JP6449564B2 - Composition for external use - Google Patents

Description

  The present invention relates to an external composition containing an azole antifungal agent.

  Antifungal agents that inhibit fungal growth are widely used to treat, prevent, and improve various diseases and symptoms resulting from fungal infection. And antifungal agents are based on their structural or functional commonality based on azole antifungal agents, allylamine antifungal agents, polyene antifungal agents, fluoropyrimidine antifungal agents, candin antifungal agents. It is broadly classified into agents.

  An azole antifungal agent has an azole skeleton in common and exhibits an antifungal action by inhibiting ergosterol synthesis in the fungal cell membrane. Azole antifungal agents have a wide antibacterial spectrum and are highly safe for the human body, and thus have been widely used as therapeutic agents for fungal infections and the like. For example, azole antifungal agents such as miconazole, lanoconazole, luliconazole, isoconazole, ketoconazole, clotrimazole, tinea (for example, foot ringworm, body ringworm, hip ringworm), candidiasis (for example, finger erosion, It is used to treat infectious diseases such as rashes. Furthermore, as an attempt to expand the antibacterial activity and antibacterial spectrum of such an azole antifungal agent, the use of a quaternary ammonium salt or an antibacterial agent has been studied (Patent Documents 1 and 2).

JP-A-9-110690 WO 2004/028502 gazette

  When preparing a composition for external use blended with an azole antifungal agent, the present inventors use a specific surfactant called coconut oil fatty acid acylamino acid anionic surfactant in combination, and the viscosity of the preparation increases over time. A new finding has been obtained that it rises and produces significant white residue after drying.

  Furthermore, the present inventors have found that when an anti-inflammatory agent is used in combination with an azole antifungal agent, the residual rate of the azole antifungal agent decreases, and in particular, this residual rate decrease is accommodated in a container made of a specific resin material. New knowledge that is not known at all has been obtained.

  The present invention improves the inconvenience in the formulation of an external composition containing such an azole antifungal agent, is excellent in viscosity stability over time, can suppress the occurrence of white residue after drying, and An object of the present invention is to provide an external composition containing an azole antifungal agent that is excellent in formulation and can suppress a decrease in the residual rate of the azole antifungal agent due to the combined use with an anti-inflammatory agent.

  As a result of intensive studies to solve the above problems, the present inventors have further increased the viscosity of the preparation by further combining an anti-inflammatory agent with an azole antifungal agent and a palm oil fatty acid acylamino acid anionic surfactant. It has been found that the occurrence of white residue after drying can be effectively suppressed. The present inventors have also found that the decrease in the residual rate of the azole antifungal agent that occurs when an anti-inflammatory agent is used in combination can be improved with a coconut oil fatty acid acylamino acid anionic surfactant.

  The present invention relates to a composition for external use containing (A) an azole antifungal agent, (B) an anti-inflammatory agent, and (C) a coconut oil fatty acid acylamino acid anionic surfactant.

  The (A) azole antifungal agent is selected from the group consisting of miconazole, ranoconazole, luliconazole, isoconazole, ketoconazole, clotrimazole, fluconazole, itraconazole, neticoconazole, sulconazole, bifonazole, phosfluconazole, voriconazole, and salts thereof. Can be at least one.

  The (B) anti-inflammatory agent is glycyrrhizic acid, glycyrrhetinic acid, tranexamic acid, ε-aminocaproic acid, allantoin, salicylic acid, prednisolone, dexamethasone, hydrocortisone, ufenamate, bufexamac, ibuprofenpiconol, indomethacin, diclofenac, piroxicam, teambellin, , Azulene, bromelain, serrapeptase, semi-alkaline proteinase and derivatives thereof, and at least one selected from the salts thereof.

  The (C) coconut oil fatty acid acylamino acid type anionic surfactant is coconut oil fatty acid acylglutamic acid, coconut oil fatty acid acylaspartic acid, coconut oil fatty acid acylglycine, coconut oil fatty acid acylglutamine, coconut oil fatty acid acylasparagine, coconut oil. From the group consisting of fatty acid acylalanine, coconut oil fatty acid acylthreonine, coconut oil fatty acid acyl sarcosine, coconut oil fatty acid acylmethylalanine, coconut oil fatty acid acyl taurine, coconut oil fatty acid acylmethyl taurine, coconut oil fatty acid acyl isethionic acid, and salts thereof There may be at least one selected.

  The present invention is also the above external composition, wherein at least a part of the surface in contact with the external composition is selected from the group consisting of a polyethylene resin, a polypropylene resin, a polyester resin, and a mixed resin thereof. It is related with the composition for external use accommodated in the container comprised by 1 type.

  The composition for external use can be provided by being housed in a pump-type container or a narrow-bottle bottle container provided with a nozzle.

  The external composition may have a viscosity at 25 ° C. of 1 mPa · s or more.

  Content of the said (A) component may be 0.01 weight% or more with respect to the external composition whole quantity.

  Content of the said (B) component may be 0.0001 weight% or more with respect to the composition whole quantity.

  Content of the said (C) component may be 0.01 weight% or more with respect to the composition whole quantity.

  The above external composition can be used for washing hair or skin.

  In the composition for external use, the present invention also provides (A) an azole antifungal agent, (B) an anti-inflammatory agent, and (C) a palm oil fatty acid acylamino acid type anionic surfactant. The present invention relates to a method for suppressing an increase in viscosity of a composition over time.

  In the composition for external use, the present invention also provides (A) an azole antifungal agent, (B) an anti-inflammatory agent, and (C) a palm oil fatty acid acylamino acid type anionic surfactant. The present invention relates to a method for suppressing white residue after drying of a composition.

  In the composition for external use, the azole type antifungal agent, (B) anti-inflammatory agent, and (C) coconut oil fatty acid acylamino acid type anionic surfactant coexist in the composition for external use. The present invention relates to a method for suppressing a decrease in the residual rate of an antifungal agent.

  The present invention also provides an external composition in which a part or all of the contacting surface is contained in a container composed of at least one selected from the group consisting of polyethylene resin, polypropylene resin, polyester resin, and mixed resins thereof. (A) an azole antifungal agent, (B) an anti-inflammatory agent, and (C) a coconut oil fatty acid amino acid anionic surfactant coexisting in the product, the azole antifungal agent in the composition for external use The present invention relates to a method for suppressing a decrease in the residual rate of a fungal agent.

  According to the present invention, excellent in viscosity stability with time, can suppress the occurrence of white residue after drying, and / or can suppress a decrease in the residual rate of azole antifungal agents due to combined use with anti-inflammatory agents, and is excellent in terms of formulation An external composition containing an azole antifungal agent can be provided.

It is a figure which shows the result of the white balance evaluation of the composition for external use of this invention, and the composition for contrast.

