External preparation

Abstract

To provide an external preparation that contains 3-10 w / v% of minoxidil, pantothenic acid or a derivative thereof or a salt thereof, and an alcohol, wherein the precipitation of the external preparation is suppressed.SOLUTION: An external composition has a container, and an external composition stored in the container. The external composition contains 3-10 w / v% of minoxidil, pantothenic acid or a derivative thereof or a salt thereof, and an alcohol. Of the container, the portion to be contact the external composition is at least partially composed of polyester.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a topical preparation.

Background Art

[0002] Minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide) is widely used as a drug for improving alopecia because excellent hair growth and hair nourishing effects can be obtained by external use. However, minoxidil has a problem that its solubility in water and ethanol is poor, and particularly, crystals are likely to precipitate when stored at low temperatures.

[0003] In addition, Patent Document 1 (Japanese Patent Application Laid-Open No. 2002-326913), Patent Document 2 (International Publication No. 01 / 76540), and Patent Document 3 (Japanese Patent Application Laid-Open No. 2009-108038) disclose topical compositions containing minoxidil, pantothenyl ethyl ether, and alcohol.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object of the present invention is to suppress precipitation in a topical composition containing 3 to 10 w / v% of minoxidil, pantothenic acid or its derivative or a salt thereof, and alcohol.

Means for Solving the Problems

[0006] As a result of intensive studies to solve the above problems, the present inventors have surprisingly found that precipitation in the external composition can be suppressed by storing an external composition containing 3 to 10 w / v% minoxidil, pantothenic acid or its derivative or a salt thereof, and alcohol in a polyester container, thereby completing the present invention. That is, the present invention is as follows.

[0007] [1] An external preparation comprising a container and an external composition contained in the container, wherein the external composition contains 3 to 10 w / v% minoxidil, pantothenic acid or its derivative or a salt thereof, and alcohol, at least a part of the portion of the container that comes into contact with the external composition is made of polyester.

[0008] [2] The external preparation according to [1], wherein the content of pantothenic acid or its derivative or a salt thereof in the external composition is 0.1 to 2 w / v%.

[0009] [3] The external preparation according to [1] or [2], wherein the pantothenic acid or its derivative or a salt thereof is pantothenyl ethyl ether.

[0010] [4] The external preparation according to any one of [1] to [3], wherein the alcohol contains a lower alcohol.

[0011] [5] The external preparation according to any one of [1] to [4], wherein the alcohol contains a polyhydric alcohol.

[0012] [6] The external preparation according to any one of [1] to [5], further comprising an acid or a salt thereof in the external composition.

[0013] [7] The external preparation according to any one of [1] to [6], further comprising a fat-soluble antioxidant in the external composition.

[0014] [8] The pH of the external composition is 5 to 8, and the external preparation according to any one of [1] to [7]. External preparation.

[0015] [9] The polyester is polyethylene terephthalate, and the external preparation according to any one of [1] to [8].

[0016]

[10] The container is a container formed by an injection blow molding method, and the external preparation according to any one of [1] to [9].

[0017]

[11] A method for suppressing precipitation in an external composition, which comprises accommodating an external composition containing 3 to 10 w / v% of minoxidil, pantothenic acid or a derivative thereof or a salt thereof, and alcohol in a container, wherein at least a part of the portion of the container that comes into contact with the external composition is made of polyester. [Advantages of the Invention]

[0018] According to the present invention, by accommodating an external composition containing 3 to 10 w / v% of minoxidil, pantothenic acid or a derivative thereof or a salt thereof, and alcohol in a polyester container, precipitation in the external composition can be significantly suppressed. [Embodiments for Carrying Out the Invention]

[0019] [External Preparation] The external preparation of the present invention includes a container and an external composition contained in the container.

[0020] [External Composition] The external composition contains 3 to 10 w / v% (weight / volume percentage) of minoxidil (including its salts), pantothenic acid or a derivative thereof or a salt thereof, and alcohol.

[0021] (Minoxidil) Minoxidil (including its salts) is a known compound, and as a method for obtaining it, commercially available products may be used. For example, it can be purchased from Tokyo Chemical Industry Co., Ltd. Examples of salts of minoxidil include inorganic acid salts such as hydrochloride and sulfate, and organic acid salts such as acetate, citrate, succinate, benzoate, and lactate.

