JP2021059525A - Oil-in-water emulsification composition and method for suppressing dripping of oil-in-water emulsification composition - Google Patents

Abstract

To provide novel formulations having both the excellent pharmacological effect of a heparinoid and good properties (usability, a feeling of use), in emulsification compositions containing a heparinoid.SOLUTION: An oil-in-water emulsified composition contains (A) a heparinoid and (B) one or more oil-soluble components selected from the group consisting of oil-soluble acyl amino acids, derivatives thereof and salts thereof, and paste-like oils. The content of the (B) oil-soluble components is preferably 0.01 mass% to 10 mass% of the entire oil-in-water emulsified composition. In addition, preferably (C) one or more active components selected from the group consisting of glycyrrhizic acid, derivatives thereof, and salts thereof, ascorbic acid, derivatives thereof, and salts thereof, nicotinic acid amide, tocopherol or derivatives thereof, retinol or derivatives thereof, tranexamic acid, and allantoin are contained.SELECTED DRAWING: None

Description

The present invention relates to an oil-in-water emulsified composition and a method for suppressing dripping of an oil-in-water emulsified composition.

Heparinoids are one of the mucopolysaccharides that have excellent moisturizing, anti-inflammatory, blood circulation promoting and other pharmacological effects (treatment and prevention of atopic dermatitis, hypertrophic scars and keloids, trauma (bruise, sprain)). , Care after contusion, etc.), so it is widely used as an active ingredient of external preparations. In order to effectively exert various effects of such heparinoids, various preparations containing heparinoids have been developed (see Patent Documents 1 and 2).

On the other hand, the emulsified preparation has properties like emulsion to cream depending on the combination of various oils and thickeners and the emulsified state. Especially when a high amount of oil is mixed or when a paste-like to solid oil is mixed, it is very difficult to control the stability and usability, and the viscosity of the preparation increases, so that the container such as a tube or bottle can be used. Since it becomes difficult to discharge the paste, the container specifications that can be selected are limited, and there is a problem that the application is narrowed. Further, in the emulsified preparation, various feelings of use such as refreshing and moist are required depending on the purpose, but in each case, there is a problem of stickiness and irritation due to oil and mucopolysaccharide. In general, the feeling of use such as stickiness and irritation tends to be avoided, and there is always a demand for a preparation having both the moisturizing power of an emulsified preparation and a good feeling of use.

While the heparinoid has various effects as described above, it is known that the emulsification stability of the emulsified composition is easily impaired, and an emulsified composition containing the heparinoid is desired. It is not easy to adjust to the viscosity of. As a method for improving the emulsification stability of an emulsified composition containing such a heparinoid, for example, Patent Document 3 describes oil-in-water emulsification containing a heparinoid by blending reduced lanolin. It has been described that lotions can be provided with excellent emulsion stability. Further, Patent Document 4 is excellent in making an emulsified composition by blending a phosphoric acid-based surfactant, glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and / or salts thereof together with a heparinoid. It is described that the emulsion stability can be obtained.

In addition, heparinoids have the disadvantage that they are inferior in skin compatibility and difficult to obtain a permeation feeling because they give a slimy feel when applied, which is peculiar to polysaccharides, particularly acidic mucopolysaccharides. It is also known that stickiness occurs after application to the affected area. As a method for solving these problems, for example, in Patent Document 5, a hyaluronic acid oligosaccharide and / or a salt thereof is blended with an oil-in-water emulsified composition containing a heparinoid to give a slimy feeling at the time of application. It is described that it is possible to provide a satisfactory permeation feeling and moisturizing feeling while having excellent skin compatibility by suppressing the above. Further, Patent Document 6 describes that the stickiness after application can be improved by blending isopropanol in a gel-like oil-in-water emulsified composition containing a heparin-like substance.

Japanese Unexamined Patent Publication No. 2015-23302 JP-A-2017-178798 Japanese Unexamined Patent Publication No. 11-180821 Japanese Unexamined Patent Publication No. 2017-048163 Japanese Unexamined Patent Publication No. 2017-066060 Japanese Unexamined Patent Publication No. 2016-193854

Under such circumstances, it is an object of the present invention to provide an emulsified composition containing a heparinoid, which has both excellent pharmacological effects and good properties (usability, usability) of the heparinoid. To do.

As a result of diligent research to solve the above problems, the present inventors, in an oil-in-water emulsified composition containing a heparinoid, consist of an oil-soluble acyl amino acid, a derivative thereof, a salt thereof, and a paste-like oil. By blending one or more oil-soluble ingredients selected from the group, it is easy to control the characteristics of the formulation while having high moisturizing power, and both various usability and excellent pharmacological effect of heparinoids are achieved. Succeeded in making the prepared formulation.

That is, the gist of the present invention is as follows.

[1] Oil in water containing one or more oil-soluble components selected from the group consisting of (A) heparinoids, (B) oil-soluble acyl amino acids, derivatives thereof and salts thereof, and paste-like oils. Molded emulsion composition.
[2] The oil-in-water emulsified composition according to [1], wherein the content of the oil-soluble component (B) is 0.01% by mass to 10% by mass of the entire oil-in-water emulsified composition.
[3] Further, from the group consisting of (C) glycyrrhizinic acid, its derivative and its salt, ascorbic acid, its derivative and its salt, nicotinamide, tocopherol or its derivative, retinol or its derivative, tranexamic acid, and allantin. The oil-in-water emulsified composition according to [1] or [2], which contains one or more selected active ingredients.
[4] The oil-soluble component of (B) above is shea butter, phytosterol fatty acid ester, cholesterol fatty acid ester, N-acylamino acid sterol ester, vaseline, tri (capril, caprin, myristin, stearic acid) glyceryl, dipentaerythrit fatty acid. The oil-in-water emulsified composition according to any one of [1] to [3], which is one or more selected from the group consisting of an ester, a dimer dilinoleic acid sterol ester, and a dimer dilinoleic acid sterol / higher alcohol ester. ..
[5] The oil-in-water emulsified composition according to any one of [1] to [4], which further contains (D) a salt-tolerant polymer.
[6] It is characterized by blending one or more oil-soluble components selected from the group consisting of (A) heparinoids, (B) oil-soluble acylamino acids, derivatives thereof and salts thereof, and paste-like oils. A method for suppressing dripping of an oil-in-water emulsified composition.

