JP7194553B2 - external composition - Google Patents

Description

The present invention relates to topical compositions.

Minoxidil is widely used because of its excellent hair-restoring, hair-nourishing or hair-regrowth effect when externally applied.

Patent Document 1 discloses that a hair restorer containing minoxidil is contained in a single-use container (unit dose container) wrapped in an aluminum pillow. Packing in a single-use container is not disclosed. In addition, a single-use product containing minoxidil and a pH-adjusting agent has not yet been marketed domestically or internationally.

JP-A-11-46849

The present inventor discovered a new problem that when a formulation (composition for external use) containing minoxidil is contained in a single-use container, bubbles generated in the container are difficult to disappear. Here, if the foam generated in the container is difficult to disappear, the composition for external use adheres to the inner wall of the container together with the foam, and the composition for external use tends to remain in the container. Since the amount of the composition for external use to be stored is small so that it can be used up at once, there is a problem that if the composition remains in the container and the entire amount cannot be used, the effect of minoxidil cannot be sufficiently exhibited.

An object of the present invention is to provide a composition for external use containing minoxidil, which has an improved foam disappearance speed (defoaming speed) while being housed in a single-use container.

The present inventors have found that adding a pH adjuster to a topical composition containing minoxidil improves the defoaming speed of the topical composition even when it is contained in a single-use container. The present invention is based on this finding, and provides the following inventions.

[1] A composition for external use containing (A) minoxidil and (B) a pH adjuster, wherein 0.1 to 2 mL of the composition for external use is contained in a single-use container.
[2] (C) The composition according to [1], further containing one or more selected from the group consisting of monohydric alcohols, polyhydric alcohols, higher fatty acids, surfactants, antioxidants, and thickeners. External composition.
[3] pantothenyl ethyl ether, panthenol, pyridoxine, tocopherol, menthol, hinokitiol, diphenhydramine, salicylic acid, glycyrrhetinic acid, glycyrrhizic acid, and carpronium chloride, and further containing one or more selected from the group consisting of salts thereof The composition for external use according to [1] or [2].
[4] The composition for external use according to any one of [1] to [3], wherein the material constituting the single-use container contains a resin.
[5] Defoaming in a composition for external use, comprising blending (A) minoxidil and (B) a pH adjuster in the composition for external use, and storing 0.1 to 2 mL of the composition for external use in a single-use container. How to improve speed.

According to the present invention, it is possible to provide a composition for external use containing minoxidil, which has improved foam disappearance speed (defoaming speed) while being housed in a single-use container.

DETAILED DESCRIPTION OF THE INVENTION Embodiments for carrying out the present invention will be described in detail below. However, the present invention is not limited to the following embodiments.

In this specification, unless otherwise specified, the content unit "%" means "w/v %" and is synonymous with "g/100 mL". In this specification, unless otherwise specified, the abbreviation "POE" means polyoxyethylene and the abbreviation "POP" means polyoxypropylene.

[1. External composition]
The external composition according to the present embodiment contains (A) minoxidil (also simply referred to as "(A) component") and (B) a pH adjuster (also simply referred to as "(B) component"). .

<(A) Component>
Minoxidil is a known compound also called 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, and may be synthesized by a known method or obtained as a commercial product. is also possible.

The content of component (A) in the composition for external use according to the present embodiment is not particularly limited, and is appropriately set according to the type and content of other compounding components, the application and formulation form of the composition for external use, and the like. As for the content of the component (A), from the viewpoint of exhibiting the effect of the present invention more remarkably, for example, the total content of the component (A) is 0.01 to 10 w/v based on the total amount of the composition for external use. %, more preferably 0.05 to 8 w/v%, even more preferably 0.1 to 6 w/v%, and 0.1 to 5.5 w/v% is even more preferred, and 0.1 to 5.0 w/v% is particularly preferred.

<(B) Component>
Component (B), the pH adjuster, contains an acid and a base that adjust the pH of the composition for external use, and component (B) is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable. If so, it is not particularly limited. However, salicylic acid is not included in the (B) component.

When the pH adjuster is an acid, specific examples of the acid include organic acids such as citric acid, lactic acid, tartaric acid, gluconic acid, acetic acid, maleic acid, malic acid and pyruvic acid, hydrochloric acid, sulfuric acid, and phosphoric acid. , inorganic acids such as boric acid and nitric acid, and salts thereof.