[0022] The content rate of minoxidil in the external composition (the ratio of the mass of minoxidil contained to the total volume of the external composition; the same shall apply hereinafter) is 3 w / v% or more, preferably 4 w / v% or more, and more preferably 4.5 w / v% or more. In a composition containing minoxidil, precipitation generally tends to occur within this range, and thus the effects of the present invention are useful within this range. Further, the content rate of minoxidil is 10 w / v% or less, preferably 9 w / v% or less, and more preferably 7 w / v% or less. This is because if this range is exceeded, there is a possibility that precipitation cannot be sufficiently suppressed or coloring of the composition over time may occur.

[0023] (Pantothenic acid or its derivative or their salts) In the present specification, "(pantothenic acid or its derivative or their salts)" means at least one compound selected from the group consisting of pantothenic acid, derivatives of pantothenic acid, salts of pantothenic acid, and salts of derivatives of pantothenic acid.

[0024] Pantothenic acid is a compound also known as D(+)-N-(2,4-dihydroxy-3,3-dimethylbutyryl)-β-alanine. Examples of salts of pantothenic acid include sodium pantothenate and calcium pantothenate.

[0025] Examples of derivatives of pantothenic acid include panthenol, pantothenyl ethyl ether, and the like. The content of pantothenic acid, its derivative, or their salt in the external composition is preferably 0.1 to 2 w / v%, more preferably 0.3 to 1.5 w / v%, and even more preferably 0.5 to 1.0 w / v%. By containing pantothenic acid, its derivative, or their salt in such a range in a polyester container, precipitation in the external composition can be significantly suppressed.

[0026] In the present invention, pantothenyl ethyl ether is preferable among pantothenic acid, its derivative, or their salt in terms of the effect of suppressing precipitation (particularly precipitation at low temperatures) in the external composition. Pantothenyl ethyl ether is a compound also known as (2R)-N-(3-ethoxypropyl)-2,4-dihydroxy-3,3-dimethylbutanamide.

[0027] (Alcohol) The external composition contains at least alcohol. Alcohol functions as a solvent for active ingredients such as minoxidil in the external composition. Examples of alcohol include lower alcohols and polyhydric alcohols. It is preferable that the alcohol contains lower alcohols. It is also preferable that the alcohol contains polyhydric alcohols.

[0028] Examples of lower alcohols (for example, alcohols having 5 or less carbon atoms) include ethanol, propanol, isopropyl alcohol, butanol, and the like. Among these, ethanol can be particularly preferably used as a lower alcohol.

[0029] Examples of the polyhydric alcohol include glycols, glycerin, polyethylene glycol, etc. Examples of the glycols include propylene glycol, dipropylene glycol, 1,3-butylene glycol, etc. Examples of the polyethylene glycol include macrogol 200, macrogol 300, macrogol 400, macrogol 600, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 8000, macrogol 10000, macrogol 20000, etc.

[0030] The polyhydric alcohol preferably contains at least one selected from propylene glycol, 1,3-butylene glycol, and glycerin, more preferably contains at least one of propylene glycol and 1,3-butylene glycol, and even more preferably contains propylene glycol and 1,3-butylene glycol.

[0031] The content of alcohol in the external composition is not particularly limited, but in order to obtain an external composition with good solubility of minoxidil and excellent usability, it is preferably within the following ranges. That is, the content of alcohol in the external composition is preferably 35 to 85 w / v%, more preferably 45 to 75 w / v%, and even more preferably 50 to 70 w / v%. Also, the content of lower alcohol in the external composition is preferably 25 to 70 w / v%, more preferably 35 to 60 w / v%, and even more preferably 40 to 55 w / v%. Also, the content of polyhydric alcohol in the external composition is preferably 1 to 30 w / v%, more preferably 5 to 25 w / v%, and even more preferably 8 to 20 w / v%.

[0032] (Solvents other than alcohol) The topical composition may contain a pharmaceutically or physiologically acceptable solvent other than alcohol (such as water) used in pharmaceutical topical agents, quasi-drugs, cosmetics, etc. The topical composition may contain one solvent alone or two or more solvents. The water content in the topical composition is not particularly limited, but in order to obtain a topical composition with good solubility of minoxidil and excellent usability, it is preferably 5 to 40 w / v%, more preferably 10 to 35 w / v%, still more preferably 15 to 30 w / v%. To obtain the topical composition, it is preferably 5 to 40 w / v%, more preferably 10 to 35 w / v%, still more preferably 15 to 30 w / v%.

