JP2019099501A - Remedy for skin blacking - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external preparation for skin containing a novel ingredient as an active ingredient for improving darkening of the skin. An external skin preparation containing glycyrrhetinic acid, glycyrrhizic acid, derivatives thereof, and / or salts thereof, and ufenamate can improve darkening of the skin. [Selection diagram] None

Description

  The present invention relates to a composition for external use on the skin which comprises glycyrrhetinic acid, glycyrrhizinic acid, their derivatives, and / or their salts, and ufenamate to improve the darkening of the skin.

  Non-steroidal anti-inflammatory agents have few concerns about serious side effects such as those seen with steroidal anti-inflammatory agents, and there are few restrictions on the amount used and the period of use, so rash, redness, dry dermatitis, atopic dermatitis It is also widely used as an external preparation for the purpose of alleviation of inflammatory skin diseases such as allergic dermatitis.

  Among non-steroidal anti-inflammatory agents, glycyrrhetinic acid, glycyrrhizinic acid, their derivatives, and salts thereof (hereinafter sometimes referred to as "glycyrrhetinic acids"), and ufenamate have anti-inflammatory activity, It is widely used as a pharmaceutical or quasi-drug external preparation.

  In addition, diphenhydramine and salts thereof have strong histamine action, and are widely used as external preparations for medicines or quasi-drugs for antipruritic or antipruritic.

  Since glycyrrhetinic acids, ufenamate, and diphenhydramine are easily destabilized in the preparation, external preparations comprising at least one of them require a formulation design with enhanced preparation stability. Therefore, conventionally, in the external preparation containing at least one of glycyrrhetinic acid, ufenamate, and diphenhydramine, a formulation technique for enhancing the formulation stability has been studied. For example, in Patent Document 1, at least one of glycyrrhetinic acid, ufenamate, and diphenhydramine, at least one selected from predetermined glycerin fatty acid esters and polyglycerin fatty acid esters, predetermined polyoxyethylene hydrogenated castor oil, silicone oil, and the like It has been reported that a water-in-oil type cream pharmaceutical preparation containing a higher alcohol liquid at 25 ° C. can secure viscosity stability at low temperature and high temperature storage and can maintain cream type.

  On the other hand, removal processing of body hair is conventionally performed. Methods for removing and treating body hair are known such as hair removal, shaving and hair removal, and in recent years, it has been widely used regardless of age and gender, as well as self-treatment and treatment by specialized institutions (medical and non-medical institutions). It has been done. The removal process of body hair causes inflammation in the pores not a little, so it is easy for the skin to become dark after the treatment. In the case of treatment by a medical institution, a steroid is usually prescribed to suppress inflammation after laser hair removal. However, the steroid agent is not only accompanied by problems such as limitations on the amount used and the period of use, but may cause further darkening and the like due to side effects. Permanent hair removal is impossible in the case of non-medical institution or self treatment, and it is necessary to repeat the treatment, it is very easy to cause skin darkening due to repeated inflammation, and it is difficult to take measures to effectively prevent the trouble It is. In particular, due to the recent outbreak of hair removal treatment, problems due to darkening of the skin after treatment can not be ruled out.

JP 2017-7958 A

  Darkening of the skin is caused by inflammation of the skin that is partially stimulated, as well as removal of body hair. For such darkening of the skin, a so-called whitening component, that is, a component capable of effectively increasing the lightness of the skin as a single component is used. However, especially for people with weak skin, the skin lightening component is often a stimulus. Therefore, an object of the present invention is to provide a skin external preparation containing a novel component as an active ingredient for improving skin darkening.

  The inventors of the present invention conducted intensive studies to solve the above-mentioned problems, and it was found that glycyrrhetinic acid, glycyrrhizinic acid, their derivatives, and / or their salts, ufenamate, diphenhydramine and / or their salts are all whitening. It has been found that even though it is not known as an ingredient and there is no effective whitening effect by itself, it is possible to improve the darkening of the skin by combining and blending them. The present invention has been completed by further investigation based on these findings.

That is, the present invention provides the invention of the aspects listed below.
Item 1. (A) at least one selected from the group consisting of glycyrrhetinic acid, glycyrrhizinic acid, and derivatives thereof, and salts thereof, (B) Ufenamate, and (C) diphenhydramine and / or a salt thereof Darkening agent.
Item 2. Item 3. The skin darkening improver according to item 1, which contains substantially no whitening component.
Item 3. The darkening agent for skin according to item 1 or 2, which is an oil-in-water emulsion composition.
Item 4. The darkening agent for skin according to any one of Items 1 to 3, which is applied to the skin after removal treatment of body hair.

  The darkening agent for skin of the present invention can improve darkening of the skin by containing glycyrrhetinic acid, ufenamate, diphenhydramine and / or a salt thereof.

Darkening agent for skin according to the present invention is at least one selected from the group consisting of glycyrrhetinic acid, glycyrrhizinic acid, derivatives thereof, and salts thereof (hereinafter referred to as (A)) It may be referred to as component), ufenamate (hereinafter sometimes referred to as component (B)), and diphenhydramine and / or a salt thereof (hereinafter sometimes referred to as component (C)) It is characterized by Hereinafter, the darkening agent for skin of the present invention will be described in detail.

(A) Glycyrrhizin acids The skin darkness improving agent of the present invention contains glycyrrhetinic acid, glycyrrhizinic acid, their derivatives, and / or their salts.

  Glycyrrhetinic acid is a known drug known to have an anti-inflammatory action, an anti-allergic action and the like.

