JP6811560B2 - A multi-phase emulsion in which a water-in-oil emulsion is dispersed in an outer phase having both continuous structures and a method for producing the same. - Google Patents

Description

The present invention relates to a multiphase emulsion in which a water-in-oil emulsion is dispersed in an outer phase having both continuous structures, and a method for producing the same. The present invention also relates to the use of polyphasic emulsions as cosmetics and cosmetic methods for suppressing and / or whitening skin pigmentation.

Tranexamic acid ester or a salt thereof is known to have a whitening effect, and is used as a whitening component in an external composition. For example, Japanese Patent Application Laid-Open No. 4-46144 (Patent Document 1) describes an anti-pigmentation external preparation containing tranexamic acid ester as an active ingredient. Further, Japanese Patent Application Laid-Open No. 2003-306419 (Patent Document 2) exemplifies tranexamic acid and its derivatives as whitening components that can be used in combination with coenzyme Q10. Further, Japanese Patent Application Laid-Open No. 2004-107262 (Patent Document 3) exemplifies tranexamic acid cetyl ester as an oil-soluble whitening agent that can be used in combination with a tetra-branched fatty acid ester derivative of L-ascorbic acid.
However, since tranexamic acid ester or a salt thereof has low solubility in water and oil, it tends to form agglomerates in the preparation, and it is difficult to disperse it in the preparation in a stable state.
In response to the above problems, the applicant has created a two-continuous structure in which the aqueous phase and the oil phase are three-dimensionally continuous by mixing a tranexamic acid ester salt, a predetermined amphipathic substance, an oil agent, water, and the like. It was found that a composition having the same composition was obtained, and the tranexamic acid ester salt could be dispersed in the composition in a stable state. Furthermore, it has been found that by adding an oil agent to this composition, an extremely stable emulsion or creamy emulsion in which the oil phase is dispersed in the outer phase having both continuous structures can be obtained (Japanese Patent Laid-Open No. 2016-). 056151 (Patent Document 4)). According to the present invention, it is expected that the tranexamic acid ester salt can be dispersed in a stable state, the tranexamic acid ester salt easily penetrates into the skin when applied to the skin, and the whitening effect of the tranexamic acid ester salt is enhanced. Will be done. Applicants have further found that as the amount of oil added to the emulsion is increased, the stability of the emulsion is improved and the phase transition temperature of the tranexamic acid ester salt can be lowered. When the phase transition temperature of the tranexamic acid ester salt is lower than the surface temperature of the skin (about 32 ° C.), the tranexamic acid ester salt can be present in the emulsion in a liquid state when the emulsion is applied to the skin. It is suggested that the permeability to tranexamic acid is improved, and it is expected that the whitening effect of tranexamic acid ester salt will be further enhanced.
However, when an attempt was made to sufficiently lower the phase transition temperature of the tranexamic acid ester salt, the amount of the oil added increased and the oiliness increased, which was a trade-off relationship.

Japanese Unexamined Patent Publication No. 4-46144 Japanese Unexamined Patent Publication No. 2003-306419 Japanese Unexamined Patent Publication No. 2004-107262 Japanese Unexamined Patent Publication No. 2016-056151

Under such circumstances, a composition capable of dispersing tranexamic acid ester or a salt thereof in a stable state in a preparation, and enhancing the whitening effect of tranexamic acid ester salt while suppressing an oily feeling. Is required to be provided.

As a result of diligent research 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"), a predetermined amphipathic substance, and the like. By dispersing a water-in-oil emulsion instead of the oil in the composition having both continuous structures obtained by mixing the oil and water, the phase transition of the tranexamic acid ester salt is suppressed while suppressing the oiliness. Succeeded in lowering the temperature. It is a surprising discovery that the phase transition temperature of tranexamic acid ester salt in the composition can be lowered even if the oil agent is replaced with a water-in-oil emulsion, and the whitening effect of tranexamic acid ester salt while suppressing the oiliness is suppressed. It is highly useful in that it can enhance. The present invention has been completed based on these findings.

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

[1] A multi-phase emulsion in which a water-in-oil emulsion is dispersed in an outer phase having both continuous structures.
Foreign Minister
A) Physiologically acceptable salt of tranexamic acid ester;
B) Mono or diether of glycerin with a linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms and a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms. An amphipathic substance selected from a combination of alkyl glyceryl ethers;
C) oil; and D) water, water-soluble organic solvent or mixture thereof
The water-in-oil emulsion, which is a dispersed phase,
E) Parent oil type nonionic surfactant F) Oil; and G) Water, water-soluble organic solvent or a mixture thereof, and the total content of the components constituting the outer phase with respect to the total mass of the polyphase emulsion. Is 55 to 95% by mass, the total content of the components constituting the dispersed phase is 5 to 45% by mass, and the ratio of the internal phase in the water-in-oil emulsion which is the dispersed phase is 60% by mass or more. , Polyphase emulsion.
[2] The tranexamic acid ester in the physiologically acceptable salt of the tranexamic acid ester has the following formula (1):
[In the formula, R represents a saturated or unsaturated hydrocarbon group having a linear or branched chain having 1 to 22 carbon atoms which may be substituted with a substituent selected from a hydroxyl group and an amino group. ]
The multiphase emulsion according to [1] shown in.
[3] The polyphasic emulsion according to [1] or [2], wherein the physiologically acceptable salt of the tranexamic acid ester of component A contains tranexamic acid cetyl ester hydrochloride.
[4] In any one of [1] to [3], the amphipathic substance of component B is a combination of cetyl alcohol and at least one selected from the group consisting of kimil alcohol and batyl alcohol. The polyphasic emulsion 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 based on the total mass of the polyphasic emulsion. The multiphase emulsion according to any one of [1] to [4], wherein the content is 1 to 25% by mass and the total content of the components A, B and C is 5 to 50% by mass.
[6] The oil-based nonionic surfactant of component E is derived from monoalkyl glyceryl ether, sucrose fatty acid ester, polyglycerin fatty acid ester; polyether-modified silicone; and polyglycerin-modified silicone having a carbon chain length of 6 to 22. The multiphase emulsion according to any one of [1] to [5], which is at least one selected.
[7] The multiphase emulsion according to any one of [1] to [6], wherein the outer phase further contains a pH adjuster as an optional component.
[8] The polyphasic emulsion according to [7], wherein the pH adjuster is selected from Lewis bases.
[9] The method for producing a polyphasic emulsion according to any one of [1] to [8].
A) Physiologically acceptable salt of tranexamic acid ester;
B) Mono or diether of glycerin with a linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms and a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms. An amphipathic substance selected from a combination of alkylglyceryl ethers;
C) The process of preparing the oil phase containing the oil agent and
D) A step of 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 both continuous structures.
Including a step of adding E) an oil-based nonionic surfactant F) an oil agent; and G) a water-in-oil emulsion containing water, a water-soluble organic solvent or a mixture thereof to the outer phase to form a dispersed phase. ,Method.
[10] An external composition containing the polyphasic emulsion according to any one of [1] to [8].
[11] Use of the polyphasic emulsion according to any one of [1] to [8] for suppressing pigmentation and / or whitening the skin in order to reduce blemishes or pigmentation as a cosmetic.
[12] A cosmetic method for suppressing pigmentation and / or whitening the skin, which comprises topically applying the polyphasic emulsion according to any one of [1] to [8] to the skin.

According to the present invention, a milky liquid or creamy emulsion containing a tranexamic acid ester salt is obtained. The polyphasic emulsion of the present invention can be used as a cosmetic for suppressing pigmentation and / or whitening the skin in order to reduce blemishes or pigmentation.
According to a preferred embodiment of the present invention, the tranexamic acid ester salt can be dispersed in the emulsion in a stable state, and the phase transition temperature of the tranexamic acid ester salt can be lowered while suppressing the oily feeling. It is expected that the tranexamic acid ester salt will easily penetrate into the skin when applied to the skin, thereby enhancing the whitening effect of the tranexamic acid ester salt.

It is a figure which shows the cryo-FIB-SEM observation result of the emulsion obtained in Example 1. FIG. FIG. 1 (a) shows the results of cryo-FIB-SEM observation before FIB treatment (magnification 1000 times), FIG. 1 (b) after FIB treatment (magnification 5000 times), and FIG. 1 (c) shows the results after FIB treatment. An enlarged view of the dispersed phase (magnification 35,000 times) and FIG. 1 (d) show an enlarged view of the continuous phase after the FIB treatment (magnification 35,000 times). It is a figure which shows the EDX chemical mapping image of the emulsion obtained in Example 1. FIG. FIG. 2A is an electron microscope image (reflected electron image), FIG. 2B is a mapping image of an oxygen element, FIG. 2C is a mapping image of a carbon element, and FIG. 2D. Is a mapping image of silicon element. It is a figure which shows the X-ray diffraction (XRD) curve and the differential scanning calorimetry (DSC) curve of the emulsion obtained in Example 1. FIG. FIG. 3A is an X-ray diffraction (XRD) curve, and FIG. 3B is a differential scanning calorimetry (DSC) curve. It is a figure which shows the evaluation result of the static / dynamic friction coefficient measured by the friction feeling tester of the emulsion obtained in Example 1, the emulsion obtained in Comparative Example 1, water and an oil agent (squalene). It is a figure which shows the result of having measured the static / dynamic friction coefficient 5 times repeatedly under the same measurement condition with the friction feeling tester about each emulsion obtained in Example 1 and Comparative Example 1. FIG. 5A shows the evaluation result of the emulsion obtained in Example 1, and FIG. 5B shows the evaluation result of the emulsion obtained in Comparative Example 1.