According to the present invention, in an oil-in-water emulsified composition containing a heparinoid, one or more oil-soluble components selected from the group consisting of oil-soluble acyl amino acids, derivatives thereof and salts thereof, and paste-like oils are used. By blending, the viscosity is adjusted appropriately and it is excellent in usability, and while it has moisturizing power, stickiness and irritation are suppressed, and a formulation that combines the excellent pharmacological effect of heparinoids with a good usability. Can be. In the oil-in-water emulsified composition of the present invention, the characteristics of the preparation can be easily controlled, and the preparation can be used in a variety of ways. Furthermore, by combining these components, an unexpected effect was obtained, which was expected to realize a fresh feeling of use even though the oil-soluble component was highly blended. Further, the external composition of the present invention is excellent because it is not sticky or sticky even though it contains a heparin-like substance which is a mucopolysaccharide that causes sliminess, spinnability, and low penetration. The unexpected effect of having familiarity with the skin was also obtained.

Hereinafter, the present invention will be described in detail. Unless otherwise specified, the terms used in the present specification are interpreted in the meanings commonly used in the art.

<Oil-in-water emulsification composition>
The oil-in-water emulsified composition of the present invention is one or more oils selected from the group consisting of (A) heparinoids, (B) oil-soluble acylamino acids, derivatives thereof and salts thereof, and paste-like oils. It is characterized by containing 0.01 to 10% by mass of a soluble component. In an oil-in-water emulsified composition containing a heparinoid, by containing the oil-soluble component (B) in a specific amount, the viscosity is appropriately adjusted, the usability is excellent, and the oil-soluble component has moisturizing power and is sticky. The irritation feeling is suppressed, and a preparation having both the excellent pharmacological effect of the heparinoid and the good usability can be obtained. In the oil-in-water emulsified composition of the present invention, in addition to the above-mentioned (A) heparinoid and (B) essential components of the oil-soluble component, (C) active ingredient, (D) salt-tolerant polymer, and (E) anion It may contain additional ingredients such as sex surfactants. Further, a component serving as a base / carrier and other optional components may be contained as long as the effects of the present invention are not impaired. Hereinafter, the essential components (A) and (B), the additional components (C) to (E), the base / carrier component, and other optional components will be described in detail. When the compounds specifically exemplified as each component are duplicated, they may be contained as any of the components.

[(A) Heparinoid]
The heparinoid is a polysulfated mucopolysaccharide such as chondroitin polysulfate, and is a known drug known to have a moisturizing effect, an anti-inflammatory effect, a blood circulation promoting effect, and the like.

The content of the heparin-like substance in the oil-in-water emulsified composition of the present invention is 0.005% by mass to 5% by mass and 0.01% by mass to 3% by mass with respect to the total amount of the composition. It is preferably 0.05% by mass to 1% by mass, further preferably 0.1% by mass to 0.5% by mass, and 0.1% by mass to 0.3% by mass. It is particularly preferable to have. By setting the content of the heparin-like substance in the oil-in-water emulsified composition of the present invention within the above range, the physiological actions such as the moisturizing action and the blood circulation promoting action of the heparin-like substance can be exhibited, and the inflammation-inducing property is sufficiently sufficient. It can be a suppressed composition.

[(B) Oil-soluble component]
The oil-soluble component (B) is one or more oil-soluble components selected from the group consisting of oil-soluble acyl amino acids, derivatives thereof and salts thereof, and paste-like oils.

Here, the above-mentioned "salt" is a pharmaceutically acceptable salt. The effect of the present invention is not particularly limited, but for example, inorganic salts such as sodium, potassium, calcium, magnesium, aluminum and zinc; organic amines such as ammonia, monoethanolamine, diethanolamine and triethanolamine, and arginine, Examples thereof include organic salts such as basic amino acids such as lysine, and one or a mixture of two or more of these can be used. Of these, salts of sodium, potassium, ammonium, triethanolamine and arginine are preferable, and salts of sodium, potassium, ammonium and triethanolamine are more preferable.

Further, the above-mentioned "derivative" refers to a product obtained by chemically modifying a part of a functional group of an acyl amino acid, a product having a protecting group added to a part of the functional group, or the like, as long as the effect of the present invention is not impaired. It refers to something that includes the body.

(Oil-soluble acyl amino acids, their derivatives and their salts)
The amino acid in the acyl amino acid may be any of neutral, acidic and basic, and may be any of L-form, D-form and DL-form. For example, glutamic acid, aspartic acid, glycine, proline, alanine, threonine, methylalanine, sarcosin, lysine, arginine, methylalanine, taurine, methyltaurine, etc. include glutamic acid, aspartic acid, glycine, proline, alanine, lysine, etc. Arginine is preferred, glutamic acid, glycine, proline, alanine, lysine, arginine are more preferred, glutamic acid, alanine, glycine, proline, alanine, lysine are even more preferred, glutamic acid, alanine, glycine, proline, lysine are even more preferred. Glutamic acid and glycine are particularly preferable.

Among the acyl amino acids, the fatty acid constituting the acyl group preferably has 2 to 32 carbon atoms, more preferably 8 to 22 carbon atoms, and even more preferably 8 to 18 carbon atoms. Hydrocarbons may be saturated or unsaturated, may be branched or cyclic, or may be mixed fatty acids. Specifically, caproic acid, caprylic acid, decanoic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitreic acid, stearic acid, oleic acid, linoleic acid, bechenic acid, coconut oil fatty acid, castor oil fatty acid, olive oil fatty acid. , Palm oil fatty acid and the like. Of these, caprylic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, bechenic acid, coconut oil fatty acid, and olive oil fatty acid are preferable, and caprylic acid, coconut oil fatty acid, lauric acid, palmitic acid, and stearic acid. Is more preferable, and lauric acid, caprylic acid, and stearic acid are even more preferable.

