JP6290050B2 - Emulsion in which oil phase is dispersed in outer phase having bicontinuous structure and method for producing the same - Google Patents

Description

  The present invention relates to an emulsion in which an oil phase is dispersed in an outer phase having a bicontinuous structure, and a method for producing the emulsion. The invention also relates to the use of the emulsion as a cosmetic and a cosmetic method for inhibiting and / or whitening the skin.

Tranexamic acid ester or a salt thereof is known to have a whitening effect and is used as a whitening component in a composition for external use. For example, JP-A-4-46144 (Patent Document 1) describes an anti-pigmentation external preparation containing tranexamic acid ester as an active ingredient. JP-A-2003-306419 (Patent Document 2) exemplifies tranexamic acid and its derivatives as whitening components that can be used in combination with Coenzyme Q10. Furthermore, in JP-A-2004-107262 (Patent Document 3), tranexamic acid cetyl ester is exemplified as an oil-soluble whitening agent that can be used in combination with an L-ascorbic acid tetra-branched fatty acid ester derivative.
However, tranexamic acid ester or a salt thereof has a problem that since it has low solubility in water and oil, it easily forms an aggregate in the preparation and is difficult to disperse stably in the preparation.

JP-A-4-46144 JP 2003-306419 A JP 2004-107262 A Japanese Patent No. 5570442

  Under such circumstances, there is a demand for a method of dispersing tranexamic acid ester or a salt thereof in a composition in a stable state.

As a result of intensive studies to solve the above problems, the present inventors have found that a physiologically acceptable salt of tranexamic acid ester (hereinafter also referred to as “tranexamic acid ester salt”), amphiphilic in an aqueous medium. By mixing the substance and the oil agent in a specific amount ratio, the tranexamic acid ester salt was successfully dispersed at a nano level in the medium by a normal stirring operation (Patent Document 4: Patent No. 5570442).
As a result of further investigation, the present inventors have mixed a tranexamic acid ester salt, a predetermined amphiphile, an oil agent, water, and the like, so that the water phase and the oil phase are respectively continuous in three dimensions. It has been found that a composition having a structure is obtained, and the tranexamic acid ester salt can be stably dispersed in the composition. Furthermore, it has been found that by adding an oil agent to this composition, an extremely stable emulsion or cream-like emulsion in which the oil phase is dispersed in the outer phase having a bicontinuous structure is obtained. Without being bound by theory, this emulsion is a unity found in general emulsions such as the Ostwald tripping phenomenon because the bicontinuous structure that is the outer phase is composed of a strong self-organized structure. It can be considered that the destabilizing factor of the plant is inhibited, thereby improving the stability. Moreover, since it can give emollient property which was not enough only by the composition which has a bicontinuous structure by using the form of an emulsion, there also exists an advantage that the touch of cosmetics can be improved. The present invention has been completed based on these findings.

  That is, the present invention relates to the following emulsion and method for producing the same. The present invention also relates to the use of the emulsion as a cosmetic and a cosmetic method for suppressing and / or whitening the skin.

[1] An emulsion in which an oil phase is dispersed in an outer phase having a bicontinuous structure,
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A) A physiologically acceptable salt of tranexamic acid ester;
B) A linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms, and a mono- or diether of a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin An amphiphile selected from a combination of alkyl glyceryl ethers;
C) an oil agent; and D) water, a water-soluble organic solvent or a mixture thereof,
The oil phase that is the dispersed phase includes E) the oil agent, and the total content of the components constituting the outer phase is 55 to 95% by mass with respect to the total mass of the emulsion, and the content of the components that constitute the dispersed phase is The emulsion whose sum total is 5-45 mass%.
[2] Tranexamic acid ester in physiologically acceptable salt of tranexamic acid ester is represented by the following formula (1):
[In formula, R represents the saturated or unsaturated hydrocarbon group which has a C1-C22 linear or branched chain which may be substituted by the substituent chosen from a hydroxyl group and an amino group. ]
The emulsion of [1] shown by these.
[3] The emulsion according to [1] or [2], wherein the physiologically acceptable salt of the tranexamic acid ester of component A comprises tranexamic acid cetyl ester hydrochloride.
[4] In any one of [1] to [3], the amphiphilic substance of component B is a combination of cetyl alcohol and at least one selected from the group consisting of chimyl alcohol and batyl alcohol. The emulsion as described.
[5] The content of component A is 0.5 to 10% by mass, the content of component B is 0.5 to 10% by mass, and the content of component C is 1 with respect to the total mass of the emulsion. The emulsion according to any one of [1] to [4], which is -25% by mass and the total content of components A, B and C is 5-50% by mass.
[6] The emulsion according to any one of [1] to [5], wherein the outer phase further contains a pH adjuster as an optional component.
[7] The emulsion according to [6], wherein the pH adjuster is selected from Lewis bases.
[8] A method for producing an emulsion according to any one of [1] to [7],
A) A physiologically acceptable salt of tranexamic acid ester;
B) A linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms, and a mono- or diether of a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin An amphiphile selected from the combination of alkyl glyceryl ethers; and
C) preparing an oil phase containing an oil agent;
D) adding the oil phase to an aqueous phase containing water, a water-soluble organic solvent or a mixture thereof to form an outer phase having a bicontinuous structure;
E) adding an oil phase containing an oil agent to the outer phase to form a dispersed phase.
[9] An external composition comprising the emulsion according to any one of [1] to [7].
[10] Use of the emulsion according to any one of [1] to [7] as a cosmetic for suppressing pigmentation and / or whitening the skin in order to reduce stains or pigmentation.
[11] A cosmetic method for suppressing and / or whitening the skin, which comprises topically applying the emulsion according to any one of [1] to [7] to the skin.

According to the present invention, an emulsion or cream-like emulsion containing tranexamic acid ester salt is obtained. The emulsion of the present invention can be used as a cosmetic for inhibiting pigmentation and / or whitening the skin in order to thin stains or pigmentation.
According to the present invention, the tranexamic acid ester salt can be stably dispersed in the emulsion, so that the tranexamic acid ester salt can easily penetrate into the skin when applied to the skin, thereby whitening the tranexamic acid ester salt. The effect is expected to increase.

4 is a photograph showing a cryo SEM observation result for the composition of Reference Example 1. FIG. 1A shows an observation result at a magnification of 12,000 times, and FIG. 1B shows an observation result at a magnification of 35,000 times. 2 is a photograph showing a cryo SEM observation result for the composition of Example 3. FIG. 2 (a) and 2 (b) are cryo SEM observation results before FIB processing. FIG. 2A shows an observation result at a magnification of 64 times, and FIG. 2B shows an observation result at a magnification of 650 times. 2C and 2D show the cryo SEM observation results after the FIB processing. FIG. 2C shows an observation result at a magnification of 5,000 times, and FIG. 2D shows an observation result at a magnification of 12,000 times. It is the graph which showed the result of the thermal analysis by DSC about each composition obtained in the reference example 1 and Examples 1-4. In the figure, (a), (b), (c), (d) and (e) are the measurements for the compositions of Reference Example 1, Example 1, Example 2, Example 3 and Example 4, respectively. It is a result.

  Hereinafter, the emulsion of the present invention, a method for producing the emulsion, a method for using the emulsion, and the like will be described in detail.

The emulsion of the present invention is an emulsion in which an oil phase is dispersed in an outer phase having a bicontinuous structure,
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A) A physiologically acceptable salt of tranexamic acid ester;
B) A linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms, and a mono- or diether of a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin An amphiphile selected from a combination of alkyl glyceryl ethers;
C) an oil agent; and D) water, a water-soluble organic solvent or a mixture thereof,
The oil phase that is the dispersed phase includes E) the oil agent, and the total content of the components constituting the outer phase is 55 to 95% by mass with respect to the total mass of the emulsion, and the content of the components that constitute the dispersed phase is The total is 5 to 45% by mass.