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

The multiphase emulsion of the present invention is a multiphase emulsion in which a water-in-oil emulsion is dispersed in an outer phase having both continuous structures.
Foreign Minister
A) Physiologically acceptable salt of tranexamic acid ester;
B) Mono or diether of glycerin with a linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms and a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms. An amphipathic substance selected from a combination of alkyl glyceryl ethers;
C) oil; and D) water, water-soluble organic solvent or mixture thereof
The water-in-oil emulsion, which is the dispersed phase, contains E) an oil-based nonionic surfactant F) an oil; and G) water, a water-soluble organic solvent or a mixture thereof, and is based on the total mass of the polyphase emulsion. The total content of the components constituting the outer phase is 55 to 95% by mass, the total content of the components constituting the dispersed phase is 5 to 45% by mass, and the inside of the water-in-oil emulsion which is the dispersed phase. The phase ratio is 60% by mass or more.

As described above, the multiphase emulsion of the present invention comprises a water-in-oil emulsion dispersed in an outer phase having both continuous structures. In the polyphase emulsion of the present invention, the outer phase comprises A) tranexamic acid ester salt, B) amphiphile, C) oil, and D) water, a water-soluble organic solvent or a mixture thereof, and A) tranexamic acid ester. A bicontinuous structure is formed by adding D) water, a water-soluble organic solvent or an aqueous phase containing a mixture thereof to an oil phase containing a salt, B) an amphipathic substance, and C) an oil agent. Here, the "bi-continuous structure" of the outer phase means a state in which the aqueous phase and the oil phase are three-dimensionally continuous, and neither the aqueous phase nor the oil phase is phase-separated and coexists. Specifically, it means that an infinite aggregate such as a liquid crystal (LC) phase, a bicontinuous microemulsion (BME), a bicontinuous α-gel (BAG), and a sponge (L3) phase is formed.
The fact that the outer phase has a bicontinuous structure can be confirmed, for example, by observing the frozen cross section of the composition of the outer phase using a cryo-focused ion beam scanning electron microscope (cryo-FIB-SEM). it can. It can also be confirmed by mapping the distribution state of arbitrary elements using energy dispersive X-ray analysis (EDX).

The polyphasic emulsion of the present invention has E) an oil-based nonionic surfactant, F) an oil agent and G) water, a water-soluble organic solvent, or a water-soluble organic solvent thereof in the outer phase having both continuous structures obtained as described above. It is obtained by dispersing a water-in-oil emulsion containing a mixture. 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 the formula, R represents a saturated or unsaturated hydrocarbon group having a linear or branched chain having 1 to 22 carbon atoms which may be substituted with a substituent selected from a hydroxyl group and an amino group. ]

In the above formula (1), R represents a saturated or unsaturated hydrocarbon group having a linear or branched chain having 1 to 22 carbon atoms, and the hydrogen atom contained in the hydrocarbon group is selected 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, a cycloalkylalkyl group and the like. Among these, an alkyl group is preferable. The number of carbon atoms is preferably 8 to 20, and particularly preferably 12 to 18.

The number of substituents of the hydrocarbon group is not particularly limited. When 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 above 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 interfere with the object of the present invention. The tranexamic acid ester salts used in the present invention are mineral salts such as hydrochlorides, phosphates, sulfates, bromine salts and nitrates of tranexamic acid esters; organic acids such as oxalates, lactates and citrates. Salt; preferably carbonate and the like. Of these, hydrochloride is preferred.

Among them, the tranexamic acid ester salts used in the present invention include tranexamic acid cetyl ester hydrochloride, tranexamic acid cetyl ester phosphate, tranexamic acid cetyl ester sulfate, tranexamic acid cetyl ester bromide, tranexamic acid cetyl ester nitrate, and tranexam. It is preferably selected from the group consisting of acid cetyl ester oxalate, tranexamic acid cetyl ester emulsion, tranexamic acid cetyl ester citrate and tranexamic acid cetyl ester carbonate. In particular, tranexamic acid cetyl ester hydrochloride is preferable.
The tranexamic acid ester salt may be used alone or in combination of two or more.

The content of the tranexamic acid ester salt (component A) in the polyphase emulsion of the present invention is preferably 0.5% by mass or more, more preferably 1% by mass or more, and 2% by mass, based on the total mass of the polyphase emulsion. The above is more preferable, 10% by mass or less is preferable, 6% by mass or less is more preferable, and 4% by mass or less is further preferable. Among them, 0.5 to 10% by mass is preferable, 1 to 6% by mass is more preferable, and 2 to 4% by mass is further preferable.

B) Amphiphile The amphipathic substance used in the present invention is a saturated or unsaturated alcohol having a linear or branched chain having 12 to 22 carbon atoms, and a linear or branched chain having 8 to 22 carbon atoms. It is selected from a combination of a saturated or unsaturated alcohol and an alkyl glyceryl ether which is a mono or diether of glycerin. In the present invention, a linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms, and a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms and glycerin. By using an alkyl glyceryl ether which is a mono or diether in combination, the outer phase can form a bicontinuous structure.

The alcohol is not particularly limited as long as it has a saturated or unsaturated alkyl group of a linear or branched chain having 12 to 22 carbon atoms. The alkyl group preferably has 14 to 20 carbon atoms, more preferably 16 to 18 carbon atoms.
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. Alcohol 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 further preferable, and cetyl is more preferable. Alcohol is particularly preferred.

The alkyl glyceryl ether which is a mono or diether of a saturated or unsaturated alcohol having a linear or branched chain 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. , A monoether of a linear saturated alcohol and glycerin is particularly preferred. The alkyl group preferably has 14 to 20 carbon atoms, more preferably 16 to 18 carbon atoms.
As alkyl glyceryl ethers, glyceryl monostearyl ether (bacyl alcohol), glyceryl monocetyl ether (chimil alcohol), monooleyl glyceryl ether (ceracyl alcohol), monobehenyl glyceryl ether, mono2-ethylhexyl glyceryl ether, mono Examples thereof include isostearyl glyceryl ether, monocapryl glyceryl ether, monoisodecyl glyceryl ether, monoisostearyl diglyceryl ether, glycerin mono2-ethylhexyl ether and the like.
Among these, monostearyl glyceryl ether (bacyl alcohol), glyceryl monocetyl ether (chimil alcohol), and monooleyl glyceryl ether (ceracyl 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. The alkyl glyceryl ether may be used alone or in combination of two or more. The amphipathic substance of component B is preferably a combination of cetyl alcohol and at least one selected from the group consisting of kimil alcohol and batyl alcohol. Of these, it is preferable to use a combination of cetyl alcohol and kimil alcohol, or a combination of cetyl alcohol and batyl alcohol. The blending ratio of the alcohol to the alkylglyceryl ether is preferably 1: 9 to 9: 1, more preferably 1: 6 to 6: 1, and even more preferably 1: 3 to 3: 1 on a mass basis.

The content of the amphoteric substance (component B) in the polyphase emulsion of the present invention is preferably 0.5% by mass or more, more preferably 1% by mass or more, based on the total mass of the polyphase emulsion. 2% by mass or more is further preferable, 10% by mass or less is preferable, 6% by mass or less is more preferable, and 4% by mass or less is further preferable. Among them, 0.5 to 10% by mass is preferable, 1 to 6% by mass is more preferable, and 2 to 4% by mass is further preferable.

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 sparingly soluble in water and has the property of being easily dissolved in oil. Preferred examples of the oil agent used as the 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, silicone elastomers and the like, which are widely used in external compositions.

Liquid fats and oils (oils and fats in a liquid state at room temperature (25 ° C.)) include, for example, avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, etc. Wheat germ oil, Southern ka oil, castor oil, flaxseed oil, saflower oil, cotton seed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnamon oil, Japanese millet oil, jojoba oil, germ oil , Triglycerin and the like.
Examples of solid fats and oils (fat and oils in a solid state at room temperature (25 ° C.)) include cacao butter, coconut oil, horse fat, hardened coconut oil, palm oil, palm kernel oil, mokuro kernel oil, hardened oil, mokuro, and hardened castor oil. Examples include oil.

Examples of waxes include honeybee, candelilla wax, cotton wax, carnauba wax, babyry wax, ibotarou, monttan wax, nukarou, lanolin, capoc wax, lanolin acetate, liquid lanolin, sugar cane, lanolin fatty acid isopropyl, hexyl laurate, reduced lanolin, and jojobaro. , Hard lanolin, cellac 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, selecin, squalene, petrolatum, microcrystalline wax, hydrogenated polydecene, isododecane and the like.