  Glycyrrhizinic acid is a known drug known to have an anti-inflammatory action, an anti-allergic action and the like.

  The derivative of glycyrrhetinic acid is not particularly limited as far as it is pharmaceutically acceptable, and specific examples thereof include pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, monoglucuronide glycyrrhetinate, and the like. These derivatives of glycyrrhetinic acid may be used alone or in combination of two or more.

  The derivative of glycyrrhizinic acid is not particularly limited as long as it is pharmaceutically acceptable, and specifically, methyl glycyrrhizinate, stearyl glycyrrhizinate and the like can be mentioned. These derivatives of glycyrrhizinic acid may be used alone or in combination of two or more.

  The salts of glycyrrhizinic acid, glycyrrhetinic acid and / or derivatives thereof are not particularly limited as long as they are pharmaceutically acceptable, but specifically, alkali metal salts such as sodium salts and potassium salts; ammonium salts and the like It can be mentioned. These salts may be used singly or in combination of two or more.

  The agent for improving skin darkening according to the present invention includes, as component (A), glycyrrhetinic acid, a salt of glycyrrhetinic acid, a derivative of glycyrrhetinic acid, a salt of a derivative of glycyrrhetinic acid, glycyrrhizinic acid, a salt of glycyrrhizinic acid, a derivative of glycyrrhizinic acid, Among salts of derivatives of glycyrrhizinic acid, one type may be selected and used, or two or more types may be used in combination.

  Among these components (A), glycyrrhetinic acid, glycyrrhizinic acid, and salts thereof are preferably from the viewpoint of improving skin darkening more effectively; salts of glycyrrhetinic acid and glycyrrhizinic acid are more preferable; and particularly preferable And glycyrrhetinic acid and dipotassium glycyrrhizinate.

  The content of the component (A) in the skin darkness improving agent of the present invention is not particularly limited and may be appropriately set according to the medicinal effect to be imparted, but for example, the total amount of the component (A) 0.01 to 10% by weight is mentioned, and from the viewpoint of improving skin darkening more effectively, preferably 0.01 to 5% by weight, more preferably 0.05 to 2% by weight.

(B) Ufenamart The darkening agent for skin of the present invention contains ufenamate. Ufenamate, also called butyl flufenamate, is a drug known as a lipid-soluble non-steroidal anti-inflammatory drug.

  In the agent for improving skin darkening according to the present invention, the content of the component (B) is appropriately set according to the medicinal effect etc. to be exhibited, but it is, for example, 1 to 20% by weight. From the viewpoint of improving the properties, it is preferably 1 to 6% by weight, more preferably 1 to 5% by weight.

  In the darkening agent for skin of the present invention, the ratio of the component (B) to the component (A) is determined according to the contents of the components (A) and (B). The total amount of the component (B) is 10 to 200000 parts by weight per 100 parts by weight of the total, and from the viewpoint of effectively improving the darkening of the skin, preferably 20 to 60000 parts by weight, more preferably 50 to 10000 parts Department is listed.

(C) Diphenhydramine and / or its salt The skin-darkening agent of the present invention comprises diphenhydramine and / or its salt. Diphenhydramine and / or a salt thereof, together with the (A) component and the (B) component, make it possible to improve skin darkening and contain the (A) component and the (B) component. It also makes it possible to improve the instability of the composition to form precipitates and precipitates, and to suppress the formation of precipitates and precipitates of the skin darkening agent of the present invention.

  Diphenhydramine is a known drug known to have antihistaminic activity.

  The salt of diphenhydramine is not particularly limited as long as it is pharmaceutically acceptable, and specifically, hydrochloride, citrate, succinate, tartrate, fumarate, maleate, salicylate And acid addition salts such as diphenyl disulfonate, tannate, lauryl sulfate, sulfate and the like. These salts may be used singly or in combination of two or more.

  The darkening agent for skin of the present invention may be used by selecting one type from diphenhydramine and its salts as the component (C), and may be used in combination of two or more types.

  Among these (C) components, diphenhydramine and diphenhydramine hydrochloride are preferably mentioned from the viewpoint of more effectively improving the darkening of the skin or from the viewpoint of effectively suppressing the formation of precipitates and precipitates.

  Although it does not restrict | limit in particular about content of (C) component in the skin blackness improving agent of this invention, For example, 0.01-5 weight% is mentioned in the total amount of (C) component. From the viewpoint of improving skin darkness more effectively or suppressing formation of precipitates and precipitates more effectively, the content of the component (C) in the skin darkening agent of the present invention is preferably 0. And 1 to 3% by weight, more preferably 0.1 to 2% by weight.

  In the skin darkening improving agent of the present invention, the ratio of the component (C) to the component (A) is determined according to the contents of the components (A) and (C), but, for example, The total amount of the component (C) is 0.1 to 50000 parts by weight per 100 parts by weight of the total. The total amount of the component (C) is preferably 100 parts by weight of the total amount of the component (A) from the viewpoint of more effectively improving the darkening of the skin or from the viewpoint of suppressing the formation of precipitates and precipitates more effectively. Is preferably from 2 to 300,000 parts by weight, more preferably from 5 to 4000 parts by weight.

Whitening component The agent for improving skin darkening according to the present invention comprises the above components (A), (B) and (C) as active ingredients, and may further comprise a whitening component, preferably It contains substantially no whitening ingredients. Substantially no whitening component means that the whitening component does not contain an effective amount for the purpose of exerting the whitening effect, for example, the content of the whitening component in the darkening agent for skin of the present invention is For example, 0.001 wt% or less, preferably 0.0001 wt% or less, more preferably 0.00001 wt% or less, particularly preferably 0 wt%.