As described above, the emulsion of the present invention has an oil phase dispersed in an outer phase having a bicontinuous structure. In the emulsion of the present invention, the external phase comprises A) tranexamic acid ester salt, B) amphiphile, C) oil agent, and D) water, water-soluble organic solvent or a mixture thereof, and A) tranexamic acid ester salt, A bicontinuous structure is formed by adding D) water, a water-soluble organic solvent or a mixture thereof to the oil phase containing B) amphiphile and C) oil. Here, the “bicontinuous structure” of the outer phase refers to a state in which the water phase and the oil phase are three-dimensionally continuous, and neither the water phase nor the oil phase coexist without phase separation. Specifically, it means that infinite aggregates such as a liquid crystal (LC) phase, a bicontinuous microemulsion (BME), a bicontinuous α-gel (BAG), and a sponge (L3) phase are formed.
It can be confirmed that the outer phase has a bicontinuous structure, for example, by adding a water-soluble dye and an oil-soluble dye and diffusing both into the outer phase. The liquid crystal (LC) phase exhibiting anisotropy can be confirmed by observing birefringence with a polarizing microscope. On the other hand, bicontinuous microemulsion (BME), bicontinuous α-gel (BAG), and sponge (L3) phase can be confirmed by observing flow birefringence. Here, “flow birefringence” refers to a phenomenon in which, when an isotropic gel-like structure is flowed by shaking or the like, the structure is oriented in the direction of flow and exhibits birefringence.
The emulsion of the present invention is obtained by dispersing an oil phase containing E) oil in the outer phase having a bicontinuous structure obtained as described above. Hereinafter, each component will be described.

A) Tranexamic acid ester salt The tranexamic acid ester in the tranexamic acid ester salt used in the present invention is preferably represented by the following formula (1).
[In formula, R represents the saturated or unsaturated hydrocarbon group which has a C1-C22 linear or branched chain which may be substituted by the substituent chosen from a hydroxyl group and an amino group. ]

In said formula (1), R represents the saturated or unsaturated hydrocarbon group which has a C1-C22 linear or branched chain, and the hydrogen atom contained in this hydrocarbon group is chosen from a hydroxyl group and an amino group. It may be substituted with a substituent.
The hydrocarbon group may be acyclic or cyclic. When the hydrocarbon group is acyclic, it may be a straight chain or a branched chain. Examples of the hydrocarbon group include an alkyl group, an alkenyl group, an alkynyl group, an alkyldienyl group, an aryl group, an alkylaryl group, an arylalkyl group, a cycloalkyl group, a cycloalkenyl group, and a cycloalkylalkyl group. Among these, an alkyl group is preferable. The carbon number is preferably 8-20, and particularly preferably 12-18.

  The number of substituents of the hydrocarbon group is not particularly limited. In the case where the hydrocarbon group has two or more substituents, the substituent may be either a hydroxyl group or an amino group, or may contain both a hydroxyl group and an amino group.

  Specific examples of the tranexamic acid ester represented by the formula (1) include tranexamic acid lauryl ester, tranexamic acid myristyl ester, tranexamic acid cetyl ester, and tranexamic acid stearyl ester. Among these, tranexamic acid cetyl ester is particularly preferable.

  The physiologically acceptable salt in the tranexamic acid ester salt used in the present invention is not particularly limited as long as it does not inhibit the object of the present invention. The tranexamic acid ester salt used in the present invention is a mineral acid salt of tranexamic acid ester hydrochloride, phosphate, sulfate, bromate, nitrate, etc .; organic acid such as oxalate, lactate, citrate, etc. Salts; carbonates are preferred. Of these, hydrochloride is preferable.

Among them, as tranexamic acid ester salt used in the present invention, tranexamic acid cetyl ester hydrochloride, tranexamic acid cetyl ester phosphate, tranexamic acid cetyl ester sulfate, tranexamic acid cetyl ester bromate, tranexamic acid cetyl ester nitrate, tranexam Those selected from the group consisting of acid cetyl ester oxalate, tranexamic acid cetyl ester lactate, tranexamic acid cetyl ester citrate and tranexamic acid cetyl ester carbonate are preferred. In particular, tranexamic acid cetyl ester hydrochloride is preferred.
Tranexamic acid ester salts may be used alone or in combination of two or more.

  The content of tranexamic acid ester salt (component A) in the emulsion of the present invention is preferably 0.5 to 10% by mass, more preferably 1 to 6% by mass, and 2 to 4% by mass with respect to the total mass of the emulsion. Is more preferable.

B) Amphiphilic substance The amphiphilic substance used in the present invention is a linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms and a linear or branched chain having 8 to 22 carbon atoms. Or a combination of alkyl glyceryl ethers which are mono- or diethers of saturated or unsaturated alcohols and glycerin. In the present invention, linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms, and linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin. By using a combination of alkyl glyceryl ethers that are mono- or diethers, the outer phase can form a bicontinuous structure.

The alcohol is not particularly limited as long as it has a linear or branched saturated or unsaturated alkyl group having 12 to 22 carbon atoms. 14-20 are preferable and, as for carbon number of an alkyl group, 16-18 are more preferable.
Specifically, lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol, 2-decyltetradecanol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, isostearyl alcohol, octyldodeca Nord and the like are preferably used. Among these, linear saturated alcohol is preferable, lauryl alcohol, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol and oleyl alcohol are more preferable, cetyl alcohol, cetostearyl alcohol and stearyl alcohol are more preferable, cetyl Alcohol is particularly preferred.

The alkyl glyceryl ether, which is a mono- or diether of a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin, is not particularly limited as long as it is a mono- or diether of the alcohol and glycerin. Monoether of linear saturated alcohol and glycerin is particularly preferable. 14-20 are preferable and, as for carbon number of an alkyl group, 16-18 are more preferable.
Examples of the alkyl glyceryl ether include glyceryl monostearyl ether (batyl alcohol), glyceryl monocetyl ether (chimyl alcohol), monooleyl glyceryl ether (ceracyl alcohol), monobehenyl glyceryl ether, mono 2-ethylhexyl glyceryl ether, mono Examples include isostearyl glyceryl ether, monocapryl glyceryl ether, monoisodecyl glyceryl ether, monoisostearyl diglyceryl ether, glycerin mono 2-ethylhexyl ether, and the like.
Among these, monostearyl glyceryl ether (batyl alcohol), glyceryl monocetyl ether (chimyl alcohol), and monooleyl glyceryl ether (ceralkyl alcohol) are preferable.

  A linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms, and a mono- or diether of a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin Each of the alkyl glyceryl ethers may be used alone or in combination of two or more. The amphiphilic substance of Component B is preferably a combination of cetyl alcohol and at least one selected from the group consisting of chimyl alcohol and batyl alcohol. Among these, it is preferable to use a combination of cetyl alcohol and chimyl alcohol or a combination of cetyl alcohol and batyl alcohol. The blending ratio of the alcohol to the alkyl glyceryl ether is preferably 1: 9 to 9: 1, more preferably 1: 6 to 6: 1, and still more preferably 1: 3 to 3: 1 on a mass basis.

  The content of the amphiphilic substance (component B) in the emulsion of the present invention is preferably 0.5 to 10% by mass, more preferably 1 to 6% by mass, based on the total mass of the emulsion, More preferably, 4% by mass.

C) Oil Agent The oil agent used in the present invention is not particularly limited as long as it is a substance that is insoluble or hardly soluble in water and easily dissolved in oil. Preferred examples of the oil used as component C in the present invention include low-viscosity liquid oils and fats, solid oils and fats, waxes, hydrocarbon oils, synthetic ester oils, silicone oils, and silicone elastomers that are widely used in compositions for external use.

Examples of liquid fats and oils (oils and fats in a liquid state at room temperature (25 ° C.)) include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, Wheat germ oil, sasanqua oil, castor oil, flaxseed oil, safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, teaseed oil, kaya oil, rice bran oil, cinnabari oil, Japanese kiri oil, jojoba oil, germ oil And triglycerin.
Examples of solid fats and oils (solid fats and oils at room temperature (25 ° C.)) include cocoa butter, coconut oil, horse fat, hydrogenated coconut oil, palm oil, palm kernel oil, owl kernel oil, hydrogenated oil, owl, and hydrogenated castor. Oil etc. are mentioned.

  Examples of waxes include beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, ibota wax, montan wax, nuka wax, lanolin, kapok wax, lanolin acetate, liquid lanolin, sugar cane wax, lanolin fatty acid isopropyl, lauryl hexyl, reduced lanolin, jojoba wax. , Hard lanolin, shellac wax, POE lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, and the like.

  Examples of the hydrocarbon oil include liquid paraffin, ozokerite, squalane, pristane, paraffin, ceresin, squalene, petrolatum, microcrystalline wax, hydrogenated polydecene, isododecane and the like.

