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

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

[Technical Field]

[0001] The present invention relates to an oil-in-water emulsion composition and a method for suppressing dripping of an oil-in-water emulsion composition. [Background technology]

[0002] Heparinoids are a type of mucopolysaccharide that have excellent moisturizing, anti-inflammatory, and blood circulation promoting effects, as well as other pharmacological effects (such as the treatment and prevention of atopic dermatitis, hypertrophic scars, and keloids, and care after trauma (bruises, sprains, and contusions)). Therefore, they are widely used as active ingredients in external preparations. To effectively utilize the diverse efficacies of heparinoids, various preparations containing heparinoids have been developed (see Patent Documents 1 and 2).

[0003] On the other hand, emulsion formulations can take on properties similar to those of a lotion or cream, depending on the blend of various oils and thickeners and the emulsification state. Controlling stability and usability is extremely difficult, especially when high oil content or paste-like or solid oils are blended. Furthermore, increased viscosity of the formulation makes it difficult to dispense from containers such as tubes or bottles, limiting the container specifications available and limiting its applications. Furthermore, while various usability sensations, such as refreshing or moisturizing, are required for emulsion formulations depending on the purpose, in all cases there are problems with stickiness and irritation due to the oils and mucopolysaccharides. Stickiness and irritation are generally disliked, and there is a constant demand for formulations that combine the moisturizing power of emulsion formulations with a good usability.

[0004] While heparinoids have the above-mentioned various effects, they are known to have the property of easily impairing the emulsion stability of emulsion compositions, and it is not easy to adjust an emulsion composition containing a heparinoid to a desired viscosity. For example, Patent Document 3 describes a method for improving the emulsion stability of such emulsion compositions containing a heparinoid, in which excellent emulsion stability can be imparted to an oil-in-water emulsion lotion containing a heparinoid by blending reduced lanolin. Patent Document 4 also describes that excellent emulsion stability can be obtained by blending a heparinoid with a phosphate surfactant, and glycyrrhizinic acid, glycyrrhetinic acid, their derivatives, and / or their salts to form an emulsion composition.

[0005] Furthermore, heparinoids have the disadvantage that they produce a slimy feeling upon application, which is characteristic of polysaccharides, particularly acidic mucopolysaccharides, resulting in poor skin compatibility and difficulty in achieving a sense of penetration. They are also known to cause stickiness after application to the affected area. To solve these problems, for example, Patent Document 5 describes how blending hyaluronic acid oligosaccharides and / or salts thereof into an oil-in-water emulsion composition containing a heparinoid reduces the slimy feeling upon application, thereby achieving excellent skin compatibility and a satisfactory sense of penetration and moisturizing. Patent Document 6 also describes how blending isopropanol into a gel-like oil-in-water emulsion composition containing a heparinoid can improve stickiness after application. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2015-232032 [Patent Document 2] Japanese Patent Application Publication No. 2017-178798 [Patent Document 3] Japanese Patent Application Publication No. 11-180821 [Patent Document 4] Japanese Patent Application Laid-Open No. 2017-048163 [Patent Document 5] Japanese Patent Application Laid-Open No. 2017-066060 [Patent Document 6] Japanese Patent Application Laid-Open No. 2016-193854 Summary of the Invention [Problem to be solved by the invention]

[0007] Under these circumstances, the objective is to provide a new formulation in an emulsion composition containing a heparinoid that combines the excellent pharmacological effects of the heparinoid with good properties (ease of use, feel when used). [Means for solving the problem]

[0008] As a result of intensive research conducted by the present inventors to solve the above problems, they have succeeded in creating a formulation that combines versatile usability with the excellent pharmacological effects of heparinoids by incorporating one or more oil-soluble components selected from the group consisting of oil-soluble acylamino acids, their derivatives and salts, and pasty oils in an oil-in-water emulsion composition containing a heparinoid, thereby providing a formulation that has high moisturizing power while making it easy to control the properties of the formulation.

[0009] That is, the gist of the present invention is as follows.

[0010] [1] An oil-in-water emulsion composition comprising (A) a heparinoid, and (B) one or more oil-soluble components selected from the group consisting of an oil-soluble acylamino acid, its derivatives and salts thereof, and a paste-like oil. [2] The oil-in-water emulsion composition according to [1], wherein the content of the oil-soluble component (B) is 0.01% by mass to 10% by mass of the total oil-in-water emulsion composition. [3] The oil-in-water emulsion composition according to [1] or [2], further comprising (C) one or more active ingredients selected from the group consisting of glycyrrhizinic acid, its derivatives and salts thereof, ascorbic acid, its derivatives and salts thereof, nicotinamide, tocopherol or its derivatives, retinol or its derivatives, tranexamic acid, and allantoin. [4] The oil-in-water emulsion composition according to any one of [1] to [3], wherein the oil-soluble component (B) is at least one selected from the group consisting of shea butter, phytosterol fatty acid esters, cholesterol fatty acid esters, N-acylamino acid sterol esters, petrolatum, caprylic / capric / myristic / stearic triglyceride, dipentaerythritol fatty acid esters, dimer dilinoleic acid sterol esters, and dimer dilinoleic acid sterol / higher alcohol esters. [5] The oil-in-water emulsion composition according to any one of [1] to [4], further comprising (D) a salt-tolerant polymer. [6] A method for suppressing dripping of an oil-in-water emulsion composition, characterized by blending (A) a heparin-like substance and (B) one or more oil-soluble components selected from the group consisting of oil-soluble acylamino acids, their derivatives and salts thereof, and paste-like oils. [Effects of the Invention]

[0011] According to the present invention, by incorporating one or more oil-soluble components selected from the group consisting of oil-soluble acylamino acids, their derivatives and salts, and pasty oils into an oil-in-water emulsion composition containing a heparinoid, the viscosity can be appropriately adjusted to provide excellent usability, and the composition has moisturizing power while reducing stickiness and irritation, thereby achieving a formulation that combines the excellent pharmacological effects of the heparinoid with a good usability. The oil-in-water emulsion composition of the present invention allows for easy control of the formulation's properties, allowing for a variety of uses. Furthermore, by combining these components, the composition for topical use achieved the unexpected effect of providing a refreshing usability despite the high content of oil-soluble components. Furthermore, the topical composition of the present invention also achieved the unexpected effect of being free from stickiness and stickiness and having excellent skin compatibility, despite containing a heparinoid, a mucopolysaccharide that causes stickiness, stringiness, and poor penetration. DETAILED DESCRIPTION OF THE INVENTION

[0012] The present invention will be described in detail below. The terms used in this specification are to be interpreted in the sense commonly used in the art unless otherwise specified.