When the pH adjuster is a base, specific examples of the base include, for example, organic bases such as sodium citrate, arginine, diethanolamine, triethanolamine, diisopropanolamine and triisopropanolamine, and sodium dihydrogen phosphate, Inorganic bases such as borax and sodium hydroxide are included.

A commercially available pH adjuster may be used. One type of pH adjuster may be used alone, or two or more types may be used in combination.

The content of component (B) in the composition for external use according to the present embodiment is not particularly limited. is set as appropriate. As for the content of the component (B), from the viewpoint of exhibiting the effect of the present invention more remarkably, for example, the total content of the component (B) is 0.01 to 8 w/v based on the total amount of the composition for external use. %, more preferably 0.01 to 6 w/v%, even more preferably 0.02 to 4 w/v%, further preferably 0.02 to 3 w/v%. More preferably, 0.05 to 2 w/v% is particularly preferred, and 0.05 to 1 w/v% is most preferred.

The content ratio of component (B) to component (A) in the composition for external use according to the present embodiment is not particularly limited. And it is appropriately set according to the dosage form and the like. As for the content ratio of component (B) to component (A), from the viewpoint of exhibiting the effect of the present invention more remarkably, for example, the total content of component (A) contained in the composition for external use according to the present embodiment is 1 mass. parts, the total content of component (B) is preferably 0.005 to 110 parts by mass, more preferably 0.01 to 90 parts by mass, and 0.05 to 70 parts by mass. more preferably 0.1 to 50 parts by mass.

<(C) Component>
The composition for external use according to the present embodiment further includes (C) one or more selected from the group consisting of monohydric alcohols, polyhydric alcohols, higher fatty acids, surfactants, antioxidants, and thickeners (simply " (C) Component") may be contained. When the composition for external use further contains the component (C), the effects of the present invention are exhibited more remarkably. Component (C) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable. However, pantothenyl ethyl ether, panthenol, pyridoxine, tocopherol, menthol, hinokitiol, salicylic acid, glycyrrhetinic acid, glycyrrhizic acid, isopropylmethylphenol, ascorbic acid, thiamine nitrate, cyanocobalamin, and biotin are not included in component (C). .

The monohydric alcohol as component (C) is an alcohol having one hydroxyl group in the molecule. Monohydric alcohols may be straight or branched chain alcohols, saturated or unsaturated alcohols. Among them, branched chain alcohols and unsaturated alcohols are preferred. Specific examples of monohydric alcohols include lower alcohols having 5 or less carbon atoms such as ethanol and isopropanol; cetyl alcohol, isostearyl alcohol, oleyl alcohol, octyldodecanol, lauryl alcohol (dodecanol), hexyldecanol, stearyl alcohol, myristyl Alcohol, behenyl alcohol (docosanol), arachyl alcohol (1-eicosanol), decyltetradecanol, diacetone alcohol, caproyl alcohol, caprylyl alcohol, capryl alcohol, carnerbil alcohol, ceryl alcohol, colyanyl alcohol, myricyl alcohol , mericyl alcohol, laxeryl alcohol, heptanol, nonanol, undecanol, tridecanol, pentadecanol, heptadecanol, nonadecanol, heneicosanol, tricosanol, pentacosanol, heptakosanol, nonacosanol, tritriacontanol, tetratriacontanol, pentatria Contanol, heptatriacontanol, lanolin alcohol, cetostearyl alcohol, isocetyl alcohol, elaidyl alcohol, octyldecanol, dodecylhexadecanol, tetradecyloctadecanol, tetradecyleicosanol, etc. A higher alcohol is mentioned.

The polyhydric alcohol as component (C) is an alcohol having two or more hydroxyl groups in the molecule. Polyhydric alcohols may be linear or branched alcohols, and saturated or unsaturated alcohols. Specific examples of polyhydric alcohols include butylene glycol (1,3-butylene glycol), propylene glycol, dipropylene glycol, glycerin, pentylene glycol, polyethylene glycol (PEG200, PEG300, PEG400, PEG600, PEG1000) and the like. mentioned.

The higher fatty acid as component (C) is a fatty acid having 10 or more carbon atoms. A higher fatty acid may be a straight chain fatty acid or a branched chain fatty acid, and may be a saturated fatty acid or an unsaturated fatty acid. Among them, branched chain fatty acids and unsaturated fatty acids are preferred. Specific examples of higher fatty acids include isostearic acid (isooctadecanoic acid), oleic acid, capric acid (decanoic acid), lauric acid (dodecanoic acid), myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, palmitoleic acid, elaidic acid, arachidic acid, behenic acid and the like.