[0033] (Additives) The topical composition may contain pharmaceutically or physiologically acceptable additives used in pharmaceutical topical agents, quasi-drugs, cosmetics, etc. Such additives include antioxidants, surfactants (such as nonionic surfactants), stabilizers (such as higher fatty acids, higher alcohols), thickeners, preservatives, pH adjusters, irritation reducers, antiseptics, colorants, fragrances, solubilizing agents, etc. The topical composition may contain one or two or more additives.

[0034] Examples of nonionic surfactants include polysorbate, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene polyoxypropylene glycol, polyethylene glycol monostearate, etc.

[0035] Examples of higher fatty acids include isostearic acid, oleic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, etc.

[0036] Examples of higher alcohols include diacetone alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol (cetanol), hexyl decanol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, araalkyl alcohol, octyldodecanol, behenyl alcohol, decyltetradecanol, etc.

[0037] Examples of the thickener include hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose, methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, xanthan gum, hyaluronate, chondroitin sulfate, and the like.

[0038] From the viewpoint of more significantly exhibiting the effects according to the present invention, the external composition preferably further contains an acid or a salt thereof. Examples of the acid or the salt thereof include organic acids, inorganic acids, etc. or salts thereof (for example, sodium salts). Examples of the organic acid include lactic acid, citric acid, malic acid, succinic acid, tartaric acid, gluconic acid, and the like. Examples of the inorganic acid include phosphoric acid, hydrochloric acid, sulfuric acid, and the like. These acids or salts thereof can function as, for example, a pH adjuster in the external composition. Also, organic bases such as triethanolamine; diisopropanolamine; triisopropanolamine; arginine, and inorganic bases such as potassium hydroxide; sodium hydroxide can be used as a pH adjuster.

[0039] (Pharmacologically active ingredient · Physiologically active ingredient) The external composition may contain a pharmacologically active ingredient or a physiologically active ingredient used in pharmaceutical external preparations, quasi-drugs, cosmetics, etc. other than minoxidil and pantothenic acid or derivatives thereof or salts thereof. Examples of such components include blood circulation promoting components, angiogenesis promoting factors, moisturizing components, anti-inflammatory components, antibacterial components, vitamins, peptides or derivatives thereof, amino acids or derivatives thereof, cell activation components, anti-aging components, keratolytic or keratolytic components, whitening components, astringent components, vasodilating components, antihistamine components, antioxidant components, metabolic activators, cooling agents, hair growth components other than minoxidil, and the like. Examples of the hair growth components other than minoxidil include spironolactone, centella extract, capsinoid, keratinocyte growth factor (KGF; FGF-7), glycyrrhizinate, glycyrrhetinic acid, ginseng extract, and the like.

[0040] The external composition preferably contains a fat-soluble antioxidant. As the fat-soluble antioxidant, for example, dibutylhydroxytoluene and butylhydroxyanisole can be used. Dibutylhydroxytoluene is a kind of aromatic compound also called 2,6-di-tert-butyl-p-cresol and is generally known as an antioxidant.

[0041] When the external composition contains a fat-soluble antioxidant, the content of the fat-soluble antioxidant in the external composition is preferably 0.01 to 1.0 w / v%, more preferably 0.03 to 0.9 w / v%, and still more preferably 0.05 to 0.8 w / v%.

[0042] By blending both pantothenic acid or its derivative or their salt and a fat-soluble antioxidant in an external composition containing 3 to 10 w / v% of minoxidil, precipitation (especially precipitation at low temperatures) in the external composition can be suppressed more than when pantothenic acid or its derivative or their salt is blended alone. In addition, since precipitation in the external composition can be prevented without containing a large amount of glycols, an external composition with good usability and excellent storage stability can be obtained.

[0043] In addition, the external composition preferably contains at least one selected from pyridoxine hydrochloride, tocopherol acetate, and menthol. In this case, compared with containers made of other resins, the polyester container is less likely to adsorb the above three components (pyridoxine hydrochloride, tocopherol acetate, and menthol), so in the present invention, changes in the composition of the external composition can be suppressed.

[0044] The compounding amounts of the above three components (pyridoxine hydrochloride, tocopherol acetate, and menthol) are not particularly limited and can be determined experimentally while considering the usability and the stability of minoxidil, etc. For example, in the topical composition, the compounding ratio of pyridoxine hydrochloride is preferably 0.01 to 0.1 w / v%, the compounding ratio of tocopherol acetate is preferably 0.01 to 0.1 w / v%, and the compounding ratio of menthol is preferably 0.1 to 0.5 w / v%.