[0013] <Oil-in-water emulsion composition> The oil-in-water emulsion composition of the present invention is characterized by containing 0.01 to 10% by mass of (A) a heparinoid and (B) one or more oil-soluble components selected from the group consisting of oil-soluble acylamino acids, their derivatives, and salts thereof, and pasty oils. By incorporating a specific amount of the oil-soluble component (B) in an oil-in-water emulsion composition containing a heparinoid, the viscosity can be appropriately adjusted to provide excellent usability, moisturizing properties while reducing stickiness and irritation, resulting in a formulation that combines the excellent pharmacological effects of the heparinoid with a pleasant feel during use. In addition to the essential components of the heparinoid (A) and the oil-soluble component (B), the oil-in-water emulsion composition of the present invention may contain additional components such as (C) an active ingredient, (D) a salt-tolerant polymer, and (E) anionic surfactant. Furthermore, the composition may contain base / carrier components and other optional components within a range that does not impair the effects of the present invention. The essential components (A) and (B), the additional components (C) to (E), the base / carrier components, and other optional components are described in detail below. Note that, if the compounds specifically exemplified as each component overlap, it is sufficient that they are included as either of the components.

[0014] [(A) Heparinoids] Heparinoids are polysulfated mucopolysaccharides such as chondroitin polysulfate, and are known drugs known to have moisturizing, anti-inflammatory, and blood circulation promoting effects.

[0015] The content of the heparinoid in the oil-in-water emulsion composition of the present invention is 0.005% by mass to 5% by mass, preferably 0.01% by mass to 3% by mass, more preferably 0.05% by mass to 1% by mass, even more preferably 0.1% by mass to 0.5% by mass, and particularly preferably 0.1% by mass to 0.3% by mass, based on the total amount of the composition. By setting the content of the heparinoid in the oil-in-water emulsion composition of the present invention within the above range, the physiological effects of the heparinoid, such as moisturizing effect and blood circulation promoting effect, can be exerted, and the composition can be made to have sufficiently suppressed inflammation induction.

[0016] [(B) Oil-soluble component] (B) The oil-soluble component is one or more oil-soluble components selected from the group consisting of oil-soluble acylamino acids, derivatives thereof and salts thereof, and pasty oils.

[0017] Here, the "salt" is a pharmaceutically acceptable salt. It is not particularly limited as long as it can achieve the effects of the present invention, but examples thereof include inorganic salts of sodium, potassium, calcium, magnesium, aluminum, zinc, etc.; organic salts of organic amines such as ammonia, monoethanolamine, diethanolamine, triethanolamine, etc., and basic amino acids such as arginine, lysine, etc., and one or more of these can be used in combination. Among these, salts of sodium, potassium, ammonium, triethanolamine, and arginine are preferred, and salts of sodium, potassium, ammonium, and triethanolamine are more preferred.

[0018] Furthermore, the above-mentioned "derivative" refers to a compound in which some of the functional groups of an acylamino acid have been chemically modified, or a compound in which a protecting group has been added to some of the functional groups, within the scope that does not impair the effects of the present invention, and also refers to isomers.

[0019] (oil-soluble acylamino acids, their derivatives and their salts) The amino acid in the acylamino acid may be neutral, acidic, or basic, and may be in any of the L-, D-, or DL-forms. Examples include glutamic acid, aspartic acid, glycine, proline, alanine, threonine, methylalanine, sarcosine, lysine, arginine, methylalanine, taurine, and methyltaurine, with glutamic acid, aspartic acid, glycine, proline, alanine, lysine, and arginine being preferred, glutamic acid, glycine, proline, alanine, lysine, and arginine being more preferred, glutamic acid, aspartic acid, glycine, proline, alanine, and lysine being even more preferred, and glutamic acid and glycine being particularly preferred.

[0020] In the acylamino acid, the number of carbon atoms of the fatty acid constituting the acyl group is preferably 2 to 32, more preferably 8 to 22, and even more preferably 8 to 18. The hydrocarbon may be saturated or unsaturated, may be branched or cyclic, or may be a mixed fatty acid. Specific examples include caproic acid, caprylic acid, decanoic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, behenic acid, coconut oil fatty acid, castor oil fatty acid, olive oil fatty acid, and palm oil fatty acid. Among these, caprylic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, behenic acid, coconut oil fatty acid, and olive oil fatty acid are preferred, caprylic acid, coconut oil fatty acid, lauric acid, palmitic acid, and stearic acid are more preferred, and lauric acid, caprylic acid, and stearic acid are even more preferred.

[0021] The acylamino acid derivative is preferably a sterol ester, and examples of the acylamino acid sterol ester include dihexyldecyl N-lauroyl-L-glutamate, dioctyldodecyl N-lauroyl-L-glutamate, di(phytosteryl / octyldodecyl) N-lauroyl-L-glutamate, di(cholesteryl / octyldodecyl) N-lauroyl-L-glutamate, di(cholesteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate, di(phytosteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate, and phytosteryl / decyltetradecyl N-myristoyl-N-methylalanine. Specifically, dioctyldodecyl N-lauroyl-L-glutamate, di(phytosteryl / octyldodecyl) N-lauroyl-L-glutamate, di(cholesteryl / octyldodecyl) N-lauroyl-L-glutamate, di(cholesteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate, di(phytosteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate are more preferred, and dioctyldodecyl N-lauroyl-L-glutamate, di(phytosteryl / octyldodecyl) N-lauroyl-L-glutamate, di(phytosteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate are even more preferred.