The surfactant as component (C) is a compound having a hydrophilic group and a hydrophobic group in its molecule. Surfactants are preferably nonionic surfactants, particularly polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene sorbitan fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene polyoxypropyl alkyl ether, polyoxyethylene Ethylene sorbitol fatty acid esters, polyoxyethylene alkyl ethers, polyglycerol fatty acid esters, sucrose fatty acid esters, polyoxyethylene sterols and polyoxyethylene polyoxypropylene glycols are preferred. Specific examples include POE (40) hydrogenated castor oil, POE (50) hydrogenated castor oil, POE (60) hydrogenated castor oil, POE (20) sorbitan monooleate, polyethylene glycol (40) monooleate, mono Polyethylene glycol stearate (40), sorbitan monooleate, POE (20) POP (4) cetyl ether, POE (30) sorbitol tetraoleate, POE (40) sorbitol tetraoleate, POE (7) cetyl ether, POE (25) cetyl ether, POE (30) cetyl ether, polyglyceryl myristate (10), polyglyceryl myristate (30), sucrose stearate, PEG30 phytosterol, POE/POP glycol and the like.

The (C) component, the antioxidant, is a compound or a salt thereof that suppresses harmful reactions involving oxygen. Specific examples of antioxidants include dibutylhydroxytoluene, sodium pyrosulfite, sodium edetate, benzotriazole, and propyl gallate.

(C) The thickener which is a component is a compound and its salt which have a thickening effect. Examples of thickening agents include polysaccharides (eg, mucopolysaccharides, cellulose-based polymer compounds, microbial-derived polysaccharides, and salts thereof) and vinyl-based polymer compounds. Specific examples of thickening agents include mucopolysaccharides such as hyaluronic acid, chondroitin sulfate, pectin and salts thereof; hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, ethylcellulose, carboxymethylcellulose and salts thereof; cellulose-based polymer compounds; microorganism-derived polysaccharides such as xanthan gum, gellan gum, dextran, and salts thereof; be done.

(C) component may use what is marketed. (C) component may be used individually by 1 type, or may be used in combination of 2 or more types.

The content of component (C) in the composition for external use according to the present embodiment is not particularly limited. is set as appropriate. As for the content of component (C), from the viewpoint of exhibiting the effects of the present invention more remarkably, for example, the total content of component (C) is 0.005 to 90 w/v based on the total amount of the composition for external use. %, more preferably 0.05 to 85 w/v%, even more preferably 0.1 to 80 w/v%, further preferably 0.5 to 75 w/v%. More preferably, 1 to 70 w/v% is particularly preferable.

When a lower alcohol is contained as the component (C), the content of the lower alcohol in the composition for external use according to the present embodiment is, for example, the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. As a standard, the total content of lower alcohols is preferably 0.1 to 80 w/v%, more preferably 1 to 70 w/v%, and even more preferably 5 to 60 w/v%. , 8 to 50 w/v % is even more preferred, and 10 to 50 w/v % is particularly preferred.

When a higher alcohol is contained as the component (C), the content of the higher alcohol in the composition for external use according to the present embodiment is, for example, the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. As a standard, the total content of higher alcohols is preferably 0.01 to 10 w/v%, more preferably 0.05 to 8 w/v%, and 0.05 to 6 w/v%. is more preferred, 0.1 to 5 w/v% is even more preferred, and 0.1 to 4 w/v% is particularly preferred.

When a polyhydric alcohol is contained as the component (C), the content of the polyhydric alcohol in the composition for external use according to the present embodiment is, for example, Based on the total amount, the total polyhydric alcohol content is preferably 1 to 50 w/v%, more preferably 3 to 40 w/v%, and further preferably 5 to 35 w/v%. Preferably, 5 to 25 w/v% is even more preferable, and 5 to 20 w/v% is particularly preferable.

When a higher fatty acid is contained as the component (C), the content of the higher fatty acid in the composition for external use according to the present embodiment is, for example, the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. As a standard, the total content of higher fatty acids is preferably 0.1 to 10 w/v%, more preferably 0.1 to 8 w/v%, and 0.15 to 7 w/v%. is more preferred, 0.15 to 6 w/v% is even more preferred, and 0.2 to 6 w/v% is particularly preferred.