As the derivative of the acyl amino acid, a sterol ester is preferable, and as the acyl amino acid sterol ester, N-lauroyl-L-glutamic acid dihexyldecyl, N-lauroyl-L-glutamic acid dioctyldodecyl, N-lauroyl-L-glutamic acid di (phytosteryl / octyl). Dodecyl), di-lauroyl-L-glutamate (cholesteryl / octyldodecyl), di-lauroyl-L-glutamate (cholesteryl / behenyl / octyldodecyl), di-lauroyl-L-glutamate (phytosteryl / behenyl / octyldodecyl) ), N-myristoyl-N-methylalanine (phytosteryl / decyltetradecyl). Specifically, N-lauroyl-L-glutamic acid dioctyldodecyl, N-lauroyl-L-glutamic acid di (phytosteryl / octyldodecyl), N-lauroyl-L-glutamic acid di (cholesteryl / octyldodecyl), N-lauroyl-L- Diglutamate (cholesteryl / behenyl / octyldodecyl), di-lauroyl-L-glutamic acid (phytosteryl / behenyl / octyldodecyl) are more preferred, and dioctyldodecyl N-lauroyl-L-glutamate, di (N-lauroyl-L-glutamate). Phytosteryl / octyldodecyl) and di-lauroyl-L-glutamic acid (phytosteryl / behenyl / octyldodecyl) are more preferred.

Commercially available products may be used as the derivative of the acyl amino acid. Eldu PS-304, Eldu PS-306, Eldu APS-307 (above, manufactured by Ajinomoto Co., Inc.), PLANDOOL-LG1, PLANDOOL-LG2, PLANDOOL-LG3, PLANDOOL-LG4 (above, manufactured by Nippon Seika Co., Ltd.), AMIER LG- 2000, AMITER LG-1600 (all manufactured by Nippon Emulsion Co., Ltd.) and the like.

As the acyl amino acid or a salt thereof, lauroyl-ε-lysine or a salt thereof is preferable.

As the acyl amino acid or a salt thereof, a commercially available product may be used, and examples thereof include Amihope (registered trademark) LL (manufactured by Ajinomoto Co., Inc.) and the like.

(Paste oil)
The paste-like oil is an oil that is paste-like at room temperature (25 ° C.) and has a melting point of 45 ° C. or lower.

As the paste-like oil, one or more selected from shea butter, sterol fatty acid ester, vaseline, tri (capril, caprin, myristin, stearic acid) glyceryl, dipentaerythrit fatty acid ester, and dimer acid ester is preferable, and shea butter. , Phytosterol fatty acid ester, cholesterol fatty acid ester, vaseline, tri (capril, caprin, myristin, stearic acid) glyceryl, dipentaerytrit fatty acid ester, dimer dilinoleic acid sterol ester, dimer dilinoleic acid sterol / higher alcohol ester One or more are more preferable, and shea butter, phytosterol fatty acid ester, cholesterol fatty acid ester, vaseline, tri (capril, caprin, myristine, stearic acid) glyceryl, hexa (hydroxystearic acid / stearic acid / logic acid) dipentaerythrityl, tetra ( Hydroxystearic acid / isostearic acid) dipentaerythrityl, dimer dilinoleic acid dimer dilinoleil, dimer dilinoleic acid di (isostearyl / phytosteryl), dimer dilinoleic acid dimer dilinoleyl bis (behenyl / isostearyl / phytosteryl), dimerge Dymerly linoleyl bisisostearyl, dymerging linoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dymerging linoleyl hydrogenated rosin condensate, more preferably one or more. Cholesteryl isostearate, phytosteryl isostearate, cholesteryl hydroxystearate, phytosteryl hydroxystearate, phytosteryl capril / phytosteryl caprice, phytosteryl lysinolate, cholesteryl oleate, phytosteryl oleate, dihydrocholesteryl oleate, branched fatty acid (C12-31) cholesteryl, Plant sterol fatty acid ester, lanolin fatty acid cholesteryl, vaseline, tri (capril, caprin, myristin, stearic acid) glyceryl, hexa (hydroxystearic acid / stearic acid / logonic acid) dipentaerythrityl, tetra (hydroxystearic acid / isostearic acid) dipentaerythrityl, die Marginolic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimerdilinolic acid (isostearyl / phytosteryl), dimerge One or more selected from dimer dilinoleyl bis (phytosteryl / behenyl / isostearyl) linoleate is even more preferable, and shealic acid, phytosteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, phytosteryl oleate, branched fatty acids (branched fatty acids). C12-31) Cholesteryl, Macademia nut oil fatty acid phytosteryl, sunflower seed oil fatty acid phytosteryl, rice bran oil fatty acid phytosteryl, vaseline, tri (capril, caprin, myristin, stearic acid) glyceryl, hexa (hydroxystearic acid / stearic acid / linoleic acid) dipentaerythrityl , Tetra (hydroxystearic acid / isostearic acid) dipentaerythrityl, dimer dilinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleic acid (isostearyl / phytosteryl), dimer dilinoleic acid dimer dilinoleyl bis ( One or more selected from phytosteryl / behenyl / isostearyl) is particularly preferable.

The fatty acid group of the sterol fatty acid ester preferably has 2 to 32 carbon atoms, more preferably 8 to 22 carbon atoms, and even more preferably 10 to 18 carbon atoms. Hydrocarbons may be saturated or unsaturated, may be branched or cyclic, or may be mixed fatty acids. Specifically, caproic acid, capric acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, bechenic acid, coconut oil fatty acid, castor oil fatty acid, olive oil fatty acid, palm oil. Examples include fatty acids and hydroxystearic acid.

