WO2023112664A1 - Pharmaceutical composition for external application which contains benzoyl peroxide - Google Patents

Abstract

A pharmaceutical composition for external application which comprises (A) benzoyl peroxide and (B) at least one component selected from (B1) glycyrrhetinic acid and derivatives and salts thereof and (B2) allantoin does not undergo the decrease in viscosity over time and can be applied and spread smoothly on the skin.

Description

Topical composition containing benzoyl peroxide

The present invention relates to a practical external pharmaceutical composition containing benzoyl peroxide.

Acne is caused by sebum that is excessively secreted due to a change in hormonal balance or the like, and accumulates in hair follicles to swell on the surface of the skin. When bacteria such as P. acnes and Staphylococcus proliferate in the hair follicle, it becomes inflamed and becomes red and swollen. In addition, dyskeratosis may occur. Acne lowers the patient's OQL and may leave scars if left untreated, so early treatment is necessary.
Initially, antibacterial agents were the mainstream of acne therapeutic agents, but due to the problem of drug resistance, adapalene and benzoyl peroxide are now widely used as components of topical preparations. Benzoyl peroxide has an antibacterial action that makes it difficult for drug resistance to develop, and an action to improve keratin deposition.

Here, for external pharmaceutical preparations, it is required that the expected amount of drug is accurately contained in the applied formulation. Therefore, it is necessary not only that the drug in the formulation does not decompose, but also that the application amount does not change. Since the external preparation is adjusted to have a viscosity that is easy to spread, if the viscosity changes over time, the applied amount and the amount of the drug released from the formulation are likely to change, and the amount of the drug to be administered is likely to change. Since the viscosity of external preparations tends to decrease due to decomposition of components or reactions with other components, it is required that the viscosity does not decrease over time.

In addition, since topical pharmaceutical preparations are required to contain the expected amount of drug accurately in the applied preparation, it is necessary not only to have viscosity but also to be able to spread smoothly on the skin. This is because if the smoothness is lacking, an unapplied portion may occur, or an unnecessarily large amount of the preparation may be applied to the skin due to difficulty in spreading. Moreover, lack of smoothness becomes a psychological hurdle to continuous use, and compliance or adherence tends to decrease. Since the purpose of topical pharmaceutical preparations is to treat a target disease, the feeling of use such as smoothness tends to be neglected compared to topical cosmetics, but it is an important characteristic.

An object of the present invention is to provide a topical pharmaceutical composition containing benzoyl peroxide, which suppresses a decrease in viscosity over time and can be smoothly spread on the skin.

The present inventor has made extensive research to solve the above problems, and has obtained the following knowledge.
(1) When benzoyl peroxide is added to the base of the composition for external use, the viscosity decreases over time.
(2) In addition to benzoyl peroxide, by blending glycyrrhetinic acid, derivatives thereof, and/or salts thereof (hereinafter sometimes referred to as "glycyrrhetinic acids"), or allantoin, by blending benzoyl peroxide The decrease in viscosity is reduced, and by blending both glycyrrhetinic acids and allantoin, the decrease in viscosity caused by blending benzoyl peroxide is remarkably reduced.
(3) By blending glycyrrhetinic acids or allantoin in addition to benzoyl peroxide to the composition for external use, friction when spreading on the skin is reduced. Friction when spreading on the skin is remarkably reduced.

The present invention has been completed based on the above findings, and provides the following [1] to [6].
[1] A medicament containing at least one component selected from the group consisting of (A) benzoyl peroxide and (B) (B1) glycyrrhetinic acid, its derivatives and/or salts thereof, and (B2) allantoin External composition.
[2] The composition according to [1], wherein the content of component (B) is 0.015 to 0.6 parts by mass per 1 part by mass of component (A).
[3] The composition according to any one of [1] or [2], which contains component (B1) and component (B2).
[4] The composition according to any one of [1] to [3], wherein component (B1) is at least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, and salts thereof.
[5] The composition according to any one of [1] to [4], which contains water in an amount of 25% by mass or more relative to the total amount of the composition.
[6] At least one selected from the group consisting of (B) (B1) glycyrrhetinic acid, derivatives thereof, and/or salts thereof, and (B2) allantoin, in (A) a topical pharmaceutical composition containing benzoyl peroxide A method for suppressing a decrease in viscosity over time of an external pharmaceutical composition, comprising containing a seed component.

As described above, the present inventors found that when benzoyl peroxide is added to the base of the composition for external use, the viscosity decreases over time. In addition, by containing a component selected from glycyrrhetinic acids and allantoin, the decrease in viscosity due to the addition of benzoyl peroxide is suppressed.
A decrease in viscosity affects the amount of drug released from the formulation, so it should be avoided in order to ensure the quality of the drug. Since the external pharmaceutical composition of the present invention has a reduced decrease in viscosity over time, it can be applied in a predetermined amount without particular consideration.

Further, the external pharmaceutical composition of the present invention contains a component selected from glycyrrhetinic acids and allantoin in addition to benzoyl peroxide, so that it can be spread smoothly when applied to the skin. there is If it cannot be applied smoothly, it cannot be used comfortably. Since the purpose of topical pharmaceutical preparations is to treat a target disease, QOL deterioration such as discomfort during or after use tends to be neglected compared to topical cosmetic preparations and the like. However, if the feeling of use of the external pharmaceutical preparation is bad, it becomes a psychological hurdle to continuous use, and compliance or adherence decreases. Since the topical pharmaceutical composition of the present invention can be spread smoothly with little friction between the skin when applied, it has a good feeling in use and can avoid a decrease in compliance or adherence.

Therefore, the topical pharmaceutical composition of the present invention has the effects of being able to suppress the decrease in viscosity over time due to the addition of benzoyl peroxide, and also being easy to spread and having a good feel during use.