When a surfactant is contained as the component (C), the content of the surfactant in the composition for external use according to the present embodiment is, for example, the Based on the total amount, the total content of the surfactant is preferably 0.01 to 15 w/v%, more preferably 0.05 to 12 w/v%, and 0.1 to 10 w/v %, even more preferably 0.15 to 8 w/v %, particularly preferably 0.2 to 6 w/v %.

When an antioxidant is contained as the component (C), the content of the antioxidant in the composition for external use according to the present embodiment is, for example, the Based on the total amount, the total content of antioxidants is preferably 0.005 to 5 w/v%, more preferably 0.01 to 3 w/v%, and 0.01 to 2 w/v %, even more preferably 0.05 to 1 w/v %, particularly preferably 0.05 to 0.8 w/v %.

(C) When a thickener is contained as the component, the content of the thickener in the composition for external use according to the present embodiment is, for example, Based on the total amount, the total content of the thickening agent is preferably 0.005 to 10 w/v%, more preferably 0.01 to 8 w/v%, and 0.05 to 7 w/v %, even more preferably 0.1 to 6 w/v %, particularly preferably 0.2 to 5 w/v %.

The content ratio of component (C) to component (A) in the composition for external use according to the present embodiment is not particularly limited. And it is appropriately set according to the dosage form and the like. As for the content ratio of component (C) to component (A), from the viewpoint of exhibiting the effects of the present invention more remarkably, for example, the total content of component (A) contained in the composition for external use according to the present embodiment is 1 mass. parts, the total content of component (C) is preferably 0.00005 to 500 parts by mass, more preferably 0.0001 to 400 parts by mass, and 0.0005 to 300 parts by mass. more preferably 0.001 to 200 parts by mass.

The composition for external use according to the present embodiment further includes pantothenyl ethyl ether (pantothenyl ethyl ether), panthenol, pyridoxine, tocopherol, menthol, hinokitiol, diphenhydramine, salicylic acid, glycyrrhetinic acid, glycyrrhizic acid, and carpronium chloride, and these It may contain one or more selected from the group consisting of salts.
In another aspect, the composition for external use according to this embodiment further comprises pantothenyl ethyl ether (pantothenyl ethyl ether), panthenol, pyridoxine, tocopherol, menthol, hinokitiol, diphenhydramine, salicylic acid, glycyrrhetinic acid, glycyrrhizic acid, and carpronium chloride. , azulene (chamomile oil), 6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, heko bird, benzyl nicotinate, assembly extract, panax ginseng extract, ginseng tincture, capsicum tincture, isothipendyl hydrochloride, guaiazulene, urea, glucon Chlorhexidine acid, isopropyl methylphenol, quaternary ammonium salts (benzalkonium chloride, benzethonium chloride), piroctone olamine, various animals and plants (yew, botan pi, licorice, St. John's wort, Bushi, loquat, Kawara mugwort, comfrey, Angelica keiskei, saffron , sansis, rosemary, sage, moss, seimokkou, hops, placenta, saw palmetto, pumpkin seed, etc.), retinol acetate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, diisopropyl adipate, isopropyl myristate, peppermint oil, and camphor (camphor), and one or more active ingredients selected from the group consisting of salts thereof.

When pantothenyl ethyl ether is contained, the content of pantothenyl ethyl ether in the composition for external use according to the present embodiment is, for example, based on the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. As, it is preferably 0.1 to 5.0 w / v%, more preferably 0.1 to 1.5 w / v%, and further preferably 0.2 to 1.0 w / v% preferable.

When panthenol is contained, the content of panthenol in the composition for external use according to the present embodiment is, for example, 0.5% based on the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. It is preferably 1 to 2.0 w/v%, more preferably 0.3 to 1.5 w/v%, even more preferably 0.5 to 1.0 w/v%.

When pyridoxine or a salt thereof is contained, the content of pyridoxine or a salt thereof in the composition for external use according to the present embodiment is, for example, based on the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. As, the total content of pyridoxine or a salt thereof is preferably 0.01 to 1.0 w/v%, more preferably 0.01 to 0.5 w/v%, 0.03 to 0 .1 w/v % is more preferred.