  Examples of whitening ingredients include those known as active ingredients for the purpose of preventing skin darkening due to melanin formation and / or whitening of darkened skin, for example, ingredients having a reducing action on produced melanin, The component known as a component which suppresses tyrosinase activity expression, a component which suppresses activation of melanocytes, etc. are mentioned. More specifically, ascorbic acid, ascorbic acid salt, ascorbic acid derivative; hydroquinone, salt of hydroquinone, hydroquinone derivative; resorcinol derivative; tranexamic acid, tranexamic acid derivative; kojic acid; arbutin; cysteine; glutathione, glutathione salt, N- Acyl glutathione, glutathione ester; ferulic acid, ferulic acid salt;

Tocopherol and / or Derivative Thereof The skin darkness improving agent of the present invention may contain tocopherol and / or a derivative thereof together with the above-mentioned components in order to enhance anti-inflammatory and analgesic action and / or to promote blood circulation.

  Tocopherol is a known compound known as vitamin E. The tocopherol may be any of d-form, l-form and dl-form, preferably dl-form. The tocopherol may be any of an α form, a β form, a γ form and a δ form, preferably an α form.

  The derivative of tocopherol is not particularly limited as far as it is pharmaceutically acceptable, and examples thereof include esters with carboxylic acids such as acetic acid, nicotinic acid and succinic acid, and diesters with phosphoric acid. Among these derivatives of tocopherols, preferred are esters with carboxylic acids, more preferably tocopherol acetate.

  The derivative of tocopherol may be any of d-form, l-form and dl-form, preferably dl-form. Furthermore, the derivative of tocopherol may be any of an α form, a β form, a γ form, and a δ form, preferably an α form.

  In the skin darkness improving agent of the present invention, as tocopherol and / or its derivative, one of tocopherol and its derivative may be selected and used alone, or two or more may be used in combination. Good. Among tocopherol and / or derivatives thereof, preferably a derivative of tocopherol, more preferably an ester of tocopherol with carboxylic acid, still more preferably tocopherol acetate, particularly preferably d-α-tocopherol acetate, l-α-tocopherol acetate, Dl-α-tocopherol acetate is mentioned.

  The content of tocopherol and / or its derivative in the skin darkness improving agent of the present invention is not particularly limited, but it is, for example, 0.01 to 10% by weight, preferably 0.01 as a total of tocopherol and / or its derivative. It is preferably 5 to 5% by weight, more preferably 0.05 to 1% by weight.

  In the agent for improving skin darkening according to the present invention, the ratio of tocopherol and / or its derivative to component (A) is determined based on the content range of each component, but per 100 parts by weight of component (A) The total amount of tocopherol and / or its derivative is 0.1 to 100000 parts by weight, preferably 0.2 to 50000 parts by weight, and more preferably 2.5 to 2000 parts by weight.

Higher Alcohols Solid at 25 ° C. The skin darkening agent of the present invention may contain higher alcohols solid at 25 ° C. By containing a higher alcohol which is solid at 25 ° C., when the darkening agent for skin of the present invention is prepared as an emulsion composition from a component forming an oil phase and a component forming an aqueous phase, It is possible to suppress the phase separation of the aqueous phase and to improve the formulation stability.

  The higher alcohol solid at 25 ° C. is not particularly limited as long as it is pharmaceutically acceptable, and includes, for example, 12 to 34 carbon atoms. As a higher alcohol solid at 25 ° C., specifically, lauryl alcohol, mythryl alcohol, cetanol, stearyl alcohol, cetostearyl alcohol, oleyl alcohol, linoleyl alcohol, behenyl alcohol, arachidyl alcohol, behenyl alcohol, lignoceryl alcohol, seryl Alcohol, montanyl alcohol, myristyl alcohol, gesil alcohol etc. are mentioned. These higher alcohols may be used alone or in combination of two or more.

  Among these higher alcohols, from the viewpoint of further improving the effect of suppressing the phase separation of the oil phase and the water phase, preferably a higher alcohol having 16 to 22 carbon atoms, more preferably lauryl alcohol and mystyl alcohol More preferably, cetanol, stearyl alcohol, stearyl alcohol, behenyl alcohol may be mentioned; and particularly preferably, cetanol and stearyl alcohol may, for example, be cetanol, stearyl alcohol, cetostearyl alcohol, behenyl alcohol.

  In the skin darkness improving agent of the present invention, the content of the higher alcohol solid at 25 ° C. is not particularly limited, but, for example, 0.3 to 20% by weight or more in total of the higher alcohol solid at 25 ° C. It can be mentioned. From the viewpoint of further effectively suppressing the phase separation of the oil phase and the water phase, the content of the higher alcohol solid at 25 ° C. in the skin darkening improver of the present invention is preferably 0.3 to 15% by weight More preferably, it is 0.5 to 10% by weight.

  In the skin darkness improving agent of the present invention, the ratio of the higher alcohol solid at 25 ° C. to the component (A) is determined according to the respective contents of the component (A) and the higher alcohol solid at 25 ° C. The total amount of higher alcohols solid at 25 ° C. is 3 to 200,000 parts by weight per 100 parts by weight of the total amount of the component (A). The total amount of higher alcohols solid at 25 ° C. is preferably 3 to 150000 parts by weight, per 100 parts by weight of the total amount of the component (A), from the viewpoint of more effectively suppressing the phase separation of the oil phase and the water phase More preferably, it is 25 to 20000 parts by weight.