Examples of sterol fatty acid esters include cholesteryl isostearate, phytosteryl isostearate, cholesteryl hydroxystearate, phytosteryl hydroxystearate, phytosteryl capryl / phytosteryl caprice, phytosteryl lysinolate, cholesteryl oleate, phytosteryl oleate, dihydrocholesteryl oleate, and branched fatty acids (phytosteryl oleate, dihydrocholesteryl oleate). C12-31) Cholesteryl, plant sterol fatty acid ester, lanolin fatty acid cholesteryl and the like can be mentioned. Among them, cholesteryl isostearate, phytosteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, phytosteryl oleate, branched fatty acid (C12-31) cholesteryl, macadamia nut oil fatty acid phytosteryl, macadamia nut oil fatty acid cholesteryl, macadamia nut oil fatty acid dihydrocholesteryl Fatty acid phytosteryl, rice bran oil fatty acid phytosteryl, lanolin fatty acid cholesteryl are preferred, phytosteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, phytosteryl oleate, branched fatty acid (C12-31) cholesteryl, macadamia nut oil fatty acid phytosteryl, sunflower seed oil. Phytosteryl, rice bran oil fatty acid phytosteryl are more preferable, and cholesteryl hydroxystearate, cholesteryl oleate, phytosteryl oleate, branched fatty acid (C12-31) cholesteryl, macadamia nut oil fatty acid phytosteryl, and sunflower seed oil fatty acid phytosteryl are particularly preferable.

Commercially available sterol fatty acid esters include Exepearl IS-CE (Kao), Saracos PO, Saracos HS (Nikko Oillio), Kairei Marine Cholesteryl Ester (Nikko Fisheries), YOFCO MAC, YOFCO MAS, and PLANDOL. -MAS, PLANDOOL-SUN, PLANDOOL-ISS, YOFCO CLE-S, YOFCO CLE-NH (above, manufactured by Nikko Chemicals), lysterol ester (manufactured by Tsukino Rice Fine Chemicals), NIKKOL phytosteryl hydroxystearate, NIKKOL Cholesteryl esterate (manufactured by Nikko Chemicals Co., Ltd.) and the like can be mentioned.

Examples of commercially available products of tri (caprylic, capry, myristic, stearic acid) glyceryl include Saracos 334 (manufactured by Nisshin Oillio Co., Ltd.).

The dipentaerythrit fatty acid ester is not particularly limited, but hexa (hydroxystearic acid / stearic acid / rosinic acid) dipentaerythrityl and tetra (hydroxystearic acid / isostearic acid) dipentaerythrityl are preferable.

Examples of commercially available dipentaerylitrit fatty acid esters include Cosmol 168ARV and Cosmol 168EV (all manufactured by Nisshin Oillio Co., Ltd.).

Examples of the dimer acid ester include dimer dilinoleic acid dimer dilinoleyl, dimer dilinoleic acid di (isostearyl / phytosteryl), dimer dilinoleic acid dimer dilinoleyl bis (behenyl / isostearyl / phytosteryl), and dimer linoleic acid. Dimer dilinoleyl bisisostearyl, dimer dilinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleyl hydrogenated rosin condensate and the like can be mentioned. Of these, dimer dilinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleic acid (isostearyl / phytosteryl), and dimer dilinoleic acid dimer dilinoleyl bis (phytosteryl / behenyl / isostearyl) are preferable.

Examples of commercially available products of dimer acid ester include Plandol-H, Plandol-G, Plandol-S, LUSPLAN PI-DA, (manufactured by Nippon Fine Chemical Co., Ltd.) and the like.

Examples of the (B) oil-soluble component in the oil-in-water emulsified composition of the present invention include lauroyl-ε-lysine, shea butter, phytosterol fatty acid ester, cholesterol fatty acid ester, N-acylamino acid sterol ester, vaseline, and tri (capril caprin). (Millistin / stearic acid) One or more selected from glyceryl, dipentaerytrit fatty acid ester, dimer dilinoleic acid sterol ester, dimer dilinoleic acid sterol / higher alcohol ester is preferable, and shea butter, phytosterol fatty acid ester, cholesterol fatty acid. Selected from esters, N-acylamino acid sterol esters, vaseline, tri (capril caprin myristine stearic acid) glyceryl, dipentaerytrit fatty acid ester, dimer dilinoleic acid sterol ester, dimer dilinoleic acid sterol / higher alcohol ester One or more are preferable, and shea butter, phytosterol fatty acid ester, cholesterol fatty acid ester, N-acyl amino acid sterol ester, vaseline, tri (capril, caprin, myristin, stearic acid) glyceryl, dipentaerytrit fatty acid ester, dimer linoleic acid. One or more selected from acid sterol ester and dimer dilinoleic acid sterol / higher alcohol ester are preferable. More specifically, shea butter, phytosterol fatty acid ester, cholesterol fatty acid ester, vaseline, tri (capril, caprin, myristin, stearic acid) glyceryl, hexa (hydroxystearic acid / stearic acid / loginic acid) dipentaerythrityl, tetra (hydroxystearic acid). Acid / isostearic acid) dipentaerythrityl, dimer dilinoleic acid dimer dinorail, dimer dilinoleic acid di (isostearyl / phytosteryl), dimer dilinoleic acid dimer dinorailbis (behenyl / isostearyl / phytosteryl), dimer dilinoleic acid One or more selected from dimer dinorail bisisostearyl, dimer dilinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), and dimer dilinoleyl hydrogenated rosin condensate are more preferable, and shea butter and isostearic acid. Cholesteryl, phytosteryl isostearate, cholesteryl hydroxystearate, phytosteryl hydroxystearate, phytosteryl capril / phytosteryl caprice, phytosteryl lysinolate, cholesteryl oleate, phytosteryl oleate, dihydrocholesteryl oleate, branched fatty acid (C12-31) cholesteryl, plant sterol Fatty ester, lanolin fatty acid cholesteryl, vaseline, tri (capril, caprin, myristin, stearic acid) glyceryl, hexa (hydroxystearic acid / stearic acid / logonic acid) dipentaerythrityl, tetra (hydroxystearic acid / isostearic acid) dipentaerythrityl, dimer dilinol One or more selected from acids (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleic acid (isostearyl / phytosteryl), dimer dilinoleyl bis (phytosteryl / behenyl / isosteryl) Even more preferable, shea butter, phytosteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, phytosteryl oleate, branched fatty acid (C12-31) cholesteryl, macadamia nut oil fatty acid phytosteryl, sunflower seed oil fatty acid phytosteryl, rice bran oil fatty acid phytosteryl, tri (Capril, Caprin, Myristin, Stearic Acid) Glyceryl, Hexa (Hydroxystearic Acid / Stearic Acid / Logic Acid) ) Dipentaerythrityl, tetra (hydroxystearic acid / isostearic acid) dipentaerythrityl, dimer dilinoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleic acid (isostearyl / phytosteryl), dimer dilinoleic acid dimer dilinoleyl One or more selected from bis (phytosteryl / behenyl / isostearyl) is particularly preferable.

