is a T.I. K. Using ROBOMIX, emulsification was performed under conditions of 6,000 rpm and 5 minutes.

  The pH of the composition of Example 1-1A was 5.5. The average particle size (median value in the volume-based particle size distribution) of the emulsion particles in the composition was measured using a particle size distribution analyzer SALD-2000 (manufactured by Shimadzu Corporation), and was 4.7 μm.

[Example 1-1B]
Using the raw materials shown in Table 1, and changing the emulsification conditions in Example 1-1A, an O / W emulsion composition of the present invention was produced. That is, in this example, an O / W emulsion composition of the present invention was produced in the same manner as Example 1-1A, except that the emulsification conditions were changed to 10,000 rpm and 5 minutes.

  The pH of the composition of Example 1-1B is 5.5 as in Example 1-1A. However, when the average particle size (median value in the volume-based particle size distribution) of the emulsion particles in the composition was measured in the same manner as in Example 1-1A, the value was 2.8 μm.

[Comparative Example 1]
Using the raw materials shown in Table 2, the composition of Comparative Example 1 was produced. The production method was performed in the same manner as in Example 1 except that the raw materials shown in Table 2 were used and the emulsification conditions were 8,000 rpm and 1 minute. In addition, the composition of the comparative example 1 contains hydrogenated soybean phospholipid as a surfactant.

  The pH of the composition of Comparative Example 1 was 6.3. The average particle size (in the volume-based particle size distribution) of the emulsion particles in the composition was measured using a particle size distribution analyzer SALD-2000 (manufactured by Shimadzu Corporation), and found to be 1.4 μm.

[Comparative Example 2]
A composition of Comparative Example 2 was produced using the raw materials shown in Table 3. The manufacturing method was the same as that of Comparative Example 1 except that the raw materials shown in Table 3 were used. The composition of Comparative Example 2 contains polyoxyethylene (20E.O.) soybean sterol, glyceryl monostearate, and hydrogenated soybean phospholipid as surfactants.

  The pH of the composition of Comparative Example 2 was 6.3. Moreover, it was 2.2 micrometers when the average particle diameter (median value in a volume reference particle size distribution) of the emulsion particle | grains in the said composition was measured using the particle size distribution analyzer SALD-2000 (made by Shimadzu Corporation).

[Drug stability test 1]
The compositions of Examples 1-1A and 1-1B and Comparative Examples 1-2 produced as described above were held in a constant temperature and humidity chamber of 40 ° C. and 75% RH, respectively. Before introducing each composition into the thermo-hygrostat, and at each time point of 2 weeks, 1 month, 3 months, and 6 months after the start of holding in the thermo-hygrostat, the tetra in each composition The amount of ascorbyl 2-hexyldecanoate and the amount of retinol palmitate contained in vitamin A oil were measured. About the measuring method, each composition of predetermined amount was melt | dissolved with 2-propanol, and each component amount in each melt | dissolution sample was quantified by the high performance liquid chromatography. The measurement conditions are as follows.
Measuring instrument: High performance liquid chromatography Column: Octadecyl silylated silica gel Mobile phase: Methanol Detection method: UV absorption Detection wavelength 1: 220 nm (ascorbyl tetra-2-hexyldecanoate)
Detection wavelength 2: 325 nm (retinol palmitate)

  Table 4 shows the measurement results. In Table 4, the amount of retinol palmitate and ascorbyl tetra-2-hexyldecanoate at each time point is shown as a relative value with the amount of each component as 100 before introducing each composition into a constant temperature and humidity chamber.

  As shown in Table 4, in the compositions of Comparative Examples 1 and 2, the oil-soluble active substances retinol palmitate and ascorbyl tetra-2-hexyldecanoate were rapidly decomposed over time after storage. On the other hand, in the compositions according to the present invention (Examples 1-1A and 1-1B), even after 6 months of storage, these substances were stably maintained at a relative residual ratio of more than 70% relative to the initial value. It had been. That is, this example shows that the composition according to the present invention is excellent in the storage stability of the oil-soluble active substance.