  The (A) azole antifungal agent of the present invention is a compound well known as an antifungal agent having an azole skeleton (a hetero 5-membered ring compound containing one or more nitrogen atoms) in common, and is pharmaceutical or physiological. Any azole-based antifungal agent that is acceptable can be used. As the azole antifungal agent, for example, an imidazole antifungal agent having an imidazole ring (hetero 5-membered ring containing 2 nitrogen atoms) or a triazole ring (hetero 5-membered hetero ring containing 3 nitrogen atoms) is used. A triconazole type antifungal agent etc. can be mentioned. More specifically, imidazole antifungal agents such as miconazole, lanoconazole, luliconazole, isconazole, ketoconazole, clotrimazole, neticoconazole, sulconazole, bifonazole and salts thereof; fluconazole, itraconazole, phosfluconazole, voriconazole and salts thereof, etc. The triconazole type antifungal agent can be mentioned and can be preferably used in the present invention. Although not particularly limited, an imidazole antifungal agent is preferably used from the viewpoint that a higher effect of the present invention can be expected with certainty. Of these, preferred are miconazole, ranoconazole, luliconazole, isoconazole, ketoconazole, clotrimazole, neticoconazole, sulconazole, bifonazole and salts thereof, more preferably miconazole, ranoconazole, luliconazole, isoconazole, ketoconazole, clotrimazole and these. A salt, more preferably miconazole and a salt thereof (for example, miconazole nitrate).

  Here, in the present specification, examples of the “salt” include salts with alkali metal salts, alkaline earth metal salts, organic bases, and the like, such as sodium, potassium, calcium, magnesium, ammonium, or diethanolamine, triethanol. Examples thereof include salts with amines, ethylenediamine and the like. In addition, for example, salts of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid; methanesulfonic acid, benzenesulfonic acid, paratoluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, Malic acid, oxalic acid, succinic acid, citric acid, benzoic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid, salts with organic acids such as salicylic acid; or aspartic acid, glutamic acid And salts with acidic amino acids such as The “salt” may include a solvate or hydrate of a salt. (A) Although it does not specifically limit as a form of the salt of a component, Preferably it is a salt of an inorganic acid, More preferably, it is a nitrate.

  The content of the component (A) in the composition for external use of the present invention is not particularly limited as long as the effects of the present invention can be achieved, but as an example, about 0.01 wt% or more and 3 wt% or less with respect to the total amount of the composition, Preferably, it is about 0.05 to 2% by weight, more preferably about 0.1 to 1% by weight.

  As the anti-inflammatory agent (B) of the present invention, any anti-inflammatory agent that is known to have a therapeutic, preventive and / or ameliorating action against inflammation and is pharmaceutically or physiologically acceptable is used. it can. The anti-inflammatory agent used in the present invention is not particularly limited, but glycyrrhizic acid, glycyrrhetinic acid, tranexamic acid, ε-aminocaproic acid, allantoin, salicylic acid, prednisolone, dexamethasone, hydrocortisone, ufenamate, bufexamac, ibuprofen piconol, indomethacin , Diclofenac, piroxicam, berberine, lysozyme, azulene, bromelain, serrapeptase, semi-alkaline proteinase and derivatives thereof, and salts thereof. Here, in the present specification, examples of the “derivative” include esterified derivatives, etherified derivatives, amidated derivatives, sulfonated derivatives, nitrated derivatives, nitrosated derivatives, halogenated derivatives, and the like. It is not limited to these. Preferably, the derivative used as component (B) is an esterified derivative and / or an etherified derivative, more preferably an esterified derivative. Examples of esterified derivatives include derivatives esterified with organic acids such as valeric acid, butyric acid, acetic acid, propionic acid and / or furan carboxylic acid, specifically, prednisolone valerate acetate, prednisolone acetate Dexamethasone acetate, hydrocortisone acetate, hydrocortisone butyrate, beclomethasone propionate, and the like.

  From the viewpoint that the effect of the present invention can be expected more reliably, glycyrrhizic acid, glycyrrhetinic acid, tranexamic acid, ε-aminocaproic acid, allantoin, salicylic acid, ibuprofen piconol, indomethacin, diclofenac and salts thereof are preferable. More preferred are glycyrrhizic acid, glycyrrhetinic acid, tranexamic acid, ε-aminocaproic acid, allantoin, and salts thereof, more preferred are glycyrrhizic acid, glycyrrhetinic acid, and salts thereof, and particularly preferred is glycyrrhizic acid and salts thereof. (For example, dipotassium glycyrrhizinate).

  The salt form of the anti-inflammatory agent (B) used in the present invention may be the same salt as listed above for the component (A). Of these, salts with sodium, potassium, calcium, magnesium, ammonium, diethanolamine, triethanolamine or ethylenediamine are preferred. Among these, a salt with sodium, potassium, or ammonium is mentioned as a more preferable example.

  The content of the component (B) in the composition for external use of the present invention is not particularly limited as long as the effects of the present invention can be achieved, but as an example, about 0.0001 wt% or more and 10 wt% or less with respect to the total amount of the composition, Preferably, it is about 0.001 to 5% by weight, more preferably about 0.01 to 3% by weight.

  Among the components of (C) coconut oil fatty acid acylamino acid type anionic surfactant used in the present invention, coconut oil fatty acid is a well-known mixed fatty acid obtained by hydrolysis of coconut oil, and is called cocoyl. Sometimes it is done. The coconut oil fatty acid acyl amino acid type anionic surfactant used in the present invention is coconut oil fatty acid and amino acids (for example, amino acids, sulfur-containing amino acids or their derivatives, and alkylation of about 1 to 4 carbon atoms thereof). Derivative) refers to a compound known as a surfactant exhibiting anionic property (anionic property). Here, the sulfur-containing amino acid-derived material refers to a compound that can be synthesized from a sulfur-containing amino acid (for example, methionine or cysteine) and does not have a carboxyl group but has a sulfone group. In particular, it refers to amino acid-like taurine or isethionic acid. Any pharmaceutically or physiologically acceptable coconut oil fatty acid acylamino acid-based anionic surfactant can be used. Specifically, coconut oil fatty acid acylamino acid-based anionic surfactants include coconut oil fatty acid acylglutamic acid (also referred to as cocoylglutamic acid), coconut oil fatty acid acylaspartic acid (also referred to as cocoylaspartic acid), coconut oil fatty acid acylglycine ( Cocoyl glycine), coconut oil fatty acyl glutamine (also called cocoyl glutamine), coconut fatty acid acyl asparagine (also called cocoyl asparagine), coconut fatty acid acyl alanine (also called cocoyl alanine), coconut oil fatty acyl threonine (cocoyl threonine) Anionic surfactants that are acylated products of coconut oil fatty acids and amino acids such as salts thereof; coconut oil fatty acid acyl sarcosine (also referred to as cocoyl sarcosine), coconut oil fatty acid acylmethylara (Also referred to as cocoyl methyl alanine) and anionic surfactants that are acylated products of coconut oil fatty acids such as salts thereof and C1-C4 alkylated amino acids; coconut oil fatty acid acyl taurine (also referred to as cocoyl taurine) An anionic surfactant which is an acylated product of a coconut oil fatty acid and a sulfur-containing amino acid derivative such as coconut oil fatty acid acylisethionic acid (cocoyl isethionic acid) and salts thereof; and coconut oil fatty acid acylmethyltaurine (cocoyl) And anionic surfactants that are acylated products of coconut oil fatty acids such as salts thereof and derivatives derived from C1-C4 alkylated sulfur-containing amino acids, and the like. It is not limited. From the viewpoint that the effect of the present invention can be expected more reliably, an anionic surfactant that is an acylated product of coconut oil fatty acid and amino acid is preferably used, and more preferably, coconut oil fatty acid acylglutamic acid, coconut oil. Fatty acyl aspartic acid, coconut oil fatty acid acyl glycine, coconut oil fatty acid acyl glutamine, coconut oil fatty acid acyl asparagine, coconut oil fatty acid acyl alanine, coconut oil fatty acid acyl threonine, and salts thereof are used, more preferably coconut oil fatty acid acyl Glutamic acid, coconut oil fatty acid acylaspartic acid, coconut oil fatty acid acylglycine, and salts thereof are used, and coconut oil fatty acid acylglutamic acid and salts thereof are particularly preferably used.