  Synthetic ester oils include dineopentanoic acid tripropylene glycol, isononyl isononanoate, isotridecyl isononanoate, isopropyl myristate, cetyl octanoate, cetyl isooctanoate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, butyl stearate, lauric acid Hexyl acid, myristyl myristate, decyl oleate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate , Dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate , Diisostearyl malate, glyceryl di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, tri-2- Glyceryl ethylhexanoate, glyceryl trioctanoate, glycerin triisopalmitate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glyceryl trimyristate, glyceride tri-2-heptylundecanoate, Castor oil fatty acid methyl ester, oleyl oleate, acetoglyceride, 2-heptylundecyl palmitate, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-oct Ludodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate , 2-ethylhexyl succinate, triethyl citrate, dimer dilinoleic acid dimer dilinoleyl bis (behenyl / isostearyl / phytosteryl), lauroyl glutamic acid (phytosteryl / behenyl / octyldodecyl / isostearyl), tri (caprylic acid / capric acid) ) Glyceryl, triethylhexanoin and the like.

  Examples of the silicone oil include linear polysiloxanes (for example, dimethicone (dimethylpolysiloxane)), methyltrimethicone, methylphenylpolysiloxane, diphenylpolysiloxane, etc .; cyclic polysiloxanes (for example, octamethylcyclotetrasiloxane, deca Methylcyclopentasiloxane, dodecamethylcyclohexasiloxane, etc.) Silicone resin, silicone rubber, various modified polysiloxanes (amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine) forming a three-dimensional network structure Modified polysiloxane, etc.).

  Examples of silicone elastomers include non-emulsifying organopolysiloxane elastomers and emulsifying organosiloxane elastomers. Examples of the non-emulsifying organopolysiloxane elastomer include dimethicone / vinyl dimethicone cross polymer, lauryl dimethicone / vinyl dimethicone cross polymer, and the like.

  Dimethicone / vinyl dimethicone crosspolymers are commercially available under the names “DC9040” and “DC9045” from DOW CORNING (Midland, Michigan), “SFE839” and “Velvasil” series products from Shinmentec, Shin-Etsu Chemical Commercially available under the names of “KSG-15”, “KSG-16”, “KSG-18” from Kogyo Co., Ltd. ([Dimethicone / Phenylvinyldimethicone crosspolymer]), “Gransil” (from GRANT INDUSTRIES) Trademark) series products.

  As the lauryl dimethicone / vinyl dimethicone cross polymer, “KSG-31”, “KSG-32”, “KSG-41”, “KSG-42”, “KSG-43” and “KSG-44” from Shin-Etsu Chemical Co., Ltd. And the like that are commercially available.

  Examples of the emulsified organosiloxane elastomer include polyalkoxylated silicone elastomer and polyglycerolated silicone elastomer.

  Polyalkoxylated silicone elastomers are commercially available under the names “DC9010” and “DC9011” from DOW CORNING, and “KSG-20”, “KSG-21” and “KSG-” from Shin-Etsu Chemical Co., Ltd. 30 "," KSG-31 "," KSG-32 "," KSG-33 "," KSG-210 "," KSG-310 "," KSG-320 "," KSG-330 "," KSG-340 " And those commercially available under names such as “X-226146”.

  As the polyglycerolated silicone elastomer, “KSG-710”, “KSG-810”, “KSG-820”, “KSG-830”, “KSG-840”, “KSG-31”, Shin-Etsu Chemical Co., Ltd., What is marketed by names, such as "KSG-32", "KSG-41", "KSG-42", "KSG-43", and "KSG-44", is mentioned. In addition, as silicone elastomers in which two types of branches of a silicone chain and an alkyl chain are introduced, “KSG-042Z”, “KSG-045Z”, “KSG-320Z”, “KSG” from Shin-Etsu Chemical Co., Ltd. -350Z "," KSG-820Z "," KSG-850Z ", etc. are marketed.

  Moreover, you may use the silicone elastomer which contains a polyalkyl ether group as a pendant or bridge | crosslinking. Particularly suitable silicone elastomers containing polyalkyl ether groups are those according to the International Nomenclature of Cosmetic Ingredients (INCI), bis-vinyl dimethicone / bis-isobutyl PPG-20 crosspolymer, bis- Examples include vinyl dimethicone / PPG-20 crosspolymer, dimethicone / bis-isobutyl PPG-20 crosspolymer, dimethicone / PPG-20 crosspolymer, and dimethicone / bis-secbutyl PPG-20 crosspolymer. Such a crosslinked elastomer is obtained from DOW CORNING under the names of test compounds such as “SOEB-1”, “SOEB-2”, “SOEB-3”, “SOEB-4”, and “DC EL-8052 IH”. It can be obtained under a trade name (draft) such as “Si Organic Elastomer Blend”. These elastomer particles are provided by pre-swelling in each solvent (isododecane is used for SOEB-1 and SOEB-2, isohexadecane is used for SOEB-3, and isodecyl neopentanoate is used for SOEB-4). The

  These oil agents may be used alone or in combination of two or more.

  1-25 mass% is preferable with respect to the total mass of an emulsion, as for content of the oil agent (component C) in the emulsion of this invention, 4-12 mass% is more preferable, and 6-10 mass% is further more preferable.

D) Water, water-soluble solvent, or a mixture thereof In the emulsion of the present invention, water, a water-soluble solvent, or a mixture thereof is used as Component D.
The water-soluble organic solvent is not particularly limited, and those commonly used in external compositions can be preferably used. For example, lower alcohols (preferably alcohols having 1 to 5 carbon atoms) such as methanol, ethanol, propanol, isopropanol; ethylene glycol, 1,3-butylene glycol, propylene glycol, dipropylene glycol, isoprene glycol, polyethylene glycol, polyoxy Examples thereof include polyhydric alcohols such as ethylene methyl glucoside, glycerin, and diglycerin. These water-soluble organic solvents may be used alone or in combination of two or more.

  The content of water, water-soluble solvent or mixture thereof (component D) is the balance of the emulsion of the present invention. The content of water, a water-soluble solvent or a mixture thereof is, for example, preferably 30 to 90% by mass, more preferably 40 to 80% by mass, and 50 to 70% by mass with respect to the total mass of the emulsion. Further preferred. Among these, 0.5-10 mass% is preferable, as for content of a water-soluble organic solvent, 1-6 mass% is more preferable, and 2-4 mass% is further more preferable. By including the water-soluble organic solvent in the above range, the outer phase tends to form a bicontinuous structure.

  In one embodiment of the present invention, the content of component A is 0.5 to 10% by mass, the content of component B is 0.5 to 10% by mass, and the content of component C is 1 to 25%. The total content of components A, B and C is preferably 5 to 45% by mass with respect to the total mass of the emulsion. The total content of components A, B and C is more preferably 8 to 30% by mass, and further preferably 10 to 20% by mass. When the content of components A, B, and C is in the above range, the outer phase tends to form a more stable bicontinuous structure.

  In the emulsion of the present invention, the bicontinuous structure of the outer phase is maintained even when components constituting the oil phase containing the oil agent (component E) are added in a predetermined quantitative ratio. In the emulsion of the present invention, the oil phase containing the oil agent (component E) is dispersed in the outer phase to become a dispersed phase, and can exist stably without phase separation.

E) Oil agent As the oil agent (component E) constituting the oil phase dispersed in the outer phase having a bicontinuous structure, a substance that is insoluble or hardly soluble in water and easily soluble in oil is particularly useful. Not limited. Preferred examples of the oil used as component E in the present invention include low-viscosity liquid oils, solid oils, waxes, hydrocarbon oils, synthetic ester oils, silicone oils, and silicone elastomers that are widely used in external compositions. Specific examples are the same as those exemplified as the oil agent (component C).

Also, for example, methoxycinnamic acid derivatives, diphenylacrylic acid derivatives, salicylic acid derivatives, paraaminobenzoic acid derivatives, triazine derivatives, benzophenone derivatives, benzalmalonate derivatives, anthranil derivatives, imidazoline derivatives, 4,4-diarylbutadiene derivatives, phenyl Oil agents such as benzimidazole derivatives and perfluoropolyether derivatives can be used.
Specifically, octyl methoxycinnamate, 2-ethylhexyl paramethoxycinnamate, homosalate, octyl salicylate, oxybenzone, 4-t-butyl-4'-methoxydibenzoylmethane, octyl triazone, methylenebisbenzotriazolyl Tetramethylbutylphenol, 2-hydroxy-4-methoxybenzophenone, dihydroxydimethoxybenzophenone, dihydroxybenzophenone, tetrahydroxybenzophenone, diethylaminohydroxybenzoyl hexyl benzoate, 2-cyano-3,3-diphenylacrylic acid-2′-ethylhexyl ester, poly Silicone-15, drometrizole polysiloxane, phenylbenzimidazole sulfonic acid, perfluoropolymethyl isopropyl ether, etc. It is below.