When tocopherol or a salt thereof is contained, the content of tocopherol or a salt thereof in the composition for external use according to the present embodiment is, for example, based on the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. As, the total content of tocopherol or a salt thereof is preferably 0.01 to 1.0 w/v%, more preferably 0.01 to 0.5 w/v%, 0.03 to 0 .1 w/v % is more preferred.

When menthol is contained, the content of menthol in the composition for external use according to the present embodiment is, for example, from 0.01 to 0.01 based on the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. It is preferably 2.5 w/v%, more preferably 0.05 to 2.0 w/v%, even more preferably 0.1 to 1.5 w/v%.

When hinokitiol is contained, the content of hinokitiol in the composition for external use according to the present embodiment is, for example, from 0.005 to 0.005 based on the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. It is preferably 0.15 w/v%, more preferably 0.005 to 0.1 w/v%, even more preferably 0.01 to 0.05 w/v%.

When diphenhydramine or a salt thereof is contained, the content of diphenhydramine or a salt thereof in the composition for external use according to the present embodiment is, for example, based on the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. As, the total content of diphenhydramine or a salt thereof is preferably 0.01 to 1.0 w / v%, more preferably 0.02 to 0.5 w / v%, 0.03 to 0 .1 w/v % is more preferred.

When salicylic acid or a salt thereof is contained, the content of salicylic acid or a salt thereof in the composition for external use according to the present embodiment is, for example, based on the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. As, the total content of salicylic acid or a salt thereof is preferably 0.01 to 5.0 w / v%, more preferably 0.05 to 4.0 w / v%, 0.1 to 3 0 w/v % is more preferred.

When glycyrrhetinic acid or a salt thereof is contained, the content of glycyrrhetinic acid or a salt thereof in the composition for external use according to the present embodiment is, for example, the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. based on, the total content of glycyrrhetinic acid or a salt thereof is preferably 0.01 to 1.0 w/v%, more preferably 0.02 to 0.5 w/v%, 03 to 0.1 w/v% is more preferable.

When glycyrrhizic acid or a salt thereof is contained, the content of glycyrrhizic acid or a salt thereof in the composition for external use according to the present embodiment is, for example, the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. Based on, the total content of glycyrrhizic acid or a salt thereof is preferably 0.001 to 2.0 w / v%, more preferably 0.01 to 1.0 w / v%, and 0.01 to 1.0 w / v%. 03 to 0.5 w/v% is more preferable.

When carpronium chloride is contained, the content of carpronium chloride in the composition for external use according to the present embodiment is, for example, 0.5% based on the total amount of the composition for external use, from the viewpoint of exhibiting the effects of the present invention more remarkably. It is preferably 1 to 5.0 w/v%, more preferably 0.5 to 5.5 w/v%, even more preferably 1.0 to 6.0 w/v%.

The pH of the composition for external use according to this embodiment is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable range. The pH of the composition for external use according to the present embodiment may be, for example, 1.5 to 9.5, preferably 3.0 to 9.0, and 4.0 to 8.5. is more preferred, 5.0 to 8.5 is even more preferred, and 5.5 to 8.5 is particularly preferred.

In the composition for external use according to the present embodiment, various additives are appropriately selected in accordance with conventional methods according to the application and formulation form, as long as the effects of the present invention are not impaired, and one or more additives are added. may be used in combination and contained in an appropriate amount. Examples of such additives include various additives described in Pharmaceutical Excipient Encyclopedia 2016 (edited by Japan Pharmaceutical Excipients Association).
Typical ingredients include the following additives.
Carrier: For example, an aqueous solvent such as water.
Base: For example, octyldodecanol, titanium oxide, potassium bromide, Plastibase and the like.
Stabilizers: sodium formaldehyde sulfoxylate (Rongalite), sodium hydrogen sulfite, aluminum monostearate, glyceryl monostearate and the like.
Preservatives or antibacterial agents: for example, zinc chloride, polyhexamethylenebiguanide, alexidine, alkylpolyaminoethylglycine, neostigmine, benzoic acid, chlorobutanol, sorbic acid, dehydroacetic acid, oxyquinoline, polyquaterniums, Grokyl (manufactured by Rhodia) , trade names), sulfisoxazole, sulfisomidine and sulfamethoxazole, and salts thereof.
Oil agents: animal oils such as beeswax, lanolin (refined lanolin, etc.), orange roughy oil, squalane and horse oil, petrolatum (white petrolatum, yellow petrolatum, etc.) and mineral oils such as liquid paraffin.