The present invention will be described in detail below.
The external pharmaceutical composition of the present invention contains at least one component selected from (A) benzoyl peroxide, (B) (B1) glycyrrhetinic acid, derivatives thereof, and/or salts thereof, and (B2) allantoin. The composition containing

(A) Benzoyl peroxide The content of benzoyl peroxide is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, and even more preferably 1% by mass or more, relative to the total amount of the composition. It can also be 2% by mass or more. Further, it is preferably 10% by mass or less, more preferably 7% by mass or less, more preferably 5% by mass or less, more preferably 3.5% by mass or less, more preferably 3% by mass or less, and 2.6% by mass or less. more preferred. Within this range, a sufficient therapeutic effect for acne can be obtained. In addition, the decrease in viscosity over time can be suppressed, and smooth application can be achieved.
The content of benzoyl peroxide relative to the total amount of the composition is 0.05-10% by mass, 0.05-7% by mass, 0.05-5% by mass, 0.05-3.5% by mass, 0.05-3.5% by mass, and 0.05-3.5% by mass. 05 to 3% by mass, 0.05 to 2.6% by mass, 0.1 to 10% by mass, 0.1 to 7% by mass, 0.1 to 5% by mass, 0.1 to 3.5% by mass, 0.1 to 3% by mass, 0.1 to 2.6% by mass, 1 to 10% by mass, 1 to 7% by mass, 1 to 5% by mass, 1 to 3.5% by mass, 1 to 3% by mass, 1 to 2.6% by mass, 2 to 10% by mass, 2 to 7% by mass, 2 to 5% by mass, 2 to 3.5% by mass, 2 to 3% by mass, and 2 to 2.6% by mass. .

The total concentration of at least one component selected from component (B) glycyrrhetinic acids and allantoin is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, and 0.1% by mass or more, based on the total amount of the composition. 5% by mass or more is more preferable. Also, it is preferably 1.5% by mass or less, more preferably 1% by mass or less, and even more preferably 0.7% by mass or less. Within this range, a sufficient anti-inflammatory action can be obtained, a decrease in viscosity over time can be suppressed, and smooth application can be achieved.
The total concentration of at least one component selected from glycyrrhetinic acids and allantoin relative to the total amount of the composition is 0.05 to 1.5% by mass, 0.05 to 1% by mass, and 0.05 to 0.7% by mass. , 0.1 to 1.5% by mass, 0.1 to 1% by mass, 0.1 to 0.7% by mass, 0.5 to 1.5% by mass, 0.5 to 1% by mass, 0.5 ~0.7% by mass.

In addition, the total content of at least one component selected from glycyrrhetinic acids and allantoin is preferably 0.005 parts by mass or more, and preferably 0.01 parts by mass or more, relative to 1 part by mass of the content of benzoyl peroxide. It is more preferably 0.015 parts by mass or more, even more preferably 0.03 parts by mass or more, and particularly preferably 0.15 parts by mass or more. Also, it is preferably 0.8 parts by mass or less, more preferably 0.6 parts by mass or less, still more preferably 0.4 parts by mass or less, and particularly preferably 0.3 parts by mass or less. Within this range, a sufficient anti-inflammatory action can be obtained, a decrease in viscosity over time can be suppressed, and smooth application can be achieved.
The ratio of the total content of at least one component selected from glycyrrhetinic acids and allantoin to 1 part by mass of the content of benzoyl peroxide is 0.005 to 0.8 parts by mass, 0.005 to 0.6 parts by mass. parts, 0.005 to 0.4 parts by mass, 0.005 to 0.3 parts by mass, 0.01 to 0.8 parts by mass, 0.01 to 0.6 parts by mass, 0.01 to 0.4 parts by mass parts, 0.01 to 0.3 parts by mass, 0.015 to 0.8 parts by mass, 0.015 to 0.6 parts by mass, 0.015 to 0.4 parts by mass, 0.015 to 0.3 parts by mass parts, 0.03 to 0.8 parts by mass, 0.03 to 0.6 parts by mass, 0.03 to 0.4 parts by mass, 0.03 to 0.3 parts by mass, 0.15 to 0.8 parts by mass parts, 0.15 to 0.6 parts by mass, 0.15 to 0.4 parts by mass, and 0.15 to 0.3 parts by mass.

(B1) Glycyrrhetinic Acid Derivatives Salts Derivatives of glycyrrhetinic acid include pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, monoglucuronide glycyrrhetinate and the like. Glycyrrhetinic acid, which is a glycoside of glycyrrhetinic acid, and glycyrrhizic acid esters such as methyl glycyrrhizinate and stearyl glycyrrhizinate are also examples of derivatives of glycyrrhetinic acid. Glycyrrhizin can also be formulated in the form of licorice or licorice extract.

Salts of glycyrrhetinic acid or glycyrrhetinic acid derivatives may be pharmaceutically acceptable salts, such as ammonium salts, alkali metal salts (sodium salts, potassium salts, etc.), alkaline earth metal salts (calcium salts, magnesium salts, etc.). , metal salts (aluminum salts, etc.), salts with inorganic bases such as ammonium salts; organic amine salts (methylamine salts, triethylamine salts, triethanolamine salts, arginine salts, glycine salts, etc.). Examples include salt.
Salts of glycyrrhetic acid or glycyrrhetic acid derivatives are preferably ammonium salts and alkali metal salts, more preferably ammonium salts, potassium salts and sodium salts, and particularly preferably monoammonium salts, dipotassium salts and trisodium salts.

Among the glycyrrhetinic acids, glycyrrhetinic acid, stearyl glycyrrhetinate, glycyrrhizic acid, and salts thereof are preferred, and glycyrrhizic acid and glycyrrhizinate are more preferred. Preferred glycyrrhizinates are monoammonium glycyrrhizinate, dipotassium glycyrrhizinate, and trisodium glycyrrhizinate.
Glycyrrhetinic acids can be used alone or in combination of two or more.