The content of the oil-soluble component (B) in the oil-in-water emulsified composition of the present invention is preferably 0.001% by mass to 15% by mass, preferably 0.001% by mass or more, from the viewpoint of the effect of the present invention. It is more preferably 10% by mass, further preferably 0.01% by mass to 8% by mass, and particularly preferably 0.1% by mass to 5% by mass. By setting the content of the oil-soluble component (B) in the oil-in-water emulsified composition of the present invention within the above range, it becomes easy to control the characteristics of the preparation, and the stickiness is suppressed while having moisturizing power. It can be a composition having malleability.

The ratio (A / B) of (A) the content (% by mass) of the (A) oil-soluble component to the content (% by mass) of the (B) oil-soluble component in the oil-in-water emulsified composition of the present invention is 0.0005-. It is preferably 500, more preferably 0.001 to 300, even more preferably 0.005 to 100, even more preferably 0.01 to 50, 0.01 to 0. 5 is particularly preferable.

[(C) Active ingredient]
The oil-in-water emulsified composition of the present invention may further contain the active ingredient (C) in order to impart a medicinal effect. (C) The active ingredient is from the group consisting of glycyrrhizic acid, its derivatives and their salts, ascorbic acid, its derivatives and their salts, nicotinamide, tocopherol or its derivatives, retinol or its derivatives, tranexamic acid, and allantin. One or more components to be selected.

The above-mentioned "salt" is a pharmaceutically acceptable salt, and is not limited to, for example, a salt with an organic base (for example, a tertiary amine salt, an ammonium salt, etc.) or a salt with an inorganic base (for example, a salt with an inorganic base). For example, inorganic acid salts such as hydrochlorides, sulfates and phosphates; alkali metal salts such as sodium salts, potassium salts, dipotassium salts, magnesium salts and zinc salts) and the like. Among them, monoammonium salt, sodium salt, potassium salt, dipotassium salt, magnesium salt and zinc salt are preferable, monoammonium salt, sodium salt, dipotassium salt and magnesium salt are more preferable, and dipotassium salt, sodium salt and magnesium salt are further preferable. ..

Examples of the active ingredient (C) include dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, allantin, ascorbic acid, sodium ascorbate, sodium ascorbic acid ester, magnesium ascorbic acid phosphate, sodium ascorbic acid sulfate 2, and 2 -O-ethylascorbic acid, 3-O-ethylascorbic acid, ascorbic acid-2-glucoside, isostearyl ascorbyl phosphate disodium, ascorbyl palmitate trisodium, glyceryl ascorbic acid, bisglyceryl ascorbic acid, hexyl 3- Glyceryl ascorbic acid, 3-glyceryl ascorbic acid, myristyl 3-glyceryl ascorbic acid, 3-lauryl glyceryl ascorbic acid, potassium (ascorbyl / tocopheryl) phosphate, ascorbyl tocopheryl maleate, ascorbyl tetrahexyl decanoate, nicotinic acid amide, α-tocopherol , Β-tocopherol, δ-tocopherol, tocopherol acetate, tocopherol nicotinate, tocopherol succinate, tocopherol succinate calcium, retinol, retinol acetate, retinol palmitate, tocopheryl retinoate, tranexamic acid are preferred, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate Allantin, sodium ascorbic acid phosphate, magnesium ascorbyl phosphate, 2-O-ethylascorbic acid, 3-O-ethylascorbic acid, ascorbic acid-2-glucoside, ascorbyl tetrahexyl decanoate, nicotinic acid amide, α-tocopherol , Β-tocopherol, δ-tocopherol, tocopherol acetate, retinol acetate, retinol palmitate, tranexamic acid are more preferable, dipotassium glycyrrhizinate, allantin, sodium ascorbic acid ester, magnesium ascorbic acid phosphate, 3-O-ethylascorbic acid. , Ascorbic acid-2-glucoside, ascorbic tetrahexyl decanoate, nicotinic acid amide, δ tocopherol, tocopherol acetate, retinol acetate, retinol palmitate, tranexamic acid are more preferred, dipotassium glycyrrhizinate, sodium ascorbic acid ester, phosphorus ascorbic acid. Acid ester magnesium, 3-O-ethylascorbic acid, ascor Vitamin-2-glucoside, ascorbyl tetrahexyldecanoate, nicotinamide, delta-tocopherol, tocopherol acetate, tranexamic acid are particularly preferred.

The content of the active ingredient (C) in the oil-in-water emulsified composition of the present invention is 0.001% by mass to 10% by mass, and 0.01% by mass to 8% by mass, based on the total amount of the composition. It is preferably 0.05% by mass to 5% by mass, more preferably 0.1% by mass to 5% by mass. By setting the content of the active ingredient (C) in the above range, the oil-in-water emulsified composition of the present invention has high usability and usability while having moisturizing power in the oil-in-water emulsified composition of the present invention. In addition to the remarkable effect of compatibility, a more preferable medicinal effect can be imparted.