Synthetic ester oils include tripropylene glycol dineopenate, isodecyl neopentate, isotridecyl neopentate, isostearyl neopentate, isononyl isononanoate, isotridecyl isononanoate, isopropyl myristate, cetyl octanoate, cetyl isooctanate, octyldodecyl myristate, Isopropyl palmitate, cetyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, isosetyl stearate, isosetyl isostearate, 12-hydroxy Cholesteryl stearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid ester, N-alkylglycol monoisostearate, neopentyl glycol dicaprate, diisostearyl malate, glycerin di-2-heptylundecanoate, tri Trimethylolpropane-2-ethylhexanoate, Trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, glycerin tri-2-ethylhexanoate, glycerin trioctanoate, glycerin triisopalmitate, triisostearate Methylolpropane, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glycerin trimyristate, glyceride tri-2-heptylundecanoate, methyl ester of castor oil fatty acid, oleyl oleate, acetoglyceride, 2-heptylun palmitate Decyl, diisobutyl adipate, N-lauroyl-L-glutamate-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyllaurate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate, palmitic acid 2-Hexyldecyl acid, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, triethyl citrate, dimer dilinoleylbis (behenyl / isostearyl / phytosteryl), lauroyl glutamate (phytosteryl /) Behenyl / octyldodecyl / isostearyl), tri (caprylic acid / capric acid) glyceryl, triethylhexanoin and the like can be mentioned.

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

Examples of the silicone elastomer include a non-emulsifying organopolysiloxane elastomer or an emulsified organosiloxane elastomer. Examples of the non-emulsifying organopolysiloxane elastomer include dimethicone / vinyldimethicone crosspolymer and lauryldimethicone / vinyldimethicone crosspolymer.

Dimethicone / vinyl dimethicone crosspolymers are commercially available from DOWN CORNING (Midland, Michigan) under names such as "DC9040" and "DC9045", and from MOMENTIVE "SFE839" and "Velvasil" series products, Shinetsu Kagaku. Commercially available products under names such as "KSG-15", "KSG-16", and "KSG-18" from Kogyo Co., Ltd. ([dimethicone / phenylvinyl dimethicone crosspolymer]), and "Grancil" from GRANT INDUSTRIES (Grancil) Trademark) Series products and the like.

As 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. , Etc., which are commercially available.

Examples of the emulsified organosiloxane elastomer include polyalkoxylated silicone elastomers and polyglycerolized silicone elastomers.

Polyalkylated silicone elastomers are commercially available under the names "DC9010" and "DC9011" from DOWN 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 polyglycerolized silicone elastomers, "KSG-710", "KSG-810", "KSG-820", "KSG-830", "KSG-840", "KSG-31", from Shin-Etsu Chemical Co., Ltd. Examples thereof include those commercially available under names such as "KSG-32", "KSG-41", "KSG-42", "KSG-43" and "KSG-44". In addition, as a silicone elastomer in which two types of branches, a silicone chain and an alkyl chain, have been introduced, "KSG-042Z", "KSG-045Z", "KSG-320Z", and "KSG" are available from Shin-Etsu Chemical Co., Ltd. Examples thereof include those commercially available under names such as "-350Z", "KSG-820Z", and "KSG-850Z".

Further, a silicone elastomer containing a polyalkyl ether group as a pendant or a crosslink may be used. Particularly suitable silicone elastomers containing polyalkyl ether groups are bis-vinyldimethicone / bis-isobutyl PPG-20 crosspolymers, bis-, which are named according to the International Nomenclature of Cosmetic Ingredients (INCI). Examples thereof include vinyl dimethicone / PPG-20 crosspolymer, dimethicone / bis-isobutyl PPG-20 crosspolymer, dimethicone / PPG-20 crosspolymer and dimethicone / bis-sec butyl PPG-20 crosspolymer. Such crosslinked elastomers are described by DOWN CORNING under test compound names such as "SOEB-1," "SOEB-2," "SOEB-3," and "SOEB-4," as well as "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 (isododecan is used for SOEB-1 and SOEB-2, isohexadecane is used for SOEB-3, and isodecylneopentanoate is used for SOEB-4). To.

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

The content of the oil agent (component C) in the polyphase emulsion of the present invention is preferably 1% by mass or more, more preferably 4% by mass or more, still more preferably 6% by mass or more, based on the total mass of the polyphase emulsion. Further, 25% by mass or less is preferable, 12% by mass or less is more preferable, and 10% by mass or less is further preferable. Among them, 6 to 30% by mass is preferable, 9 to 17% by mass is more preferable, and 11 to 15% by mass is further preferable.

D) Water, water-soluble organic solvent or mixture thereof In the polymorphic emulsion of the present invention, water, a water-soluble organic solvent or a mixture thereof is used as component D.
The water-soluble organic solvent is not particularly limited, and those widely used in the external composition can be preferably used. For example, lower alcohols such as methanol, ethanol, propanol and isopropanol (preferably alcohols with 1 to 5 carbon atoms); 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, a water-soluble organic solvent or a mixture thereof (Component D) is the rest of the polyphasic emulsion of the present invention. The content of water, a water-soluble organic solvent or a mixture thereof is, for example, preferably 30% by mass or more, more preferably 40% by mass or more, and 50% by mass or more, based on the total mass of the polyphasic emulsion. Further, 90% by mass or less is preferable, 80% by mass or less is more preferable, and 70% by mass or less is further preferable. Among them, 30 to 90% by mass is preferable, 40 to 80% by mass is more preferable, and 50 to 70% by mass is further preferable. Of these, the content of the water-soluble organic solvent is preferably 3.5 to 13% by mass, more preferably 4 to 9% by mass, and even more preferably 5 to 7% by mass. By containing the water-soluble organic solvent in the above range, the foreign phase tends to easily form a bicontinuous structure.

In one embodiment of the polyphasic emulsion 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% by mass, and the total content of the components A, B, and C is preferably 5 to 45% by mass with respect to the total mass of the polyphasic emulsion. The total content of the components A, B and C is more preferably 8 to 30% by mass, further preferably 10 to 20% by mass. When the contents of the components A, B and C are in the above range, the foreign phase tends to form a more stable bicontinuous structure.

In the multiphase emulsion of the present invention, the bicontinuous structure of the outer phase is maintained even when the water-in-oil emulsion is added in a predetermined amount ratio. In the multiphase emulsion of the present invention, the water-in-oil emulsion is dispersed in the outer phase to become a dispersed phase, and can exist stably without phase separation.

Next, the water-in-oil emulsion constituting the dispersed phase in the polyphase emulsion of the present invention will be described. The water-in-oil emulsion used in the present invention contains E) an oil-based nonionic surfactant, F) an oil agent and G) water, a water-soluble organic solvent or a mixture thereof.

E) Oil-based nonionic surfactant As the parent oil-type nonionic surfactant (component E) used in the present invention, those generally used in external compositions can be used. Specifically, fatty acid esters, fatty acid ethers, glycerin fatty acid esters, sucrose fatty acid esters, polyglycerin fatty acid esters or monoalkyl glyceryl ethers having carbon chain lengths 6 to 22, preferably carbon chain lengths 12 to 22; polyethers. Modified silicones; and polyglycerin-modified silicones. Among these, at least one selected from a monoalkyl glyceryl ether having a carbon chain length of 6 to 22, preferably a carbon chain length of 12 to 22; a polyether-modified silicone; and a polyglycerin-modified silicone is preferable.

Examples of the fatty acid ester include polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene sorbit fatty acid ester.

Examples of the fatty acid ether include polyoxyethylene fatty acid ether and polyoxypropylene fatty acid ether.

Examples of the glycerin fatty acid ester include glyceryl monomyristate, glyceryl monopalmitate, glyceryl monostearate, glyceryl isostearate, glyceryl monooleate, glyceryl monoolive oil fatty acid, glyceryl dioleate, and glyceryl distearate.
Examples of the sucrose fatty acid ester include sucrose dilaurate, sucrose polylaurate, sucrose polypalmitate, sucrose distearate, sucrose tristearate, sucrose polystearate, sucrose polyoleate, sucrose pentaerucate, sucrose hexaerkaate, and tribehen. Examples include acid sucrose.
Examples of the polyglycerin fatty acid ester include diglyceryl monooleate, diglyceryl monoisostearate, hexaglyceryl pentaoleate, hexaglyceryl polylysinoleate, decaglyceryl pentahydroxystearate, decaglyceryl pentaisostearate, and deca pentaoleate. Examples thereof include glyceryl, decaglyceryl heptaoleate, and decaglyceryl polylysinoleate.
Examples of the monoalkyl glyceryl ether include kimil alcohol (glycerin monocetyl ether), ceracyl alcohol (glycerin monooleyl ether), batyl alcohol (glycerin monostearyl ether), oleyl glyceryl ether, isostearyl glyceryl ether and the like. ..

Examples of the polyether-modified silicone include (dimethicone / (PEG-10 / 15)) crosspolymer, (PEG-10 / lauryldimethicone) crosspolymer, (PEG-15 / lauryldimethicone) crosspolymer, and (PEG-15 / laurylpoly). Dimethylsiloxyethyl dimethicone) Crosspolymer and the like can be mentioned.

Examples of the polyglycerin-modified silicone include (dimethicone / polyglycerin-3) crosspolymer, (lauryldimethicone / polyglycerin-3) crosspolymer, and (polyglyceryl-3 / laurylpolydimethylsiloxyethyl dimethicone) crosspolymer.