When the composition for external use according to the present embodiment contains water, the water content is preferably 2 w/v% or more, more preferably 5 w/v% or more, and 10 w/v% or more. more preferably 15 w/v % or more, particularly preferably 20 w/v % or more, and most preferably 25 w/v % or more. The water content is preferably less than 80 w/v%, more preferably less than 75 w/v%, even more preferably less than 70 w/v%, and less than 65 w/v%. is even more preferred, particularly preferably less than 60 w/v %, most preferably less than 50 w/v %.

The water used in the composition for external use according to this embodiment may be pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable. Examples of such water include distilled water, ordinary water, purified water, sterile purified water, water for injection, and distilled water for injection. These definitions are based on the 17th revision of the Japanese Pharmacopoeia.

The composition for external use according to the present embodiment can be prepared by adding and mixing desired amounts of components (A), (B) and, if necessary, other components to achieve desired concentrations.

The composition for external use according to this embodiment can take various formulation forms depending on the purpose. Examples of dosage forms include liquids, gels, semi-solids (ointments, etc.), suspensions, emulsions, creams, liniments, lotions, and aerosols.

The composition for external use according to this embodiment can be used for hair restoration, hair nourishing or hair growth. The usage and dosage of the composition for external use according to this embodiment is not particularly limited as long as it exhibits hair growth, hair nourishing or hair growth effects and has few side effects. For adults (aged 20 and over), for example, several times a day (eg, about 1 to 5 times, preferably 2 times), an appropriate amount (eg, about 0.5 to 2 g, or 0.5 to 2 g), although it varies depending on gender and the like. 5-2 mL (preferably 1 mL)) may be applied to the skin (eg, scalp). Also, the daily dose of minoxidil may be, for example, about 1 to 1000 mg. The application method may be coating, dropping, spraying, or the like, depending on the dosage form. An applicator can also be used when applying the composition for external use to the skin.

<Container>
The composition for external use according to this embodiment is provided by storing 0.1 to 2 mL of the composition for external use in a single-use container. The external composition according to the present embodiment includes a plurality of single-use containers (for example, 2, 3, 4, 5, 6, 7 , 8, 9, or 10) may be provided as an external composition kit (external composition in a continuous container). The external composition kit can be used in such a manner that the connecting portion is cut off with a finger or the like after each use, and the external composition stored in the cut single-use container is used.

As used herein, "single-use container" means a container for single use. A single-use container may also be referred to as a single-use container.

The amount of the composition for external use contained in the single-use container is not particularly limited as long as it is within the range of 0.1 to 2 mL. It is more preferably 5 mL, still more preferably 0.8 to 1.2 mL, and particularly preferably 1 mL.

The capacity of the single-use container is not particularly limited as long as it is a dose that accommodates 0.1 to 2 mL of the composition for external use. It is more preferably 0.3 mL or more, even more preferably 0.4 mL or more, particularly preferably 0.5 mL or more, and most preferably 0.6 mL or more. The volume of the single-use container is, for example, preferably 5 mL or less, more preferably 4 mL or less, even more preferably 3.5 mL or less, and even more preferably 3 mL or less; 5 mL or less is particularly preferred, and 2 mL or less is most preferred.

The shape of the single-use container is not particularly limited, and may be appropriately set according to the purpose and application. The shape of the housing portion of the single-use container may be, for example, bottle-shaped, stick-shaped, dropper-shaped, syringe-shaped, portion-shaped. The single-use container may be, for example, a single-piece container, a tube container (preferably a lidded tube container), or a sheet-laminated container (preferably a sachet). ).

The material constituting the single-use container is not particularly limited, and may be appropriately set according to the purpose and application. Materials constituting the single-use container may include, for example, one or more selected from the group consisting of resin, metal and glass. From the viewpoint of exhibiting the effects of the present invention more remarkably, it is preferable that the material constituting the single-use container contains a resin.

Examples of the resin contained in the material constituting the single-use container include thermoplastic resins and thermosetting resins.