[Examples 1-2 to 1-11]
In the composition of Example 1-1A, the amount of L-arginine was adjusted to prepare compositions of Examples 1-2 to 1-5 having the pH values shown in Table 5 below. In addition, by adding sodium hydroxide instead of L-arginine in the composition of Example 1-1A and adjusting the amount thereof, Examples 1-6 to 1 showing the pH values shown in Table 5 The composition of -8 was produced. In addition, from Example 1-9 showing the pH values shown in Table 5 by adding potassium hydroxide instead of L-arginine in the composition of Example 1-1A and adjusting the amount thereof. The composition of 1-11 was produced.
The production method of each composition was as described in Examples except that the amount of L-arginine was adjusted as described above, or sodium hydroxide or potassium hydroxide was added instead of L-arginine and the amount was adjusted. It is the same as 1-1A.

  The average particle size (median value in the volume-based particle size distribution) of the emulsion particles in each composition was measured using a particle size distribution analyzer SALD-2000 (manufactured by Shimadzu Corporation). It was.

[Drug stability test 2]
For the compositions of Examples 1-2 to 1-11, the same tests as in the above-mentioned drug stability test 1 were performed. However, the measurement after 2 weeks was omitted.
The results are shown in Table 5. Since there was no difference in the stability of retinol palmitate, Table 5 shows only the results for ascorbyl tetra-2-hexyldecanoate.

  According to this drug stability test 2, in the composition of the present invention in which the pH value is changed, both oil-soluble substances of retinol palmitate and ascorbyl tetra-2-hexyldecanoate are stably maintained at a high level even after long-term storage. It was shown that. In addition, since the difference in stability was not seen about retinol palmitate, the measured value is not shown in Table 5. That is, in the compositions of Examples 1-2 to 1-11, the value of retinol palmitate showed the same value as the measured values of Examples 1-1A and 1-1B shown in Table 4 ( (Relative residual rate over 80% after 6 months of storage) That is, it was shown that the composition of the present invention is excellent in the storage stability of the oil-soluble active substance. Furthermore, when the results in Table 5 are examined in detail, the composition having a pH value in the range of 5.0 to 6.0 has a stability of ascorbyl tetra-2-hexyldecanoate with respect to the initial value after storage for 6 months. The relative residual ratio was 70% or more, and it was revealed that the storage stability was more excellent.

[Example 2]
Using the raw materials shown in Table 6, the composition of Example 2 was produced. The manufacturing method is the same as that of Example 1-1A except that the raw materials shown in Table 6 were used.

  The pH of the composition of Example 2 was 5.5. Moreover, it was 5.4 micrometers when the average particle diameter (median value in a volume reference particle size distribution) of the emulsion particle | grains in the said composition was measured using the particle size distribution analyzer SALD-2000 (made by Shimadzu Corporation).

[Comparative Example 3]
Using the raw materials shown in Table 7, a composition of Comparative Example 3 was produced. The manufacturing method is the same as Comparative Example 1 except that the raw materials shown in Table 7 were used. The composition of Comparative Example 3 contains polyoxyethylene (20E.O.) soybean sterol, glyceryl monostearate, and hydrogenated soybean phospholipid as a surfactant.

  The pH of the composition of Comparative Example 3 was 6.3. Moreover, it was 2.2 micrometers when the average particle diameter (median value in a volume reference particle size distribution) of the emulsion particle | grains in the said composition was measured using the particle size distribution analyzer SALD-2000 (made by Shimadzu Corporation).

[Transdermal absorption test 1]
Using the compositions of Example 2 and Comparative Example 3 prepared as described above as test products, the percutaneous absorbability of the oil-soluble active substance was examined for each composition by the following test method.

(Test method)
Yucatan micro-pig-extracted skin (purchased from Charles River Japan) was thawed to remove subcutaneous fat and muscle, and a 3.0 cm square skin section was prepared. Next, 50 mg of the test product was applied to the skin sections, and each skin section was held on a filter paper moistened with buffered saline in a petri dish. After incubating the petri dish in a 32 ° C. incubator for 3 hours, the test article applied to the surface of each skin section was thoroughly wiped off with a Kimwipe, and the skin surface was peeled off three times with cellophane tape. . Next, the epidermis side of this skin section was pressed against a hot plate heated to 60 ° C. for 30 seconds. Since this operation loosens the bond between the epidermis and the dermis of the skin section, the epidermis is collected with tweezers. The test samples were 3 cases (n = 3) for each group.