In addition, a mixture of (hydrolyzed silk / PG propylmethylsilanediol) crosspolymer, octyldodecanol, octyldodecylxyloxyloside and PEG30 dipolyhydroxystearate (“EASYNOV” manufactured by SEPPIC, France) and the like can be mentioned.

Among these, since it is possible to form an aqueous emulsion in high internal aqueous phase oil, (dimethicone / (PEG-10 / 15)) crosspolymer, (PEG-10 / lauryldimethicone) crosspolymer, (PEG-15) Polyether-modified silicones such as / lauryl dimethicone) crosspolymer, (PEG-15 / laurylpolydimethylsiloxyethyl dimethicone) crosspolymer; (dimethicone / polyglycerin-3) crosspolymer, (lauryldimethicone / polyglycerin-3) crosspolymer , (Polyglyceryl-3 / laurylpolydimethylsiloxyethyl dimethicone) Polyglycerin-modified silicone such as crosspolymer; monoalkylglyceryl ether such as oleylglyceryl ether and isostearylglyceryl ether; sucrose fatty acid ester such as sucrose pentaerucate and sucrose hexaerucate. A mixture containing a (hydrolyzed silk / PG propylmethylsilanediol) crosspolymer (“Protesyl WO” manufactured by Seiwa Kasei Co., Ltd.), a mixture of octyldodecanol, octyldodecylxyloxyloside and PEG30 dipolyhydroxystearate (France, Japan). "EASYNOV") manufactured by SEPPIC, etc. is preferably used.

The lipophilic nonionic surfactant may be used alone or in combination of two or more.

The content of the lipophilic nonionic surfactant (component E) is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and 0.2% by mass, based on the total mass of the polyphase emulsion. % Or more is more preferable, 15% by mass or less is preferable, 10% by mass or less is more preferable, and 7% by mass or less is further preferable. Among them, 0.01 to 15% by mass is preferable, 0.1 to 10% by mass is more preferable, and 0.2 to 7% by mass is further preferable.

F) Oil agent The oil agent (component F) is not particularly limited as long as it is a substance that is insoluble or sparingly soluble in water and has a property of being easily dissolved in oil. Preferred examples of the oil agent used as the component F in the present invention include low-viscosity liquid oils and fats, solid oils and fats, waxes, hydrocarbon oils, synthetic ester oils, silicone oils, silicone elastomers and the like, which are widely used in external compositions. Specific examples include the same as those exemplified as the oil agent (component C).

Also, for example, methoxycinnamic acid derivative, diphenylacrylic acid derivative, salicylic acid derivative, paraaminobenzoic acid derivative, triazine derivative, benzophenone derivative, benzalmaronate derivative, anthranil derivative, imidazoline derivative, 4,4-diarylbutadiene derivative, phenyl. Oil agents such as benzimidazole derivatives and perfluoropolyether derivatives can be used.
Specifically, octyl methoxycinnamate, 2-ethylhexyl paramethoxysilicate, homosalate, octyl salicylate, oxybenzophenone, 4-t-butyl-4'-methoxydibenzoylmethane, octylriazone, methylenebisbenzotriazolyl. Tetramethylbutylphenol, 2-hydroxy-4-methoxybenzophenone, dihydroxydimethoxybenzophenone, dihydroxybenzophenone, tetrahydroxybenzophenone, diethylaminohydroxybenzoyl hexyl benzoate, 2-cyano-3,3-diphenylacrylic acid-2'-ethylhexyl ester, poly Examples thereof include silicone-15, drometrizole polysiloxane, phenylbenzimidazole sulfonic acid and perfluoropolymethylisopropyl ether.

The oil agent (component F) that can be used in the present invention can be arbitrarily selected from non-polar oil (squalene or the like) to highly polar oil (octyl methoxycinnamonate, hexyl diethylaminohydroxybenzoyl benzoate, etc.).
These oil agents may be used alone or in combination of two or more.

The content of the oil agent (component F) is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, still more preferably 1% by mass or more, and 15% by mass, based on the total mass of the polyphase emulsion. It is preferably mass% or less, more preferably 10 mass% or less, and even more preferably 5 mass% or less. Among them, 0.1 to 15% by mass is preferable, 0.5 to 10% by mass is more preferable, and 1 to 5% by mass is further preferable.

G) Water, water-soluble organic solvent or mixture thereof Water, water-soluble organic solvent or mixture thereof (component G) includes the same as those exemplified as component D.
The content of water, a water-soluble organic solvent or a mixture thereof (component G) is preferably 1% by mass or more, more preferably 5% by mass or more, and further preferably 10% by mass or more, based on the total mass of the polyphase emulsion. It is preferable, 30% by mass or less is preferable, 25% by mass or less is more preferable, and 20% by mass or less is further preferable. Among them, 1 to 30% by mass is preferable, 5 to 25% by mass is more preferable, and 10 to 20% by mass is further preferable.

The water-in-oil emulsion constituting the dispersed phase in the polyphase emulsion of the present invention can be obtained by mixing the components E, F and G. In the present invention, the ratio of the internal phase (aqueous phase) in the water-in-oil emulsion is 60% by mass or more, preferably 70% by mass or more, and more preferably 80% by mass or more. The ratio of the internal phase (aqueous phase) in the water-in-oil emulsion is preferably 95% by mass or less. When the ratio of the internal phase in the water-in-oil emulsion is within the above range, the effect of lowering the phase transition temperature of the tranexamic acid ester salt is high while suppressing the oily feeling.

According to a preferred embodiment of the present invention, the polyphasic emulsion of the present invention is prepared by formulating the tranexamic acid ester salt (component A) in a stable state without phase separation as described above. It is considered that the acid ester salt easily penetrates into the skin and its whitening effect can be maximized. Further, the polyphase emulsion of the present invention can lower the phase transition temperature of the tranexamic acid ester salt while suppressing the oily feeling, so that it is excellent in usability, and when applied to the skin, the tranexamic acid ester salt is transferred to the skin. It is expected that it will be easier to penetrate and the whitening effect of tranexamic acid ester salt will be further enhanced.

In the multiphase emulsion of the present invention, the content of the components constituting the outer phase is 55 to 95% by mass in total, preferably 60% by mass or more, and 65% by mass or more, based on the total mass of the polyphase emulsion. More preferably, 75% by mass or more is further preferable, 90% by mass or less is preferable, 87% by mass or less is more preferable, and 85% by mass or less is further preferable. Among them, 60 to 90% by mass is preferable, 65 to 87% by mass is more preferable, and 75 to 85% by mass is further preferable.
The total amount of the water-in-oil emulsion as the dispersed phase is 5 to 45% by mass, preferably 7% by mass or more, and more preferably 10% by mass or more, based on the total mass of the multiphase emulsion. , 15% by mass or more is further preferable, 40% by mass or less is preferable, 35% by mass or less is more preferable, and 25% by mass or less is further preferable. Among them, 7 to 40% by mass is preferable, 10 to 35% by mass is more preferable, and 15 to 25% by mass is further preferable.

According to a preferred embodiment of the present invention, the polyphase emulsion of the present invention has small (or almost no peaks) peaks due to melting or phase transition observed by differential scanning calorimetry (DSC). This means that in the polyphasic emulsion of the present invention, the tranexamic acid ester salt (component A), which is originally a solid, exists in a state close to a liquid state. According to a preferred embodiment of the present invention, when the polyphasic emulsion of the present invention is applied to the skin, the tranexamic acid ester salt (component A) is present in a state close to a liquid state, so that the tranexamic acid ester salt is applied to the skin. Since it is considered that the permeability will be further enhanced, it is expected that the whitening effect will be further enhanced.
Further, according to a preferred embodiment of the present invention, in the polyphase emulsion of the present invention, the aqueous component (component G) in the water-in-oil emulsion which is a dispersed phase moves to the vicinity of the surface due to friction when applied to the skin. It can give a fresh feeling of use.

As described above, the multi-phase emulsion of the present invention has a multi-phase structure in which a water-in-oil emulsion is dispersed in an outer phase having both continuous structures. According to a preferred embodiment of the present invention, the polyphase emulsion of the present invention does not undergo phase separation over a wide temperature range (eg, in the range of -20 to 70 ° C, preferably -10 to 50 ° C) and heats the above structure. It can be maintained in a dynamically stable state.

The pH value of the polyphasic emulsion of the present invention is not particularly limited, but it is preferably set to 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 multiphase 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 nicotinic acid amide does not increase the pH value by donating a hydroxide ion, but increases the pH value by donating an electron pair. The addition of a Lewis base to the phase emulsion does not affect the solubility of the tranexamic acid ester salt (component A) in water. Therefore, the Lewis base is preferably used because the tranexamic acid ester salt can be raised to an arbitrary pH value without being precipitated as crystals.
Examples of the Lewis base include nitrogen-containing basic compounds or salts thereof, carboxylic acids, alcohols and the like. Above all, it is preferable to use a nitrogen-containing basic compound.
Specific examples of the nitrogen-containing basic compound include triethylamine, trin-propylamine, trii-propylamine, trin-butylamine, trin-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. Amine compound;
Imidazole compounds such as imidazole, 4-methylimidazole, 4-methyl-2-phenylimidazole, and thiabendazole;
Pyridine compounds such as pyridine, 2-methylpyridine, 4-ethylpyridine, 2-hydroxypyridine, 4-hydroxypyridine, 2-phenylpyridine, 4-phenylpyridine, nicotinic acid, nicotinamide (niacinamide), quinoline, and acrydin. ;
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, and urazole may be mentioned. be able to.
The Lewis base may be used alone or in combination of two or more.
Even pH adjusters other than Lewis bases, such as ionic bases such as sodium hydroxide and arginine, are less susceptible to hydroxide ions at low concentrations, and the tranexamic acid ester salt crystallizes. It can be raised to any pH value without precipitating.
The amount of the pH adjusting agent used may be any amount as long as the pH of the polyphasic emulsion of the present invention is in a desired range, and may be appropriately determined depending on the type of the pH adjusting agent.