[(D) Salt-tolerant polymer]
(D) A salt-tolerant polymer may be blended for the purpose of adding an appropriate viscosity to the external composition of the present invention and for the purpose of stabilizing the preparation. Examples of the salt-tolerant polymer (D) include polyacrylamide, a polymer having dimethyl taurine or a salt thereof in a side chain, and a hydrophobically modified polyurethane. Among them, polyacrylamide, (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer, (acryloyldimethyltaurinammonium / vinylpyrrolidone) copolymer, (acryloyldimethyltaurinammonium / behenes-25 methacrylate) cross-polymer, (acryloyldimethyltaurineammonium / Steareth methacrylate-25) Crosspolymer, (Acrylic acid / Acryloyldimethyltaurin / Dimethylacrylamide) Crosspolymer, (Na acrylate / Acryloyldimethyltaurine Na) copolymer, (PEG-240 / Decyltetradeceth-20 / HDI) copolymer Is preferable, polyacrylamide, (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer, (acrylic acid / acryloyldimethyltaurin / dimethylacrylamide) crosspolymer, (Na acrylate / acryloyldimethyltaurine Na) copolymer, (PEG-240 / A decyltetradeceth-20 / HDI) copolymer is preferred.

(D) Commercially available salt-tolerant polymers include, for example, Aristoflex AVC, Aristoflex HMB, Aristoflex HMS (all manufactured by Clariant Japan Co., Ltd.), SEPIGEL305, SEPINOV EMT 10, SIMULGEL NS, SIMULGEL FL, SIMULGEL , SEPINOV P88 (all manufactured by SEPPIC), Adecanol GT700 (manufactured by ADEKA) and the like.

The content of the (D) salt-resistant polymer in the oil-in-water emulsified composition of the present invention is usually 0.01% by mass to 5% by mass, preferably 0.05% by mass to 4% by mass. , 0.1% by mass to 3% by mass, more preferably 0.5% by mass to 3% by mass. By setting the content of the (D) salt-tolerant polymer in the oil-in-water emulsified composition of the present invention within the above range, the viscosity of the oil-in-water emulsified composition can be appropriately adjusted and the stability can be improved. It is possible to facilitate the control of the properties of the formulation in order to enhance usability or usability.

[(E) Anionic surfactant]
The oil-in-water emulsified composition of the present invention may contain (E) anionic surfactant and anionic surfactant for the purpose of appropriately modifying the feeling of use and stabilizing the preparation. Anionic Surfactants Examples of anionic surfactants include sodium N-stearoyl glutamate, sodium dilauroyl glutamate, monosodium N-lauroyl glutamate, sodium N-stearoyl-L-glutamate, arginine N-stearoyl-L-glutamate, and the like. Examples thereof include N-myristoyl-L-glutamic acid sodium, N-stearoylmethyl taurine sodium, N-myristoyl methyl taurine sodium, N-cocoyl methyl taurine sodium and the like. Of these, sodium N-stearoyl glutamate and sodium N-stearoyl methyl taurine are preferable from the viewpoint of promoting the effects of the present invention.

The content of the (E) anionic surfactant in the oil-in-water emulsified composition of the present invention is usually 0.001% by mass to 10% by mass, and 0.01% by mass to 8% by mass. , More preferably 0.05% by mass to 5% by mass, and even more preferably 0.1% by mass to 3% by mass. By setting the content of the (E) anionic surfactant in the oil-in-water emulsified composition of the present invention within the above range, the viscosity of the oil-in-water emulsified composition is appropriately adjusted, and the viscosity of the oil-in-water emulsified composition is appropriately adjusted. It is possible to facilitate the control of the properties of the formulation in order to improve stability, usability or usability.

(Base or carrier)
The oil-in-water emulsified composition of the present invention contains the essential components and the components described above together with a base or carrier usually used for pharmaceuticals, quasi-drugs, cosmetics, etc., and if necessary, additives. , Can be mixed and emulsified according to a conventional method to prepare a composition in a formulation form suitable for various uses.

The oil-in-water emulsified composition of the present invention contains known components added to cosmetics, pharmaceuticals, non-pharmaceutical products, etc., as long as the effects of the present invention are not impaired, such as blood circulation promoters, astringents, and ultraviolet scattering. Agents, UV absorbers, surfactants, stabilizers, antioxidants, colorants, pearl gloss enhancers, dispersants, chelating agents, pH adjusters, preservatives, thickeners, irritation reducers, anti-inflammatory Optional ingredients such as ingredients, bactericidal and disinfectant ingredients (antibacterial ingredients), keratin softening ingredients, warmth ingredients, hair growth promoting ingredients, moisturizing ingredients, anti-wrinkle agents, anti-glycation ingredients, cell activating ingredients, whitening ingredients, etc. Can be added. These additives may be used alone or in combination of two or more. In addition, the components contained in the above-mentioned components (A) to (E) are excluded from these optional components.

The method for preparing the oil-in-water emulsified composition of the present invention is not particularly limited, and the above-mentioned various components necessary for preparing the oil-in-water emulsified composition are appropriately selected, blended and mixed, and prepared by a conventional method. can do. The application amount and usage of the oil-in-water emulsified composition of the present invention are not particularly limited, and an appropriate amount can be usually applied once to several times a day to the area including the affected area.

The oil-in-water emulsified composition of the present invention is usually in the range of pH 4 to 9, preferably pH 4.5 to 8.5, and more preferably pH 5 to 8 from the viewpoint of the effect of the present invention. .. This pH can be adjusted by using a pH adjuster.