The collected epidermis was weighed and immersed in 10 ml of 2-propanol for 18 hours to extract vitamin A oil (retinol palmitate) and ascorbyl tetra-2-hexyldecanoate in the epidermis. The extracted 2-propanol solution was passed through a 0.45 μm pore size filter, and the amounts of vitamin A oil (retinol palmitate) and ascorbyl tetra-2-hexyldecanoate were measured by high performance liquid chromatography.
The conditions for high performance liquid chromatography are as described in the above-mentioned drug stability test 1.

(result)
The result of vitamin A oil (retinol palmitate) is shown in FIG. 1, and the result of ascorbyl tetra-2-hexyldecanoate is shown in FIG.
As shown in FIGS. 1 and 2, for the vitamin A oil (retinol palmitate) or ascorbyl tetra-2-hexyldecanoate, which is an oil-soluble active substance, the composition of Example 2 is skin compared to the composition of Comparative Example 3. It was shown that the amount of absorption into That is, according to this example, it was shown that the composition according to the present invention has excellent transdermal absorbability of the active ingredient.

[Example 3]
Using the raw materials shown in Table 8, the composition of Example 3 was produced. The manufacturing method is the same as that of Example 1-1A except that the raw materials shown in Table 8 were used.

  The pH of the composition of Example 3 was 5.5. Moreover, it was 5.1 micrometers when the average particle diameter (median value in a volume reference particle size distribution) of the emulsion particle | grains in the said composition was measured using the particle size distribution analyzer SALD-2000 (made by Shimadzu Corporation).

[Comparative Example 4]
Using the raw materials shown in Table 9, a composition of Comparative Example 4 was produced. The manufacturing method is the same as Comparative Example 1 except that the raw materials shown in Table 9 were used. In addition, the composition of Comparative Example 4 contains polyoxyethylene (20E.O.) soybean sterol, glyceryl monostearate, and hydrogenated soybean phospholipid as a surfactant.

  The pH of the composition of Comparative Example 4 was 6.3. Moreover, it was 2.3 micrometers when the average particle diameter (median value in a volume reference particle size distribution) of the emulsion particle | grains in the said composition was measured using the particle size distribution analyzer SALD-2000 (made by Shimadzu Corporation).

[Comparative Example 5]
A composition of Comparative Example 5 was produced using the raw materials shown in Table 10. The manufacturing method is the same as that of Comparative Example 1 except that the raw materials shown in Table 10 were used. The composition of Comparative Example 5 contains glyceryl monostearate, POE (20E.O.) sorbitan monostearate, POE (60E.O.) hydrogenated castor oil, and hydrogenated soybean phospholipid as surfactants. contains.

  The composition of Comparative Example 5 had a pH of 5.3. Moreover, when the average particle diameter (median value in the volume-based particle size distribution) of the emulsion particles in the composition was measured using a particle size distribution analyzer SALD-2000 (manufactured by Shimadzu Corporation), it was 1.0 μm.

[Comparative Example 6]
A composition of Comparative Example 6 was produced according to the same formulation as Example 3. About the manufacturing method, the A group and the B group were each heated to 80 degreeC, the A group was added and emulsified, stirring the B group. The emulsifying device is T.I. K. Robomix was used and the emulsification conditions were 6,000 rpm and 5 minutes. Furthermore, it processed at 18000 psi with the high-pressure emulsifier (The product made from Microfluidics corp., Microfluidizer M-110 E / H), and cooled to 35 degreeC.

  The composition of Comparative Example 6 had a pH of 5.5. Moreover, when the average particle diameter (median value in the volume-based particle size distribution) of the emulsion particles in the composition was measured using a particle size distribution analyzer SALD-2000 (manufactured by Shimadzu Corporation), it was 0.8 μm.

[Transdermal absorption test 2]
Each composition of Example 3 and Comparative Examples 4 to 6 prepared as described above was used as a test product, and the percutaneous absorbability of the oil-soluble active substance was examined for each composition by the following test method.