The polyphasic emulsion of the present invention may optionally contain components other than the above as long as the object and effect of the present invention are not impaired. For example, it may contain ingredients that can be incorporated into external compositions such as pharmaceuticals, quasi-drugs, and cosmetics. The optional component can be blended in the polyphase 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 blend in the external phase or the dispersed phase according to the type of the arbitrary component.

Optional components that can be used in the present invention include, for example, powder components, surfactants, coser factors, moisturizers, film agents, thickeners, gelling agents, inorganic minerals, metal ion sequestering agents, and polyhydric alcohols. , Monosaccharides, oligosaccharides, amino acids, plant extracts, organic amines, high molecular weight emulsions, antioxidants, antioxidants, skin nutrients, vitamins, blood flow promoters, bactericides, anti-inflammatory (anti-inflammatory) agents , Cell (skin) activator, keratolytic agent, refreshing agent, astringent agent, whitening agent, ultraviolet absorber, fading inhibitor, preservative, buffer, fragrance and the like can be appropriately blended as needed. These optional components may be appropriately selected according to the desired dosage form, application, and the like.

Examples of the powder component include inorganic powders (for example, talc, kaolin, mica, silk mica (serisite), white mica, gold mica, synthetic mica, red mica, black mica, vermiculite, magnesium carbonate, calcium carbonate, silicic acid. Aluminum, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungrate, silica, zeolite, barium sulfate, magnesium sulfate, calcined calcium sulfate (baked sekko), calcium phosphate, fluoroapatite, hydroxyapatite, ceramic Powders, metal soaps (eg zinc myristate, calcium palmitate, aluminum stearate, magnesium stearate, etc.); organic powders (eg polyamide resin powder (nylon powder), polyethylene powder, polymethylmethacrylate powder) , Polystyrene powder, styrene and acrylic acid copolymer resin powder, benzoguanamine resin powder, polytetrafluorinated ethylene powder, cellulose powder, etc.); Metal powder pigments (eg, aluminum powder, copper powder, etc.); Zirconium, barium or aluminum Organic pigments such as rake; natural pigments (eg, chlorophyll, β-carotene, etc.) and the like can be mentioned. The powder component may be hydrophobized.

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

Examples of the anionic surfactant include fatty acid sulphates (eg, sodium laurate, sodium palmitate, etc.); higher alkyl sulfates (eg, sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfates (eg, sodium lauryl sulfate, etc.). , POE-sodium lauryl sulfate triethanolamine, POE-sodium lauryl sulfate, etc.); N-acylsarcosic acid (eg, sodium lauroyl sarcosin, etc.); higher fatty acid amide sulfonate (eg, N-myristyl-N-methyltaurine sodium, etc.) Palm oil fatty acid methyl taurid sodium, lauryl methyl taurid sodium, etc.); Phosphate ester salts (POE-oleyl ether phosphate sodium, POE-stearyl ether phosphoric acid, etc.); Sulfonic acid salts (for example, di-2-ethylhexyl sulfosuccinate) Sodium acid, monolauroyl monoethanolamide polyoxyethylene sodium sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, etc.; alkylbenzene sulfonates (eg, sodium linadodecylbenzene sulfonate, triethanolamine linadodecylbenzene sulfonate, linadodecylbenzene) Sulfonic acid, etc.); Higher fatty acid ester sulfate ester salt (eg, hardened coconut oil fatty acid sodium glyceryl sulfate, etc.); N-acylglutamate (eg, N-lauroyl glutamate monosodium, N-stearoyl glutamate disodium, N-myristoyl- L-monosodium glutamate, etc.); Sulfated oil (eg, funnel oil, etc.); POE-alkyl ether carboxylic acid; POE-alkylallyl ether sulfonate; α-olefin sulfonate; higher fatty acid ester sulfonate; Examples thereof include higher alcohol sulfate ester salt; higher fatty acid alkylolamide sulfate ester salt; sodium lauroyl monoethanolamide succinate; N-palmitoyl aspartate ditriethanolamine; sodium caseinate and the like.

Examples of the cationic surfactant include alkyltrimethylammonium salts (eg, stearyltrimethylammonium chloride, lauryltrimethylammonium chloride, etc.); alkylpyridinium salts (eg, cetylpyridinium chloride, etc.); distearyldimethylammonium chloride dialkyldimethylammonium salts. Poly (N, N'-dimethyl-3,5-methylenepiperidinium); alkyl quaternary ammonium salt; alkyldimethylbenzylammonium salt; alkylisoquinolinium salt; dialkylmoriphonium salt; POE-alkylamine Alkylamine salts; polyamine fatty acid derivatives; ammonium alcohol fatty acid derivatives; benzalconium chloride; benzethonium chloride and the like.

Examples of the amphoteric tenside include imidazoline-based amphoteric tenside agents (for example, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazolin sodium, 2-cocoyl-2-imidazolinium hydroki. Side-1-carboxyethyroxy disodium salt, etc.); Betaine-based surfactants (eg, 2-heptadecyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkyl betaine, amide betaine) , Sulfobetaine, etc.) and the like.

Examples of the oil-based nonionic surfactant include sorbitan fatty acid esters (for example, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, and sorbitan sesquioleate. , Sorbitan trioleate, penta-2-ethylhexylate diglycerol sorbitan, tetra-2-ethylhexylate diglycerol sorbitan, etc.; glycerin polyglycerin fatty acids (for example, monocotton oil fatty acid glycerin, monoerucate glycerin, sesquioleate glycerin, mono Glycerin stearate, α, α'-glycerin pyroglutamate oleate, glycerin monostearate, malic acid, etc.); propylene glycol fatty acid esters (eg, propylene glycol monostearate, etc.); cured castor oil derivative; glycerin alkyl ether; steerless -2 etc. can be mentioned.

Examples of the hydrophilic nonionic surfactant include POE-sorbitan fatty acid esters (for example, POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate, etc.). POE sorbit fatty acid esters (eg, POE-solbit monolaurate, POE-solbit monooleate, POE-solbit pentaoleate, POE-sorbit monostearate, etc.); POE-glycerin fatty acid esters (eg, POE- Glycerin monostearate, POE-glycerin monoisostearate, POE-glycerin triisostearate, etc.); POE-fatty acid esters (eg, POE-monooleate, POE-distearate, POE-monodiolate, ethylene glycol distearate, etc.); POE-alkyl ethers (eg, POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE-2-octyldodecyl ether, POE-cholestanol ether, etc.); Pluronic, etc.); POE / POP-alkyl ethers (eg, POE / POP-cetyl ether, POE / POP-2-decyltetradecyl ether, POE / POP-monobutyl ether, POE / POP-hydrous lanolin, POE / POP -Glycerin ether etc.); Stairless-21 etc. can be mentioned.

A water-soluble polymer can be used as the thickener. Examples of the water-soluble polymer include Arabic gum, carrageenan, karaya gum, tragacanth gum, quince seed (malmero), casein, dextrin, gelatin, sodium pectinate, sodium alginate, locust bean gum, guar gum, tara gum, tamarind gum, and glucomannan. , Xylan, mannan, xanthan gum, agar, pectin, fucoidan, galactomannan, curdran, gellan gum, fucogel, casein, collagen, starch, sodium hyaluronate, natural polymers such as alcacylan (alkaligenes-producing polysaccharide); methylcellulose, ethylcellulose , Semi-synthetic polymers such as sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxymethi cellulose, hydroxypropyl cellulose, methyl hydroxypropyl cellulose, hydroxypropyl methyl cellulose stearoyl ester, propylene glycol alginate, dialkyldimethylammonium sulfate cellulose, PVA (polypoly alcohol), Examples thereof include synthetic polymers such as PVM (polyvinyl methyl ether), PVP (polypolypyrrolidone), polyethylene oxide, sodium polyacrylate, carboxyvinyl polymer, acrylate / C _10-30 alkyl acrylate cross polymer, and sodium polyacrylate.
Of 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 hydroxypropylmethyl cellulose stearoyl ester is preferable. More preferably, a nonionic association type thickener is mentioned. The nonionic association type thickener can provide a sufficient thickening effect to maintain both continuous structures by addition in a small amount that does not affect the feel. Specific examples include polyoxyethylene distearates such as PEG-150 distearate and PEG-250 distearate, and hydrophobically modified polyether urethanes such as (PEG-240 / decyltetradeceth-20 / HDI) copolymers. Be done.