[0022] As the acylamino acid derivative, commercially available products may be used, such as Eldew CL-301 and Eldew CL-202 (both manufactured by Ajinomoto Co., Inc.), Estemoll CHS (manufactured by Nisshin Oillio Co., Ltd.), Eldew PS-203, Eldew PS-304, Eldew PS-306, and Eldew APS-307 (all manufactured by Ajinomoto Co., Inc.), PLANDOOL-LG1, PLANDOOL-LG2, PLANDOOL-LG3, and PLANDOOL-LG4 (all manufactured by Nippon Fine Chemicals Co., Ltd.), AMITER LG-2000, and AMITER LG-1600 (all manufactured by Nippon Emulsion Co., Ltd.).

[0023] As the acylamino acid or a salt thereof, lauroyl-ε-lysine or a salt thereof is preferred.

[0024] As the acylamino acid or a salt thereof, commercially available products may be used, for example, Amihope (registered trademark) LL (manufactured by Ajinomoto Co., Inc.).

[0025] (paste oil) Paste-like oil refers to oil that is pasty at room temperature (25°C) and has a melting point of 45°C or lower.

[0026] The paste-like oil is preferably one or more selected from shea butter, sterol fatty acid esters, petrolatum, tri(caprylic / capric / myristic / stearic acid)glyceryl, dipentaerythritol fatty acid esters, and dimer acid esters, and more preferably one or more selected from shea butter, phytosterol fatty acid esters, cholesterol fatty acid esters, petrolatum, tri(caprylic / capric / myristic / stearic acid)glyceryl, dipentaerythritol fatty acid esters, dimer dilinoleic acid sterol esters, and dimer dilinoleic acid sterol / higher alcohol esters. More preferably, one or more selected species are selected from shea butter, phytosterol fatty acid esters, cholesterol fatty acid esters, petrolatum, tri(caprylic / capric / myristic / stearic acid)glyceryl, dipentaerythrityl hexa(hydroxystearate / hexastearic acid / rosinic acid), dipentaerythrityl tetra(hydroxystearate / isostearate), dimer dilinoleyl dimer dilinoleate, di(isostearyl / phytosteryl) dimer dilinoleate, dimer dilinoleyl bis(behenyl / isostearyl) dimer dilinoleate / phytosteryl), dimer dilinoleyl bisisostearyl dimer dilinoleate, dimer dilinoleyl (phytosteryl / isostearyl / cetyl / stearyl / behenyl) dimer dilinoleate, and dimer dilinoleyl hydrogenated rosin condensate are more preferred, and shea butter, cholesteryl isostearate, phytosteryl isostearate, cholesteryl hydroxystearate, phytosteryl hydroxystearate, phytosteryl caprylate / caprate, phytosteryl ricinoleate, cholesteryl oleate, and phytosteryl oleate are more preferred. , Dihydrocholesteryl oleate, C12-31 branched fatty acid cholesteryl, plant sterol fatty acid ester, lanolin fatty acid cholesteryl, petrolatum, tri(caprylic / capric / myristic / stearic acid)glyceryl, dipentaerythrityl hexa(hydroxystearate / hexastearic acid / rosinic acid), dipentaerythrityl tetra(hydroxystearate / isostearate), phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate, isostearyl / phytosteryl dimer dilinoleate,Even more preferred are one or more selected from dimer dilinoleyl bis(phytosteryl / behenyl / isostearyl) dimer dilinoleate, shea butter, phytosteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, phytosteryl oleate, cholesteryl branched fatty acid (C12-31), phytosteryl macadamia nut oil fatty acid, phytosteryl sunflower seed oil fatty acid, phytosteryl rice bran oil fatty acid, petrolatum, tri(caprylic / capric / myristyl) oleate, hydroxypropyl ... Particularly preferred are one or more selected from the group consisting of glyceryl hexanoate / hexa(hydroxystearate / hexastearate / hexarosinate), dipentaerythrityl tetra(hydroxystearate / hexaisostearate), phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate, isostearyl / phytosteryl dimer dilinoleate, and dimer dilinoleyl bis(phytosteryl / behenyl / isostearyl) dimer dilinoleate.

[0027] 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. The hydrocarbon may be saturated or unsaturated, may be branched or cyclic, or may be a mixed fatty acid. Specific examples include caproic acid, caprylic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, behenic acid, coconut oil fatty acid, castor oil fatty acid, olive oil fatty acid, palm oil fatty acid, and hydroxystearic acid.

[0028] Examples of sterol fatty acid esters include cholesteryl isostearate, phytosteryl isostearate, cholesteryl hydroxystearate, phytosteryl hydroxystearate, phytosteryl caprylate / caprate, phytosteryl ricinoleate, cholesteryl oleate, phytosteryl oleate, dihydrocholesteryl oleate, branched fatty acid (C12-31) cholesteryl, plant sterol fatty acid esters, and lanolin fatty acid cholesteryl. Among these, cholesteryl isostearate, phytosteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, phytosteryl oleate, branched fatty acid (C12-31) cholesteryl, phytosteryl macadamiate, cholesteryl macadamiate, dihydrocholesteryl macadamiate, phytosteryl sunflower seed oil fatty acid, phytosteryl rice bran oil fatty acid, and cholesteryl lanolinate are preferred, and phytosteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, cholesteryl oleate, branched fatty acid (C12-31) cholesteryl, phytosteryl macadamiate, cholesteryl macadamiate, dihydrocholesteryl macadamiate, phytosteryl sunflower seed oil fatty acid, phytosteryl rice bran oil fatty acid, and cholesteryl lanolinate are preferred. Cholesteryl hydroxystearate, cholesteryl oleate, phytosteryl oleate, branched fatty acid (C12-31) cholesteryl, macadamia nut oil fatty acid phytosteryl, sunflower seed oil fatty acid phytosteryl, and rice bran oil fatty acid phytosteryl are more preferred, 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 preferred.