(Usability)
The "usability" that is a feature of the oil-in-water emulsified composition of the present invention will be described. In the present invention, the usability means the ease of use, usability, and ease of handling of the oil-in-water emulsified composition. Furthermore, it also includes high handling and convenience such as easy care, easy partial application, easy portability, and easy care for invisible parts. In general, emulsified compositions are awkward (decreased in usability) due to the increased viscosity or hardness of the formulation due to the concentration of oil or the mix of paste to solid oils, especially sprays, bottles, tubes and dispensers. When it is housed in a container of the type that extrudes or ejects, it is often difficult to extrude or eject. In such a case, it is necessary to devise the diameter of the mouth, the size of the pump straw, the softness of the container (selection of the container material), and the like. As described above, it is difficult to prepare an emulsified composition in various forms, so that there is a problem that its use and specifications are limited. The oil-in-water emulsified composition of the present invention contains a heparinoid and an oil-soluble component, and by adjusting the blending amount thereof, it is possible to greatly control the characteristics of the preparation, which is a preferable preparation characteristic. Therefore, it is excellent in usability and can increase the degree of freedom in formulation design. As a result, the oil-in-water emulsified composition of the present invention can be easily used in a wide variety of containers such as mist sprays, bottles, tubes and dispensers, as well as jars and sticks, even if the preparation contains a high concentration of oil. It can be used for. In addition, even when a small container specification such as portable or point use for partial moisturizing is required, there is no problem with ejection and extrusion, so we will realize a product that suits various purposes, specifications, and situations. be able to. Further, since the oil-in-water emulsified composition of the present invention can be easily discharged, for example, in a tube or bottle type product, the components and container specifications (large size) to be blended with concern about difficulty in discharging and extrusion. There are no restrictions on the design, material, shape, etc.). The composition can be highly effective in terms of use, especially in mist sprays, bottles, tubes and dispenser type containers.

(Formulation form)
The form of the oil-in-water emulsified composition of the present invention is not particularly limited as long as it is a formulation suitable for each drug, quasi-drug, cosmetic, etc., but is, for example, liquid, fluid, or semi-solid. can do. The formulation forms include, for example, liquids, suspensions, emulsions, creams, emulsions, ointments, gels, liniments, lotions, non-woven fabrics impregnated with chemicals, mists, sticks, and foams. Examples include foaming agents. These preparations can be produced according to a conventional method, for example, the method described in the 17th revised Japanese Pharmacopoeia General Rules for Preparations.

Further, the oil-in-water emulsified composition of the present invention has the effect of smoothing the skin due to its high water retention and moisturizing properties, while having a slimy, non-greasy and fresh feeling of use and excellent skin compatibility. Further, in the oil-in-water emulsified composition of the present invention, the characteristics of the preparation can be easily controlled by adjusting the blending amount of the heparinoid and the oil-soluble component. For example, by blending a high concentration of oil, it is possible to prepare a preparation that has high malleability and can be spread over a wide range without irritation or burden on the skin. Therefore, it is highly effective to make it an all-in-one preparation that can be used regardless of the season or site. In addition, due to its excellent usability and moisturizing power, it is possible to make a formulation that combines the excellent points of cream and lotion, such as a milky lotion or lotion with a moisturizing effect like cream, or a cream with high malleability. Is. In addition, since the characteristics of the preparation can be easily controlled to form various formulation designs, it is possible to give a different feeling of use while maintaining high usability. For example, by providing the oil-in-water emulsified composition of the present invention with a "rich moisturizing feeling", it is also useful as a point use for a portion where dryness or wrinkles are a concern.

Since the oil-in-water emulsified composition of the present invention can easily control the characteristics of the preparation and suppress dripping regardless of the oil concentration, it can be used in a container having a shape and material appropriately selected according to the purpose of use and application. Can be housed and used. Specific examples of the container include a spray type (non-vertical or upside-down type), a bottle type, a tube type, a jar type, a dropper type, a dispenser type, a stick type, a pouch bag, and a cheer pack.

Examples of the material of these containers include polyethylene terephthalate, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, and metal (aluminum, etc.). In addition, these materials are subjected to various coating treatments in consideration of strength, flexibility, weather resistance, stability of components, etc., and these materials are combined or laminated by, for example, mixing them. , Can be used as a container material. Examples of the coating material include polyethylene terephthalate, epoxy resin, and polyamide-imide. Of these, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ethylene vinyl alcohol resin, and metal (aluminum, etc.) are preferably used. As the resin for coating the inner surface, polyamide-imide, polyethylene terephthalate, or the like can be used.

Further, in the case of a sticky or slimy preparation, there may be a concern about adhesion to clothes after application, but the oil-in-water emulsified composition of the present invention is a case where a high concentration of oil is blended. However, because the characteristics of the formulation can be easily controlled and it has a good feeling of use (freshness, familiarity with the skin), it is difficult to reach the affected area or skin such as the scalp, back and hips, or the baby. It is easy to apply even when used by infants, children, elderly people, etc., and it is expected that the concern of adhesion to clothes after application will be improved.

(Application site)
The oil-in-water emulsified composition for skin of the present invention is not particularly limited, but in addition to its use on the face and body for skin care applications, symptoms such as sweat and sebum-prone areas, rubbing against clothes, bedsores, and atopy. It can be used for parts, dry parts, or parts with reduced barrier function. Scalp, face, neck, chest (including bust top), back, arms, elbows (inside / outside), hands, nails, axillae, abdomen, genitals, buttocks, delicate zones, anus, legs, fingers It can be used according to each symptom such as toenail and sole.

(Use)
The oil-in-water emulsified composition of the present invention is, for example, not only for normal skin, but also for babies, infants, children, elderly people, nursing care, sensitive skin, sensitive skin, and sensitive skin. It can be used for dry skin, fluctuating skin, troubled skin, temporary sensitive skin, atopy skin, rash and rash skin, etc.

<Method of suppressing dripping of oil-in-water emulsified composition>
The present invention is characterized by blending one or more oil-soluble components selected from the group consisting of (A) heparinoids, (B) oil-soluble acyl amino acids, derivatives thereof and salts thereof, and paste-like oils. Also included is the invention of a method for suppressing dripping of an oil-in-water emulsified composition. In an oil-in-water emulsified composition containing (A) a heparinoid, one or more oil-soluble components selected from the group consisting of (B) oil-soluble acyl amino acids, derivatives thereof and salts thereof, and paste-like oils are used. By blending, the characteristics of the preparation can be appropriately adjusted, and dripping after being discharged from the container can be effectively suppressed. The specific description of (A) heparinoid, (B) oil-soluble component, and oil-in-water emulsification composition containing these can be applied to the above description in the section of oil-in-water emulsification composition.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

[Test 1] Characteristic test The oil-in-water emulsified compositions of Examples and Comparative Examples were prepared by a conventional method according to the formulations shown in Tables 1 to 4 below. Unless otherwise specified, the unit of numerical value in each table is mass (%). The viscosity, container discharge property, and stability of each of the prepared compositions were measured and evaluated. The method is as described below. The results are shown in Tables 1 to 4.