  As a form of the salt of (C) component used by this invention, it may be a salt similar to what was enumerated about (A) component above. Of these, salts with sodium, potassium, calcium, magnesium, ammonium, diethanolamine, triethanolamine or ethylenediamine are preferred. Among these, a salt with sodium, potassium, ammonium, or triethanolamine is mentioned as a more preferable example.

  The content of the component (C) in the composition for external use of the present invention is not particularly limited as long as the effects of the present invention can be achieved, but as an example, about 0.01 wt% or more and 50 wt% or less with respect to the total amount of the composition, The amount is preferably about 0.1% by weight to 40% by weight, more preferably about 0.3% by weight to 30% by weight.

  The blending ratio of (A) :( B) in the composition for external use of the present invention is not particularly limited as long as the effects of the present invention can be achieved, but is, as an example, a weight ratio of 1: 0.001 to 30, preferably 1: 0.005. -20, more preferably 1: 0.01-10. The blending ratio of (A) :( C) in the composition for external use of the present invention is not particularly limited as long as the effects of the present invention can be obtained, but by weight ratio, for example, 1: 0.01 to 70, preferably 1: It is 0.1-60, More preferably, it is 1: 1-50.

  The preferred pH of the external composition of the present invention is 4-8. Among them, the pH of the external composition of the present invention is particularly preferably 5 to 7.

  The composition for external use of the present invention can be provided by being contained in any container. It has been found that the decrease in the residual rate of the azole antifungal agent caused by the combined use with the anti-inflammatory agent is particularly remarkable when accommodated in a container having an inner wall composed of a specific resin material such as polyethylene resin. . As a specific example, when glycyrrhizic acid or a salt thereof and miconazole or a salt thereof are used as an anti-inflammatory agent, the decrease in the residual rate of miconazole is particularly significant when stored in a container having an inner wall made of polyethylene resin or the like. It is remarkable. According to the present invention, such a decrease in the residual rate of the azole antifungal agent can be effectively suppressed. Therefore, this invention can be used especially suitably when accommodated in the container which has such a specific resin raw material in at least one part of the surface which contacts the external composition to accommodate.

  Specifically, in the external composition of the present invention, at least a part of the container is made of polyethylene (PE) resin; polypropylene (PP) resin; polyethylene terephthalate (PET) resin, polybutylene terephthalate (PBT) resin, polytrimethylene terephthalate. Polyester (PEs) resins such as (PTT) resin, poly (1,4-cyclohexyldimethylene terephthalate) (PCT) resin, polyethylene naphthalate (PEN) resin, polybutylene naphthalate (PBT) resin; and mixed resins thereof It can be suitably provided by being housed in a container composed of a thermoplastic resin (thermoplastic plastic).

  In this specification, that at least a part of the container is the specific resin material means that a part or all of the container for the composition for external use is formed of the specific resin material. Here, the specific resin material is polyethylene resin, polypropylene resin, polyester resin (for example, polyethylene terephthalate resin, polybutylene terephthalate resin, polytrimethylene terephthalate resin, poly (1,4-cyclohexyldimethylene terephthalate) resin, polyethylene naphthalate. Resin, polybutylene naphthalate resin and the like) and mixed resins thereof. Here, the “part of the container” is at least a part of a part that comes into contact with the external composition contained therein. The part in contact with the composition for external use may be an inner stopper, a nozzle, a valve, an inner surface of the container, an innermost layer of a structure composed of a plurality of layers formed on the inner surface of the container, and the like. For example, in a container having an inner plug, only the inner plug portion may be formed of a specific resin material. Alternatively, the main body portion other than the inner plug may be formed of a specific resin material. Or the whole container may be shape | molded with the specific resin raw material. It is sufficient that at least a part of the surface in contact with the external composition is made of the specific resin material, but it is preferable that most of the contact surface is made of the specific resin.

  As described above, the present invention is also suitable in the case where at least a part of the inner wall is provided by being accommodated in a container made of the resin material. The ratio of the resin material in the entire inner wall that is in contact with the composition for external use of the present invention is not particularly limited, but for example, 30% or more of the inner wall portion, further 50% or more, further 70% or more, further 90% or more, In particular, the case where almost 100% (almost all of the inner wall) is the resin material can be mentioned.

  In the present invention, the shape of the specific resin material container and the capacity that can be accommodated therein are not particularly limited. For example, if it is a container as a shampoo for scalp, it can be a container that can accommodate an internal volume of 10 ml to 1000 ml, preferably 50 ml to 500 ml.

  In addition, the container filled with the external composition of the present invention may be an aerosol, a spray container or the like.

  In the present invention, the polyethylene resin refers to a crystalline thermoplastic resin containing a polymer obtained by polymerizing ethylene. The homopolymer of ethylene may be a constituent polymer. All types of high density polyethylene (HDPE), high pressure method low density polyethylene (LDPE), and linear low density polyethylene (L-LDPE) are included. A resin having a copolymer of another monomer and ethylene as a constituent polymer is also included in the polyethylene resin. When other monomers are contained, 80% or more, preferably 90% or more of ethylene as a structural unit is contained. Additives such as stabilizers and flame retardant aids can be added to such polymers to form polyethylene resins. As such a resin or a resin material container, a commercially available product can be used.

  In the present invention, the polypropylene resin refers to a resin containing a homopolymer of propylene and a random copolymer containing other monomer units (for example, ethylene or butene-1). Furthermore, although not limited, a polypropylene resin including 40 to 50% by weight of an ethylene-propylene copolymer and 50 to 60% by weight of a propylene homopolymer is also included in the polypropylene resin. Additives such as stabilizers and flame retardant aids can be added to such polymers to form polypropylene resins. As such a resin or a resin material container, a commercially available product can be used.

  In the present invention, the polyester resin refers to an ester resin obtained by copolymerizing a polyhydric alcohol and a polyvalent carboxylic acid (for example, terephthalic acid). Typical examples thereof include a polyethylene terephthalate (PET) resin and a polyresin. Examples include but are not limited to butylene terephthalate (PBT) resin.

  In the present invention, the polyethylene terephthalate resin refers to a resin comprising a condensation polymer of terephthalic acid or its dimethyl ester and ethylene glycol as a constituent polymer. Additives such as stabilizers and flame retardant aids can be added to such polymers to form polyethylene terephthalate resins. Preferably, the polyethylene terephthalate resin used in the present invention is a polymer synthesized by polycondensation of terephthalic acid or a dimethyl ester thereof and ethylene glycol, 50% by weight or more of the polymer components constituting the resin, more preferably It occupies 60% by weight or more. As such a resin or a resin material container, a commercially available product can be used.