Lanolin Alcohol The skin darkening agent of the present invention may contain lanolin alcohol. In particular, by containing lanolin alcohol together with the above-mentioned higher alcohol solid at 25 ° C., the composition for improving skin blackness of the present invention is prepared as an emulsion composition from the component forming the oil phase and the component forming the water phase. In such a case, it is possible to more effectively suppress the phase separation of the oil phase and the water phase, and it is possible to dramatically improve the stability of the preparation.

  Lanolin alcohol is an alcohol component obtained by saponifying and degrading sheep sebum (wool grease) or lanolin, and is also referred to as wool wax alcohol.

  Lanolin alcohol is rich in compounds having a steroid skeleton such as cholesterol, lanosterol, dihydrolanosterol, etc., and includes monohydric or dihydric alcohols having about 14 to 36 carbon atoms (normal alcohol, isoalol, and anteisoalcohol) It is done.

  Although it does not restrict | limit in particular about content of lanolin alcohol in the skin blackness improving agent of this invention, For example, 0.1-20 weight% is mentioned in the total amount of lanolin alcohol. The content of the lanolin alcohol in the agent for improving skin darkening of the present invention is preferably 0.1 to 15% by weight, more preferably 0 from the viewpoint of suppressing the phase separation of the oil phase and the water phase more effectively. And 3 to 10% by weight.

  In the agent for improving skin darkening according to the present invention, the ratio of lanolin alcohol to component (A) is determined according to each content of component (A) and lanolin alcohol, but for example, 100 parts by weight in total of component (A) The total amount of lanolin alcohol is 1 to 200,000 parts by weight. The total amount of lanolin alcohol is preferably 2 to 150,000 parts by weight, and more preferably 15 to 15 parts by weight per 100 parts by weight of the total amount of component (A) from the viewpoint of suppressing the phase separation of the oil phase and the water phase more effectively. There are 20000 parts by weight.

Nonpolar Oil The non-polar oil according to the present invention is a nonpolar oil as a component forming an oil phase when it is prepared as an emulsion composition from a component forming an oil phase and a component forming an aqueous phase. It may be included. In the prior art, when a nonpolar oil is contained in a composition containing the components (A) and (B), the formation of precipitates and precipitates tends to be remarkable, but with the skin darkening improver of the present invention Even if nonpolar oil is contained, the formation of precipitates and precipitates can be effectively suppressed.

  The nonpolar oil means an oil having an IOB (inorganic / organic balance) of 0 or more and less than 0.05, and specific examples include hydrocarbon oils extracted from mineral oils. Such hydrocarbon oils are not particularly limited as far as they are pharmaceutically acceptable, but, for example, liquid paraffin (liquid normal paraffin, liquid isoparaffin), α-olefin oligomers, vaseline, microcrystalline wax, gelation Examples thereof include hydrocarbons (such as plastibase), hydrogenated polyisobutene and the like. These nonpolar oils may be used alone or in combination of two or more.

  Among these nonpolar oils, preferred are liquid paraffin, α-olefin oligomers, petrolatum and microcrystalline wax, more preferred are liquid paraffin and petrolatum, and particularly preferred is liquid paraffin.

  In the skin darkening improver of the present invention, the content of the nonpolar oil may be appropriately set in consideration of the emulsion form of the skin darkening improver, feeling in use, etc. For example, darkening of the skin of the present invention is improved When the agent is prepared as an oil-in-water emulsion composition, the total amount of nonpolar oil is 1% by weight or more, preferably 1 to 30% by weight. In the prior art, when the nonpolar oil is contained in an amount of 5% by weight or more, particularly 8% by weight or more in the skin darkening improver containing the components (A) and (B), the precipitate or precipitate is Although the formation tends to be significantly promoted, the agent for improving skin darkening according to the present invention can suppress the formation of precipitates and precipitates even if the nonpolar oil is thus contained at a high content. ing. In view of such effects of the present invention, the content of the nonpolar oil in the skin darkening agent of the present invention is more preferably 5 to 30% by weight, particularly preferably 8 to 30% by weight. In addition, when preparing the darkening agent for skin of this invention as a water-in-oil type emulsion composition, nonpolar oil may be further contained by high content. In this case, the content of the nonpolar oil in the composition for external use on skin of the present invention is, for example, 40 to 95% by weight, preferably 50 to 90% by weight.

Polar oil The skin darkening agent of the present invention comprises a polar oil as an oil phase forming component when it is prepared as an emulsified composition from an oil phase forming component and an aqueous phase forming component. It may be In the skin darkness improving agent of the present invention, when the nonpolar oil is contained, the polar oil may not be contained, and the nonpolar oil and the polar oil may be used in combination.

  Polar oil means an oil having an IOB (inorganic / organic balance) in the range of 0.05 to 1.1. The polar oil is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include animal oil, mineral oil, fatty acid alkyl ester, fatty acid and the like.

  Specific examples of vegetable oils include olive oil, wheat germ oil, rice bran oil, safflower oil, soybean oil, camellia oil, camel oil, corn oil, rapeseed oil, sesame oil, castor oil, sunflower oil, sunflower oil, cottonseed oil, peanut oil, jojoba oil, hydrogenated oil And avocado oil, fennel oil, clove oil, pepper oil, eucalyptus oil, lemon oil, lemon oil, orange oil, carnauba wax, candelilla wax, rice bran wax, tree wax and the like. These vegetable oils may be used alone or in combination of two or more.