When the topical pharmaceutical composition of the present invention contains glycyrrhetinic acids, the concentration of glycyrrhetinic acids is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, more preferably 0.2% by mass, relative to the total amount of the composition. % by mass or more is more preferable. Moreover, 1 mass % or less is preferable, 0.75 mass % or less is preferable, and 0.5 mass % or less is more preferable. Within this range, a sufficient anti-inflammatory action can be obtained, a decrease in viscosity over time can be suppressed, and smooth application can be achieved.
The concentration of glycyrrhetinic acids relative to the total amount of the composition is 0.05 to 1% by mass, 0.05 to 0.75% by mass, 0.05 to 0.5% by mass, 0.1 to 1% by mass, 0.05% to 0.75% by mass, 0.05% to 0.5% by mass, 0.1% to 1% by mass. 1 to 0.75% by mass, 0.1 to 0.5% by mass, 0.2 to 1% by mass, 0.2 to 0.75% by mass, and 0.2 to 0.5% by mass.

In addition, when the external pharmaceutical composition of the present invention contains glycyrrhetinic acids, the content of glycyrrhetinic acids is preferably 0.005 parts by mass or more, and preferably 0.01 part by mass, with respect to 1 part by mass of the content of benzoyl peroxide. Part or more is more preferable, 0.02 mass part or more is still more preferable, 0.04 mass part or more is even more preferable, and 0.08 mass part or more is particularly preferable. Also, it is preferably 0.8 parts by mass or less, more preferably 0.4 parts by mass or less, still more preferably 0.32 parts by mass or less, and particularly preferably 0.2 parts by mass or less. Within this range, a sufficient anti-inflammatory action can be obtained, a decrease in viscosity over time can be suppressed, and smooth application can be achieved.
The ratio of the glycyrrhetic acid content to 1 part by mass of the benzoyl peroxide content is 0.005 to 0.8 parts by mass, 0.005 to 0.4 parts by mass, and 0.005 to 0.32 parts by mass. , 0.005 to 0.2 parts by weight, 0.01 to 0.8 parts by weight, 0.01 to 0.4 parts by weight, 0.01 to 0.32 parts by weight, 0.01 to 0.2 parts by weight , 0.02 to 0.8 parts by weight, 0.02 to 0.4 parts by weight, 0.02 to 0.32 parts by weight, 0.02 to 0.2 parts by weight, 0.04 to 0.8 parts by weight , 0.04 to 0.4 parts by weight, 0.04 to 0.32 parts by weight, 0.04 to 0.2 parts by weight, 0.08 to 0.8 parts by weight, 0.08 to 0.4 parts by weight , 0.08 to 0.32 parts by mass, and 0.08 to 0.2 parts by mass.

(B2) Allantoin When the external pharmaceutical composition of the present invention contains allantoin, the concentration of allantoin is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, relative to the total amount of the composition. Also, it is preferably 5% by mass or less, more preferably 2% by mass or less, more preferably 1% by mass or less, more preferably 0.5% by mass or less, and more preferably 0.2% by mass or less. Within this range, a sufficient anti-inflammatory action can be obtained, a decrease in viscosity over time can be suppressed, and smooth application can be achieved.
The concentration of allantoin with respect to the total amount of the composition is 0.05 to 5% by mass, 0.05 to 2% by mass, 0.05 to 1% by mass, 0.05 to 0.5% by mass, 0.05 to 0.05% by mass. .2% by mass, 0.1 to 5% by mass, 0.1 to 2% by mass, 0.1 to 1% by mass, 0.1 to 0.5% by mass, and 0.1 to 0.2% by mass. be done.

In addition, when the external pharmaceutical composition of the present invention contains allantoin, the content of allantoin is preferably 0.005 parts by mass or more, more preferably 0.01 parts by mass or more with respect to 1 part by mass of the content of benzoyl peroxide. is more preferable, 0.02 parts by mass or more is preferable, and 0.03 parts by mass or more is more preferable. Moreover, 0.8 mass part or less is preferable, 0.4 mass part or less is more preferable, 0.2 mass part or less is preferable, and 0.08 mass part or less is more preferable. Within this range, a sufficient anti-inflammatory action can be obtained, a decrease in viscosity over time can be suppressed, and smooth application can be achieved.
The ratio of the allantoin content to 1 part by mass of the benzoyl peroxide content is 0.005 to 0.8 parts by mass, 0.005 to 0.4 parts by mass, 0.005 to 0.2 parts by mass, 0.01 to 0.8 parts by mass, 0.01 to 0.4 parts by mass, 0.01 to 0.2 parts by mass, 0.02 to 0.8 parts by mass, 0.02 to 0.4 parts by mass, 0.02 to 0.2 parts by mass, 0.03 to 0.8 parts by mass, 0.03 to 0.4 parts by mass, and 0.03 to 0.2 parts by mass.

Preferred combinations when both component (B1) and component (B2) are blended include glycyrrhetinic acid and allantoin, stearyl glycyrrhetinate and allantoin, glycyrrhizic acid and allantoin, monoammonium glycyrrhizinate and allantoin, dipotassium glycyrrhizinate and allantoin, and glycyrrhizin. acid trisodium salt and allantoin.

Other Components The topical pharmaceutical composition of the present invention can be prepared by mixing the above components (A) and (B) with additives used in topical preparations and other physiologically active or pharmacologically active ingredients. can be done. Additives include oils, surfactants, humectants, polyhydric alcohols, antioxidants, thickeners, antiseptics or preservatives, pH adjusters, chelating agents, coloring agents, perfumes, and the like. 1 type, or 2 or more types can be used for an additive. In addition, additives can be used within a range that does not impair the effects of the present invention.

Since benzoyl peroxide is a highly reactive substance, the composition of the present invention desirably contains water. The concentration of water is preferably 25% by mass or more, more preferably 28% by mass or more, and even more preferably 40% by mass or more, relative to the total amount of the composition. Moreover, 90 mass % or less is preferable, and 80 mass % or less is more preferable. Within this range, destabilization of the composition due to benzoyl peroxide can be avoided, and the effects of the present invention can be sufficiently obtained.
The concentration of water relative to the total amount of the composition includes 25 to 90% by mass, 25 to 80% by mass, 28 to 90% by mass, 28 to 80% by mass, 40 to 90% by mass, and 40 to 80% by mass.

Examples of oils include ester oils, fats and oils, waxes, higher fatty acids, higher alcohols, sterols, hydrocarbons, and silicone oils.