  The polybutylene terephthalate resin includes a polymer obtained by a known polymerization method such as polycondensation of terephthalic acid or an ester-forming derivative thereof and 1,4-butanediol. Additives such as stabilizers and flame retardant aids can be added to such polymers to form PBT resins. The polymer synthesized by polycondensation of terephthalic acid or its ester-forming derivative and 1,4-butanediol may optionally contain other monomers as constituent components. It may be included. Other polymers include, but are not limited to, polycarbonate, (meth) acrylic acid polymers, polystyrene, polyethylene naphthalate, polyethylene terephthalate (PET), polyethylene (PE), polyarylate, and the like. Here, although not limited, examples of the ester-forming derivative of terephthalic acid include dimethyl terephthalate. Preferably, the PBT resin used in the present invention is a polymer synthesized by polycondensation of terephthalic acid or an ester-forming derivative thereof and 1,4-butanediol, and 50% by weight or more of the polymer components constituting the resin. More preferably, it occupies 60% by weight or more. These can also use a commercially available thing.

  The specific material resin of the present invention further includes a resin in which the resin is reinforced with a reinforcing agent such as glass fiber.

  In the composition for external use of this invention, arbitrary components other than (A) component, (B) component, and (C) component may be included.

  The external composition of the present invention may contain a local anesthetic. One or two selected from the group consisting of procaine, tetracaine, lidocaine, dibucaine, bupivacaine, mepivacaine, ropivacaine, levobupivacaine, and pharmaceutically acceptable salts thereof, and ethyl aminobenzoate as the local anesthetic agent It is preferable that it is a seed or more.

  The external composition of the present invention may contain a vitamin preparation. Vitamins such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate and the like, ubiquinone derivatives and their pharmacologically acceptable Salts, riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin sodium 5'-phosphate, riboflavin tetranicotinate, nicotinic acid dl-α-tocopherol, benzyl nicotinate, Methyl nicotinate, β-butoxyethyl nicotinate, 1- (4-methylphenyl) ethyl nicotinate, ascorbigen-A, ascorbyl stearate, ascorbyl palmitate L-ascorbyl dipalmitate, methyl hesperidin, ergocalciferol, cholecalciferol, phylloquinone, farnoquinone, γ-oryzanol, dibenzoylthiamine, dibenzoylthiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, Thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate Ester, thiamine triphosphate monophosphate, pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-pyridoxal phosphate, pyridoxamine hydrochloride, cyanocobala Min, hydroxocobalamin, deoxyadenosylcobalamin, folic acid, pteroylglutamic acid, nicotinic acid, nicotinic acid amide, pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-panthecin, D-panthetin, coenzyme A Pantothenic acids such as pantothenyl ethyl ether, biotin, bioticin, ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, carnitine, ferulic acid, α-lipoic acid, orot It is preferably one or more selected from the group consisting of acid, hesperidin, γ-oryzanol, orotic acid, rutin, eriocitrin and pharmacologically acceptable salts thereof.

  The composition for external use of the present invention may contain a bactericidal agent. Disinfectants include isopropylmethylphenol, decalinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, alkyldiaminoethylglycine hydrochloride, cetylpyridinium chloride, sodium benzoate, ethanol, chlorobutanol, sorbic acid 1 selected from the group consisting of potassium sorbate, sodium dehydroacetate, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, and biguanide compounds It is preferable to be a seed or two or more.

  The composition for external use of the present invention may contain an antipruritic component. Such other antipruritic components are preferably one or more selected from the group consisting of crotamiton, ectamol, moctamol, thymol acid and pharmacologically acceptable salts thereof.

  The composition for external use of the present invention is provided in any form that can be widely used as a pharmaceutical, a quasi-drug, a cosmetic and the like. Preferably, it is provided as a preparation that can be used as an external preparation for skin and / or hair.

(External preparation form for skin and / or hair)
The composition for external use containing the (A) azole antifungal agent, (B) anti-inflammatory agent, and (C) coconut oil fatty acid acylamino acid anionic surfactant of the present invention is a pharmaceutical, quasi-drug, cosmetic. As such, it can be used in the form of an external preparation for skin and / or hair. In these external preparation forms, in addition to the component (A), the component (B), and the component (C), the external preparation for skin and / or hair (pharmaceutical part) within a range not impairing the effects of the present invention. A known base or carrier added to external products, pharmaceuticals, cosmetics, etc.) can be used by mixing. In addition, such external preparations for skin and / or hair include, for example, transdermal absorption enhancers, other surfactants, oils, alcohols, hydrophilic gelling agents, lipophilic gelling agents, humectants, Thickeners, preservatives, antioxidants, chelating agents, preservatives, pH adjusters, stabilizers, dispersants, fragrances, colorants, dyes, pearlescent agents, blood circulation promoting ingredients, moisturizing ingredients, UV absorbing ingredients UV scattering components, cleaning components, astringent components, peptides, amino acids, keratin softening components, cell activation components, solubilizing agents, water, and the like can be blended. An additive can be used individually by 1 type or in combination of 2 or more types.

  Oils that can be used in the present invention include mineral oil (fluid petroleum jelly), vegetable oil (liquid fraction of karite butter, sunflower oil), animal oil (perhydrosqualene), synthetic oil (purserine oil), silicone oil or Examples include wax (cyclomethicone), fluorinated oil (perfluoropolyether), beeswax, carnauba wax, and paraffin wax.

  In the present invention, other surfactants can be used in combination.

  The alcohol that can be used in the present invention is preferably a lower alcohol, particularly ethanol, isopropanol, or propylene glycol.

  Hydrophilic gelling agents that can be used in the present invention can include carboxyvinyl polymers, acrylic copolymers such as acrylate / alkyl acrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays. . The lipophilic gelling agent that can be used in the present invention includes modified clays such as bentone, metal salts of fatty acids such as aluminum stearate, and hydrophobic silica, ethylcellulose and polyethylene.

  Other bases or carriers include liquid paraffin; isopropyl palmitate; carboxyvinyl polymer; water based bases such as water.

  Solvents such as alcohols, gelling agents, bases or carriers can be used singly or in combination of two or more.

  The composition for external use of the present invention can be any dosage form suitable for use on, for example, hair and skin, as a known form of a pharmaceutical product, quasi-drug, cosmetic product and the like. The external composition of the present invention may be a leave-on-type external composition that is not washed away after use, or may be a cleaning composition that is washed away after use. When the external composition of the present invention is a cleaning composition, the form is not particularly limited, but soap (solid soap, liquid soap, foam soap, body soap (also called body shampoo), hand soap, etc., cleansing foam Shampoo (hair shampoo, dry shampoo, rinse-in shampoo, etc.) Further, it may be in the form of a rinse, a conditioner, etc. Among these, liquid soap, body soap, hand soap, shampoo, rinse are preferred, The composition for external use of the present invention includes lotions, gels, mousses, solutions, suspensions, emulsions, creams, ointments, gels, liniments, aerosols, powders, poultices, non-woven fabrics, etc. It is also provided as a sheet agent, a spray or the like obtained by impregnating a sheet with a chemical solution. However, it is preferably used in the form of a solution, a suspension, an emulsion, a cream, an ointment, a gel, etc. By using such a form, the composition for external use of the present invention sufficiently exhibits a superior effect. The composition for external use of the present invention is preferably used as a shampoo, a body soap, a hand soap, or a face wash, which is also supposed to be used in a pump container equipped with a nozzle. .