(viscosity)
The viscosity (Pa · s) of each composition was measured using VISCOMETER TV-10M (Toyo Sangyo Co., Ltd.) under the conditions of a temperature of 25 ° C., a rotor M-4, a speed of 6 rpm, and 60 seconds.

(Container discharge property)
15 g of each composition is filled in a container with a pump (Honda Plus: Z-100-101 (pump), MDC-15 PET (bottle), capacity: 12 mL), and the product is pushed upright until the preparation starts to be discharged. I counted the number. The counts are listed in the table as dischargeability scores from the container. Further, when each composition was discharged from the pump, it was determined whether or not the liquid drips from the discharge port of the pump. If there was no dripping, it was marked with "○", and if it was dripping, it was marked with "x", and these results are shown in the table. In addition, "ND" in the table indicates that the evaluation was not carried out.

(Stability)
Each composition was filled in a 30 mL glass bottle and stored in a constant temperature bath at 50 ° C. After 1 week, the test preparation was taken out from the constant temperature bath, and after sufficiently constant temperature to room temperature, the appearance was visually evaluated according to the following evaluation criteria.

Evaluation item: Stability Evaluation criteria:
×: A state in which the feeling of use is affected by a large separation or a large change in properties.
△: There was some separation and separation on the surface, but there was no effect on usability.
○: There is no separation or separation on the surface, and there is no change in properties.

Generally, in emulsions, the viscosity of the emulsion is reduced, which often destabilizes the preparation. However, by adding (A) a heparinoid, the viscosity of the emulsion is reduced and the characteristics of the preparation are changed. However, it was found that all of them maintained high thermal stability.

[Test 2] Usability (freshness, moistness, skin familiarity) Monitor test The usability of each composition was scored on a 5-point scale by 6 expert panelists according to the following criteria, and the values were averaged. The average score of 4 or more was evaluated as ⊚, the average score of 3.0 or more and less than 4.0 was evaluated as ◯, the average score of 2.5 or more and less than 3.0 was evaluated as Δ, and the average score of less than 2.5 was evaluated as ×. In addition, the difference between the usability score of each example and the corresponding usability score of the comparative example (value obtained by subtracting the score of the comparative example from the score of the example) is 1.5 or more ⊚, 0.5 or more 1.5. Less than 〇, greater than 0, less than 0.5 was Δ, and less than 0 was ×, and these results are shown in the table.

Evaluation items: Freshness, moist feeling, familiarity with the skin Evaluation criteria:
Feel: Score 5
Feel a little: Score 4
Neither: Score 3
I don't feel much: Score 2
I don't feel: Score 1

As shown in Tables 1 to 4, when a heparin-like substance was added to the oil-in-water emulsified composition, the viscosity was lowered and the discharge property from the container was improved. On the other hand, surprisingly, the shape-retaining property of the discharged preparation was improved, so that the dripping of the preparation from the pump port of the discharge container could be suppressed. That is, the oil-in-water emulsified composition of the example had an unexpected effect that it could be discharged without dripping while maintaining the shape of the droplets while having a low viscosity and a fresh and light texture. .. Further, the decrease in viscosity raises a concern about stability, but none of the oil-in-water emulsified compositions of Examples showed a problem in long-term stability. Further, in the evaluation of usability, since heparin-like substances are blended and a high concentration of oil is blended, all the preparations have a high moisturizing score and have high moisturizing power. However, despite the addition of a heparinoid, which is generally a cause of sliminess, stickiness, and low penetration, the freshness at the time of application was improved, and excellent skin familiarity could be obtained. Further, as an evaluation item other than the above evaluation items, all the preparations of the examples were preparations without any problem without feeling irritation.

An example of formulation of the oil-in-water emulsified composition of the present invention is shown below.

According to the present invention, in an oil-in-water emulsified composition containing a heparinoid, one or more oil-soluble components selected from the group consisting of oil-soluble acyl amino acids, derivatives thereof and salts thereof, and paste-like oils are used. By blending, the viscosity is adjusted appropriately, which makes it easier to control the characteristics of the formulation, which makes it excellent in usability, and while having moisturizing power, it suppresses stickiness and irritation, and is excellent in heparinoids. It is possible to prepare a preparation having both good pharmacological effects and good properties (usability, usability).

Claims (6)

Oil-in-water emulsified composition containing one or more oil-soluble components selected from the group consisting of (A) heparinoids, (B) oil-soluble acylamino acids, derivatives thereof and salts thereof, and paste-like oils. Stuff. The oil-in-water emulsified composition according to claim 1, wherein the content of the oil-soluble component (B) is 0.01% by mass to 10% by mass of the entire oil-in-water emulsified composition. Further, it is selected from the group consisting of (C) glycyrrhizinic acid, its derivative and its salt, ascorbic acid, its derivative and its salt, nicotinamide, tocopherol or its derivative, retinol or its derivative, tranexamic acid, and allantin. The oil-in-water emulsified composition according to claim 1 or 2, which contains one or more active ingredients. The oil-soluble component (B) is shea butter, phytosterol fatty acid ester, cholesterol fatty acid ester, N-acyl amino acid sterol ester, vaseline, tri (capril, caprin, myristin, stearic acid) glyceryl, dipentaerytrit fatty acid ester, die. The oil-in-water emulsified composition according to any one of claims 1 to 3, which is one or more selected from the group consisting of merger linoleic acid sterol ester and dimer linoleic acid sterol / higher alcohol ester. The oil-in-water emulsified composition according to any one of claims 1 to 4, further comprising (D) a salt-tolerant polymer. In water, one or more oil-soluble components selected from the group consisting of (A) heparinoids and (B) oil-soluble acylamino acids, derivatives thereof and salts thereof, and paste-like oils are blended. A method for suppressing dripping of an oil-type emulsified composition.