  Specific examples of animal oils include lard, fish oil, beeswax and the like. These animal oils may be used alone or in combination of two or more.

  Examples of fatty acid alkyl esters include esters of fatty acids having 4 to 30 carbon atoms and alcohols having 1 to 34 carbon atoms. Specifically, glyceryl triisopalmitate, glyceryl tri-2-ethylhexanoate, glyceryl triisooctoate, octyldodecyl myristate, diisostearyl malate, neopentyl glycol dioctoate, dipentaerythritol fatty acid ester, hydroxystearin Cholesteryl adipate, isobutyl adipate, diethyl sebacate, isopropyl sebacate, isopropyl sebacate, diisopropyl ethyl selenate, cetyl ethylhexanoate, isopropyl myristate, myristyl myristate, isopropyl palmitate, cetyl palmitate, ethyl oleate, batyl stearate Hexyldecyl isostearate, isopropyl linoleate, glyceryl tri (caprylic caprate), cetyl octanoate, stear Butyl hexyl laurate, decyl oleate, hexyl dimethyl octanoate, 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, glycerin di 2-heptylundecanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, tetra 2-ethyl ester Hexanoic acid pentaerythritol, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, Diethyl phthalatedicarboxylate, benzoic acid (C12-C15) alkyl, cetearyl isononanoate, tri (caprylic acid / capric acid) glycerin, (dicaprylic acid / capric acid) butylene glycol, trimyristate glycerin, tri 2-Heptylundecanoic acid glyceride, castor oil fatty acid methyl ester, oleyl oleate, cetostearyl alcohol, acetoglyceride, 2-heptylundecyl palmitate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, adipic acid di-2 -Heptylundecyl, ethyl laurate, di 2-ethylhexyl sebacate, 2- hexyl decyl myristate, 2- hexyl decyl palmitate, 2- hexyl decyl adipate, di 2- ethyl hexyl succinate And the like. These fatty acid alkyl esters may be used alone or in combination of two or more.

  Examples of the fatty acid include fatty acids having 4 to 30 carbon atoms, and specific examples include lauric acid, myristic acid, palmitic acid, sebacic acid, oleic acid, linoleic acid and the like. These fatty acids may be used alone or in combination of two or more.

  Among these polar oils, fatty acid alkyl esters are preferably mentioned.

  These polar oils may be used alone or in combination of two or more.

  In the skin darkness improving agent of the present invention, the content of the polar oil may be appropriately set in consideration of the emulsion form of the skin darkness improving agent, the feeling of use, etc., but, for example, 0.5 to 20% by weight Preferably, it is 1 to 20% by weight, more preferably 3 to 15% by weight.

Polyoxyethylene Cured Castor Oil The skin blackness improver of the present invention may contain polyoxyethylene hardened castor oil. By containing polyoxyethylene hydrogenated castor oil, it is possible to further improve the effect of suppressing the formation of precipitates and precipitates.

  The polyoxyethylene hydrogenated castor oil used in the present invention is not particularly limited. For example, polyoxyethylene (5) hydrogenated castor oil, polyoxyethylene (10) hydrogenated castor oil, polyoxyethylene (20) hydrogenated castor Oil, polyoxyethylene (30) hydrogenated castor oil, polyoxyethylene (40) hydrogenated castor oil, polyoxyethylene (50) hydrogenated castor oil, polyoxyethylene (60) hydrogenated castor oil, polyoxyethylene (80) hydrogenated castor Oil, polyoxyethylene (100) hydrogenated castor oil, etc. may be mentioned. These polyoxyethylene hydrogenated castor oils may be used alone or in combination of two or more.

  Among these polyoxyethylene hydrogenated castor oils, polyoxyethylene (20) hydrogenated castor oil, polyoxyethylene (30) hydrogenated castor is preferable from the viewpoint of more effectively suppressing the formation of precipitates and precipitates. Oil, polyoxyethylene (40) hydrogenated castor oil, polyoxyethylene (50) hydrogenated castor oil, polyoxyethylene (60) hydrogenated castor oil, polyoxyethylene (80) hydrogenated castor oil, polyoxyethylene (100) hydrogenated castor More preferably, polyoxyethylene (50) hydrogenated castor oil is mentioned.

  Although it does not restrict | limit in particular about content of polyoxyethylene hydrogenated castor oil in the skin blackness improving agent of this invention, For example, 0.1-10 weight% is mentioned in the total amount of polyoxyethylene hydrogenated castor oil. From the viewpoint of further effectively suppressing the formation of precipitates and precipitates, the content of polyoxyethylene hydrogenated castor oil in the skin darkening agent of the present invention is preferably 0.1 to 8% by weight, more preferably Is 0.2 to 5% by weight.

  In the agent for improving skin darkening according to the present invention, the ratio of polyoxyethylene hydrogenated castor oil to component (A) is determined according to the content of component (A) and polyoxyethylene hydrogenated castor oil, for example, The total amount of polyoxyethylene hydrogenated castor oil is 1 to 100,000 parts by weight per 100 parts by weight of the total amount of the component A). From the viewpoint of further effectively suppressing the formation of precipitates and precipitates, the total amount of polyoxyethylene hydrogenated castor oil is preferably 2 to 80000 parts by weight, and more preferably 100 parts by weight of the total amount of component (A). 10 to 10000 parts by weight can be mentioned.