  The external composition of the present invention can be provided in any container. According to the composition for external use of the present invention, it is possible to suppress an increase in formulation viscosity over time, and to suppress white residue after drying. Such an increase in viscosity or generation of white residue is generally observed when used in a bottle-type container having a discharge port with a small diameter or a pump-type container having an elongated nozzle that sucks and discharges a preparation. The problem is likely to cause clogging. Therefore, the composition for external use of the present invention can be suitably used by being housed in a container having such a small discharge port or a long and narrow nozzle, for example, a narrow bottle or a pump container. The diameter of the discharge port and the nozzle is not particularly limited, and examples thereof include a diameter of about φ1.5 to 5.0 mm. As the size of the long and narrow nozzle used in the pump type container or the like, one having a length from the suction port to the discharge port of about 10 to 25 cm can be exemplified.

  In addition, the increase in the viscosity of the preparation over time tends to cause problems such as clogging in a preparation having a relatively high viscosity, which is a serious problem. ADVANTAGE OF THE INVENTION According to this invention, a viscosity rise can be suppressed effectively, although it is an external composition containing an azole type antifungal agent with a coconut oil fatty-acid amino acid type anionic surfactant. In view of this viewpoint, the present invention has a viscosity of about 1 to 2000000 mPa · s, generally 1 to 1000000 mPa · s when measured at 25 ° C. using an E-type viscometer or a B-type viscometer depending on the viscosity. For example, it may be a preparation having a high viscosity of about 100 to 100000 mPa · s or about 300 to 100,000 mPa · s.

  Since the composition for external use of the present invention contains an azole antifungal agent, it can be used in any scene where it is desired to exert an antifungal effect. For example, the composition for external use of the present invention has scalp eczema, dandruff, ringworm (for example, foot ringworm, body ringworm, hip ringworm), candidiasis (for example, finger erosion, rash), folding screen, etc. It is suitably used for the treatment, prevention and / or improvement. The composition for external use of the present invention can be applied to skin and hair where the symptoms caused by fungi are anxious, and is applied to the skin and hair where symptoms caused by fungi are anxious. It can also be used after being washed away with moisture or the like. Preferably, the composition for external use of the present invention is used for washing hair and skin. The usage is not particularly limited, and may be used about once a day as long as it is a shampoo. Alternatively, it may be used regularly several times a day (for example, three times in the morning, noon, and evening), or may be used in a timely manner as necessary. In the case of an external preparation for skin and / or hair, an appropriate amount (for example, about 0.1 to 10 g) can be applied by applying, rubbing or spraying to the skin and / or hair.

  The present invention also provides a product in which a composition for external use is contained in a specific resin container. The composition for external use of the present invention can be provided as a shampoo, body soap, hand soap, face wash, etc. in a container.

  The present invention provides a composition for external use by allowing (A) an azole antifungal agent, (B) an anti-inflammatory agent, and (C) a palm oil fatty acid acylamino acid based anionic surfactant to coexist in the composition for external use. The present invention relates to a method for suppressing an increase in viscosity of a product over time. As one aspect of the present method, the present invention includes (B) an anti-inflammatory agent in a composition containing (A) an azole antifungal agent and (C) a coconut oil fatty acid acylamino acid anionic surfactant. Thus, the present invention relates to a method for suppressing an increase in viscosity of the composition over time.

  Here, “suppressing the increase in viscosity over time” is not limited, but for example, the viscosity increase rate shown in the examples preferably shows a numerical value within 70%, or more preferably 60% Indicates a numerical value within.

  In the composition for external use, the present invention also provides (A) an azole antifungal agent, (B) an anti-inflammatory agent, and (C) a palm oil fatty acid acylamino acid type anionic surfactant. The present invention relates to a method for suppressing white residue after drying of a composition. As one aspect of the present method, the present invention includes (B) an anti-inflammatory agent in a composition containing (A) an azole antifungal agent and (C) a coconut oil fatty acid acylamino acid anionic surfactant. It is related with the method of suppressing the white residue after drying of this composition.

  Here, “suppresses the white residue after drying” means an absorbance at 660 nm after drying of the composition of 0.8 or less, preferably 0.7 or less, more preferably 0.6 or less, and still more preferably 0.4. Indicates the following:

  In the composition for external use, the azole type antifungal agent, (B) anti-inflammatory agent, and (C) coconut oil fatty acid acylamino acid type anionic surfactant coexist in the composition for external use. The present invention relates to a method for suppressing a decrease in the residual rate of an antifungal agent. As one aspect of the present method, the present invention includes (A) an azole antifungal agent and (B) an anti-inflammatory agent, and (C) a coconut oil fatty acid acylamino acid anionic surfactant. It is related with the method of suppressing the residual rate fall of an azole type antifungal agent.

  Here, the residual rate of the azole antifungal agent is not limited, but is obtained by the measurement method in the examples, and is preferably 75% or more, more preferably 80% or more, and further preferably 90% or more. Point to.

  In the present invention, part or all of the contact surface may be polyethylene resin, polypropylene resin, polyester resin (for example, polyethylene terephthalate resin, polybutylene terephthalate resin, polytrimethylene terephthalate resin, poly (1,4-cyclohexyldimethylene). Terephthalate) resin, polyethylene naphthalate resin, polybutylene naphthalate resin, etc.), and a composition for external use contained in a container composed of at least one selected from the group consisting of mixed resins thereof (A) The coexistence of an azole antifungal agent, (B) an anti-inflammatory agent, and (C) a coconut oil fatty acid acylamino acid anionic surfactant reduces the residual rate of the azole antifungal agent in the composition for external use. The present invention relates to a suppression method. As one aspect of the present method, the present invention provides a container in which a part or all of the contacting surface is made of at least one selected from the group consisting of a polyethylene resin, a polypropylene resin, a polyester resin, and a mixed resin thereof. (C) a topical composition containing (A) an azole antifungal agent and (B) an anti-inflammatory agent, and (C) a coconut oil fatty acid acylamino acid anionic surfactant. The present invention relates to a method for suppressing a decrease in the residual rate of an azole antifungal agent in a composition.

  In the above-described viscosity increase suppressing method, white residue suppressing method, and azole antifungal agent residual rate decrease suppressing method, (A) the azole antifungal agent is miconazole, lanconazole, luliconazole, isoconazole, ketoconazole, clotrimazole, fluconazole. , Itraconazole, neticonazole, sulconazole, bifhonazole, phosfluconazole, voriconazole, and salts thereof.

  In the above method, (B) anti-inflammatory agent is glycyrrhizic acid, glycyrrhetinic acid, tranexamic acid, ε-aminocaproic acid, allantoin, salicylic acid, prednisolone, dexamethasone, hydrocortisone, ufenamate, bufexamac, ibuprofen piconol, indomethacin, diclofenac, piroxicam, It may be at least one selected from the group consisting of berberine, lysozyme, azulene, bromelain, serrapeptase, semi-alkaline proteinase and derivatives thereof (for example, esterified derivatives, etherified derivatives, etc.) and salts thereof.