The oil agent (component E) that can be used in the present invention can be arbitrarily selected from a nonpolar oil (such as squalane) to a highly polar oil (such as octyl methoxycinnamate and hexyl diethylaminohydroxybenzoyl benzoate).
These oil agents may be used alone or in combination of two or more.

  As for content of the oil agent (component E) in the emulsion of this invention, 5-45 mass% is preferable with respect to the total mass of an emulsion, 10-35 mass% is more preferable, 15-25 mass% is further more preferable.

  The emulsion of the present invention, as described above, is a formulation of tranexamic acid ester salt (component A) in a stable state without phase separation, so that tranexamic acid ester salt easily penetrates into the skin, It is thought that the whitening effect can be maximized. Moreover, since the emulsion of this invention can increase the compounding quantity of an oil agent, disperse | distributing tranexamic acid ester salt in the stable state, it can provide emollient property. As described in the Background Art section, tranexamic acid ester salt has low solubility in water and oil, and it has been very difficult to increase the amount of oil agent while dispersing tranexamic acid ester salt in a stable state. It was thought. The present invention addresses such problems of the prior art, first, the tranexamic acid ester salt forms an outer phase having a bicontinuous structure and is dispersed (or dissolved) in a stable state, and then, in the obtained outer phase. With a completely new idea of dispersing the oil phase, the present inventors succeeded in increasing the amount of the oil agent while dispersing the tranexamic acid ester salt in a stable state, thereby overcoming the conventional problems.

In the emulsion of the present invention, the content of the components constituting the outer phase is 55 to 95% by weight in total with respect to the total mass of the emulsion, preferably 60 to 87% by weight, more preferably 65 to 90% by weight. 75 to 85% by mass is more preferable.
Moreover, the compounding quantity of the component which comprises the oil phase which is a dispersed phase is 5-45 mass% in total with respect to the total mass of an emulsion, 7-40 mass% is preferable, and 10-35 mass% is more. Preferably, 15 to 25% by mass is more preferable.
Although it depends on the type of component constituting the dispersed phase, the viscosity of the emulsion tends to increase as the amount of the component constituting the dispersed phase increases. What is necessary is just to select suitably the compounding ratio of an outer phase and a dispersed phase according to a use.

  According to a preferred embodiment of the present invention, the emulsion of the present invention has a small peak (or almost no peak is observed) derived from melting or phase transition observed by differential scanning calorimetry (DSC). This means that in the emulsion of the present invention, the tranexamic acid ester salt (component A) that is originally solid exists in a state close to a liquid state. In one embodiment of the present invention, unlike the conventional composition in which the tranexamic acid ester salt is dispersed in a solid state (gel form), the tranexamic acid ester salt (component A) exists in a state close to a liquid state. As a result, it is considered that the penetration property of tranexamic acid ester salt into the skin is further enhanced, so that the whitening effect is expected to be further enhanced.

  The emulsion of the present invention has a structure in which an oil phase is dispersed in an outer phase having a bicontinuous structure. According to a preferred embodiment of the present invention, the emulsion of the present invention does not undergo phase separation in a wide temperature range (for example, in the range of −20 to 70 ° C., preferably in the range of −10 to 50 ° C.). Can be maintained in a stable state.

The pH value of the emulsion of the present invention is not particularly limited, but it is preferably in a weakly acidic region (pH 5.0 to 5.5) having a higher affinity for the skin. The pH adjuster that can be used in the emulsion of the present invention is not particularly limited as long as it is generally used for external compositions. Among them, the Lewis base represented by nicotinamide does not increase the pH value by donating hydroxide ions, but increases the pH value by donating electron pairs. Even if a Lewis base is added therein, the solubility of tranexamic acid ester salt (component A) in water is not affected. For this reason, since the tranexamic acid ester salt can be raised to an arbitrary pH value without being precipitated as crystals, a Lewis base is preferably used.
Examples of the Lewis base include nitrogen-containing basic compounds or salts thereof, carboxylic acids, alcohols and the like. Among these, it is preferable to use a nitrogen-containing basic compound.
Specific examples of the nitrogen-containing basic compound include triethylamine, tri-n-propylamine, tri-i-propylamine, tri-n-butylamine, tri-n-hexylamine, triethanolamine, triphenylamine, aniline, N, N-dimethylaniline, 2-methylaniline, 3-methylaniline, 4-methylaniline, 4-nitroaniline, 1-naphthylamine, 2-naphthylamine, diphenylamine, ethylenediamine, tetramethylenediamine, hexamethylenediamine, pyrrolidine, piperidine, etc. An amine compound;
Imidazole compounds such as imidazole, 4-methylimidazole, 4-methyl-2-phenylimidazole, thiabendazole;
Pyridine compounds such as pyridine, 2-methylpyridine, 4-ethylpyridine, 2-hydroxypyridine, 4-hydroxypyridine, 2-phenylpyridine, 4-phenylpyridine, nicotinic acid, nicotinamide (niacinamide), quinoline and acridine ;
Other nitrogen-containing heterocyclic compounds such as purine, 1,3,5-triazine, triphenyl-1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, urazole, etc. be able to.
A Lewis base may be used individually by 1 type, or may be used 2 or more types.
In addition, pH adjusters other than Lewis bases, such as ionic bases typified by sodium hydroxide and arginine, are less susceptible to hydroxide ions at low concentrations and tranexamic acid ester crystals are Can be raised to any pH value without precipitation.
The amount of the pH adjusting agent used may be an amount that brings the pH of the emulsion of the present invention into a desired region, and may be appropriately determined depending on the type of the pH adjusting agent.

  The emulsion of the present invention can optionally contain components other than those described above as long as the object and effects of the present invention are not impaired. For example, a component that can be blended in an external composition such as a pharmaceutical, a quasi-drug, or a cosmetic can be included. The optional component can be blended in the emulsion of the present invention by blending in the outer phase or the dispersed phase. A person skilled in the art can appropriately determine whether to mix in the outer phase or the dispersed phase depending on the type of the optional component.

  Examples of optional components that can be used in the present invention include powder components, surfactants, cosurfactants, humectants, film agents, thickeners, gelling agents, inorganic minerals, sequestering agents, polyhydric alcohols. , Monosaccharides, oligosaccharides, amino acids, plant extracts, organic amines, polymer emulsions, antioxidants, antioxidant aids, skin nutrients, vitamins, blood flow promoters, bactericides, anti-inflammatory (anti-inflammatory) agents Cell (skin) activators, keratolytic agents, refreshing agents, astringents, whitening agents, UV absorbers, anti-fading agents, preservatives, buffers, fragrances, and the like can be appropriately blended as necessary. These optional components may be appropriately selected according to the intended dosage form and application.

  Examples of the powder component include inorganic powders (for example, talc, kaolin, mica, sericite (sericite), muscovite, phlogopite, synthetic mica, saucite, biotite, vermiculite, magnesium carbonate, calcium carbonate, silicic acid. Aluminum, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, silica, zeolite, barium sulfate, magnesium sulfate, calcined calcium sulfate (calcined gypsum), calcium phosphate, fluorine apatite, hydroxyapatite, ceramic Powder, metal soap (eg, zinc myristate, calcium palmitate, aluminum stearate, magnesium stearate), boron nitride, etc.); organic powder (eg, polyamide resin powder (nylon powder), polyethylene powder, Methyl methacrylate powder, polystyrene powder, copolymer resin powder of styrene and acrylic acid, benzoguanamine resin powder, polytetrafluoroethylene powder, cellulose powder, etc.); metal powder pigment (eg, aluminum powder, copper powder, etc.); Organic pigments such as zirconium, barium or aluminum lake; natural pigments (for example, chlorophyll, β-carotene, etc.) and the like. The powder component may be hydrophobized.