Ester oils include isopropyl myristate, butyl myristate, decyl myristate, myristyl myristate, cetyl myristate, isopropyl palmitate, cetyl palmitate, ethyl stearate, butyl stearate, stearyl stearate, isocetyl stearate, laurin hexyl acid, ethyl oleate, ethyl linoleate, isopropyl linoleate, cetyl caprylate, decyl oleate, oleyl oleate, isodecyl oleate, cetyl octanoate, 2-octyldodecyl myristate, 2-octyldodecyl dimethyloctanoate, Hexyldecyl dimethyloctanoate, diethyl sebacate, diisopropyl sebacate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, diisopropyl adipate, diisobutyl adipate, di-2-adipate Esters of C8-C22 fatty acids with fatty alcohols, such as heptylundecyl, 2-hexyldecyl adipate, isocetyl isostearate, isostearyl isostearate, isononyl isononanoate, isotridecyl isononanoate, 12-hydroxystearyl cholesteryl acid, cholesteryl stearate, cholesteryl oleate, macadamia nut fatty acid phytosteryl, phytosteryl oleate, inulin stearate, ethylene glycol di-2-ethylhexylate, cetyl 2-ethylhexanoate, N-alkyl glycol monoisostearate, neo dicaprate Pentyl glycol, glyceryl di-2-heptylundecanoate, tri-2-ethylhexyl trimellitate, tridecyl trimellitate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate , glyceryl tri-2-ethylhexanoate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, glyceryl trimyristate, caprylic/capric triglyceride, tri(caprylic/capric/myristate) / stearic acid) glyceryl, medium chain fatty acid triglyceride, castor oil fatty acid methyl ester, di (phytosteryl/octyldodecyl) lauroyl glutamate, di (octyldodecyl/phytosteryl/behenyl) lauroyl glutamate, diisostearyl malate, cetyl lactate, myristyl lactate , diethoxyethyl succinate, diethylhexyl succinate, bisethoxydiglycol cyclohexane-1,4-dicarboxylate, lanolin acetate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, dimer dilinoleic acid (phytosteryl/isostearyl /cetyl/stearyl/behenyl), dimer dilinoleyl dimer dilinoleate, dipentaerythrityl tripolyhydroxystearate, and glyceryl tri(behenate/isostearate/eicosanedioate).

Fats and oils include avocado oil, linseed oil, camellia oil, macadamia nut oil, corn oil, olive oil, safflower oil, Chinese nut oil, jojoba oil, grape seed oil, sunflower oil, almond oil, sasanqua oil, rapeseed oil, sesame oil, Castor oil, cocoa butter, coconut oil, hydrogenated coconut oil, palm oil, palm kernel oil, Japanese magnolia kernel oil, Japanese magnolia, wheat germ oil, rice germ oil, rice bran oil, cottonseed oil, soybean oil, peanut oil, teaseed oil, Evening primrose oil, kukui nut oil, hazelnut oil, shea butter, orange oil, chamomile oil and the like.

Waxes include candelilla wax, rice bran wax, cotton wax, carnauba wax, lanolin, lanolin fatty acid isopropyl, POE lanolin alcohol ether, POE lanolin alcohol acetate, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, shellac wax, beeswax, and the like. be done.

As higher fatty acids, for example, saturated or unsaturated linear or branched fatty acids having 12 to 22 carbon atoms can be used, preferably lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and the like. Straight-chain saturated fatty acids (solid at room temperature); unsaturated fatty acids (liquid at room temperature) such as oleic acid, linoleic acid, linolenic acid, palmitoleic acid, eicosapentaenoic acid, paxenoic acid, and docosahexaenoic acid; branched fatty acids such as isostearic acid and lanolin fatty acid Fatty acids; 12-hydroxystearic acid and the like.

Higher alcohols include higher alcohols with 12 to 22 carbon atoms. Preferably, linear saturated alcohols such as lauryl alcohol, myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, arachyl alcohol, behenyl alcohol; unsaturated alcohols such as oleyl alcohol, selachyl alcohol; hexyldecanol, isostearyl alcohol, octyldodeca decyltetradecanol, lanolin alcohol, branched alcohols such as isostearyl glyceryl ether, and the like.

Examples of sterols include animal sterols such as cholesterol, ergosterol and lanosterol; plant sterols (phytosterols) such as sitosterol, campesterol, stigmasterol, spinasterol and brassicasterol; and sterol derivatives such as phytosteryl hydroxystearate. .

Hydrocarbons include paraffin, ceresin, isoparaffin, hard fat, microcrystalline wax, polybutene, polyethylene powder, liquid paraffin, squalane, vaseline, gelling hydrocarbons (plastibase, etc.), ozokerite, α-olefin oligomer, light liquid paraffin, and light liquid paraffin.

Examples of silicone oils include methylpolysiloxane, dimethylpolysiloxane, methylphenylpolysiloxane, decamethyltetrasiloxane, methylcyclopentasiloxane, highly polymerized methylpolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and methylhydrogenpolysiloxane. Siloxane such as siloxane, methyltrimethicone, dimethiconol, dimethiconol crosspolymer; alkyl-modified silicone such as caprylyl methicone; amino-modified silicone such as aminopropyl dimethicone and amodimethicone; crosslinked methylpolysiloxane, crosslinked alkyl-modified silicone, amino-modified Silicone, polyether-modified silicone, polyglycerin-modified silicone, cross-linked polyether-modified silicone, cross-linked alkyl polyether-modified silicone, silicone/alkyl chain co-modified polyether-modified silicone, silicone/alkyl chain co-modified polyglycerin-modified silicone, poly Ether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, silicone resin, and the like.

The base used in the present invention is preferably a combination of water and a polyhydric alcohol and/or an oil agent. 1 type selected from the group consisting of linear saturated or unsaturated alcohols of number 12 to 22, etc.) and ester oils (esters of fatty acids with 12 to 22 carbon atoms such as isopropyl myristate and fatty alcohols, etc.) A combination of the above is preferred.