  In the above method, (C) coconut oil fatty acid acylamino acid type anionic surfactant is coconut oil fatty acid acylglutamic acid, coconut oil fatty acid acylaspartic acid, coconut oil fatty acid acylglycine, coconut oil fatty acid acylglutamine, coconut oil fatty acid acylasparagine. , Coconut oil fatty acid acyl alanine, coconut oil fatty acid acyl threonine, coconut oil fatty acid acyl sarcosine, coconut oil fatty acid acyl methylalanine, coconut oil fatty acid acyl taurine, coconut oil fatty acid acyl methyl taurine, coconut oil fatty acid acyl isethionic acid, and salts thereof It may be at least one selected from the group consisting of:

  The external composition in the above method may have a viscosity at 25 ° C. of 1 mPa · s or more.

  In the said method, content of (A) component may be 0.01 weight% or more with respect to the external composition whole quantity.

  In the said method, content of (B) component may be 0.0001 weight% or more with respect to the external composition whole quantity.

  In the said method, content of (C) component may be 0.01 weight% or more with respect to the external composition whole quantity.

The composition for external use of this invention contains the following (A), (B), and (C) component, for example.
(A) miconazole, (B) salicylic acid, and (C) coconut oil fatty acid acylmethylalanine triethanolamine;
(A) Ranoconazole, (B) monoammonium glycyrrhizinate, and (C) coconut oil fatty acid acylmethyl taurine sodium;
(A) ketoconazole, (B) monoammonium glycyrrhizinate, and (C) coconut oil fatty acid acylalanine sodium;
(A) luliconazole, (B) dipotassium glycyrrhizinate, and (C) sodium coconut oil fatty acid acyl glutamate.

  The present invention also provides an external composition containing (A) an azole antifungal agent, (B) an anti-inflammatory agent, and (C) a coconut oil fatty acid acylamino acid anionic surfactant, at least partly of a specific resin. The present invention relates to a product of an external composition contained in a container, which is housed in a container as a raw material.

  Although not particularly limited, the present invention particularly preferably comprises (A) miconazole nitrate, (B) dipotassium glycyrrhizinate, allantoin, tranexamic acid, or ε-aminocaproic acid, and (C) coconut oil fatty acid acyl glutamate. There is provided a cleaning product as an external composition in a container, wherein the external composition is contained in a container in which at least part or all of the inner wall is made of a polyethylene material, a polypropylene material, and / or a polyethylene terephthalate material.

  EXAMPLES The present invention will be described in detail below based on examples, but the present invention is not limited to these examples.

Example 1
The formulation shown in Table 1 below was prepared according to a conventional method. Specifically, each compound was weighed into a 100 ml glass vial and a required amount of distilled water was added. The mixture was stirred at a temperature of about 80 ° C. to obtain a uniform preparation.

(Comparative Examples 1-2)
In the same manner as in Example 1, the formulations shown in Table 1 were prepared.

(Test Example 1: Evaluation of viscosity stability)
Immediately after the preparation, the viscosity (25 ° C.) of the compositions of Example 1 and Comparative Examples 1 and 2 was measured with an E-type rotational viscometer (manufactured by TOKIMEC), and the average value was calculated (initial viscosity value).

Next, 5 mL of each test composition was added to a 6-well plate (φ33.78 mm, manufactured by TPP) and allowed to stand at room temperature for 24 hours. Thereafter, the viscosity (25 ° C.) of each test composition was measured in the same manner as immediately after preparation, and the average value was calculated for each test composition (viscosity value after storage). Then, the viscosity increase value was calculated by subtracting the viscosity value after storage for each test composition from the initial viscosity value. Then, for example, in Example 1, according to the following formula I, the rate of increase in viscosity of the test composition (comparative example 2) containing miconazole nitrate is 100 with respect to the control (comparative example 1) containing no miconazole nitrate. The viscosity increase rate (%) was calculated. The results are also shown in Table 1 below. Hereinafter, the values of Examples 2 to 4 also conform to this formula.
[Formula I] Viscosity increase rate (%) = {(Viscosity increase value of Example 1−Viscosity increase value of Comparative Example 1) / (Viscosity increase value of Comparative Example 2−Viscosity increase value of Comparative Example 1)} × 100

  Comparative Example 2 prepared by adding miconazole nitrate to the same base in this test example, compared to a test composition containing only a base containing a palm oil fatty acid acylamino acid-based anionic surfactant (Comparative Example 1, Control) In the test composition, a clear increase in viscosity was observed even after storage for only 24 hours. On the other hand, it was completely unexpected that it was found that when the test composition containing these two components was further combined with dipotassium glycyrrhizinate, the rate of increase in viscosity could be effectively suppressed.

(Examples 2 to 4)
Test compositions shown in Table 2 below were prepared in the same procedure as in Example 1.

(Test Example 2: Viscosity stability evaluation)
Similarly, the initial viscosity value immediately after preparation and the viscosity value after storage for 24 hours are measured, and the viscosity of the test composition (comparative example 2) containing miconazole nitrate is compared with the control not containing miconazole nitrate (comparative example 1). The viscosity increase rate (%) when the increase rate was 100 was calculated. The results are also shown in Table 2 below.

  As shown in the results of this test, (B) even when allantoin, tranexamic acid, or ε-aminocaproic acid is used as an anti-inflammatory agent, a base containing a palm oil fatty acid acylamino acid anionic surfactant is used. It was revealed that the increase in viscosity can be suppressed when miconazole nitrate is added.

(Examples and Comparative Examples 3 to 5)
Test compositions of Examples and Comparative Examples 3 to 5 were prepared according to the formulation shown in Table 3 below. The preparation method is the same as in Example 1.

(White remaining evaluation (1))
The test composition of Example 1 and Comparative Examples 1 to 5 was added to each well of a plastic petri dish (FALCON EASY GRIP Petri Dish (35 × 10 mm), polystyrene, BECTON DICKINSON Labware, NJ, USA) at room temperature. The water was evaporated by leaving still for 4 days. After evaporation of water, the absorbance at 660 nm was measured for each well using a microplate reader (SH-9000, manufactured by Corona Electric Co., Ltd.), and the turbidity of each well was determined to determine the white residue (precipitation of white crystals). It was.

The absorbance (660 nm) after drying of each test composition is also shown in the bottom column of Table 3 above. Moreover, the photograph which image | photographed each test composition after drying is shown in FIG. From the upper left of FIG. 1: Comparative Example 2 [A + C], Example 1 [A + B + C], Comparative Example 1 [C]
From the lower left: Comparative Example 3 [B + C], Comparative Example 4 [A + C (increase)], and Comparative Example 5 [C (increase)]. As shown in these results, no white residue is observed after drying in Comparative Example 1 in which only the base of the palm oil fatty acid acylamino acid-based anionic surfactant is used. And in the comparative example 2 which added miconazole nitrate to this, it turns out that a lot of white crystals precipitate in the petri dish after drying, and a white residue is intense. On the other hand, in Example 1 in which dipotassium glycyrrhizinate was added to the test composition containing these two components, white residue was suppressed to a level that was apparent even visually. Since it was considered that the white residue improvement effect observed in Example 1 was due to the surface-active action of dipotassium glycyrrhizinate, the amount of coconut oil fatty acid acylamino acid-based anionic surfactant was adjusted to the amount of surfactant in Example 1. When Comparative Example 4 was prepared by increasing the total amount (sodium coconut oil fatty acid acyl glutamate 3% by weight + dipotassium glycyrrhizinate 0.5% by weight = 3.5% by weight) and evaluated in the same manner, Comparative Example 4 was almost white. It became clear that the rest did not improve. From the above results, it was also clarified that the high white balance improvement effect recognized in Example 1 was not due to mere surface active action.