[0029] Commercially available sterol fatty acid esters include Exepar IS-CE (Kao Corporation), Salacos PO, Salacos HS (Nisshin Oillio Co., Ltd.), Kairei Marine Cholesterol Ester (Nippon Suisan Co., Ltd.), YOFCO MAC, YOFCO MAS, PLANDOOL-MAS, PLANDOOL-SUN, PLANDOOL-ISS, YOFCO CLE-S, YOFCO CLE-NH (all manufactured by Nippon Fine Chemicals Co., Ltd.), rice sterol ester (Tsukuno Rice Fine Chemicals Co., Ltd.), NIKKOL Phytosteryl Hydroxystearate, and NIKKOL Cholesteryl Stearate (manufactured by Nikko Chemicals Co., Ltd.).

[0030] Commercially available products of tri(caprylic / capric / myristic / stearic acid)glyceryl include Salacos 334 (manufactured by Nisshin Oillio Co., Ltd.).

[0031] The dipentaerythritol fatty acid ester is not particularly limited, but among them, dipentaerythrityl hexa(hydroxystearate / stearic acid / rosin acid) and dipentaerythrityl tetra(hydroxystearate / isostearate) are preferred.

[0032] Commercially available dipentaerythritol fatty acid esters include Cosmol 168ARV and Cosmol 168EV (both manufactured by Nisshin Oillio Co., Ltd.).

[0033] Examples of dimer acid esters include dimer dilinoleyl dimer dilinoleate, di(isostearyl / phytosteryl) dimer dilinoleate, dimer dilinoleyl bis(behenyl / isostearyl / phytosteryl) dimer dilinoleate, dimer dilinoleyl bisisostearyl dimer dilinoleate, dimer dilinoleyl (phytosteryl / isostearyl / cetyl / stearyl / behenyl) dimer dilinoleate, and dimer dilinoleyl hydrogenated rosin condensate. Among these, dimer dilinoleate (phytosteryl / isostearyl / cetyl / stearyl / behenyl) dimer dilinoleate, dimer dilinoleyl (isostearyl / phytosteryl) dimer dilinoleate, and dimer dilinoleyl bis(phytosteryl / behenyl / isostearyl) dimer dilinoleate are preferred.

[0034] Commercially available dimer acid esters include, for example, Plandool-H, Plandool-G, Plandool-S, and LUSPLAN PI-DA (manufactured by Nippon Fine Chemical Co., Ltd.).

[0035] The oil-soluble component (B) in the oil-in-water emulsion composition of the present invention is preferably one or more selected from lauroyl-ε-lysine, shea butter, phytosterol fatty acid esters, cholesterol fatty acid esters, N-acyl amino acid sterol esters, petrolatum, tri(caprylic-capric-myristic-stearic acid)glyceryl, dipentaerythritol fatty acid esters, dimer dilinoleic acid sterol esters, and dimer dilinoleic acid sterol / higher alcohol esters. Preferably, the composition is at least one selected from the group consisting of caprylic / capric / myristic / stearate glyceryl, dipentaerythritol fatty acid ester, dimer dilinoleic acid sterol ester, and dimer dilinoleic acid sterol / higher alcohol ester, and more preferably, the composition is at least one selected from the group consisting of shea butter, phytosterol fatty acid ester, cholesterol fatty acid ester, N-acyl amino acid sterol ester, petrolatum, tri(caprylic / capric / myristic / stearate)glyceryl, dipentaerythritol fatty acid ester, dimer dilinoleic acid sterol ester, and dimer dilinoleic acid sterol / higher alcohol ester. More specifically, shea butter, phytosterol fatty acid ester, cholesterol fatty acid ester, petrolatum, tri(caprylic / capric / myristic / stearic acid)glyceryl, dipentaerythrityl hexa(hydroxystearate / hexastearic acid / rosinic acid), dipentaerythrityl tetra(hydroxystearate / isostearate), dimer dilinoleyl dimer dilinoleate, di(isostearyl / phytosteryl) dimer dilinoleate, dimer dilinoleate More preferred is one or more selected from dimer dilinoleyl bis(behenyl / isostearyl / phytosteryl), dimer dilinoleyl bisisostearyl dimer dilinoleate, dimer dilinoleyl (phytosteryl / isostearyl / cetyl / stearyl / behenyl) dimer dilinoleate, and dimer dilinoleyl hydrogenated rosin condensate, and further preferred are shea butter, cholesteryl isostearate, phytosteryl isostearate, cholesteryl hydroxystearate, phytosteryl hydroxystearate,Even more preferred are one or more selected from the group consisting of caprylic / capric acid phytosteryl, ricinoleate phytosteryl, cholesteryl oleate, phytosteryl oleate, dihydrocholesteryl oleate, branched fatty acid (C12-31) cholesteryl, plant sterol fatty acid esters, cholesteryl lanolinate, petrolatum, caprylic / capric / myristic / stearic triglyceride, dipentaerythrityl hexahydroxystearate / hexastearate / hexarosinate, dipentaerythrityl tetrahydroxystearate / isostearate, phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate, isostearyl / phytosteryl dimer dilinoleate, and dimer dilinoleyl bis(phytosteryl / behenyl / isostearyl) dimer dilinoleate. Shea butter is also preferred. Particularly preferred are one or more selected from the group consisting of phytosteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, phytosteryl oleate, cholesteryl branched fatty acids (C12-31), phytosteryl macadamia nut oil fatty acid, phytosteryl sunflower seed oil fatty acid, phytosteryl rice bran oil fatty acid, caprylic / capric / myristic / stearic triglyceride, dipentaerythrityl hexahydroxystearate / hexastearic acid / hexarosinate, dipentaerythrityl tetrahydroxystearate / isostearate, phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate, isostearyl / phytosteryl dimer dilinoleate, and dimer dilinoleyl bis(phytosteryl / behenyl / isostearyl) dimer dilinoleate.