Surfactants may be nonionic surfactants, cationic surfactants, anionic surfactants, amphoteric surfactants, or the like.
Nonionic surfactants include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate, and the like. sorbitan fatty acid esters; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor Hydrogenated castor oil derivatives such as oil 60 (HCO-60), polyoxyethylene hydrogenated castor oil 80; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60) ), polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan monooleate (polysorbate 80), polyoxyethylene (20) sorbitan isostearate; polyoxyethylene monococonut oil fatty acid glyceryl; glycerin alkyl ether; stearin Glycerin fatty acid esters such as glyceryl acid, glyceryl myristate, glyceryl oleate, glyceryl isostearate, glyceryl stearate; polyglyceryl-2 oleate, polyglyceryl-2 stearate, polyglyceryl-10 oleate, polyglyceryl-10 stearate, lauric acid Polyglycerol fatty acid esters such as polyglyceryl-10, polyglyceryl-10 distearate, polyglyceryl-10 trioleate, polyglyceryl-10 pentaoleate, polyglyceryl-10 pentastearate; alkyl glucoside; polyoxyethylene stearyl ether, polyoxyethylene lauryl polyoxyalkylene alkyl ethers such as ethers, polyoxyethylene cetyl ethers, polyoxyethylene behenyl ethers and polyoxyethylene cetyl ethers; polyethylene glycol fatty acid esters such as polyethylene glycol monostearate; amines such as stearylamine and oleylamine; Silicone-based surfactants such as ethylene/methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, PEG-9 polydimethylsiloxyethyl dimethicone, and the like.

Moisturizing agents include, for example, hyaluronic acid, salts thereof, or derivatives thereof (e.g., sodium hyaluronate, zinc hyaluronate, low-molecular-weight hyaluronic acid, acetylated hyaluronic acid, crosslinked hyaluronic acid derivatives, cationized hyaluronic acid, etc.); chondroitin; Sulfuric acid or its salts; Amino acids such as heparinoids, alanine, serine, aspartic acid, glycine, arginine and derivatives thereof; Polyhydric alcohols such as glycerin, dipropylene glycol and 1,3-butanediol; Sorbitol, xylitol, erythritol, Sugar alcohols such as maltose/sucrose condensate (glucooligosaccharide), hydrolyzed xylan (xylo-oligosaccharide); /5/3 glycerin, alkylene oxides such as polyoxyalkylene diglyceryl; glycosyltrehalose, trehalose; ceramide, glucosylceramide, cholesterol, phytosterol, cholesterol derivatives, phytosterol derivatives; phospholipids; MPC polymers; lactic acid, sodium lactate, pyrrolidone NMF-derived components such as sodium carboxylate and urea; collagen, elastin, keratin, chitin, chitosan, etc. and their hydrolysates; hydroxyethyl urea; , tea, perilla, grapefruit, Gynostemma pentaphyllum, etc.).

Examples of polyhydric alcohols include low molecules having two or more hydroxy groups, such as glycerin, diglycerin, triglycerin, 1,3-propylene glycol, dipropylene glycol, 1,4-butanediol, ethylene glycol, Diethylene glycol, isoprene glycol, 1,3-butylene glycol, 1,4-propanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, decanediol, neopentyl glycol, sorbitol, xylitol , erythritol, mannitol and the like. Among them, 1,3-propylene glycol is preferable from the viewpoint of exhibiting remarkable effects of the invention. The concentration of the total amount of polyhydric alcohol relative to the total amount of the composition includes 5 to 50% by mass, 10 to 30% by mass, and 15 to 20% by mass.

Antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, p-hydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivatives (ascorbyl stearate, ascorbyl palmitate, ascorbyl dipalmitate, ascorbyl acid monophosphate, ascorbyl diphosphate, ascorbate triphosphate, ascorbate sulfate, etc.), tocopherol, tocopherol derivatives (tocopherol acetate, tocopherol succinate, tocopherol calcium succinate, etc.), erythorbic acid, L-cysteine hydrochloride etc.

Examples of thickeners include polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, alkyl acrylate copolymer, alkyl acrylate methacrylate copolymer, and vinyl-based thickeners such as sodium polyacrylate. Thickeners, cellulosic thickeners such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, hydrophobized hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether , guar gum, sclerotium gum, tamarind gum, xanthan gum, dextran, pectin, pullulan, gelatin, locust bean gum, carrageenan, agar, biosaccharide gum, alkyl acrylate methacrylate copolymer, sodium polyacrylate, bentonite, dextrin Fatty acid ester, dimethyldistearylammonium hectorite, sodium alginate, propylene glycol alginate, polyethylene glycol, macrogol, trimethylammonium chloride hydroxypropyl guar gum, trimethylammonio hydroxypropyl hydroxyethylcellulose chloride, (hydroxyethyl acrylate/acryloyldimethyltaurate Na ) copolymer, (acryloyldimethyltaurate ammonium/vinylpyrrolidone) copolymer, and the like. Among them, carboxyvinyl polymer is preferable from the viewpoint of exhibiting remarkable effects of the invention. The concentration of the total amount of thickening agent relative to the total amount of the composition may be 0.01 to 0.8% by mass, 0.05 to 0.5% by mass, and 0.1 to 0.2% by mass.

Antiseptics or preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, parahydroxybenzoic acid. benzyl, methyl p-oxybenzoate, phenoxyethanol, benzyl alcohol, chlorobutanol, sorbic acid and its salts, chlorhexidine gluconate, alkanediols, glycerin fatty acid esters, and the like.

Examples of pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.). ), organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, arginine, glycine, etc.), and the like.

Chelating agents include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetate (sodium salt (edetate sodium: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, gluconic acid, polyphosphoric acid, metalin acids and the like.

Examples of coloring agents include pigments listed in the legal pigment handbook (edited by the Japan Cosmetic Industry Association (2004)).

Fragrances include herbal essential oils such as lavender oil, rosemary oil, clary sage oil, thyme oil, bergamot oil, and eucalyptus oil; mint essential oils such as peppermint oil, spearmint oil, and peppermint oil; orange oil, lemon oil, and grapefruit oil. Various essential oils such as citrus essential oils such as, and compounded fragrances.