(Examples 5-6)
A composition having the formulation shown in Table 4 was prepared in the same manner as in Example 1.
(Comparative Examples 6-7)
In the same manner as in Examples 5 to 6, compositions having the formulations of Comparative Examples 6 to 7 were prepared.

(White remaining evaluation (2))
Evaluation was made on the occurrence and degree of white residue after drying. The absorbance value (660 nm) measured after drying for each test composition is also shown in the bottom column of Table 4 below.

  As shown in the above test results, (B) even when tranexamic acid is used as the anti-inflammatory agent, white when miconazole nitrate is added to a base containing a palm oil fatty acid acylamino acid type anionic surfactant is used. It became clear that the remaining occurrence can be suppressed. In addition, from the results of this test example, when (C) coconut oil fatty acid acylamino acid-based anionic surfactant was used, coconut oil fatty acid acylmethyl taurine sodium was used as (B) glycyrrhizic acid as an anti-inflammatory agent. It was also clarified that when tranexamic acid was used, the white residue improvement effect was higher.

(Example 7)
A composition having the formulation shown in Table 5 was prepared in the same manner as in Example 1.

(Comparative Examples 8-9)
In the same manner as in Example 7, compositions having the formulations of Comparative Examples 8 and 9 were prepared.

(Stability evaluation of azole antifungal agents (1))
Each of the prepared test compositions was filled in a sealed container at 5 mL, and a high temperature accelerated test was conducted at 60 ° C. for 2 weeks in a thermostatic bath. Then, the test preparation was extracted with an internal standard substance (ethyl acetate solution of benzyl salicylate (1 → 5000)), and the sample obtained by diluting the obtained upper layer with methanol twice was analyzed by high performance liquid chromatography (HPLC). Was quantified. HPLC measurement conditions are as follows. Further, the content of miconazole nitrate in each test composition was determined by an internal standard method by HPLC method, and the initial content at the time of preparation was taken as 100%, miconazole nitrate in each test composition after storage for 1 week The content ratio was calculated as the residual rate (%). The results are also shown in the bottom column of Table 5 below.

(HPLC measurement method)
・ Column: GL Sciences Inc., filled with octadecylsilica gel (Inertsil ODS-2)
・ Column size: 5μm, φ4.6 × 150mm
Eluent: Methanol: 50 mM ammonium dihydrogen phosphate solution = 85:15
-Flow rate: Adjusted so that the retention time of miconazole nitrate is about 8 minutes.-Detector: Ultraviolet absorptiometer (measurement wavelength: 267 mm)
-Column temperature: 40 ° C
・ Injection volume: 10 μl

  As shown in the results of Table 5 above, it can be seen that miconazole nitrate significantly decreases the residual rate when it coexists with dipotassium glycyrrhizinate. On the other hand, unexpectedly, when coconut oil fatty acid acyl glutamate sodium is further added to the test composition containing these two components, the residual ratio of miconazole nitrate is highly improved, resulting in a very stable preparation. It became clear.

(Examples 8 to 9)
In the same manner as in Example 1, compositions having the formulations shown in Table 6 were prepared.

(Stability evaluation of azole antifungal agents (2))
For the formulation shown in Table 6 below, the remaining rate of miconazole nitrate (%) after the high-temperature accelerated test was substantially the same as the stability evaluation (1) except that the accelerated test condition was changed to 60 ° C for one week. ) Was evaluated. The results are also shown in the bottom column of Table 6 below.

  As shown in the results of Table 6 above, the decrease in the residual rate of miconazole nitrate caused by the coexistence with dipotassium glycyrrhizinate is in the case of using coconut oil fatty acid sodium acylaspartate or coconut oil fatty acid acylglycine potassium in combination. It became clear that it can be improved to a high degree.

(Example 10)
In the same manner as in Example 1, compositions were prepared for the formulations shown in Table 7.

(Stability evaluation of azole antifungal agents (3))
For the formulation shown in Table 7 below, the remaining rate of miconazole nitrate (%) after the high-temperature accelerated test was substantially the same as the stability evaluation (1) except that the accelerated test conditions were changed to 4 weeks at 60 ° C. Was evaluated. The results are also shown in the bottom column of Table 7 below.

  As shown in the results of Table 7 above, when (C) coconut oil fatty acid acylamino acid-based anionic surfactant is sodium coconut oil fatty acid acylmethyltaurine sodium, miconazole nitrate in the presence of dipotassium glycyrrhizinate is used. It was confirmed that the decrease in the residual rate can be suppressed. However, the improvement rate of the residual ratio was more excellent when sodium coconut fatty acid acyl glutamate was used as the component (C).

(Reference example)
A composition having the formulation shown in Table 8 was prepared in each container.

(Stability evaluation of azole antifungal agents (4))
The relationship between the container material and the change in the residual rate of the azole antifungal agent was evaluated. Specifically, the composition of the formulation shown in Table 8 below is placed in containers (PE: polyethylene resin container, PP: polypropylene resin container, PET: polyethylene terephthalate resin container, glass: glass container) composed of various materials. Each was filled and subjected to a high temperature accelerated test at 60 ° C. for 2 weeks in a thermostatic bath. Thereafter, the content of miconazole nitrate in each test composition was determined by HPLC, and the residual rate (%) after the high-temperature acceleration test was calculated. The results are shown in Table 8 below together with the notation of each container material.

  As shown in the results of Table 8 above, the decrease in the residual rate of miconazole nitrate in the presence of dipotassium glycyrrhizinate is composed of polyethylene resin, polypropylene resin, polyethylene terephthalate resin, etc., as compared with the case where it is accommodated in a glass container. It was found to be particularly remarkable when stored in a plastic container.

(Comparative Examples 10-15)
(Examples 11 to 16)
Next, external compositions shown in Table 9 and Table 10 were prepared.

  About these external compositions, the residual rate improvement effect when accommodated in a plastic container was further evaluated. Specifically, preparations shown in Tables 9 and 10 below were prepared, filled in containers (PE, PP, PET) composed of various materials, stored at 60 ° C. for 3 weeks, and miconazole nitrate was prepared by HPLC. The residual rate (%) was calculated. The results are also shown in Tables 9 and 10 below.

  As shown in the results of Tables 9 and 10 above, the palm oil fatty acid acylamino acid type anionic surfactant is added even when it is contained in a resin container that tends to cause a significant decrease in the residual rate of miconazole nitrate due to the coexistence of dipotassium glycyrrhizinate. Furthermore, it was recognized that the residual ratio was improved by combining them in particular, and in particular, when palm oil fatty acid sodium acylglutamate was used as component (C), a particularly high residual ratio improvement effect was obtained.

  Hereinafter, formulation formulation examples of the composition for external use of the present invention will be shown.