[0036] From the viewpoint of the effects of the present invention, the content of the oil-soluble component (B) in the oil-in-water emulsion composition of the present invention is preferably 0.001% by mass to 15% by mass, more preferably 0.001% by mass to 10% by mass, even more 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 emulsion composition of the present invention within the above range, it becomes easy to control the properties of the formulation, and it is possible to obtain a composition that has moisturizing power while being reduced in stickiness and having high spreadability.

[0037] In the oil-in-water emulsion composition of the present invention, the ratio (A / B) of the content (mass%) of the oil-soluble component (A) to the content (mass%) of the oil-soluble component (B) is preferably 0.0005 to 500, more preferably 0.001 to 300, even more preferably 0.005 to 100, even more preferably 0.01 to 50, and particularly preferably 0.01 to 0.5.

[0038] [(C) Active ingredient] The oil-in-water emulsion composition of the present invention may further contain (C) an active ingredient to impart medicinal effects. The (C) active ingredient is one or more components selected from the group consisting of glycyrrhizinic acid, its derivatives and salts thereof, ascorbic acid, its derivatives and salts thereof, nicotinamide, tocopherol or its derivatives, retinol or its derivatives, tranexamic acid, and allantoin.

[0039] The "salt" is a pharmaceutically acceptable salt, and includes, but is not limited to, salts with organic bases (e.g., tertiary amine salts, ammonium salts, etc.) or salts with inorganic bases (e.g., inorganic acid salts such as hydrochloride, sulfate, phosphate, etc.; alkali metal salts such as sodium salt, potassium salt, dipotassium salt, magnesium salt, zinc salt, etc.). Among these, monoammonium salts, sodium salts, potassium salts, dipotassium salts, magnesium salts, and zinc salts are preferred, monoammonium salts, sodium salts, dipotassium salts, and magnesium salts are more preferred, and dipotassium salts, sodium salts, and magnesium salts are even more preferred.

[0040] (C) Examples of active ingredients include dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, allantoin, ascorbic acid, sodium ascorbate, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, disodium ascorbyl sulfate, 2-O-ethyl ascorbic acid, 3-O-ethyl ascorbic acid, ascorbic acid-2-glucoside, disodium isostearyl ascorbyl phosphate, trisodium ascorbyl palmitate phosphate, glyceryl ascorbate, bisglyceryl ascorbate Ascorbic Acid, Hexyl 3-Glyceryl Ascorbate, 3-Glyceryl Ascorbate, Myristyl 3-Glyceryl Ascorbate, 3-Laurylglyceryl Ascorbate, Potassium Ascorbyl / Tocopheryl Phosphate, Tocopheryl Ascorbate Maleate, Ascorbyl Tetraisopalmitate, Nicotinamide, Alpha Tocopherol, Beta Tocopherol, Delta Tocopherol, Tocopheryl Acetate, Tocopheryl Nicotinate, Tocopheryl Succinate, Calcium Tocopheryl Succinate, Retinol, Retinyl Acetate, Retinyl Palmitate dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, allantoin, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, 2-O-ethyl ascorbic acid, 3-O-ethyl ascorbic acid, ascorbic acid-2-glucoside, ascorbyl tetrahexyldecanoate, nicotinamide, α-tocopherol, β-tocopherol, δ-tocopherol, tocopherol acetate, retinol acetate, retinol palmitate, and tranexamic acid are more preferred. Dipotassium glycyrrhizinate, allantoin, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, 3-O-ethyl ascorbic acid, ascorbic acid-2-glucoside, ascorbyl tetrahexyldecanoate, nicotinamide, δ tocopherol, tocopherol acetate, retinol acetate, retinol palmitate, and tranexamic acid are preferred, and dipotassium glycyrrhizinate, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, 3-O-ethyl ascorbic acid,Ascorbic acid-2-glucoside, ascorbyl tetrahexyldecanoate, nicotinamide, delta tocopherol, tocopherol acetate, and tranexamic acid are particularly preferred.

[0041] The content of the active ingredient (C) in the oil-in-water emulsion composition of the present invention is 0.001% by mass to 10% by mass, preferably 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 5% by mass, based on the total amount of the composition. By setting the content of the active ingredient (C) within the above range, the oil-in-water emulsion composition of the present invention can impart more preferable medicinal effects in addition to the remarkable effect of achieving both high usability and a good feel while maintaining the moisturizing power of the oil-in-water emulsion composition of the present invention.

[0042] [(D) Salt-resistant polymer] To impart an appropriate viscosity to the topical composition of the present invention and to stabilize the formulation, a salt-tolerant polymer (D) may be blended in. Examples of salt-tolerant polymers (D) include polyacrylamide, polymers having dimethyltaurine or a salt thereof in the side chain, and hydrophobically modified polyurethane. Among these, polyacrylamide, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer, (ammonium acryloyldimethyltaurate / beheneth-25 methacrylate) crosspolymer, (ammonium acryloyldimethyltaurate / steareth-25 methacrylate) crosspolymer, (acrylic acid / acryloyldimethyltaurate / dimethylacrylamide) crosspolymer, (sodium acrylate / sodium acryloyldimethyltaurate) copolymer, and (PEG-240 / decyltetradeceth-20 / HDI) copolymer are preferred, and polyacrylamide, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, (acrylic acid / acryloyldimethyltaurate / dimethylacrylamide) crosspolymer, (sodium acrylate / sodium acryloyldimethyltaurate) copolymer, and (PEG-240 / decyltetradeceth-20 / HDI) copolymer are more preferred.

[0043] (D) Commercially available salt-resistant polymers include, for example, Aristoflex AVC, Aristoflex HMB, and Aristoflex HMS (all manufactured by Clariant Japan K.K.), SEPIGEL 305, SEPINOV EMT 10, SIMULGEL NS, SIMULGEL FL, SIMULGEL EG, SEPIPLUS S, and SEPINOV P88 (all manufactured by SEPPIC), and ADEKA NOL GT700 (manufactured by ADEKA Corporation).