[0045] In addition, the topical composition may contain, for example, panthenol, hinokitiol, diphenhydramine or its salt, salicylic acid or its salt, glycyrrhetinic acid or its salt, glycyrrhizic acid or its salt, etc.

[0046] (Dosage form) The dosage form of the topical composition is not particularly limited, and examples include solutions, suspensions, emulsions, creams, gels, liniments, lotions, aerosols, etc. The topical composition of the present invention is preferably a solution, suspension, emulsion, lotion, or aerosol, and more preferably a solution, lotion, or aerosol. In addition, the topical composition may be an ointment containing a solvent capable of dissolving minoxidil. Further, the topical composition may be a cosmetic composition such as lotion, emulsion, foam, shampoo, rinse, conditioner, hair tonic, hair cream, hair liquid, etc.

[0047] The topical composition can be produced by mixing each component, for example, in accordance with or in conformity with the General Rules of the Japanese Pharmacopoeia.

[0048] (pH) The pH of the topical composition is preferably 5.0 or higher, more preferably 5.5 or higher, and even more preferably 6.0 or higher. Also, the pH of the topical composition is preferably 8.0 or lower, more preferably 7.5 or lower, and even more preferably 7.0 or lower. If the pH of the topical composition is within the range of 5 to 8, minoxidil is easily dissolved in the topical composition, and also This is because it is less likely to cause irritation to the scalp due to high pH. The pH of the external composition can be adjusted using the above pH adjuster.

[0049] 〔Container〕 In the present invention, at least a part of the portion of the container that comes into contact with the external composition is composed of polyester.

[0050] Preferably, all of the portion of the container that comes into contact with the external composition is substantially composed of polyester. The container that houses the external composition is composed of a main body, a cap, a discharge member, a stopper, a seal member, etc. In each of these constituent members, preferably, at least the portion that comes into contact with the external composition is composed of polyester. Specifically, for example, when the container main body has a laminated structure, the innermost layer that comes into contact with the external composition is preferably composed of polyester. Further, among the plurality of members constituting the container, it is more preferable that all the members that come into contact with the external composition are composed of polyester, and it is even more preferable that all of the container (constituent members) are composed of polyester.

[0051] Polyester is a polycondensate of a polyvalent carboxylic acid (preferably a dicarboxylic acid) and a polyalcohol (preferably a diol). Examples of polyester include polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene naphthalate (PEN), polybutylene naphthalate (PBN), etc. In the present invention, the polyester is preferably polyethylene terephthalate (PET). This is because precipitation in the external composition in the container (especially precipitation at low temperatures) can be more significantly suppressed.

[0052] The polyethylene terephthalate (PET) used in the present invention may contain plastic resins other than PET (for example, polyesters other than PET such as polybutylene terephthalate (PBT), polyethylene naphthalate (PEN), polybutylene naphthalate (PBN), polyamides such as nylon and aramid, polyarylate, polycarbonate, etc.) as long as the effects of the present invention are not impaired.

[0053] In addition, for example, when the member constituting the container has a laminated structure and the layer in contact with the outermost external composition is made of PET, as the material of the layer other than the layer in contact with the external composition (PET layer), considering the gas (oxygen) permeability, water permeability, strength, flexibility, weather resistance, etc. of the container, materials other than PET may be used. Examples of such materials other than PET include polybutylene terephthalate (PBT), polyethylene naphthalate (PEN), polybutylene naphthalate (PBN), polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), acrylonitrile-butadiene-styrene copolymer resin (ABS resin), ethylene-vinyl alcohol resin (EVOH), acrylonitrile styrene resin (AS resin), epoxy resin, polyamideimide resin (PAI resin), aluminum, glass, etc.

[0054] In the present invention, the container is preferably an injection blow molded container (a container molded by the injection blow molding method). This is because precipitation in the external composition in the container (especially precipitation at low temperatures) can be more significantly suppressed.

[0055] In the present invention, the thickness of the member constituting the container (the thickness of the container wall) is preferably 0.1 to 3 mm, more preferably 0.3 to 2.5 mm, and even more preferably 0.5 to 2 mm.

[0056] The polyester used in the present invention is a germanium-based catalyst, a titanium-based catalyst, and aluminum It is preferably a polyester polymerized using at least one catalyst selected from the group consisting of nickel-based catalysts. This is because it can suppress the time-dependent coloring of the external composition.