Moreover, you may use a clay mineral as a thickener. For example, clay minerals such as bentonite, hectorite, AlMg silicate (beegum), and laponite that bring about a thickening effect on the aqueous phase, and clay minerals such as organically modified clay minerals that bring about a thickening effect on the oil phase can be mentioned.

Examples of the metal ion 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 (eg, 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 alcohol (eg, glycerin, trimethylolpropane, etc.); tetravalent alcohol (eg, 1). , Pentaerythritol such as 2,6-hexanetriol); pentavalent alcohol (eg, xylitol, etc.); hexavalent alcohol (eg, sorbitol, mannitol, etc.); polyhydric alcohol polymer (eg, diethylene glycol, dipropylene glycol, etc.) Triethylene glycol, polypropylene glycol, tetraethylene glycol, etc.); Divalent alcohol alkyl ethers (eg, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, etc.); Dihydric alcohol alkyl ethers (eg, diethylene glycol monomethyl ether, diethylene glycol, etc.) Monoethyl ether, diethylene glycol monobutyl ether, etc.); Dihydric alcohol ether ester (eg, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, etc.); Glycerin monoalkyl ether (eg, chimil alcohol, ceracyl alcohol, batyl alcohol, etc.) Etc.); Sugar alcohols (for example, sorbitol, martitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, starch-degrading sugar, maltose, xylitol, starch-degrading sugar-reducing alcohol, etc.) and the like.

Examples of the monosaccharide include tricarbose (eg, D-glycerylaldehyde, dihydroxyacetone, etc.); tetracarbose (eg, D-erythulose, D-elittlerose, D-treose, erythritol, etc.); , L-arabinose, D-xylulose, L-lyxose, D-arabinose, D-ribose, D-libulose, D-xylulose, L-xylulose, etc.; Hexalactoses (eg, D-glucose, D-talose, D) -Psicose, D-galactose, D-fructose, L-galactose, L-mannose, D-tagatose, etc.); Seven-carbon sugar (eg, aldoheptose, heprose, etc.); Eight-carbon sugar (eg, octulose, etc.); For example, 2-deoxy-D-ribose, 6-deoxy-L-galactose, 6-deoxy-L-mannose, etc.; aminosaccharides (eg, D-glucosamine, D-galactosamine, sialic acid, aminouronic acid, muramic acid, etc.) ); Uronic acid (for example, D-glucuronic acid, D-mannuronic acid, L-glulonic acid, D-galacturonic acid, L-izuronic acid, etc.) and the like.

Examples of oligosaccharides include sucrose, lactose, maltose, trehalose, cellobiose, gentiobiose, umbilicin, raffinose, gentianose, maltotriose, melegitose, planteose, umbelliferose, stachyose, and velva course.

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

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. Can be mentioned.

Examples of the polymer emulsion include an acrylic resin emulsion, an ethyl polyacrylate emulsion, an acrylic resin solution, a polyacrylic 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 their derivatives, pantothenic acid and its derivatives, biotin and the like.

Examples of the antioxidant include ascorbic acid such as ascorbyl palmitate, ascorbyl tetraisopalmitate, glucoside ascorbyl, ascorbyl magnesium phosphate, sodium ascorbyl phosphate, and ascorbic acid sorbate and derivatives thereof;
Tocopherols and derivatives thereof 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; succin Acids; fumaric acid; kefarin; hexametaphosphates; phytic acid; ethylenediaminetetraacetic acid: and Irish moss (Chondrus crispus), Rhodiola, hyperthermophilic bacteria, mate tea leaves, oak wood, kayu lape bark (kayu) Examples include plant extracts such as rapet bark), cherry leaves, and ylang ylang leaves.

Moisturizers include, for example, polyethylene glycol; propylene glycol; dipropylene glycol; glycerin; 1,3-butylene glycol; xylitol; sorbitol; martitol; mucopolysaccharides such as chondroitin sulfate; hyaluronic acid; sodium hyaluronate; hyaluronic acid. Acetylsodium; mucoitin sulfate; caronic acid; atelocollagen; cholesteryl-12-hydroxystearate; bile acid salt; main component of NMF (natural moisturizing factor) such as pyrrolidone carboxylate and lactate; amino acids such as urea, cysteine and serine Kind; short-chain soluble collagen; diglycerin (EO) PO adduct; homopolymer or copolymer of 2-methacryloyloxyethyl phosphorylcholine commercially available from Nichiyu Co., Ltd. under names such as "Lipidure HM" and "Lipidure PBM"; Pantenol; Allantin; Commercially available under the name "Wilbride S 753" from Nichiyu Co., Ltd. PEG / PPG / Polybutylene glycol-8 / 5/3 Glycerin; Commercially available under the name "AMINOCOAT" from Asahi Kasei Chemicals Co., Ltd. Trimethylglycerin; sweet chestnut (Castanea sativa) extract, hazelnut protein hydrolyzate, tuberose (Polianthes tuberosa) polysaccharide, Argania spinosa kernel oil, "pearl extract" from Maruzen Pharmaceutical Co., Ltd. ( Examples include various plant extracts such as conchiolin-containing pearl extract commercially available under the name of (registered trademark).

Examples of the skin softening agent include polyglyceryl methacrylate and methyl gluceth-20.

Anti-aging agents include, for example, acyl amino acids (specifically, those marketed by SEDERMA under the names "Maxilip", "MatrixyL3000", and "Biopeptide CL", and those marketed by SEPPIC under the name "Sepilift". ); Peas (Pisum sativum) extract; Soybean protein hydrolyzate; Methylsilanol mannuronate; Hydrolyzed pepo pumpkin seed oil cake; Senedesmus extract and the like.

Anti-contamination agents include, for example, Moringa pterygosperma seed extracts (specifically, those commercially available from LSN under the name "Purisoft"); Shea butter extract (specifically). Is marketed by SILAB under the name "Detoxyl", a blend of sardine extract (ivy extract), phytic acid, and sunflower seed extract (for example, marketed by SEDERMA under the name "OSMOPUR"). ) Etc. are exemplified.) And the like.

Examples of the keratolytic agent include α-hydroxy acids (specifically, glycolic acid, lactic acid, citric acid, malic acid, mandelic acid, tartaric acid and the like), β-hydroxy acids (specifically, specific examples). Examples thereof include tartaric acid and the like), their esters (specifically, C _12-13 alkyl lactate) and plant extracts containing these hydroxy acids (specifically, Hibiscus sabdriffa extract). ) And so on.

Examples of the anti-inflammatory agent include bisabolol, allantin, tranexamic acid, zinc oxide, sulfur oxide and its derivative, chondroitin sulfate, glycyrrhizic acid and its derivative (glycyrrhizinate and the like) and the like.

Further, the polyphasic 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 melanin formation mechanism (stage I). Good. Examples of the whitening agent include ferulic acid-containing cytovectors (water, glycol, lecithin, ferulic acid, hydroxyethyl cellulose) marketed by BASF under the name of "Cytovector" (registered trademark).

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

Furthermore, the polyphasic emulsion of the present invention may contain a whitening agent having an inhibitory effect on melanin synthesis, microphthalmia-associated transcription factor expression, antityrosinase activity, and endoterin-1 synthesis. For example, licorice extract (Glycyrrhiza glabra extract) marketed by Maruzen Pharmaceuticals Co., Ltd. under the name of "Licorice extract" (registered trademark) can be mentioned.

Furthermore, the polyphasic emulsion of the present invention may contain a whitening agent having an antioxidant effect such as a vitamin C compound. For example, ascorbic acid salt, ascorbic acid ester of fatty acid or sorbic acid, other ascorbic acid derivatives and the like can be mentioned. 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, etc.) is exemplified. This type of active ingredient is commercially available from DKSH under the name "Ascorbyl glucoside"®.

Furthermore, the polyphasic emulsion of the present invention may contain other whitening agents. For example, plant extracts (extracts such as Fusasaki Narcissus), cetyl tranexamic acid (manufactured by Nikko Chemicals Co., Ltd., product name "NIKKOL TXC"), arbutin, kojic acid, ellagic acid, cysteine, 4-thioresorcin, resorcinol or rucinol or It may contain such derivatives, pigmentation inhibitors such as glycyrrhizinic acid and hydroquinone-β-glucoside.

The polyphasic emulsion of the present invention may further contain an organic sunscreen and / or an inorganic sunscreen.
Organic sunscreens include dibenzoylmethane derivatives such as butylmethoxydibenzoylmethane (such as those marketed by HOFFMANN LA ROCHE under the name "Parsol 1789"); silicic acid derivatives such as octyl methoxycinnamate (HOFFMANN LA). (Commercially available from ROCHE under the name of "Parsol MCX");salicylate; paraaminobenzoic acid; β, β'-diphenylacrylate derivative; benzophenone derivative; benzylidene camphor derivative such as terephthalidene dicamer sulfonic acid; phenyl Examples thereof include benziimidazole derivatives; triazine derivatives; phenylbenzotriazole derivatives; anthranyl acid derivatives. These may be coated or encapsulated.
Examples of the inorganic sunscreen include a pigment or a nanopigment formed by optionally coating a metal oxide. Examples of the nano-pigment include titanium oxide, iron oxide, zinc oxide, zirconium oxide, cerium oxide and the like. All of these compounds are well known as UV protection agents.