[0044] The content of the salt-tolerant polymer (D) in the oil-in-water emulsion composition of the present invention is usually 0.01% by mass to 5% by mass, preferably 0.05% by mass to 4% by mass, more preferably 0.1% by mass to 3% by mass, and even more preferably 0.5% by mass to 3% by mass. By setting the content of the salt-tolerant polymer (D) in the oil-in-water emulsion composition of the present invention within the above range, the viscosity of the oil-in-water emulsion composition can be appropriately adjusted, and it is possible to easily control the properties of the formulation to improve stability, usability, and usability.

[0045] [(E) Anionic surfactant] The oil-in-water emulsion composition of the present invention may contain (E) an anionic surface-active anionic surfactant for the purpose of appropriately modifying the feel during use and stabilizing the formulation. Examples of anionic surface-active anionic surfactants include sodium N-stearoyl glutamate, sodium dilauroyl glutamate, monosodium N-lauroyl glutamate, sodium N-stearoyl-L-glutamate, arginine N-stearoyl-L-glutamate, sodium N-myristoyl-L-glutamate, sodium N-stearoyl methyl taurate, sodium N-myristoyl methyl taurate, and sodium N-cocoyl methyl taurate. Among these, sodium N-stearoyl glutamate and sodium N-stearoyl methyl taurate are preferred from the viewpoint of enhancing the effects of the present invention.

[0046] The content of the anionic surface-active anionic surfactant (E) in the oil-in-water emulsion composition of the present invention is usually 0.001% by mass to 10% by mass, preferably 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 anionic surface-active anionic surfactant (E) in the oil-in-water emulsion composition of the present invention within the above range, the viscosity of the oil-in-water emulsion composition can be appropriately adjusted, and it is possible to easily control the properties of the formulation to improve stability, usability, and usability.

[0047] (Base or carrier) The oil-in-water emulsion composition of the present invention can be prepared into a composition in a formulation suitable for various uses by mixing and emulsifying the essential components and the components described above together with a base or carrier commonly used in pharmaceuticals, quasi-drugs, cosmetics, etc., and, if necessary, additives, in a conventional manner.

[0048] The oil-in-water emulsion composition of the present invention may contain optional components, such as known components added to cosmetics, pharmaceuticals, quasi-drugs, etc., within the scope of the present invention, such as blood circulation promoters, astringents, UV scattering agents, UV absorbers, surfactants, stabilizers, antioxidants, colorants, pearlescent agents, dispersants, chelating agents, pH adjusters, preservatives, thickeners, irritation reducers, anti-inflammatory components, bactericidal and disinfecting components (antibacterial components), keratin softening components, warming components, hair growth promoting components, moisturizing components, anti-wrinkle agents, anti-glycation components, cell activating components, and whitening components, as long as the optional components do not impair the effects of the present invention. These additives may be used alone or in combination of two or more. Note that these optional components exclude the components included in the above-mentioned components (A) to (E).

[0049] The method for preparing the oil-in-water emulsion composition of the present invention is not particularly limited, and the composition can be prepared by a conventional method by appropriately selecting, blending, and mixing the above-mentioned various components necessary for preparing the oil-in-water emulsion composition. Furthermore, the amount and method of application of the oil-in-water emulsion composition of the present invention are not particularly limited, and the composition can generally be used by applying an appropriate amount to the area including the affected area once to several times a day.

[0050] The oil-in-water emulsion composition of the present invention generally has a pH in the range of 4 to 9, and from the viewpoint of the effects of the present invention, the pH is preferably 4.5 to 8.5, and more preferably 5 to 8. This pH can be adjusted by using a pH adjuster.

[0051] (Usability) The "usability" characteristic of the oil-in-water emulsion composition of the present invention will now be described. In the present invention, usability refers to the ease of use, convenience, and ease of handling of the oil-in-water emulsion composition. Furthermore, it also includes high handleability and convenience, such as ease of frequent care, easy localized application, portability, and ease of care for hard-to-reach areas. Generally, emulsion compositions become difficult to handle (reduced usability) due to increased viscosity or hardness of the formulation depending on the oil concentration or the incorporation of oils in paste to solid forms. This often makes extrusion or dispensing difficult, particularly when packaged in a container that extrudes or dispenses, such as a spray bottle, bottle, tube, or dispenser. In such cases, it is necessary to consider the diameter of the nozzle, the size of the pump straw, the flexibility of the container (selection of container material), and other factors. Because it is difficult to formulate emulsion compositions into a variety of forms, their applications and specifications have been limited. The oil-in-water emulsion composition of the present invention incorporates a heparinoid and an oil-soluble component, and by adjusting the amounts of these components, it is possible to greatly control the formulation properties and achieve favorable formulation characteristics, resulting in excellent usability and increased flexibility in formulation design. As a result, the oil-in-water emulsion composition of the present invention, even when formulated with a high oil concentration, can be easily used in a wide variety of containers, including jars and sticks as well as mist sprays, bottles, tubes, and dispensers. Furthermore, even when small containers are required for portable use or for spot moisturizing, dispensing and extrusion are not an issue, allowing for the creation of products suitable for a variety of purposes, specifications, and situations. Furthermore, because the oil-in-water emulsion composition of the present invention can be easily dispensed, there are no restrictions on the ingredients to be incorporated or the container specifications (size, design, material, shape, etc.) for tube- or bottle-type products due to concerns about difficulty in dispensing and extruding. The composition is particularly effective in mist sprays, bottles, tubes, and dispenser-type containers.

[0052] (Form of formulation) The form of the oil-in-water emulsion composition of the present invention is not particularly limited as long as it is a formulation suitable for each drug, quasi-drug, cosmetic, etc., and can be, for example, liquid, fluid, or semi-solid. Examples of formulation forms include solutions, suspensions, emulsions, creams, milky lotions, ointments, gels, liniments, lotions, sheets in which nonwoven fabric is impregnated with a drug solution, mists, sticks, and foams. These formulations can be produced according to conventional methods, such as those described in the General Provisions for Preparations in the 17th Edition of the Japanese Pharmacopoeia.