[0057] The shape of the container is not particularly limited, and a container having a shape appropriately selected according to the intended use in the technical field can be used. The container may be a multi-dose type container that can be used multiple times (for example, 30 to 360 times, preferably 60 to 240 times), or a unit-dose type container that is used up in a single use.

[0058] (Method of use) The method of using the external preparation of the present invention varies depending on the state of the hair of the subject to be used, the state of the scalp, age, gender, etc., but for example, the following method may be used. That is, it may be applied to the skin (for example, the scalp) several times a day (for example, 1 to 5 times, preferably 1 to 3 times) in an appropriate amount (for example, 0.5 to 2 g, or 0.5 to 2 mL). Further, the external composition may be applied to the skin (for example, the scalp) so that the daily usage amount of minoxidil is, for example, 1 to 1000 mg. As the application method, methods such as coating and spraying can be used according to the dosage form. The application period may be a period in which a hair growth effect can be sufficiently obtained, for example, 7 days or more, 4 months or more, or 6 months or more.

[0059] The external composition of the present invention is expected to have a hair growth effect. The hair growth effect may include at least one of the effects such as a hair growth action, a hair growth promoting action, a hair growth promoting action, a hair nourishing action, and a preventive action against hair loss (falling hair, thinning hair).

[0060] <Method for suppressing precipitation in an external composition containing minoxidil> The present invention relates to a method for suppressing precipitation in an external composition, which comprises containing an external composition containing 3 to 10 w / v% of minoxidil, pantothenic acid or its derivative or a salt thereof, and alcohol in a container, wherein at least a part of the portion of the container that comes into contact with the external composition is composed of polyester. By containing an external composition containing 3 to 10 w / v% of minoxidil, pantothenic acid or its derivative or a salt thereof, and alcohol in the above container, precipitation in the external composition can be suppressed.

Examples

[0061] Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

[0062] External compositions (sample solutions 1 to 3 and control solutions 1 to 3) having the compositions shown in Table 1 and Table 4 were prepared according to a conventional method, and the low-temperature stability was evaluated.

[0063] The evaluation of low-temperature stability was carried out by filling each external composition into a container made of polyethylene terephthalate (PET) (injection blow molded container) or a glass container, allowing it to stand in a thermostat at -5°C for 14 days or in a thermostat at -20°C for 12 days, and then visually observing crystal precipitation. Here, PET was polymerized using a germanium-based catalyst. The results are shown in the "Low-temperature stability" column of Table 2, Table 3 and Table 5. Here, those in which precipitation was not observed are indicated by "○", and those in which precipitation was observed are indicated by "×".

[0064]

Table 1

[0065]

Table 2

[0066]

Table 3

[0067]

Table 4

[0068]

Table 5

[0069] As shown in Table 2, Table 3 and Table 5, when external compositions (sample solutions 1 to 3) containing 5 w / v% of minoxidil, pantothenyl ethyl ether and alcohol (ethanol) were stored in PET containers, no crystal precipitation was observed after low-temperature storage. In contrast, when sample solutions 1 to 3 were stored in glass containers, crystal precipitation was observed after low-temperature storage. Also, when control solutions 1 to 3 that did not contain pantothenyl ethyl ether were used, crystal precipitation was observed after low-temperature storage regardless of whether they were stored in PET containers or glass containers.

[0070] From the above results, it is considered that by storing an external composition containing 3 to 10 w / v% of minoxidil, pantothenyl ethyl ether and alcohol in a PET container, precipitation of minoxidil after low-temperature storage can be significantly suppressed.

[0071] 〔Formulation Example〕 Each of the external compositions 1 to 42 shown in Tables 6 to 8 below was filled into a PET container (injection blow molded container) to produce external preparations A1 to A42, respectively. Also, each of the external compositions 1 to 42 was filled into a PET container (injection blow molded container) mixed with polyethylene naphthalate to produce external preparations B1 to B42, respectively. The unit of each component in the table is w / v%.

[0072]

Table 6

[0073]

Table 7

[0074]

Table 8

[0075] The embodiments and examples disclosed this time should be considered illustrative in all respects and not restrictive. The scope of the present invention is shown not by the above description but by the claims, and it is intended that all modifications within the meaning and scope equivalent to the claims be included.

Claims

【Claim 1】 The invention described in this specification.

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