Examples of the preservative include paraoxybenzoic acid esters (methylparaben, propylparaben, etc.), phenoxyethanol and the like.

In addition, as an optional component used in the polyphasic emulsion of the present invention, it is listed in the "International Cosmetic Ingredient Dictionary and Handbook" (13th edition, 2010) published by the Personal Care Products Council. You can use what has been done.
The blending amount of these optional components is not particularly limited as long as the object of the present invention is not impaired.

The polyphasic emulsion of the present invention
A) Physiologically acceptable salt of tranexamic acid ester;
B) Mono or diether of glycerin with a linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms and a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms. An amphipathic substance selected from a combination of alkylglyceryl ethers;
C) The process of preparing the oil phase containing the oil agent and
D) A step of 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 both continuous structures.
By a method including a step of adding a water-in-oil emulsion containing E) an oil-based nonionic surfactant F) an oil agent G) water, a water-soluble organic solvent or a mixture thereof into the outer phase to form a dispersed phase. Can be manufactured. Hereinafter, each step will be described.

First, an oil phase containing components A, B and C is prepared. The preferable blending amount of each component is as described above, the content of the component A is 0.5 to 10% by mass, the content of the component B is 0.5 to 10% by mass, and the content of the component C is 0.5 to 10% by mass. The content of is preferably 1 to 25% by mass, and the total content of the components A, B and C is preferably 5 to 45% by mass with respect to the total mass of the polyphasic 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 a small amount (about 4 to 8% by mass with respect to the total mass of the polyphase emulsion) of the component D constituting the aqueous phase in the oil phase in advance. Although not bound by theory, by mixing a small amount of aqueous phase components in the oil phase in advance, the oil-soluble part (oil agent, tranexamic acid ester salt and amphipathic substance lipophilic part) and water-soluble part It is thought that the sex moieties (aqueous medium, tranexamic acid ester salt and hydrophilic site of the amphipathic substance) can be arranged to some extent, and when the oil phase is added to the aqueous phase, the formation of both continuous structures is promoted. be able to.

Before adding the oil phase to the aqueous phase, it is preferable to heat the oil phase and the aqueous phase to maintain the dissolved state. 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. Although it is stated that "the oil phase is added to the aqueous phase", 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, it can be cooled to 30 ° C. or lower with stirring to form an outer phase having both continuous structures. The cooling method is not particularly limited, and may be, for example, natural cooling or ice cooling.
As described above, according to the method of the present invention, an external phase having both continuous structures can be formed by a normal stirring operation without using a special device.
An oil-soluble or water-soluble optional component may be added to the oil phase and the aqueous phase in advance, provided that the stability of the composition is not impaired.

Next, a water-in-oil emulsion containing the components E, F and G is added to the outer phase having both continuous structures obtained in the above step to form a dispersed phase. The water-in-oil emulsion can be prepared as follows.

First, components E and F are mixed to prepare an oil phase. An optional oil-soluble component may be added to the oil phase in advance, provided that the stability of the emulsified particles is not impaired.

Next, the obtained oil phase is added to an aqueous phase containing water, a water-soluble organic solvent or a mixture thereof (component G). An optional water-soluble component may be added to the aqueous phase in advance.

The obtained water-in-oil emulsion may further contain an arbitrary component as long as the object of the present invention is not impaired.
The preferable blending amount of each component constituting the dispersed phase has already been described, and the total content of the components constituting the dispersed phase is 5 to 45% by mass with respect to the total mass of the polyphase emulsion. Yes, 10 to 35% by mass is preferable, and 15 to 25% by mass is more preferable.

Before adding the water-in-oil emulsion to the outer phase, it is preferable to maintain the water-in-oil emulsion and the water-in-oil emulsion in the range of 20 to 35 ° C., respectively. After mixing the external phase and the water-in-oil emulsion, a creamy multiphase emulsion can be obtained from the emulsion by sufficiently stirring.

As described above, the polymorphic emulsion of the present invention can be produced. According to the present invention, it is possible to obtain a multiphase emulsion in which a water-in-oil emulsion is dispersed in an outer phase having both continuous structures by a normal stirring operation without using a special device.

Since the polyphasic emulsion of the present invention contains a tranexamic acid ester salt (component A) having a whitening effect, it can exert an effect of suppressing pigmentation and / or whitening the skin by topically applying it to the skin. That is, the present invention provides a cosmetic method for suppressing pigmentation and / or whitening the skin by locally applying the polyphasic emulsion of the present invention to the skin.
According to a preferred embodiment of the present invention, by using the polyphasic emulsion of the present invention as an external composition such as cosmetics (particularly emulsions and creams), the skin is suppressed from pigmentation and / or whitened, and spots or pigments are formed. It is possible to obtain the effect that the deposition can be thinned.

The polyphasic emulsion of the present invention can be suitably used as an external composition for pharmaceuticals, quasi-drugs, cosmetics and the like. The product form of the external composition can be arbitrarily selected. For example, facial cosmetics such as washing pigments, lotions, beauty essences, milky lotions, creams, packs; makeup cosmetics such as foundations, lipsticks, eye shadows; body cosmetics; aromatic cosmetics; body cleaning agents; ointments, etc. be able to. In particular, it can be preferably used as a whitening beauty essence, whitening cream, and whitening pack.

Hereinafter, the present invention will be described with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples. Unless otherwise specified, the composition ratio is based on the mass ratio (mass%).

<Examples 1 to 3, reference example >
Preparation of Emulsion and Evaluation of Physical Properties Emulsion was prepared as follows with the composition shown in Table 1. The stirring was performed by hand using a stirring rod.
1) Dipropylene glycol (3% by mass) and purified water (3% by mass) of the component D are mixed with the oil phase containing components A, B and C, heated to 85 ± 5 ° C., and stirred. However, these components were completely dissolved.
2) Next, the aqueous phase containing the remaining component D was heated to 85 ± 5 ° C., and the mixture obtained in 1) above was gradually added and homogenized while sufficiently stirring.
3) Then, the mixture obtained in 2) above was naturally cooled to 25 ± 5 ° C. or lower with stirring to obtain a liquid composition having a transparent to translucent appearance.
4) Next, the components E and F were mixed at room temperature (25 ± 5 ° C.), and these components were completely dissolved while stirring.
5) Subsequently, while sufficiently stirring the component G, the mixture obtained in 4) above was gradually added and homogenized to obtain a gel-like composition having a milky white appearance.
6) Next, the composition obtained at room temperature (25 ± 5 ° C.) was added to the composition obtained in 3) above with sufficient stirring to obtain an emulsion. .. The physical characteristics of the obtained emulsion were evaluated as follows. The results are shown in Table 1.

[1] Dosage Form of Emulsion The obtained multi-phase emulsion is subjected to freeze cross-section observation using a cryo-focused ion beam scanning electron microscope (cryo-FIB-SEM) (manufactured by FEI, model [HeliosNanoLab 650]). It can be confirmed by. Specifically, the obtained polyphase emulsion is instantly frozen in liquid nitrogen, introduced into a FIB-SEM apparatus, and a cut surface is obtained by FIB treatment for cryo-SEM observation. At the same time, by mapping the distribution state of arbitrary elements using energy dispersive X-ray analysis (EDX), a more detailed emulsion state can be confirmed.
[2] Static / dynamic friction coefficient The static / dynamic friction measurement was performed using an apparatus (Tribo master TL201Ts manufactured by Tribity Lab) under the conditions of a sliding width of 30 mm, a sliding speed of 10 mm ^-1 , and a vertical load of 3.061 N. Each sample was repeatedly measured 5 times.
[3] Phase transition temperature (° C)
Differential scanning calorimetry (DSC) measurement method (device:) in which X-ray diffraction (XRD) measurement is performed, the peak near 2θ = 22 ° is used as an index of α-gel, and the temperature at which the peak disappears is simultaneously measured. The phase transition temperature (° C.) was determined by thermal analysis using a model [multipurpose X-ray diffractometer SmartLab-XRD-DSC] manufactured by Rigaku Co., Ltd., and a heating rate of 2 ° C./min).
[4] Sensory evaluation (freshness)
The obtained emulsion was subjected to sensory evaluation by 15 expert evaluators. The evaluation criteria were as follows, with an average of 4 or more being "A", 3 or more and less than 4 being "B", and less than 3 being "C".
1: Not felt 2: Almost not felt 3: Neither 4: Slightly felt 5: Feeled [5] Stability Fill a 200 mL transparent glass tube bottle with the obtained emulsion and room temperature (25 ± 5 ° C). The mixture was allowed to stand for 3 months under the conditions of 40 ° C. and 40 ° C., and the appearance was visually evaluated. "A" is defined as "A" when the initial state is maintained for 3 months under both room temperature and 40 ° C. conditions, and "B" is defined as when separated within 3 months under either room temperature or 40 ° C. conditions. When both were separated within several days under the conditions of room temperature and 40 ° C., they were evaluated as "C".