(Bioactive or pharmacologically active ingredient)
Biologically active or pharmacologically active ingredients other than benzoyl peroxide, glycyrrhetinic acids, and allantoin include anti-inflammatory agents (other than glycyrrhetinic acids and allantoin), antipruritic agents (including antihistamines), local anesthetics, and disinfectants (other than benzoyl peroxide). , cooling agents, vitamins, keratin softening ingredients (chemical peeling ingredients), astringent ingredients, and the like.
Among them, anti-inflammatory agents, anti-allergic agents, antibacterial agents, keratin softening ingredients, and vitamins are ingredients that are recommended to be used in combination with benzoyl peroxide.
One or two or more physiologically active or pharmacologically active ingredients other than benzoyl peroxide, glycyrrhetinic acids, and allantoin can be used. Moreover, it can be used within a range that does not impair the effects of the present invention.

Glycyrrhetinic acids (glycyrrhetinic acid, derivatives thereof, salts thereof), non-steroidal anti-inflammatory agents other than allantoin, ufenamate, heparinoids, epsilon-aminocaproic acid, berberine, azulene, bromelain, zinc oxide; lysozyme, serrapeptase, Enzymatic anti-inflammatory agents such as semi-alkaline proteinase, ibuprofen piconol, and the like. These may be salts.

Steroidal anti-inflammatory agents include prednisolone, hydrocortisone, cortisone, dexamethasone, triamcinolone, triamcinolone acetonide, difluprednate, mometasone, diflucortolone, fluocinonide, beclomethasone, deprodone, alclomethasone, flumethasone, amcinonide, clobetasone, diflorazone, and derivatives thereof.

Antihistamines include diphenhydramine, diphenhydramine hydrochloride, bromodiphenhydramine hydrochloride, clemastine fumarate, chlorphenoxamine hydrochloride, chlorpheniramine, chlorpheniramine maleate, promethazine hydrochloride, cetirizine hydrochloride, meclizine hydrochloride, ketotifen fumarate, olopatadine hydrochloride, fexofenadine hydrochloride, antazoline hydrochloride, azatadine dimaleate, epinastine hydrochloride and the like.

Antipruritic agents include crotamiton, ictamol, and moktar.

Local anesthetics include lidocaine, lidocaine hydrochloride, dibucaine hydrochloride, benzocaine, bupivacaine hydrochloride, tetracaine hydrochloride, and the like.

Bactericides other than benzoyl peroxide include isopropylmethylphenol, phenoxyethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, cetylpyridinium chloride, sodium benzoate, ethanol, chlorobutanol, sorbic acid, sorbin potassium salt, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, salicylic acid, cresol, triclosan and the like.

Cooling agents include terpenes such as menthol, camphor, borneol, geraniol, cineole, anethole, limonene, and eugenol (these may be d-, l-, or dl-forms); eucalyptus oil, bergamot oil, Essential oils such as peppermint oil, cool mint oil, spearmint oil, fennel oil, peppermint oil, cinnamon oil, rose oil and turpentine oil.

Vitamins include retinol, retinol acetate, retinol palmitate, retinol propionate, retinol derivatives such as retinol linoleate, retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoate, d-δ-tocopheryl retino Vitamin A such as ate, α-tocopheryl retinoate, β-tocopheryl retinoate; , Vitamin E such as (ascorbyl/tocopheryl) potassium phosphate; riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate sodium, riboflavin tetranicotinate, etc. of vitamin B2; nicotinic acids such as methyl nicotinate, nicotinic acid, benzyl nicotinate, and nicotinamide; Ascorbyl 2-hexyldecanoate), ascorbyl palmitate trisodium phosphate, ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, ascorbate glucoside, 2-O-ethyl ascorbine acid, 3-O-ethylascorbic acid, glyceryl ascorbic acid, bisglyceryl ascorbic acid, alkylglyceryl ascorbic acid and other vitamin Cs; methylhesperidin, ergocalciferol, cholecalciferol and other vitamin Ds; phylloquinone, farnoquinone and the like vitamin Ks; vitamin B1s such as thiamine and their salts (e.g., dibenzoylthiamine hydrochloride, thiamine hydrochloride, thiamine diphosphate); pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5′-pyridoxal phosphate, vitamin B6 such as pyridoxamine hydrochloride; vitamin B12 such as cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin; folic acid such as folic acid and pteroylglutamic acid; pantothenic acids such as pantethein, D-pantethine, coenzyme A, pantothenyl ethyl ether, calcium pantetheine sulfonate; biotins such as biotin and biocytin; vitamin-like agents such as oryzanol, pyrroloquinoline quinone, hesperidin, glucosylhelperidin, ubiquinone, and salts thereof;

Among them, vitamin C is preferable because it suppresses inflammation and post-inflammatory erythema by its antioxidant effect, vitamin A is preferable because it prevents keratinization, vitamin B2 and B6 are preferable because it suppresses sebum secretion, and vitamin E is preferable. It is preferable because it suppresses the production of lipid peroxide and promotes blood circulation.

Keratin softening ingredients include salicylic acid, salicylic acid derivatives (macrogol salicylate, ethanol salicylate, etc.), glycolic acid, fruit acid, phytic acid, sulfur, urea, resorcinol, phytic acid, lactic acid, lactate, sodium hydroxide, potassium hydroxide. etc.

Astringent components include zinc paraphenolsulfonate, zinc oxide, menthol, and ethanol.

FORMULATION FORM The formulation form of the composition for external use of the present invention is not particularly limited. Examples include spray agents, aerosol agents, pump foam agents, sheet agents obtained by impregnating a sheet such as nonwoven fabric with a chemical liquid, and stick agents.
Among them, gel formulations (gel formulations), emulsion formulations, and cream formulations are preferable because they are easy to spread on the skin and have a good feeling in use.
In addition, since the composition of the present invention is smooth, it can be easily spread over a wide area even in the form of a bulky preparation such as a stick type. A stick-type formulation is preferable because the formulation does not stick to the hands.
In the case of emulsified formulations such as emulsions, creams and emulsion ointments, either oil-in-water type or water-in-oil type may be used. oil-in-water type is preferred.