  Examples of the surfactant include an anionic surfactant, a cationic surfactant, an amphoteric surfactant, a lipophilic nonionic surfactant, and a hydrophilic nonionic surfactant.

  Examples of the anionic surfactant include fatty acid soap (eg, sodium laurate, sodium palmitate, etc.); higher alkyl sulfates (eg, sodium lauryl sulfate, potassium lauryl sulfate); alkyl ether sulfates (eg, POE-lauryl sulfate triethanolamine, POE-sodium lauryl sulfate, etc.); N-acyl sarcosine acids (eg, sodium lauroyl sarcosine, etc.); higher fatty acid amide sulfonates (eg, sodium N-myristoyl-N-methyl taurate, Palm oil fatty acid methyl tauride sodium, lauryl methyl tauride sodium, etc .; Phosphate ester salt (POE-oleyl ether sodium phosphate, POE-stearyl ether phosphate etc.); Sulfosuccinate ( For example, sodium di-2-ethylhexyl sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sodium sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, etc .; alkylbenzene sulfonates (eg, sodium linear dodecyl benzene sulfonate, linear dodecyl benzene sulfone) Acid triethanolamine, linear dodecylbenzene sulfonic acid, etc.); higher fatty acid ester sulfates (eg, hydrogenated coconut oil fatty acid sodium glyceryl sulfate); N-acyl glutamate (eg, monosodium N-lauroyl glutamate, N-stearoyl) Disodium glutamate, N-myristoyl-L-monosodium glutamate, etc.); sulfated oil (eg funnel oil); PO -Alkyl ether carboxylic acid; POE-alkyl allyl ether carboxylate; α-olefin sulfonate; higher fatty acid ester sulfonate; secondary alcohol sulfate ester; higher fatty acid alkylolamide sulfate ester; lauroyl monoethanolamide succinate Examples include sodium acid; N-palmitoyl aspartate ditriethanolamine; sodium caseinate and the like.

  Examples of the cationic surfactant include alkyltrimethylammonium salts (for example, stearyltrimethylammonium chloride and lauryltrimethylammonium chloride); alkylpyridinium salts (for example, cetylpyridinium chloride); distearyldimethylammonium dialkyldimethylammonium chloride Poly (N, N′-dimethyl-3,5-methylenepiperidinium) chloride; alkyl quaternary ammonium salt; alkyldimethylbenzylammonium salt; alkylisoquinolinium salt; dialkyl morpholinium salt; POE-alkylamine Alkylamine salts; polyamine fatty acid derivatives; amyl alcohol fatty acid derivatives; benzalkonium chloride; benzethonium chloride and the like.

  Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants (eg, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide). Side-1-carboxyethyloxy disodium salt, etc.); betaine surfactants (for example, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkylbetaine, amide betaine) , Sulfobetaine, etc.).

  Examples of the lipophilic nonionic surfactant include sorbitan fatty acid esters (for example, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, Sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexyl); glycerin polyglycerin fatty acids (for example, mono-cotton oil fatty acid glycerin, mono-erucic acid glycerin, sesquioleate glycerin, monostearin) Glycerin acid, α, α′-oleic acid pyroglutamic acid glycerin, monostearic acid glycerin malic acid, etc.); propylene glycol fatty acid esters (for example, , Propylene glycol monostearate, etc.); hardened castor oil derivative; glycerin alkyl ether; steareth-2 and the like.

  Examples of hydrophilic nonionic surfactants include POE-sorbitan fatty acid esters (for example, POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate). POE sorbite fatty acid esters (eg, POE-sorbite monolaurate, POE-sorbite monooleate, POE-sorbite pentaoleate, POE-sorbite monostearate, etc.); POE-glycerin fatty acid esters (eg, POE- Glycerol monostearate, POE-glycerol monoisostearate, POE-glycerol triisostearate, etc.); POE-fatty acid esters (for example, POE-monooleate, POE-distearate, P) E-monodiolate, ethylene glycol distearate, etc.); POE-alkyl ethers (for example, POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE-2-octyldodecyl ether, POE-core) Stanol ether, etc.); Pluronic type (for example, Pluronic, etc.); POE • POP-alkyl ethers (for example, POE • POP-cetyl ether, POE • POP-2-decyltetradecyl ether, POE • POP-monobutyl ether, POE · POP-hydrogenated lanolin, POE · POP-glycerin ether, etc.); steareth-21 and the like.

A water-soluble polymer can be used as the thickener. Examples of the water-soluble polymer include gum arabic, carrageenan, caraya gum, gum tragacanth, quince seed (malmello), casein, dextrin, gelatin, sodium pectate, sodium alginate, locust bean gum, guar gum, tara gum, tamarind gum, glucomannan Natural polymers such as xylan, mannan, xanthan gum, agar, pectin, fucoidan, galactomannan, curdlan, gellan gum, fucogel, casein, collagen, starch, sodium hyaluronate, alkacilan (alkalinenes-producing polysaccharide); , Sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, methyl Semi-synthetic polymers such as droxypropylcellulose, hydroxypropylmethylcellulose stearoyl ester, propylene glycol alginate, cellulose dialkyldimethylammonium sulfate, PVA (polyvinyl alcohol), PVM (polyvinyl methyl ether), PVP (polyvinyl pyrrolidone), polyethylene oxide, _Examples thereof include synthetic polymers such as sodium polyacrylate, carboxyvinyl polymer, acrylate / C _10-30 alkyl acrylate crosspolymer, sodium polyacrylate, and the like.
Among these, a water-soluble polymer selected from the group consisting of nonionic or cationic water-soluble polymers having good compatibility with tranexamic acid ester salts is preferable. In particular, a water-soluble polymer selected from the group consisting of locust bean gum, guar gum, tara gum, tamarind gum and hydroxypropylmethylcellulose stearoyl ester is preferred. More preferably, a nonionic associative thickener is used. The nonionic associative thickener can give a thickening effect sufficient to maintain a bicontinuous structure by adding a small amount without affecting the feel. Specific examples include polyoxyethylene distearate such as PEG-150 distearate and PEG-250 distearate, and hydrophobically modified polyether urethane such as (PEG-240 / decyltetradeceth-20 / HDI) copolymer. It is done.

  Moreover, you may use a clay mineral as a thickener. For example, in addition to clay minerals such as bentonite, hectorite, AlMg silicate (beegum), laponite and the like that provide a thickening effect in the aqueous phase, clay minerals that provide a thickening effect in the oil phase such as organically modified clay minerals.

  Examples of the sequestering agent include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, and tetrasodium edetate. Sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, trisodium ethylenediaminehydroxyethyl triacetate and the like.

  Examples of the polyhydric alcohol include divalent alcohols (for example, ethylene glycol, propylene glycol, pentylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene glycol, 2,3 -Butylene glycol, pentamethylene glycol, 2-butene-1,4-diol, hexylene glycol, octylene glycol, etc.); trivalent alcohols (eg, glycerin, trimethylolpropane, etc.); tetravalent alcohols (eg, 1 , 2,6-hexanetriol, etc.); pentahydric alcohol (eg, xylitol, etc.); hexavalent alcohol (eg, sorbitol, mannitol, etc.); polyhydric alcohol polymer (eg, diethylene glycol, dipro) Ren glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, etc.); Divalent alcohol alkyl ethers (eg, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, etc.); Divalent alcohol alkyl ethers (eg, diethylene glycol monomethyl, etc.) Ethers, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, etc.); dihydric alcohol ether esters (eg, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, etc.); glycerin monoalkyl ethers (eg, chimyl alcohol, ceralkyl alcohol) Sugar alcohol (eg, sorbitol, ma Chitoru, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, amylolytic sugar, maltose, xylitose, amylolytic sugar reducing alcohol) and the like.

  Examples of monosaccharides include tricarbon sugars (eg, D-glyceryl aldehyde, dihydroxyacetone, etc.); tetracarbon sugars (eg, D-erythrose, D-erythrulose, D-treose, erythritol, etc.); pentose sugars (eg, L-arabinose, D-xylose, L-lyxose, D-arabinose, D-ribose, D-ribulose, D-xylulose, L-xylulose, etc .; hexose (eg, D-glucose, D-talose, D) -Psicose, D-galactose, D-fructose, L-galactose, L-mannose, D-tagatose, etc.); heptacarbon (eg, aldoheptose, heproose, etc.); octose sugar (eg, octulose, etc.); For example, 2-deoxy-D-ribose, 6-deoxy-L-galactose, 6-deoxy-L Mannose, etc.]; amino sugars (eg, D-glucosamine, D-galactosamine, sialic acid, aminouronic acid, muramic acid, etc.); uronic acids (eg, D-glucuronic acid, D-mannuronic acid, L-guluronic acid, D- Galacturonic acid, L-iduronic acid, etc.).