(Test method)
Yucatan micro-pig-extracted skin (purchased from Charles River, Japan) was thawed to remove subcutaneous fat and muscle, and a 3.5 cm square skin section was prepared. Hold the flange part of a 2.1cm diameter syringe cylinder (made of polypropylene, with the tip cut) and the skin section with a clamp, put 1g of the test article into the syringe cylinder part, and immerse the skin in a beaker containing physiological saline. And left for 3 hours. Next, after wiping the surface of the skin section with Kimwipe (registered trademark) (Nippon Paper Crecia Co., Ltd. Wiper S-200), stripping was performed 50 times using an adhesive tape (trade name Nexcare Blender, manufactured by Sumitomo 3M Co., Ltd.). went. Methanol was added to the adhesive tape to obtain a required concentration, which was recovered as a liquid sample, and the amount of dl-α-tocopherol acetate in the liquid sample was measured by high performance liquid chromatography. In the high performance liquid chromatography, the detection wavelength was 285 nm, and the other conditions were the same as in the transdermal absorption test 1.

(result)
The test results are shown in FIG.
As shown in FIG. 3, the oil-soluble active substance dl-α-tocopherol acetate shows that the composition of Example 3 has a higher amount of absorption into the skin than the compositions of Comparative Examples 4 to 6. It was done. That is, according to this example, it was shown that the composition according to the present invention has excellent transdermal absorbability of the active ingredient.

[Examples 4 to 10]
Further, examples of the O / W type emulsion composition of the present invention include those having the respective compositions and particle sizes of Examples 4 to 10 shown in Table 11 below. These O / W emulsion compositions can be produced in the same manner as in the production method shown in Example 1-A. At that time, the emulsification conditions are appropriately adjusted so that each composition has the particle diameter shown in Table 11 (average particle diameter of emulsion particles).

  As described above, the O / W emulsion composition of the present invention has high storage stability and transdermal absorbability of an oil-soluble active ingredient in addition to having high emulsion stability.

Claims (11)

An O / W emulsion composition containing an oil-soluble active substance and an alkyl-modified carboxyvinyl polymer and / or a salt thereof,
The pH of the composition is 4.0 to 8.0;
The emulsion particles in the composition have an average particle size of 2 μm to 10 μm, and
The content of the surfactant other than the alkyl-modified carboxyvinyl polymer and / or salt thereof is 0.1% by weight or less of the amount of the oil phase,
The above composition. The composition according to claim 1, comprising at least one selected from the group consisting of oil-soluble vitamins, derivatives or salts thereof; and oil-soluble derivatives of water-soluble vitamins or salts thereof as the oil-soluble active substance. object. As said oil-soluble active substance, vitamin A, its derivatives or salts thereof; vitamin E, its derivatives or salts thereof; vitamin D, its derivatives or salts thereof; vitamin K, its derivatives or salts thereof; oil-soluble ascorbine The composition according to claim 1 or 2, comprising at least one selected from the group consisting of an acid derivative or a salt thereof; and an oil-soluble pyridoxine derivative or a salt thereof. Vitamin A, its derivatives or salts thereof; vitamin E, its derivatives or salts thereof; vitamin D, its derivatives or salts thereof; oil-soluble ascorbic acid derivatives or salts thereof; and oil-soluble pyridoxine The composition according to any one of claims 1 to 3, comprising one or more selected from the group consisting of a derivative or a salt thereof. The oil-soluble active substance contains at least one selected from the group consisting of vitamin A, derivatives thereof or salts thereof; vitamin E, derivatives or salts thereof; and oil-soluble ascorbic acid derivatives or salts thereof. Item 5. The composition according to any one of Items 1 to 4. The oil-soluble active substance contains two or more selected from the group consisting of vitamin A, derivatives thereof or salts thereof; vitamin E, derivatives or salts thereof; and oil-soluble ascorbic acid derivatives or salts thereof. Item 6. The composition according to any one of Items 1 to 5. The composition according to any one of claims 1 to 6, comprising vitamin A, a derivative thereof or a salt thereof; and an oil-soluble ascorbic acid derivative or a salt thereof as the oil-soluble active substance. The composition according to any one of claims 1 to 7, wherein the pH is 4.5 to 7.5. The composition according to any one of claims 1 to 8, wherein the pH is 4.5 to 7.0. A skin external preparation containing the composition according to any one of claims 1 to 9. The skin external preparation of Claim 10 which is a cosmetic composition, a skin care composition, or a pharmaceutical composition.