Viscosity The viscosity of the composition of the present invention is preferably 10 mPa·s to 100 Pa·s, more preferably 100 mPa·s to 100 Pa·s, and more preferably 100 mPa·s to 50 Pa·s. , more preferably 100 mPa s to 10 Pa s, more preferably 500 mPa s to 5 Pa s, more preferably 500 mPa s to 3 Pa s, and 800 mPa s to 3 Pa s. is more preferable. Within this range, the preparation can be easily applied to the skin and easily discharged from a container with a small discharge port, and the decrease in viscosity over time can be sufficiently suppressed by incorporating the component (B).
In the present invention, the viscosity is a value measured at room temperature using a viscometer (TVB-15 (M); Toki Sangyo), specifically a value measured by the method described in Examples.

pH
The pH of the pharmaceutical composition of the present invention can be pH 3 to 7.5, preferably pH 3 to 7, more preferably pH 3 to 6.5, and pH 3.5 to 6. is even more preferred, and pH 3.8 to 5.5 is particularly preferred. This pH can be adjusted, for example, by using a pH adjuster. However, this does not apply to formulation forms for which pH measurement is impossible or difficult.

Method of use The external pharmaceutical composition of the present invention can be used for treating or improving acne and pimples. Among acnes, acne vulgaris is preferred. In addition, since it contains an anti-inflammatory agent selected from glycyrrhetinic acids and allantoin, it can be used to treat or improve acne and pimples while suppressing irritation caused by benzoyl peroxide.
The external pharmaceutical composition of the present invention may be applied to the affected area 1 to 3 times, 1 to 2 times, or once a day. When applying the topical pharmaceutical composition of the present invention, as a guideline, about 0.5 g may be applied to the entire face.
The external pharmaceutical composition of the present invention is preferably applied to the skin, and more preferably the skin of the face (especially forehead, chin, cheeks, around the mouth, nose), neck and back.

Container The container for containing the external pharmaceutical composition of the present invention includes bottle type, tube type, jar type, roll-on type, dropper type, spray type, dispenser type, stick type, pouch bag, chia pack and the like.
Roll-on type, dropper type, spray type, and dispenser type containers tend to leave part of the contents in the container or clog the discharge port, but the composition of the present invention is smooth, Even relatively hard or highly viscous formulations can flow smoothly from such containers.

The material of the container containing the external pharmaceutical composition of the present invention is not particularly limited as long as it can be used as a container for external pharmaceutical preparations. Examples of such container materials include polyolefin resins, acrylic acid resins, polyesters, polycarbonates, fluororesins, polyvinyl chloride, polyamides, and ABS, which are partially or entirely, preferably entirely, in contact with the external pharmaceutical composition for skin. A container made of at least one material selected from the group consisting of resin, AS resin, polyacetal, modified polyphenylene ether, polyarylate, polysulfone, polyimide, cellulose acetate, aluminum, and glass.

From the viewpoint of ease of handling of the formulation and ease of molding, for example, aluminum, polyethylene (PE) (high density polyethylene (HDPE), low density polyethylene (LDPE), ultra-low density polyethylene, linear low-density polyethylene (LLDPE), ultra-high molecular weight polyethylene, etc.), polypropylene (PP) (isotactic polypropylene, syndiotactic polypropylene, atactic polypropylene, etc.) ), polyolefin resins such as ethylene/propylene copolymer, polymethylpentene, polybutene-1,1,2-polybutadiene, polyester resins such as polyethylene terephthalate, polybutylene terephthalate, and polyethylene naphthalate are preferred, and polyethylene, polypropylene, and polyethylene terephthalate are preferred. more preferred. In addition, as the material of the innermost layer (surface in contact with the external pharmaceutical composition) of the container filled with the external pharmaceutical composition according to the present embodiment, for example, polyethylene (PE) (high density polyethylene (HDPE), low density Polyethylene (LDPE), ultra low density polyethylene, linear low density polyethylene (LLDPE), polypropylene, aluminum are preferred.
One or more container materials can be used. When two or more materials are used, when two or more materials are mixed, when layers containing two or more different materials are laminated, different parts of the container (receiving part, lid, nozzle, etc.) This includes cases where different materials are included.

Method for Suppressing Decrease in Viscosity In the present invention, (A) a topical pharmaceutical composition containing benzoyl peroxide is selected from (B) (B1) glycyrrhetinic acid, derivatives thereof, and/or salts thereof, and (B2) allantoin. It includes a method for suppressing a decrease in viscosity over time of a composition for external use, comprising at least one component of the composition for external use.
The type and content of each component, the properties of the composition, etc. are as described for the topical pharmaceutical composition of the present invention.

Method for lowering dynamic friction coefficient The present invention provides (A) a topical pharmaceutical composition containing benzoyl peroxide, (B) (B1) glycyrrhetinic acid, derivatives thereof, and/or salts thereof, and (B2) allantoin. A method for reducing the dynamic friction coefficient (particularly, the dynamic friction coefficient between the skin) of an external pharmaceutical composition containing at least one component.
The type and content of each component, the properties of the composition, etc. are as described for the topical pharmaceutical composition of the present invention.
The topical pharmaceutical composition of the present invention has little friction with the skin during application and can be spread smoothly, thus avoiding situations such as unapplied or excessive application. Ability to spread smoothly includes less squeaking, less snagging, or less stickiness.

EXAMPLES The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these.
(1) Preparation of a composition for external use A composition for external use was prepared so as to have the composition shown in Table 1.
First, the carboxyvinyl polymer was dispersed in water. When dipotassium glycyrrhizinate or allantoin was added, it was added in advance. An aqueous solution of triethanolamine was added to this to neutralize it. This mixture was dispersed in 1,3-propylene glycol and finally benzoyl peroxide hydrate was added.
The dosage form of the resulting composition is a gel.