  Examples of the oligosaccharide include sucrose, lactose, maltose, trehalose, cellobiose, gentiobiose, umbilicin, raffinose, gentianose, maltotriose, melezitose, planteose, umbelliferose, stachyose, verbusose and the like.

  Examples of amino acids include neutral amino acids (eg, threonine, cysteine, etc.); basic amino acids (eg, hydroxylysine, etc.) and the like. Examples of the amino acid derivative include acyl sarcosine sodium (lauroyl sarcosine sodium), acyl glutamate, acyl β-alanine sodium, glutathione, and pyrrolidone carboxylic acid.

  Examples of the organic amine include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methyl-1-propanol, and the like. Is mentioned.

  Examples of the polymer emulsion include an acrylic resin emulsion, a polyethyl acrylate emulsion, an acrylic resin liquid, a polyacryl alkyl ester emulsion, a polyvinyl acetate resin emulsion, and a natural rubber latex.

Examples of vitamins include vitamins A, B ₁ , B ₂ , B ₆ , C, E and derivatives thereof, pantothenic acid and derivatives thereof, biotin and the like.

Examples of the antioxidant include ascorbic acid such as ascorbyl palmitate, ascorbyl tetraisopalmitate, glucoside ascorbyl, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate and derivatives thereof;
Tocopherol and its derivatives such as tocopherol acetate, tocopherol sorbate and other tocopherol esters; dibutylhydroxytoluene (BHT) and butylhydroxyanisole (BHA); gallic acid ester; phosphoric acid; citric acid; maleic acid; malonic acid; Acid; fumaric acid; kephalin; hexametaphosphate; phytic acid; ethylenediaminetetraacetic acid: and Irish moss (Rhodiola), hyperthermophilic bacteria, mate tea leaves, oak, kayu rape bark plant extracts such as rapet bark), cherry leaves, and ylang ylang leaves.

  Examples of humectants include polyethylene glycol; propylene glycol; dipropylene glycol; glycerin; 1,3-butylene glycol; xylitol; sorbitol; maltitol; mucopolysaccharides such as chondroitin sulfate; hyaluronic acid; sodium hyaluronate; Sodium acetyl; mucoitin sulfate; caronic acid; atelocollagen; cholesteryl-12-hydroxystearate; bile salts; main components of NMF (natural moisturizing factor) such as pyrrolidone carboxylate and lactate; amino acids such as urea, cysteine and serine Short chain soluble collagen; Diglycerin (EO) PO adduct; 2-Methacryloyloxyethyl phosphorylcholine commercially available under the names “Lipidure HM” and “Lipidure PBM” from NOF Corporation Homopolymer or copolymer; Panthenol; Allantoin; PEG / PPG / polybutylene glycol-8 / 5/3 glycerin sold under the name of “Wilbride S 753” from NOF Corporation; “AMINOCOAT” from Asahi Kasei Chemicals Corporation Trimethylglycine marketed under the name of: Sweet chestnut (Castanea sativa) extract, hazelnut protein hydrolyzate, Polythethes tuberosa polysaccharide, Argania spinosa kernel oil, Maruzen Pharmaceutical Co., Ltd. Examples include various plant extracts such as conchiolin-containing pearl extract marketed under the name “pearl extract” (registered trademark).

  Examples of emollients include polyglyceryl methacrylate and methyl gluceth-20.

  Antiaging agents include, for example, acylamino acids (specifically, those marketed under the names “Maxilip”, “MatrixyL3000”, and “Biopeptide CL” from SEDERMA, and commercially available under the name “Sepilift” from SEPPIC. Peas extract; soy protein hydrolyzate; methyl silanol mannuronate; hydrolyzed peppo pumpkin seed oil lees; Senedesmus extract and the like.

  Examples of the anti-fouling agent include horseradish seed extract (specifically, commercially available under the name “Purisoft” from LSN); shea butter extract (specifically Is marketed by SILAB under the name “Detoxyl”, a blend of ivy extract, phytic acid and sunflower seed extract (for example, under the name “OSMOPUR” by SEDERMA) And the like are exemplified) and the like.

Examples of keratolytic agents include α-hydroxy acids (specifically, glycolic acid, lactic acid, citric acid, malic acid, mandelic acid, tartaric acid, etc.), β-hydroxy acids (specifically, and salicylic acid are exemplified), (specifically, the plant extract (specifically comprising lactic acid C _12-13 alkyl) and their hydroxy acids, Rozerisou (Hibiscus Sabdriffa) their esters such extracts is exemplified ) And the like.

  Examples of the anti-inflammatory agent include bisabolol, allantoin, tranexamic acid, zinc oxide, sulfur oxide and derivatives thereof, chondroitin sulfate, glycyrrhizic acid and derivatives thereof (such as glycyrrhizinate) and the like.

  The emulsion of the present invention may contain at least one whitening agent for the purpose of inhibiting the synthesis of structural proteins such as Pmel17, which is a melanocyte-specific protein contained in the melanogenesis mechanism (stage I). Examples of whitening agents include ferulic acid-containing site vectors (water, glycol, lecithin, ferulic acid, hydroxyethyl cellulose) marketed under the name “Cytovector” (registered trademark) by BASF.

  Furthermore, the emulsion of the present invention may contain at least one peptide described in International Publication No. 2009/010356 pamphlet.

  Furthermore, the emulsion of the present invention may contain a whitening agent having an inhibitory effect on melanin synthesis, microphthalmia-related transcription factor expression, anti-tyrosinase activity, and endothelin-1 synthesis. Examples thereof include licorice extract (Glycyrrhiza glabra extract) marketed under the name of “Licorice extract” (registered trademark) by Maruzen Pharmaceutical Co., Ltd.

  Furthermore, the emulsion of the present invention may contain a whitening agent having an antioxidant action such as a vitamin C compound. Examples include ascorbate, fatty acid or sorbic acid ascorbyl ester, and other ascorbic acid derivatives. Specifically, ascorbyl phosphate salt (ascorbyl magnesium phosphate, ascorbyl sodium phosphate, etc.), saccharide ester of ascorbic acid (ascorbyl-2-glucoside, 2-O-α-D-glucopyranosyl L-ascorbic acid, 6- O-β-D-galactopyranosyl L-ascorbic acid and the like). This type of active ingredient is commercially available from DKSH under the name “Ascorbyl glucoside” ®.

  Furthermore, the emulsion of the present invention may contain other whitening agents. For example, plant extracts (extracts such as bosaki narcissus), cetyl tranexamate (manufactured by Nikko Chemicals, product name “NIKKOL TXC”), arbutin, kojic acid, ellagic acid, cysteine, 4-thioresorcin, resorcinol or lucinol or A pigmentation inhibitor such as a derivative thereof, glycyrrhizic acid and hydroquinone-β-glucoside may be included.

The emulsion of the present invention may further contain an organic sunscreen agent and / or an inorganic sunscreen agent.
Organic sunscreen agents include dibenzoylmethane derivatives such as butylmethoxydibenzoylmethane (such as those sold under the name “Parsol 1789” from HOFFMANN LA ROCHE); cinnamic acid derivatives such as octyl methoxycinnamate (HOFFMANN LA Such as those commercially available from ROCHE under the name “Parsol MCX”); salicylates; paraaminobenzoic acids; β, β′-diphenyl acrylate derivatives; benzophenone derivatives; benzylidene camphor derivatives such as terephthalylidene dicamphor sulfonic acid; Examples thereof include benzimidazole derivatives; triazine derivatives; phenylbenzotriazole derivatives; anthranilic acid derivatives. These may be coated or encapsulated.
Examples of inorganic sunscreen agents include nanopigments that are optionally coated with pigments or metal oxides. Examples of nanopigments include titanium oxide, iron oxide, zinc oxide, zirconium oxide, and cerium oxide. All of these compounds are well known as UV photoprotective agents.

  Examples of the preservative include paraoxybenzoic acid esters (methyl paraben, propyl paraben, etc.), phenoxyethanol and the like.