Surfactant (other than polyoxyethylene hydrogenated castor oil)
The darkening agent for skin of the present invention, when prepared as an emulsion composition from a component forming an oil phase and a component forming an aqueous phase, in order to stably form an emulsified state, the polyoxyethylene curing Surfactants other than castor oil may be included. The surfactant (other than polyoxyethylene hydrogenated castor oil) is not particularly limited as long as it is pharmaceutically acceptable, and is a nonionic surfactant (other than polyoxyethylene hydrogenated castor oil), an anionic surfactant Any of cationic surfactants and amphoteric surfactants may be used.

  Specific examples of nonionic surfactants (other than polyoxyethylene hydrogenated castor oil) include polyoxyethylene (10 to 50 moles) phytosterol ether, polyoxyethylene (10 to 50 moles) dihydrocholesterol ether, and polyoxyethylene (10 to 50 mol) 2-octyldodecyl ether, polyoxyethylene (10 to 50 mol) decyl tetradecyl ether, polyoxyethylene (10 to 50 mol) oleyl ether, polyoxyethylene (2 to 50 mol) cetyl ether, Polyoxyethylene (5 to 50 mol) behenyl ether, polyoxyethylene (5 to 30 mol) polyoxypropylene (5 to 30 mol) 2-decyl tetradecyl ether, polyoxyethylene (10 to 50 mol) polyoxypropylene ( 2 to 30 mo ) Polyoxyethylene alkyl ethers such as cetyl ether, phosphoric acid / phosphates thereof (polyoxyethylene cetyl ether sodium phosphate etc.), polyoxyethylene (20 to 60 mol) sorbitan monooleate, polyoxyethylene (10 to 10 mol) 60 mol) sorbitan monoisostearate, polyoxyethylene (10 to 80 mol) glyceryl monoisostearate, polyoxyethylene (10 to 30 mol) glyceryl monostearate, polyoxyethylene (20 to 100 mol) · polyoxy Propylene-modified silicone, polyoxyethylene / alkyl-modified silicone, polyethylene glycol monolaurate, polyethylene glycol monopalmitate, polyethylene glycol monostearate, polyethylene glycol dilaurate , Polyethylene glycol dipalmitate, polyethylene glycol distearate, polyethylene glycol dioleate, polyethylene glycol diricinoleate, polyoxyethylene hydrogenated castor oil (5 to 100), polysorbate (20 to 85), glycerin fatty acid ester (monostearin Acid glycerin etc. etc. are mentioned. One of these nonionic surfactants (other than polyoxyethylene hydrogenated castor oil) may be used alone, or two or more thereof may be used in combination.

  Specific examples of the anionic surfactant include sodium polyoxyethylene lauryl ether sulfate, sodium lauryl sulfate, sodium myristyl sulfate, sodium N-lauroyl sarcosinate, sodium N-myristryl sarcosinate, sodium dodecyl benzene sulfonate, Hydrogenated coconut fatty acid monoglyceride sodium monosulfate, sodium lauryl sulfoacetate, sodium α-olefin sulfonate, sodium N-palmitoyl glutarate, sodium N-methyl-N-acyl taurine and the like can be mentioned. These anionic surfactants may be used alone or in combination of two or more.

  Specific examples of the cationic surfactant include lauryl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, benzethonium chloride, benzalkonium chloride, stearyl dimethyl benzyl ammonium chloride and the like. One of these cationic surfactants may be used alone, or two or more thereof may be used in combination.

  Specifically as an amphoteric surfactant, coconut oil fatty acid amidopropyl betaine, lauryl dimethylamino acetic acid betaine, lauryl dimethyl amine oxide, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolium betaine, N-lauryl Examples include diaminoethyl glycine, N-myristyl diaminoethyl glycine, N-alkyl-1-hydroxyethyl imidazoline betaine sodium and the like. These amphoteric surfactants may be used alone or in combination of two or more.

  Among these surfactants, preferred are nonionic surfactants (other than polyoxyethylene hydrogenated castor oil) from the viewpoint of stably maintaining the emulsified state.

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

  The content of the surfactant (other than polyoxyethylene hydrogenated castor oil) in the skin darkness improving agent of the present invention may be appropriately set according to the type of surfactant, the form of emulsification, etc. There may be 5 to 10% by weight, preferably 1 to 9% by weight, and more preferably 2 to 8% by weight.

Darkening improving agent of the skin of the water present invention may contain water as a substrate for forming an aqueous phase.

  In the skin darkening improver of the present invention, the water content may be appropriately set based on the properties (eg, emulsified state) of the skin darkening improver, the feeling of use, etc., but it is, for example, 10 to 90% by weight Preferably it is 20-85 weight%, More preferably, 30-85 weight% is mentioned.

Polyhydric Alcohol In addition to the components described above, the agent for improving darkening of the skin of the present invention may optionally contain polyhydric alcohol in order to provide moisturizing properties and the like.

  The polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol and the like. These polyhydric alcohols may be used alone or in combination of two or more.

  In the skin darkness improving agent of the present invention, the content of polyhydric alcohol is not particularly limited, but, for example, 0.5 to 30% by weight, preferably 0.5 to 25% by weight, more preferably 1 to 20% % Is listed.

Thickener In addition to the components described above, the agent for improving darkening of the skin of the present invention may optionally contain a thickener in order to provide desired viscosity and the like.