[0053] Furthermore, the oil-in-water emulsion composition of the present invention has a refreshing, non-sticky feel and excellent skin compatibility, while also providing a skin-smoothing effect due to its high water-retaining and moisturizing properties. Furthermore, the properties of the oil-in-water emulsion composition of the present invention can be easily controlled by adjusting the amounts of heparinoid and oil-soluble components. For example, by incorporating a high concentration of oil, it is possible to create a formulation with high spreadability that can be applied over a wide area without irritating or burdening the skin. Therefore, it is highly effective as an all-in-one formulation that can be used regardless of season or area. Furthermore, its excellent feel and moisturizing power make it possible to create a formulation that combines the advantages of a cream and a lotion, such as an emulsion or lotion with a cream-like moisturizing effect, or a cream with high spreadability. In addition, the properties of the formulation can be easily controlled to create a variety of formulations, making it possible to impart a different feel while maintaining high usability. For example, by imparting a "rich moisturizing feel" to the oil-in-water emulsion composition of the present invention, it can be used specifically on areas where dryness or wrinkles are a concern.

[0054] The oil-in-water emulsion composition of the present invention can easily control the properties of the formulation regardless of the oil concentration and can also suppress dripping, so it can be stored and used in a container of an appropriate shape and material selected according to the purpose and application. Specific examples of containers include spray types (non-inverted or inverted), bottle types, tube types, jar types, dropper types, dispenser types, stick types, pouch bags, and cheer packs.

[0055] Examples of materials for these containers include polyethylene terephthalate, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, and metal (aluminum, etc.). Taking into consideration strength, flexibility, weather resistance, component stability, and the like, these materials can be used as container materials by applying various coating treatments, combining these materials by mixing, or laminating them. Examples of coating materials include polyethylene terephthalate, epoxy resin, and polyamide-imide. Among these, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ethylene vinyl alcohol resin, and metal (aluminum, etc.) are preferred. Polyamide-imide, polyethylene terephthalate, etc. can be used as the resin for coating the inner surface.

[0056] Furthermore, in the case of sticky or slimy formulations, there may be concerns about the composition sticking to clothes after application. However, the oil-in-water emulsion composition of the present invention allows for easy control of the properties of the formulation, even when a high concentration of oil is blended, and has a good feel when used (freshness and good compatibility with the skin). Therefore, it is easy to apply to affected areas or skin that are hard to reach, such as the scalp, back, and waist, or when used by babies, infants, children, and the elderly, and is expected to alleviate concerns about the composition sticking to clothes after application.

[0057] (application site) The oil-in-water skin emulsion composition of the present invention can be used for skin care purposes on the face and body, as well as on areas prone to sweating and sebum production, areas affected by friction with clothing, bedsores, atopic dermatitis, dry skin, or areas with a weakened barrier function, etc. It can also be used on the scalp, face, neck, chest (including the top of the bust), back, arms, elbows (inside and outside), hands, around the nails, armpits, abdomen, vulva, buttocks, delicate areas, anal area, legs, fingers, toes, and soles, depending on the symptoms.

[0058] (Application) The oil-in-water emulsion composition of the present invention can be used, for example, not only for normal skin but also for babies, infants, children, the elderly, those requiring nursing care, those with weak skin, sensitive skin, hypersensitive skin, dry skin, unstable skin, troubled skin, those with temporarily sensitive skin, atopic skin, and skin suffering from heat rash or rash.

[0059] <Method for suppressing dripping of oil-in-water emulsion composition> The present invention also relates to a method for suppressing dripping of an oil-in-water emulsion composition, characterized by incorporating (A) a heparinoid and (B) one or more oil-soluble components selected from the group consisting of oil-soluble acylamino acids, their derivatives and salts, and pasty oils. By incorporating (B) one or more oil-soluble components selected from the group consisting of oil-soluble acylamino acids, their derivatives and salts, and pasty oils into an oil-in-water emulsion composition containing (A) a heparinoid, the properties of the formulation can be appropriately adjusted and dripping after discharge from the container can be effectively suppressed. The specific descriptions of (A) a heparinoid, (B) the oil-soluble components, and the oil-in-water emulsion composition containing them are the same as those described above in the section on oil-in-water emulsion compositions. [Example]

[0060] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0061] [Test 1] Characteristics test Oil-in-water emulsion compositions of Examples and Comparative Examples were prepared by conventional methods according to the formulations shown in Tables 1 to 4 below. The units of values ​​in each table are mass (%) unless otherwise specified. The viscosity, dischargeability from a container, and stability of each prepared composition were measured and evaluated using the methods described below. The results are also shown in Tables 1 to 4.

[0062] (viscosity) The viscosity (Pa·s) of each composition was measured using a 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 a time of 60 seconds.

[0063] (container dischargeability) 15 g of each composition was filled into a container with a pump (Honda Plus: Z-100-101 (pump), MDC-15PET (bottle), capacity: 12 mL), and the container was placed upright to count the number of pushes until the formulation began to be expelled. The counted number is recorded in the table as a score for expellability from the container. In addition, when each composition was expelled from the pump, it was determined whether or not there was dripping from the pump outlet. If there was no dripping, it was marked "Good", and if there was dripping, it was marked "Poor", and these results are recorded in the table. In the table, "ND" indicates that no evaluation was performed.

[0064] (stability) Each composition was filled into a 30 mL glass bottle and stored in a thermostatic chamber at 50° C. After one week had passed, the test formulation was removed from the thermostatic chamber and allowed to fully warm to room temperature, after which the appearance was visually evaluated according to the following evaluation criteria. Evaluation item: Stability Evaluation criteria: ×: Significant separation or significant change in properties that affects usability. △: There is some separation or peeling on the surface, but it does not affect the usability. ○: No separation or surface segregation, and no change in properties.

[0065] Generally, in emulsions, a decrease in viscosity often leads to instability of the formulation. However, it was found that the formulation in this study, which contained (A) a heparinoid, maintained high thermal stability despite the decrease in viscosity and changes in formulation properties.