The cryo-FIB-SEM observation results of the emulsion obtained in Example 1 are shown in FIG. FIG. 1 (a) shows the results of cryo-FIB-SEM observation before the FIB treatment (magnification 1000 times), FIG. 1 (b) after the FIB treatment (magnification 5000 times), and FIG. 1 (c) shows the results after the FIB treatment. An enlarged view of the dispersed phase (magnification 35,000 times) and FIG. 1 (d) show an enlarged view of the continuous phase after the FIB treatment (magnification 35,000 times). As shown in FIGS. 1 (b) to 1 (d), the emulsion obtained in Example 1 is an emulsion in which a water-in-oil emulsion is dispersed in an external phase having both continuous structures (“W / O” in the table. / BAG ") was confirmed.

The EDX chemical mapping image of the emulsion obtained in Example 1 is shown in FIG. FIG. 2 (a) is an electron microscope image (reflected electron image), and the distribution state of each element is shown in FIGS. 2 (b) to 2 (d) using EDX. FIG. 2B is a mapping image of an oxygen element. FIG. 2B shows the distribution of oxygen and reflects the presence of water. FIG. 2C is a mapping image of carbon elements. FIG. 2C shows the distribution state of carbon and reflects the presence of the oil agent. FIG. 2D is a mapping image of the silicon element. FIG. 2D shows the distribution state of silicon and reflects the presence of the silicone derivative. As shown in FIGS. 2 (b) to 2 (d), it was confirmed that the emulsion obtained in Example 1 was an emulsion in which a water-in-oil emulsion was dispersed in an external phase having both continuous structures. ..

The X-ray diffraction (XRD) curve and the differential scanning calorimetry (DSC) curve of the emulsion obtained in Example 1 are shown in FIG. FIG. 3A is an X-ray diffraction (XRD) curve, and FIG. 3B is a differential scanning calorimetry (DSC) curve. A peak is observed in the vicinity of 2θ = 22 ° of the XRD curve in FIG. 3A, and the formation of α-gel can be confirmed. From the DSC curve of FIG. 3 (b) measured at the same time, the temperature at which this peak disappears, 28.2 ° C., can be obtained as the phase transition temperature.

The evaluation results of the static / dynamic friction coefficients measured by the friction feeling tester of the emulsion obtained in Example 1 are shown in FIG. 4 together with the evaluation results of the emulsion, water and oil (squalene) obtained in Comparative Example 1. The large peak at the initial stage of movement was defined as static friction, the relatively flat region of 6 to 20 mm was defined as dynamic friction, and the average thereof was defined as the dynamic friction coefficient. FIG. 5 shows the results of repeated measurements of the emulsions obtained in Example 1 and Comparative Example 1 five times under the same measurement conditions. FIG. 5 (a) is an evaluation result of the emulsion obtained in Example 1, and FIG. 5 (b) is an evaluation result of the emulsion obtained in Comparative Example 1. As shown in FIG. 4, it was confirmed that the emulsion obtained in Example 1 was lower than the coefficient of kinetic friction of water or oil alone. Further, as shown in FIG. 5, the dynamic friction region of the emulsion obtained in Comparative Example 1 does not fluctuate from around 6 in COF value, whereas the dynamic friction region of the emulsion obtained in Example 1 keeps track of the number of times. The COF value increased with each measurement, and in the fifth measurement, the COF value increased to the same level as that of water or oil. Results measured by Leometer FTIR / ATR (Thermo Scientific, model [HAAKE MARS III and Nicolet iS 10 hybrid system]) (Measurement conditions: plate-plate ・ 35 mm, shear rate 0.0001 to 4000 s ^-1 , The measurement temperature was 35 ° C, and the Fourier transform infrared spectrophotometer (FT-IR) was performed 37 times during the measurement time of 400 seconds.) The cause of this increase was the surface of the water in the water-in-oil emulsion from the bulk. It is considered that this is because it moved to the vicinity. This result is also consistent with the sensory evaluation result that the emulsion obtained in Example 1 has a fresh feeling of use.

<Comparative Examples 1, 5, 8>
Emulsions were prepared as follows with the compositions shown in Table 2. The stirring was performed by hand using a stirring rod.
1) Ingredients A and D were mixed, heated to 85 ± 5 ° C., and these components were completely dissolved while stirring.
2) Next, the components B, C, E and F were mixed, heated to 85 ± 5 ° C., and while sufficiently stirring, the mixture obtained in 1) above was gradually added to homogenize.
3) Then, the mixture obtained in 2) above was naturally cooled to 25 ± 5 ° C. or lower with stirring to obtain an emulsion composition having a milky white appearance. The physical properties of the obtained emulsion were evaluated in the same manner as in Examples. The results are shown in Table 2.

<Comparative Examples 2, 6 and 9>
Emulsions were prepared as follows with the compositions shown in Table 2. The stirring was performed by hand using a stirring rod.
1) Dipropylene glycol (3% by mass) and purified water (3% by mass) of component D are mixed with the oil phase containing components A, B and C, heated to 85 ± 5 ° C., and stirred. However, these components were completely dissolved.
2) Next, the aqueous phase containing the remaining component D was heated to 85 ± 5 ° C., and the mixture obtained in 1) above was gradually added and homogenized while sufficiently stirring.
3) Then, the mixture obtained in 2) above was naturally cooled to 25 ± 5 ° C. or lower with stirring to obtain a liquid composition having a transparent to translucent appearance.
4) Next, the components E and F kept at room temperature (25 ± 5 ° C.) are mixed with the composition obtained in 3) above at the ratio shown in Table 2 and added with sufficient stirring. Emulsion was obtained. The physical properties of the obtained emulsion were evaluated in the same manner as in Examples. The results are shown in Table 2.

<Comparative Examples 3, 4, 7>
Emulsions were prepared in the same manner as in Examples except that the compositions shown in Table 2 were used, and their physical characteristics were evaluated. The results are shown in Table 2.

As shown in Table 1, the polyphasic emulsion of the present invention can disperse the tranexamic acid ester salt in a stable state in the preparation, has excellent stability, and can give a fresh feeling of use. .. On the other hand, as shown in Table 2, the emulsion of the comparative example could not achieve both stability and a fresh feeling of use.

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

Claims (12)

A multi-phase emulsion in which a water-in-oil emulsion is dispersed in an outer phase having both continuous structures.
Foreign Minister
A) Physiologically acceptable salt of tranexamic acid ester;
B) Mono or diether of glycerin with a linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms and a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms. An amphipathic substance selected from a combination of alkyl glyceryl ethers;
C) oil; and D) water, water-soluble organic solvent or mixture thereof
The water-in-oil emulsion, which is a dispersed phase,
E) Parent oil type nonionic surfactant F) Oil; and G) Water, water-soluble organic solvent or a mixture thereof, and the total content of the components constituting the outer phase with respect to the total mass of the polyphase emulsion. Is 55 to 95% by mass, the total content of the components constituting the dispersed phase is 5 to 45% by mass, and the ratio of the internal phase in the water-in-oil emulsion which is the dispersed phase is 60% by mass or more. , Polyphase emulsion. The tranexamic acid ester in the physiologically acceptable salt of the tranexamic acid ester has the following formula (1):

[In the formula, R represents a saturated or unsaturated hydrocarbon group having a linear or branched chain having 1 to 22 carbon atoms which may be substituted with a substituent selected from a hydroxyl group and an amino group. ]
The multiphase emulsion according to claim 1. The polyphasic 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 polyphasic emulsion according to any one of claims 1 to 3, wherein the amphipathic substance of component B is a combination of cetyl alcohol and at least one selected from the group consisting of kimil alcohol and batyl alcohol. .. 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 1 to the total mass of the polyphasic emulsion. The polyphasic emulsion according to any one of claims 1 to 4, wherein the content is 25% by mass and the total content of the components A, B and C is 5 to 45 % by mass. Claims 1 to 5 wherein the oil-based nonionic surfactant of component E is at least one selected from monoalkyl glyceryl ether having a carbon chain length of 6 to 22; polyether-modified silicone; and polyglycerin-modified silicone. The polyphasic emulsion according to any one of the above. Foreign Minister, in which further comprising a p H adjusting agent, multiple emulsion according to any one of claims 1 to 6. The multiphase emulsion according to claim 7, wherein the pH adjuster is selected from Lewis bases. The method for producing a polyphasic emulsion according to any one of claims 1 to 8.
A) Physiologically acceptable salt of tranexamic acid ester;
B) Mono or diether of glycerin with a linear or branched saturated or unsaturated alcohol having 12 to 22 carbon atoms and a linear or branched saturated or unsaturated alcohol having 8 to 22 carbon atoms. An amphipathic substance selected from a combination of alkylglyceryl ethers;
C) The process of preparing the oil phase containing the oil agent and
D) A step of 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 both continuous structures.
Including a step of adding E) an oil-based nonionic surfactant F) an oil agent; and G) a water-in-oil emulsion containing water, a water-soluble organic solvent or a mixture thereof to the outer phase to form a dispersed phase. ,Method. An external composition containing the polyphasic emulsion according to any one of claims 1 to 8. Use of the polyphasic emulsion according to any one of claims 1 to 8 for suppressing and / or whitening the skin to reduce blemishes or pigmentation as a cosmetic. A cosmetic method for suppressing pigmentation and / or whitening the skin, which comprises topically applying the polyphasic emulsion according to any one of claims 1 to 8 to the skin.