(2) Evaluation of Viscosity Decrease Suppressing Effect The composition of each example was placed in a 50 ml glass screw-capped bottle, closed with a lid, and allowed to stand at 40° C. for 7 days.
The viscosity of each composition before and after standing was measured in a glass screw-capped bottle at room temperature using a viscometer (TVB-15 (M); Toki Sangyo).
The compositions of Reference Example 1, Comparative Examples 1 and 2, and Example 1 were measured using an M4 rotor at a rotation speed of 3 rpm for 60 seconds. was measured at 12 rpm for 60 seconds using an M2 rotor. It is normal to select an appropriate rotor and rotation speed according to the viscosity of the test sample, and the same rotor and rotation speed were adopted before and after standing at 40 ° C for 7 days, so the effect on the viscosity ratio no.
The ratio of the viscosity after standing to the viscosity before standing at 40° C. for 7 days (viscosity after standing/viscosity before standing) was calculated. A larger value indicates that the viscosity is less likely to decrease over time.

Table 1 shows the results.
By blending benzoyl peroxide (Comparative Example 1) with a composition containing only a base that does not contain benzoyl peroxide (Reference Example 1), the viscosity ratio decreased. By adding allantoin (Example 1) or dipotassium glycyrrhizinate (Example 2) there, recovery of the viscosity ratio was observed. Moreover, when both allantoin and dipotassium glycyrrhizinate were blended (Example 3), the viscosity ratio was remarkably recovered.
On the other hand, allantoin (Comparative Example 2), dipotassium glycyrrhizinate (Comparative Example 3), or both allantoin and dipotassium glycyrrhizinate (Comparative Example 4) were added to a composition containing only a base not containing benzoyl peroxide (Reference Example 1). was blended, the viscosity ratio remained almost unchanged. It was shown that allantoin and dipotassium glycyrrhizinate themselves have no effect of increasing viscosity.
Therefore, it was revealed that allantoin and dipotassium glycyrrhizinate have the effect of suppressing viscosity decrease over time due to the addition of benzoyl peroxide, that is, they have the effect of suppressing viscosity decrease in combination with benzoyl peroxide.
This effect became even more remarkable by blending both allantoin and dipotassium glycyrrhizinate.
The viscosities of the compositions of Examples 1, 2, and 3 before standing at 40° C. for 7 days were 1,060 mPa·s, 1,034 mPa·s, and 1,050 mPa·s, respectively.

(3) Evaluation of friction during application to skin The dynamic friction coefficient of each composition was measured by the following method.
The artificial leather was fixed on a moving table, and a 2 cm x 5 cm area was marked as a measurement site. Using a static/dynamic friction measuring machine (TL201Sa; Trinity Lab), the dynamic friction coefficient was measured when the contactor (contact surface 1 cm x 1 cm) was moved 3 cm at a speed of 2 mm/sec under a load of 50 g. Subsequently, about 45 mg of each composition was applied to the measurement site, left for 1 minute, and then the dynamic friction coefficient was measured in the same manner.
The ratio of the dynamic friction coefficient after application to the dynamic friction coefficient before application of each composition (dynamic friction coefficient after application/dynamic friction coefficient before application) was calculated. It measured 3 times and calculated the average value. The smaller this value, the better the slip between the composition and the skin during the act of application.

Table 1 shows the results.
By adding allantoin (Example 1) or dipotassium glycyrrhizinate (Example 2) to a composition containing benzoyl peroxide and a base (Comparative Example 1), the dynamic friction coefficient ratio was reduced, and allantoin and dipotassium glycyrrhizinate were mixed. (Example 3), the dynamic friction coefficient ratio was remarkably reduced.
Therefore, it was clarified that blending allantoin or dipotassium glycyrrhizinate in combination with benzoyl peroxide improves slipping on the skin. This effect became more pronounced by blending both allantoin and dipotassium glycyrrhizinate.

Formulation examples of the external pharmaceutical composition of the present invention are shown below. The unit is % by mass.
Formulation example 1 (gel)
Benzoyl peroxide 5
Dipotassium glycyrrhizinate 1
Allantoin 0.1
Glycerin 5
Propylene glycol 10
Carboxyvinyl polymer 1
EDTA disodium 0.05
Perfume 0.05
Methylparaben 0.1
Sodium citrate 0.05
Sodium hydroxide appropriate amount Xanthan gum 0.1
Water remaining gauge 100

Formulation example 2 (oil-in-water cream)
Benzoyl peroxide 2.5
Dipotassium glycyrrhizinate 0.5
Allantoin 0.2
Propylene glycol 8
Self-emulsifying glyceryl monostearate 8 8
Stearyl alcohol 3
Isopropyl myristate 5
Methylparaben 0.1
Carboxyvinyl polymer 1
Potassium hydroxide appropriate amount Propylparaben 0.05
Water remaining gauge 100

Since the composition for external use of the present invention contains benzoyl peroxide, the decrease in viscosity during storage is suppressed, so no special consideration is required for distribution and storage. In addition, since the external pharmaceutical composition of the present invention can be applied smoothly, it is easy to apply a predetermined amount, and therefore, a predetermined medicinal effect can be obtained. In addition, since it can be applied smoothly, it can be used comfortably.

Claims (6)

1. (A) benzoyl peroxide, and (B) (B1) glycyrrhetinic acid, derivatives thereof, salts thereof, and (B2) an external pharmaceutical composition containing at least one component selected from the group consisting of allantoin.
2. The composition according to claim 1, wherein the content of component (B) is 0.015 to 0.6 parts by mass with respect to 1 part by mass of component (A).
3. The composition according to claim 1 or 2, comprising (B1) component and (B2) component.
4. The composition according to any one of claims 1 to 3, wherein the component (B1) is at least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, and salts thereof.
5. The composition according to any one of claims 1 to 4, which contains 25% by mass or more of water relative to the total amount of the composition.
6. (A) A topical pharmaceutical composition containing benzoyl peroxide contains at least one component selected from the group consisting of (B) (B1) glycyrrhetinic acid, derivatives thereof, salts thereof, and (B2) allantoin. , a method for suppressing a decrease in viscosity over time of a composition for external use.