[0066] [Test 2] Usability (freshness, moisturizing feeling, skin compatibility) Monitor test Six expert panelists scored the feel of use of each composition on a 5-point scale according to the following criteria, and the values ​​were averaged. An average score of 4 or more was designated as ⊚, an average score of 3.0 or more but less than 4.0 as ◯, an average score of 2.5 or more but less than 3.0 as △, and an average score of less than 2.5 as ×. Furthermore, the difference between the feel of use score of each Example and the feel of use score of the corresponding Comparative Example (the value obtained by subtracting the score of the Comparative Example from the score of the Example) was designated as ⊚ when it was 1.5 or more, 0.5 or more but less than 1.5 as ◯, greater than 0 but less than 0.5 as △, and 0 or less as ×. These results are shown in the table. Evaluation items: freshness, moisturizing feeling, skin compatibility Evaluation criteria: Feel: Score 5 Somewhat: Score 4 Neutral: Score 3 Not much: score 2 No feeling: Score 1

[0067] [Table 1]

[0068] [Table 2]

[0069] [Table 3]

[0070] [Table 4]

[0071] As shown in Tables 1 to 4, the incorporation of a heparinoid into an oil-in-water emulsion composition reduced viscosity, thereby improving dischargeability from the container. Surprisingly, the shape retention of the discharged formulation was improved, thereby suppressing dripping of the formulation from the pump port of the discharge container. In other words, the oil-in-water emulsion compositions of the Examples achieved the unexpected effect of maintaining the droplet shape and being discharged without dripping, despite their low viscosity and light, fresh texture. Furthermore, while reduced viscosity can raise concerns about stability, none of the oil-in-water emulsion compositions of the Examples exhibited any problems with long-term stability. Furthermore, in the evaluation of usability, because the formulations contained a heparinoid and a high concentration of oil, all formulations scored highly for moisturizing sensation and possessed high moisturizing power. However, despite the incorporation of a heparinoid, which is generally considered to be a cause of stickiness, stickiness, and poor penetration, the formulations exhibited improved moisturizing sensation upon application and excellent skin compatibility. Furthermore, in terms of evaluation items other than those mentioned above, all of the preparations of the Examples were found to be satisfactory, with no irritation felt.

[0072] Examples of formulations for the oil-in-water emulsion composition of the present invention are shown below.

[0073] [Table 5-1]

[0074] [Table 5-2]

[0075] [Table 6-1]

[0076] [Table 6-2]

[0077]

Table 7-1

[0078]

Table 7-2

[0079]

Table 8-1

[0080]

Table 8-2

[0081]

Table 9-1

[0082]

Table 9-2

[0083]

Table 10-1

[0084]

Table 10-2

[0085]

Table 11-1

[0086]

Table 11-2

[0087] [Table 12-1]

[0088] [Table 12-2] [Industrial Applicability]

[0089] According to the present invention, by blending one or more oil-soluble components selected from the group consisting of oil-soluble acylamino acids, their derivatives and salts, and pasty oils in an oil-in-water emulsion composition containing a heparin-like substance, the viscosity can be appropriately adjusted, making it easier to control the properties of the formulation, resulting in excellent usability, moisturizing properties while reducing stickiness and irritation, and a formulation that combines the excellent pharmacological effects of the heparin-like substance with good properties (usability and feel when used).

Claims

1. (A) a heparinoid; (B) one or more oil-soluble components selected from the group consisting of dioctyldodecyl N-lauroyl-L-glutamate, di(phytosteryl / octyldodecyl) N-lauroyl-L-glutamate, di(cholesteryl / octyldodecyl) N-lauroyl-L-glutamate, di(cholesteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate, and di(phytosteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate; and (D) one or more salt-tolerant polymers selected from the group consisting of polyacrylamide and (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymers, An oil-in-water emulsion composition, wherein the content of (A) the heparinoid is 0.01% by mass to 3% by mass of the total oil-in-water emulsion composition, the content of (B) the oil-soluble component is 0.001% by mass to 10% by mass of the total oil-in-water emulsion composition, and the content of (D) the salt-tolerant polymer is 0.05% by mass to 4% by mass of the total oil-in-water emulsion composition.

2. Furthermore, (C) dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, allantoin, ascorbic acid, sodium ascorbate, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, disodium ascorbyl sulfate, 2-O-ethyl ascorbic acid, 3-O-ethyl ascorbic acid, ascorbic acid-2-glucoside, disodium isostearyl ascorbyl phosphate, trisodium ascorbyl palmitate phosphate, glyceryl ascorbate, bisglyceryl ascorbate, hexyl 3-glyceryl ascorbate, 3-glyceryl ascorbate , myristyl 3-glyceryl ascorbate, 3-laurylglyceryl ascorbate, potassium ascorbyl / tocopheryl phosphate, tocopheryl ascorbate maleate, ascorbyl tetraisopalmitate, nicotinamide, α-tocopherol, β-tocopherol, δ-tocopherol, tocopherol acetate, tocopherol nicotinate, tocopherol succinate, tocopherol calcium succinate, retinol, retinol acetate, retinol palmitate, tocopheryl retinoate, and tranexamic acid.

3. (A) a heparinoid; (B) one or more oil-soluble components selected from the group consisting of dioctyldodecyl N-lauroyl-L-glutamate, di(phytosteryl / octyldodecyl) N-lauroyl-L-glutamate, di(cholesteryl / octyldodecyl) N-lauroyl-L-glutamate, di(cholesteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate, and di(phytosteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate; and (D) one or more salt-tolerant polymers selected from the group consisting of polyacrylamide and (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymers, A method for suppressing dripping from a discharge port of a container of an oil-in-water emulsion composition, characterized by blending (A) a heparinoid substance in an amount of 0.01% to 3% by mass of the total oil-in-water emulsion composition, (B) an oil-soluble component in an amount of 0.001% to 10% by mass of the total oil-in-water emulsion composition, and (D) a salt-tolerant polymer in an amount of 0.05% to 4% by mass of the total oil-in-water emulsion composition.

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