(Formulation Formulation Example 1)
Miconazole nitrate 0.7% by weight
Glycyrrhizic acid dipotassium salt 0.5% by weight
Ibuprofen piconol 0.5% by weight
N-coconut oil fatty acid acyl-L-sodium glutamate 10.0% by weight
Coconut oil fatty acid diethanolamide 3.0% by weight
Concentrated glycerin 1.0% by weight
Chelating agent
pH adjuster Appropriate amount of preservative Appropriate amount of antioxidant Appropriate amount of perfume Appropriate amount of purified water

(Preparation Example 2)
Ranoconazole 1.0% by weight
Salicylic acid 0.5% by weight
Glycyrrhetinic acid 0.1% by weight
N-coconut oil fatty acid acyl-DL-alanine triethanolamine 5.0 wt%
Palm oil fatty acid diethanolamide 1.0 wt%
Concentrated glycerin 5.0% by weight
Chelating agent
pH adjuster appropriate amount preservative appropriate amount perfume appropriate amount antioxidant appropriate amount purified water balance

(Prescription Formulation Example 3)
Luliconazole 1.0% by weight
Dipotassium glycyrrhizinate 0.5% by weight
Allantoin 0.5% by weight
Coconut oil fatty acid acylmethyl taurine sodium 3.0% by weight
Coconut oil fatty acid diethanolamide 3.0% by weight
Concentrated glycerin 10.0% by weight
Chelating agent
pH adjuster appropriate amount preservative appropriate amount perfume appropriate amount antioxidant appropriate amount purified water balance

Claims (15)

  (A) miconazole or a salt thereof, (B) at least one anti-inflammatory agent selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, tranexamic acid, ε-aminocaproic acid, allantoin and salts thereof, and (C) palm Oil fatty acid acyl glutamic acid (cocoyl glutamic acid), coconut oil fatty acid acyl aspartic acid (cocoyl aspartic acid), coconut oil fatty acid acyl glycine (cocoyl glycine), coconut oil fatty acid acyl glutamine (cocoyl glutamine), coconut oil fatty acid acyl asparagine (cocoyl asparagine) An anionic surface activity that is an acylated product of a coconut oil fatty acid and an amino acid selected from the group consisting of coconut oil fatty acid acylalanine (cocoyl alanine), coconut oil fatty acid acyl threonine (cocoyl threonine), and salts thereof Agent containing, external composition.   The composition for external use according to claim 1, wherein the (A) miconazole or a salt thereof is a nitrate of miconazole.   The composition for external use according to claim 1 or 2, wherein the (B) anti-inflammatory agent is dipotassium glycyrrhizinate or tranexamic acid.   The component (C) is at least one selected from the group consisting of coconut oil fatty acid acylglutamic acid, coconut oil fatty acid acylaspartic acid, coconut oil fatty acid acylglycine, coconut oil fatty acid acylalanine, and salts thereof. Item 4. The external composition according to any one of Items 1 to 3.   It is an external composition of any one of Claims 1-4, Comprising: Part or all of the surface which contacts this external composition consists of polyethylene resin, polypropylene resin, polyester resin, and those mixed resins. The composition for external use accommodated in the container comprised by at least 1 sort (s) selected from a group.   The composition for external use of any one of Claims 1-5 accommodated in the pump type container provided with the nozzle, or a narrow mouth type bottle container.   The composition for external use of any one of Claims 1-6 whose viscosity in 25 degreeC is 1 mPa * s or more.   The composition for external use of any one of Claims 1-7 whose content of the said (A) component is 0.01 weight% or more with respect to the composition whole quantity.   The external composition of any one of Claims 1-8 whose content of the said (B) component is 0.0001 weight% or more with respect to the composition whole quantity.   The composition for external use of any one of Claims 1-9 whose content of the said (C) component is 0.01 weight% or more with respect to the composition whole quantity.   The external composition of any one of Claims 1-10 used in order to wash | clean hair or skin.   (A) miconazole or a salt thereof, and (C) coconut oil fatty acid acylglutamic acid (cocoylglutamic acid), coconut oil fatty acid acylaspartic acid (cocoylaspartic acid), coconut oil fatty acid acylglycine (cocoylglycine), coconut oil fatty acid acylglutamine ( Coconut glutamine), coconut oil fatty acid acyl asparagine (cocoyl asparagine), coconut oil fatty acid acyl alanine (cocoyl alanine), coconut oil fatty acid acyl threonine (cocoyl threonine), and coconut oil fatty acids and amino acids selected from the group consisting of these salts And (B) glycyrrhizic acid, glycyrrhetinic acid, tranexamic acid, ε-aminocaproic acid, allantoin, and salts thereof are selected from the group consisting of an anionic surfactant and an anionic surfactant. At least one by the coexistence of anti-inflammatory agent, a method of suppressing the temporal increase in the viscosity of the external composition that. (A) miconazole or a salt thereof, and (C) coconut oil fatty acid acylglutamic acid (cocoylglutamic acid), coconut oil fatty acid acylaspartic acid (cocoylaspartic acid), coconut oil fatty acid acylglycine (cocoylglycine), coconut oil fatty acid acylglutamine ( Coconut glutamine), coconut oil fatty acid acyl asparagine (cocoyl asparagine), coconut oil fatty acid acyl alanine (cocoyl alanine), coconut oil fatty acid acyl threonine (cocoyl threonine), and coconut oil fatty acids and amino acids selected from the group consisting of these salts is acylated with a topical composition containing an anionic surfactant, (B) glycyrrhizic acid, glycyrrhetinic acid, tranexamic acid, Contact and at least one anti-inflammatory agent selected from the group consisting of salts Coexist In Rukoto, method of suppressing the white remaining after drying of the external composition. (A) miconazole or a salt thereof and (B) glycyrrhizic acid, glycyrrhetinic acid, a topical composition comprising at least one anti-inflammatory agent selected from the Contact and the group consisting of salts, (C) coconut oil Fatty acid acyl glutamic acid (cocoyl glutamic acid), coconut oil fatty acid acyl aspartic acid (cocoyl aspartic acid), coconut oil fatty acid acyl glycine (cocoyl glycine), coconut oil fatty acid acyl glutamine (cocoyl glutamine), coconut oil fatty acid acyl asparagine (cocoyl asparagine), An anionic surfactant that is an acylated product of a coconut oil fatty acid and an amino acid selected from the group consisting of coconut oil fatty acid acylalanine (cocoyl alanine), coconut oil fatty acid acyl threonine (cocoyl threonine), and salts thereof is allowed to coexist. (A A method of suppressing the decrease residual rate of component. Part or all of the contacting surface is accommodated in a container composed of at least one selected from the group consisting of polyethylene resin, polypropylene resin, polyester resin, and mixed resins thereof, (A) miconazole or its salt, and (B) glycyrrhizic acid, glycyrrhetinic acid, Contact and the composition for external application containing at least one anti-inflammatory agent selected from the group consisting of salts, (C) coconut oil fatty acid acyl glutamic acid (cocoyl glutamate ), Coconut fatty acid acyl aspartic acid (cocoyl aspartic acid), coconut oil fatty acid acyl glycine (cocoyl glycine), coconut oil fatty acid acyl glutamine (cocoyl glutamine), coconut oil fatty acid acyl asparagine (cocoyl asparagine), coconut oil fatty acid acyl alanine ( Cocoyl Alanine), Ya An oily fatty acyl threonine (cocoyl threonine), and an anionic surfactant that is an acylated product of a coconut oil fatty acid and an amino acid selected from the group consisting of these salts, coexisting miconazole or A method for suppressing a decrease in the residual rate of the salt.