  The thickener is not particularly limited as long as it is pharmaceutically acceptable, but, for example, xanthan gum, guar gum, locust bean gum, carrageenan, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylcellulose, hydroxypropyl Cellulose, hydroxypropyl methylcellulose, sodium alginate, alginic acid propylene glycol ester, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, acrylic acid methacrylic acid alkyl methacrylate copolymer, sodium polyacrylate bentonite, dextrin fatty acid ester, pectin, etc. It can be mentioned. Among these thickeners, preferred are xanthan gum and carboxyvinyl polymers. These thickeners can be used alone or in combination of two or more.

  In the agent for improving skin darkening according to the present invention, the content of the thickener may be appropriately set according to the viscosity to be applied, but it is, for example, 0.01 to 5% by weight, preferably 0.1 to 4 % By weight, more preferably 0.1 to 3% by weight can be mentioned.

Other Components In addition to the above-described components, the agent for improving skin darkness of the present invention may further contain other additives that are usually used for external skin preparations and the like, as necessary. Such additives include, for example, pH adjusters (for example, inorganic bases such as sodium hydroxide and potassium hydroxide, and basic substances such as organic amines such as triethanolamine and diisopropanolamine); Acids, organic acids such as tartaric acid and lactic acid, and acidic substances such as inorganic acids such as phosphoric acid, sulfuric acid, nitric acid and hydrochloric acid), buffers, solubilizers, chelating agents (eg, edetic acid and edetic acid salts) ), Preservatives (eg, parahydroxybenzoic acid esters such as methylparaben, ethylparaben, propylparaben, butylparaben, etc .; benzoic acid and benzoates; and sorbic acid and sorbate etc.), preservatives, antioxidants, stabilizers Agents, perfumes, coloring agents, etc.

  Furthermore, the agent for improving skin darkening of the present invention may contain a pharmaceutically active ingredient other than the above-mentioned ingredient, as necessary. Such agents include, for example, steroids (dexamethasone, dexamethasone hydrochloride, dexamethasone acetate, hydrocortisone hydrochloride, prednisolone valerate, prednisolone acetate etc), antihistamines (eg chlorpheniramine maleate), local anesthetics (lidocaine, dibucaine, Procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, proparacaine, meprilcaine or salts thereof, benzoic acid alkyl ester (eg, ethyl aminobenzoate, diethylaminoethyl p-butylaminobenzoate hydrochloride), orthokine, oxesazein, oxypolyentoxydecane, Rohto extract, Perkamine Pase, Tesitdectin etc., Anti-inflammatory agent (Allantoin, salicylic acid, glycol salicylate, methyl salicylate Indomethacin, felbinac, diclofenac sodium, loxoprofen sodium etc., bactericidal agents (benzalkonium chloride, decarinium chloride, benzethonium chloride, cetyl pyridinium chloride, isopropylmethylphenol, chlorhexidine hydrochloride, chlorhexidine gluconate, ammonia water, sulfadiazine, lactic acid, phenol etc. ), Antipruritic agents (crotamiton, thiantol, etc.), skin protective agents (collodion, castor oil, etc.), blood circulation promoting components (nonyl acid crocodylanilide, nicotinic acid benzyl ester, capsaicin, pepper extract, etc.), vitamins (vitamins A, B, D and the like), mucopolysaccharides (sodium chondroitin sulfate, hyaluronic acid and the like) and the like.

Properties / Formulation Forms, etc. Properties of the darkening improver of the present invention are not particularly limited, and examples thereof include aqueous liquid compositions, aqueous gel compositions, oily gel compositions, emulsion compositions and the like. Among them, from the viewpoint of formulation stability, preferably, an aqueous gel composition, an oily gel composition, and an emulsion composition are mentioned, and more preferably an emulsion composition is mentioned. The emulsified state of the emulsified composition may be either oil-in-water type or water-in-oil type, but from the viewpoint of feeling in use such as stickiness suppression, oil-in-water type is preferable.

  The formulation form of the darkening improving agent of the present invention is not particularly limited, and examples thereof include lotions, emulsions, ointments, creams and the like. Among these, from the viewpoint of formulation stability, preferably, emulsions and creams are mentioned.

  Specific examples of the darkening improving agent of the present invention include external medicines and cosmetics. Among these formulation forms, preferably an external preparation is mentioned.

Method of Use The skin darkening agent of the present invention is used by applying to the skin to improve the lightness of the skin. The portion of the skin to be applied is not particularly limited as long as the user is aware of the darkening. Specifically, the portion of the skin to be applied includes a portion which is irritated and inflamed by the skin, and more specifically, a portion subjected to a hair removal treatment and a repeated friction stimulation A part is mentioned, More preferably, the part which performed the hair removal treatment is mentioned.

  Hair removal methods include hair removal (treatment by removing body hair, including physically removing body hair, and treatment that damages or destroys the hair papilla by light irradiation), shaving (body hair is shaved) Treatment by treatment) and hair removal (treatment by dissolving body hair). In particular, since it is necessary to continue to treat the hair that continues to be regenerated, it is necessary for the treatment that does not destroy the dermal papilla to continue processing the hair, so the skin is likely to darken due to repeated stimulation. is there. It does not specifically limit as a part which performed the body hair removal process, An upper limb part, a leg part, an axillary part, a chest, an abdomen, a back, a waist, a lower abdomen, a face part etc. are mentioned.

  The portion subjected to repeated friction stimulation includes, but is not limited to, a portion causing friction by the wearing article without particular limitation, for example, a portion such as the groin portion or waist portion tightened by underwear or the like, other portions by clothing etc. There are sites such as joints that are easy to do.