Other optional ingredients used in the emulsion of the present invention are listed in the “International Cosmetic Ingredient Dictionary and Handbook” (13th edition, 2010) published by the Personal Care Products Council. You can use what you have.
The amount of these optional components is not particularly limited as long as it does not impair the object of the present invention.

The emulsion of the present invention is
A) A physiologically acceptable salt of tranexamic acid ester;
B) A linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms, and a mono- or diether of a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin An amphiphile selected from the combination of alkyl glyceryl ethers; and
C) preparing an oil phase containing an oil agent;
D) adding the oil phase to an aqueous phase containing water, a water-soluble organic solvent or a mixture thereof to form an outer phase having a bicontinuous structure;
E) It can be produced by a method including a step of adding an oil phase containing an oil agent to form a dispersed phase. Hereinafter, each step will be described.

First, an oil phase containing components A, B and C is prepared. About the preferable compounding quantity of each component, it is as having already demonstrated, Content of the component A is 0.5-10 mass%, Content of the component B is 0.5-10 mass%, Component C Is preferably 1 to 25% by mass, and the total content of components A, B and C is preferably 5 to 45% by mass with respect to the total mass of the emulsion.
The oil phase is preferably heated and completely dissolved. The heating temperature is preferably in the range of 65 to 95 ° C, more preferably in the range of 75 to 90 ° C, and particularly preferably in the range of 80 to 85 ° C.

  Next, the obtained oil phase is added to the aqueous phase containing the component D. At this time, it is preferable to mix in advance a small amount (about 4 to 8% by mass with respect to the total mass of the emulsion) of component D constituting the aqueous phase in the oil phase. Without being bound by theory, by mixing a small amount of the aqueous phase component in advance with the oil phase, the oil-soluble part (oil agent, tranexamic acid ester salt and the lipophilic part of the amphiphile) and water-soluble It is considered that the water-soluble part (aqueous medium, tranexamic acid ester salt and hydrophilic part of the amphiphile) can be arranged to some extent, and when the oil phase is added to the aqueous phase, it promotes the formation of a bicontinuous structure. be able to.

  Before adding the oil phase to the aqueous phase, it is preferable to maintain the dissolved state by heating the oil phase and the aqueous phase, respectively. The heating temperature is preferably in the range of 65 to 95 ° C, more preferably in the range of 75 to 90 ° C, and particularly preferably in the range of 80 to 85 ° C. In addition, although “adding the oil phase to the aqueous phase” is described, the aqueous phase may be added to the oil phase as long as the oil phase and the aqueous phase can be mixed uniformly.

After mixing the oil phase and the aqueous phase, the mixture can be cooled to 30 ° C. or lower with stirring to form an outer phase having a bicontinuous structure. The cooling method is not particularly limited, and may be natural cooling or ice cooling, for example.
As described above, according to the method of the present invention, an external phase having a bicontinuous structure can be formed by a normal stirring operation without using a special apparatus.
In addition, an oil-soluble or water-soluble optional component may be added to the oil phase and the water phase in advance on the condition that the stability of the composition is not inhibited.

Next, an oil phase containing an oil agent (component E) is added to the outer phase having a bicontinuous structure obtained in the above step to form a dispersed phase.
About the preferable compounding quantity of the component which comprises a dispersed phase, it is as having already demonstrated, 5-45 mass% is preferable with respect to the total mass of an emulsion, 10-35 mass% is more preferable, 15-25 mass% Is more preferable.
An optional component may be added to the oil phase together with the oil agent (component E) on the condition that the object of the present invention and the stability of the emulsion are not impaired.

  Before adding an oil phase containing an oil agent (component E) in the outer phase, it is preferable to maintain the outer phase and the oil phase in a range of 20 to 35 ° C, respectively. After mixing the outer phase and the oil phase, a creamy emulsion can be obtained from the emulsion by sufficiently stirring.

  As described above, the emulsion of the present invention can be produced. According to the present invention, an emulsion in which an oil phase is dispersed in an outer phase having a bicontinuous structure can be obtained by a normal stirring operation without using a special apparatus.

Since the emulsion of the present invention contains tranexamic acid ester salt (component A) having a whitening effect, by applying it locally to the skin, the effect of suppressing and / or whitening the skin can be achieved. That is, the present invention provides a cosmetic method for suppressing and / or whitening the skin by locally applying the emulsion of the present invention to the skin.
According to a preferred embodiment of the present invention, by using the emulsion of the present invention as a composition for external use such as cosmetics (particularly, emulsions and creams), the skin is inhibited from pigmentation and / or whitened to cause stains or pigmentation. The effect that it can be made thin can be acquired.

  The emulsion of the present invention can be suitably used as a composition for external use such as pharmaceuticals, quasi drugs and cosmetics. The product form of the composition for external use can be arbitrarily selected. For example, facial cosmetics such as facial cleansers, lotions, cosmetic liquids, emulsions, creams, packs, etc .; makeup cosmetics such as foundations, lipsticks and eye shadows; body cosmetics; aromatic cosmetics; body cleansers; ointments, etc. be able to. In particular, it can be preferably used as a whitening serum, whitening cream or whitening pack.

  EXAMPLES Hereinafter, although an Example and a comparative example demonstrate this invention, this invention is not limited to these Examples. Unless otherwise specified, the composition ratio is based on a mass ratio (mass%).

<Reference Examples 1 to 11>
Preparation and physical property evaluation of a composition (external phase) having a bicontinuous structure A composition having a bicontinuous structure containing the tranexamic acid ester salt having the composition shown in Table 1 was prepared as follows. The stirring was performed by hand using a stirring bar.
1) Dipropylene glycol (3% by mass) and purified water (3% by mass) of component D are mixed with the oil phase component containing components A, B and C, and the mixture is heated to 85 ± 5 ° C. and stirred. However, these components were completely dissolved.
2) Next, the aqueous phase component containing the remaining component D was heated to 85 ± 5 ° C., and the mixture obtained in 1) above was gradually added and homogenized with sufficient stirring.
3) Thereafter, the mixture obtained in the above 2) was cooled to 25 ± 5 ° C. or lower while stirring to obtain a liquid composition having a transparent to translucent appearance.

  The composition obtained in the above 3) was tested for the following items at room temperature (25 ± 5 ° C.). The results are shown in Table 1.

(1) Diffusion of dyes It can be confirmed that a sample has a bicontinuous structure by adding a water-soluble dye and an oil-soluble dye and diffusing each dye into the solution.
An oil (squalane) having an oil-soluble dye (red No. 225) and water having a water-soluble dye (blue No. 1) were dropped on the surface of the sample, and formation of bicontinuous phases was confirmed with each diffusion. When the oil-soluble dye diffuses, it indicates that the continuous phase is an oil phase, and when the water-soluble dye diffuses, it indicates that the continuous phase is an aqueous phase. When both the oil-soluble dye and the water-soluble dye are dropped at the same time and both diffusions are observed, it can be said that the oil-soluble dye and the water-soluble dye have a bicontinuous structure in which the oil phase and the water phase exist continuously.
The case where both the water-soluble dye and the oil-soluble dye diffused was evaluated as “A”, and the case where only one of the water-soluble dye and the oil-soluble dye diffused was evaluated as “C”.

(2) Flowing birefringence Flowing birefringence means that when an isotropic gel-like structure is shaken, the phenomenon of birefringence is observed when the structure is oriented in the flow direction. Having flow birefringence can be confirmed by light transmitted through the orthogonal polarizing plate.
A transparent glass tube bottle containing the sample was sandwiched between the polarizing plates orthogonal to each other, light was irradiated from the rear of the polarizing plate, and the sample was held by hand and shaken to the left and right. It can be said that the birefringence was caused by temporarily exhibiting anisotropy while shaking, and the flow birefringence was observed when the phenomenon of light passing through was observed. The case where flow birefringence was shown was evaluated as “A”, and the case where it was not shown was evaluated as “C”.

(3) State immediately after sample preparation (transparency)
The sample was poured into a 50 mL transparent glass tube bottle, and the transparency was visually evaluated. The sample that can clearly read the letter of the printed matter seen through the tube bottle is “A: very high”, the sample that has a transparent to translucent appearance and the character that can be read is “B: high”, and the letter of the printed matter is The unreadable sample was evaluated as “C: cloudiness”. Moreover, the sample which isolate | separated and the crystal | crystallization precipitated was excluded from the object of evaluation (it set to D in Table 1).

  As shown in Table 1, it was confirmed that the composition containing components A, B, C, and D had a bicontinuous structure (Reference Examples 1 to 7). On the other hand, when either component was absent, the composition did not form a bicontinuous structure. Moreover, the composition containing only one of alcohol or alkyl glyceryl ether as the B component did not form a bicontinuous structure.

  About the composition of the reference example 1, the freezing cross-section observation of the composition was performed using the cryo-focused ion beam scanning electron microscope (cry FIB-SEM) (the product made by FEI, model [HeliosNanoLab 650]). First, after instantaneously freezing the composition of Reference Example 1 with liquid nitrogen, the composition was introduced into a FIB-SEM apparatus, and cryo FIB processing and cryo SEM observation were performed. The cryo SEM observation result is shown to Fig.1 (a) and (b). FIG. 1A shows an observation result at a magnification of 12,000 times, and FIG. 1B shows an observation result at a magnification of 35,000 times. From the observation results of FIGS. 1 (a) and (b), it is clearly confirmed that in the composition of Reference Example 1, the water phase and the oil phase are three-dimensionally continuous and form a bicontinuous structure. I was able to.

<Examples 1 to 12>
Preparation of emulsion and evaluation of physical properties An emulsion containing tranexamic acid ester salt having the composition shown in Table 2 was prepared as follows. The stirring was performed by hand using a stirring bar.
1) Dipropylene glycol (3% by mass) and purified water (3% by mass) of component D are mixed with the oil phase component containing components A, B and C, and the mixture is heated to 85 ± 5 ° C. and stirred. However, these components were completely dissolved.
2) Next, the aqueous phase component containing the remaining component D was heated to 85 ± 5 ° C., and the mixture obtained in 1) above was gradually added and homogenized with sufficient stirring.
3) Thereafter, the mixture obtained in 2) above was naturally cooled to 25 ± 5 ° C. or lower while stirring to obtain a liquid composition having a transparent to translucent appearance.
4) Next, to the composition obtained in 3) above, component E, which is an arbitrary oil kept at room temperature (25 ± 5 ° C.), is added at a quantitative ratio described in Table 2 with sufficient stirring. And an emulsion was obtained. About the obtained emulsion, stability was evaluated as follows. The results are shown in Table 2.

(4) Sample stability The sample was fully poured into a 200 mL transparent glass tube bottle, allowed to stand at room temperature (25 ± 5 ° C.) and 40 ° C. for 1 month, and the appearance was visually evaluated. A sample maintaining the initial state was evaluated as “A: stable”, and a sample on which separation or crystals were precipitated was evaluated as “C: separation”.

<Comparative Examples 1 and 2>
Except having used the composition shown in Table 2, the emulsion containing a tranexamic acid ester salt was prepared like the Example, and the physical property was evaluated. The results are shown in Table 2.

As shown in Table 2, the emulsion of the present invention maintained the initial state without phase separation even when allowed to stand for 1 month at room temperature and 40 ° C. From this, the emulsion of the present invention can maintain the bicontinuous structure even after the oil phase containing the component E is added to the external phase having the bicontinuous structure, and the oil phase is dispersed in the external phase having the bicontinuous structure. As a result, it was confirmed that the stability of the structure was extremely high.
On the other hand, when the blending ratio of component E (oil agent), which is a constituent component of the dispersed phase, exceeds the range defined by the present invention (5-45 mass% with respect to the total mass of the emulsion), sufficient stability cannot be obtained. It was.

  The composition of Example 3 was subjected to observation of a frozen section of the composition using a cryo-focused ion beam scanning electron microscope (cry FIB-SEM) (manufactured by FEI, model [Helios NanoLab 650]). The composition of Example 3 was snap-frozen with liquid nitrogen, and then introduced into the FIB-SEM apparatus, followed by cryo FIB processing and cryo SEM observation, as shown in FIGS. Fig. 2 (a) shows an observation result at a magnification of 64 times, and Fig. 2 (b) shows an observation result at a magnification of 650. Fig. 2 (c) and (d) show FIB processing. Fig. 2 (c) shows an observation result at a magnification of 5,000 and Fig. 2 (d) shows an observation result at a magnification of 12,000. Observation More, it was possible to clearly confirm that the external phase in the composition of Example 3 maintains the bicontinuous structure.

(5) Differential scanning calorimetry (DSC)
Each composition obtained in Reference Example 1 and Examples 1 to 4 was subjected to thermal analysis by DSC (apparatus: DSC822 manufactured by METTTLER, heating rate 2 ° C./min). FIG. 3 shows the results. In the figure, (a), (b), (c), (d) and (e) are the measurement results of the compositions of Reference Example 1, Example 1, Example 2, Example 3 and Example 4, respectively. Is shown.
As apparent from FIG. 3, it was found that the downward peak as seen in the vicinity of 20 to 40 ° C. becomes smaller as the blending amount of Component E increases. This indicates that the crystallinity of the solid component of the composition is weakened as the blending amount of component E is increased, and the solid state is approaching the liquid state. Thus, according to one embodiment of the present invention, the solid component contained in the emulsion can be brought into a state close to a liquid state by appropriately adjusting the blending amount of the component E, and is originally in a solid state. The tranexamic acid ester salt can be dispersed in the emulsion in a state close to the liquid state. Thereby, tranexamic acid ester salt, which is a whitening component, easily penetrates into the skin, and the whitening effect of the emulsion is considered to be further enhanced.

  The emulsion of the present invention is suitably used as a composition for external use such as pharmaceuticals, quasi drugs and cosmetics. According to a preferred embodiment of the present invention, the effect of suppressing and / or whitening the skin can be obtained by applying the composition of the present invention to the skin topically.

Claims (11)

An emulsion in which an oil phase is dispersed in an outer phase having a bicontinuous structure,
The foreign minister
A) A physiologically acceptable salt of tranexamic acid ester;
B) A linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms, and a mono- or diether of a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin An amphiphile selected from a combination of alkyl glyceryl ethers;
C) an oil agent; and D) water, a water-soluble organic solvent or a mixture thereof,
The oil phase that is the dispersed phase includes E) the oil agent, and the total content of the components constituting the outer phase is 55 to 95% by mass with respect to the total mass of the emulsion, and the content of the components that constitute the dispersed phase is The emulsion whose sum total is 5-45 mass%. Tranexamic acid ester in a physiologically acceptable salt of tranexamic acid ester is represented by the following formula (1):
[In formula, R represents the saturated or unsaturated hydrocarbon group which has a C1-C22 linear or branched chain which may be substituted by the substituent chosen from a hydroxyl group and an amino group. ]
The emulsion according to claim 1, wherein   The emulsion according to claim 1 or 2, wherein the physiologically acceptable salt of the tranexamic acid ester of component A comprises tranexamic acid cetyl ester hydrochloride.   The emulsion according to any one of claims 1 to 3, wherein the amphiphilic substance of component B is a combination of cetyl alcohol and at least one selected from the group consisting of chimyl alcohol and batyl alcohol.   The content of component A is 0.5 to 10% by mass relative to the total mass of the emulsion, the content of component B is 0.5 to 10% by mass, and the content of component C is 1 to 25% by mass. %, And the total content of components A, B and C is 5 to 50% by mass, according to any one of claims 1 to 4.   The emulsion according to any one of claims 1 to 5, wherein the external phase further contains a pH adjuster as an optional component.   The emulsion according to claim 6, wherein the pH adjuster is selected from Lewis bases. It is a manufacturing method of the emulsion according to any one of claims 1 to 7,
A) A physiologically acceptable salt of tranexamic acid ester;
B) A linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms, and a mono- or diether of a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin An amphiphile selected from the combination of alkyl glyceryl ethers; and
C) preparing an oil phase containing an oil agent;
D) adding the oil phase to an aqueous phase containing water, a water-soluble organic solvent or a mixture thereof to form an outer phase having a bicontinuous structure;
E) adding an oil phase containing an oil agent to the outer phase to form a dispersed phase.   The external composition containing the emulsion as described in any one of Claims 1-7.   Use of the emulsion according to any one of claims 1 to 7 as a cosmetic for suppressing and / or whitening the skin in order to make the spots or pigmentation thinner.   A cosmetic method for inhibiting skin pigmentation and / or whitening, comprising topically applying the emulsion according to any one of claims 1 to 7 to the skin.