  At the skin site to which the darkening agent of the present invention is applied, darkening of the skin is improved. For example, the rate of increase in skin lightness defined by the L value can be synergistically improved.

Production Method The darkening agent of the present invention can be produced according to a known method for producing a composition. As a manufacturing method in case the darkness improving agent of this invention is an emulsion composition, the method shown below is mentioned, for example. First, the composition for the oil phase is prepared by mixing the component (A), the component (B), the component (C), the nonpolar oil and / or the polar oil, and other lipophilic components added as needed. Do. Separately, water and other water-soluble components added as needed are mixed to prepare a composition for aqueous phase. When containing polyoxyethylene hydrogenated castor oil and / or a surfactant (other than polyoxyethylene hydrogenated castor oil), these may be either one or both of an oil phase composition or a water phase composition. It is preferable to add to the composition for oil phase although it may be added and mixed. Next, the obtained composition for oil phase and the composition for aqueous phase are mixed and emulsified by an emulsification method such as a homogenizer to produce the darkening agent of the present invention.

  EXAMPLES The present invention will be more specifically described below by way of Examples, but the present invention is not limited thereto.

Test Example An emulsified darkening improver having the composition shown in Table 1 was produced, and the effect of improving darkening was evaluated. The method for producing the emulsified darkening improver and the test method are as follows.

[Method for producing emulsified darkening agent]
First, among the components shown in the oil phase starting material in Table 1, components other than the component (A) (glycyrrhetinic acid or dipotassium glycyrrhizinate) were weighed out in a predetermined amount, heated to 80 ° C. and mixed. Thereafter, a predetermined amount of the component (A) was added and mixed to prepare an oil phase composition. Separately, predetermined amounts of the components shown in the aqueous phase raw material in Table 1 were measured and mixed to prepare an aqueous phase composition. After the composition for aqueous phase was heated to 80 ° C., the composition for oil phase at 80 ° C. was added little by little and emulsification was carried out while mixing. Then, it cooled to 30 degreeC and obtained the emulsion-like darkness improvement agent (cream preparation).

[Test method]
(The degree of darkening improvement)
The subject was asked to repeat shaving once in a week with the razor (both front and back knees and both knees) and to apply the darkening improving agent to the shaving once a day. Four weeks later, the shaved area was photographed with a microscope (manufactured by SCARA CORPORATION), and the lightness (L value) of the skin was calculated from the obtained image using image analysis software (ImageJ). The rate of change in lightness (L value) after 4 weeks when lightness (L value) before the start of the test was 100% was calculated as the darkening improvement rate by the following equation.
Darkening improvement rate (%) = lightness L after 4 weeks / lightness L × 100% before test start

(Use feeling evaluation)
Six subjects were asked to perform shaving with a razor (both front and back knees and both knees) and application of each darkening improving agent to the shaved part. The feeling of use of the darkening improver was evaluated according to the following criteria.
<Criteria for judging the feeling of use>
:: 5 to 6 people who feel good without feeling of stickiness △: 3 or 4 people who feel good of use without feeling of stickiness 3 × 4: feels good of use without feeling of stickiness 0 to 2 people

[Test results]
The obtained results are shown in Table 1. By repeating the shaving, as shown in Comparative Example 5, the degree of darkening improvement is less than 100% and the darkening is deteriorated. According to the darkening improver (comparative examples 1 to 4) containing glycyrrhetinic acid, ufenamate and diphenhydramine, respectively, the degree of darkening improvement is less than 100% (darkening aggravated) or slightly over 100% There was no effective darkening suppression effect.

  On the other hand, according to the darkening improver (Examples 1 to 3) containing glycyrrhetinic acid, ufenamate and diphenhydramine, an effective darkening inhibitory effect was recognized. The darkening inhibitory effect observed in these examples is intended to improve not only the darkening due to repeated shaving but also the darkening that has already occurred, and using glycyrrhetinic acids, ufenamate and diphenhydramine alone respectively. It was recognized as a synergy effect that surpassed the simple sum, not the simple sum of the degree of darkening improvement in the case.

  In addition, the darkening improver of Example 1 and Example 2 is an oil-in-water emulsion composition, and a feeling in use better than that of the water-in-oil emulsion composition of Example 3 was obtained.

  In addition, when the external appearance immediately after preparation was observed visually about the composition for oil phases prepared in the manufacturing process of each darkening agent, the liquid is clear and the precipitation is suppressed in Examples 1-3. It had been. Moreover, after each darkening improving agent was stored at room temperature for 1 day, the formation of precipitates was observed with a polarizing microscope. As a result, the darkening improving agents in Examples 1 to 3 were suppressed in precipitates. Furthermore, when the appearance was observed after storing each darkening improving agent at 40 ° C. for 3 months and at 50 ° C. for 1 month, the darkening improving agent of Examples 1 to 3 had an oil phase and an aqueous phase under any storage conditions. Phase separation was suppressed. Thus, the darkening improving agents of Examples 1 to 3 were also excellent in formulation stability.

Claims (4)

  (A) at least one selected from the group consisting of glycyrrhetinic acid, glycyrrhizinic acid, and derivatives thereof, and salts thereof, (B) Ufenamate, and (C) diphenhydramine and / or a salt thereof Darkening agent.   The skin darkening improver according to claim 1, which is substantially free of a whitening component.   The darkening agent for skin according to claim 1 or 2, which is an oil-in-water emulsion composition.   The darkening agent for skin according to any one of claims 1 to 3, which is applied to the skin after removal treatment of body hair.