Examples of thermoplastic resins include thermoplastic resins having a heat distortion temperature (melting point) of 150° C. or more and less than 380° C. (non-crystalline resins such as PES (polyethersulfone), PEI (polyetherimide), PAI ( polyamideimide), etc.; as crystalline resins, PEEK (polyetheretherketone), PTFE (polytetrafluoroethylene), PPS (polyphenylene sulfide), PEN (polyethylene naphthalate), etc.); Thermoplastic resins at 100 ° C. or more and less than 150 ° C. (as amorphous resins, PC (polycarbonate), PPE (modified polyphenylene ether), etc.; as crystalline resins, PA (polyamide), PET (polyethylene terephthalate), PBT ( polybutylene terephthalate), POM (polyacetal), EVOH (ethylene-vinyl alcohol copolymer), COC (cyclic olefin copolymer), COP (cyclic olefin polymer), etc.); Noncrystalline resins such as PMMA (polymethyl methacrylate), PS (polystyrene), ABS (acrylonitrile butadiene styrene); crystalline resins such as PP (polypropylene), PE (polyethylene; LDPE (low density polyethylene), MDPE (medium density polyethylene), HDPE (high density polyethylene), LLDPE (linear low density polyethylene), etc.).

Examples of thermosetting resins include epoxy resins, phenolic resins, melamine resins, and resins obtained by combining at least two of these resins (eg, epoxyphenol, epoxyphenolmelamine, etc.).

PET (polyethylene terephthalate), PP (polypropylene), PE (polyethylene), and COC (cyclic olefin copolymer) are preferable as the resin contained in the material constituting the single-use container. The resin contained in the material constituting the single-use container may be of one kind alone or two or more kinds thereof.

Examples of the metal contained in the material constituting the single-use container include aluminum and the like.

The container body of the single-use container may have a single-layer structure consisting of only an inner layer in contact with the composition for external use, and includes an inner layer in contact with the composition for external use and a layer (outer layer, intermediate layer, etc.) not in contact with the composition for external use. A multilayer structure consisting of two or more layers may be used. From the viewpoint of exhibiting the effects of the present invention more remarkably, it is preferable that the inner layer in contact with the composition for external use contains a resin. Moreover, from the viewpoint of exhibiting the effects of the invention more remarkably, the inner layer that is in contact with the composition for external use is preferably a layer that does not contain metal or glass. When the container body of the single-use container has a multi-layered structure, the material constituting the layer (outer layer or intermediate layer) that does not come into contact with the external composition is not particularly limited. (thermoplastic resin, thermosetting resin), metal (aluminum, etc.), glass, etc.) can be selected and used. Examples of a single-use container having a multi-layered container body include a tube container, a sachet, and the like, in which the inner layer is a layer containing resin and the outer layer is a layer containing aluminum.

Materials that make up single-use containers include additives such as stabilizers, modifiers, colorants, UV absorbers, metal oxides, oxygen absorbers, antibacterial agents, plasticizers, and glass fibers. may

The topical composition according to this embodiment may also be provided as a single-use container-packed topical composition.

[2. Method for Improving Defoaming Speed in External Composition]
When an external composition is stored in a single-use container, particularly compared to a multiple-use container, 1) the single-use container is suitable for portability and is therefore susceptible to vibration and impact, and the stored external composition is 2) Since the container is small, the area of the container in contact with the composition for external use is relatively large, and the generated bubbles tend to adhere to the inner wall of the container.
In this respect, the topical composition according to the present embodiment contains minoxidil and a pH adjuster, and 0.1 to 2 mL of the topical composition is contained in a single-use container, so that defoaming in the topical composition Speed is noticeably improved. Therefore, one embodiment of the present invention comprises blending (A) minoxidil and (B) a pH adjuster in an external composition and storing 0.1 to 2 mL of the external composition in a single-use container. SUMMARY OF THE INVENTION There is provided a method for improving the defoaming rate in a topical composition.

In the present embodiment, the content of component (A), the type and content of component (B), the type and content of other components, the formulation form and application of the composition for external use, etc. For single-use containers containing composition for external use].

The present invention will be specifically described below based on test examples, but the present invention is not limited to these. The unit of each component amount in Tables 1 to 13 is all "w/v %".

[Test Example 1-1: Defoaming Evaluation]
Test solutions shown in Tables 1 to 5 were prepared in a conventional manner. The pH of Examples 1-24 was 6.0. The pH of Examples 1-25 was 8.2. 1 mL of the prepared test solution was placed in a polyethylene terephthalate (PET) container (main body maximum inner diameter 11.9 mm, 3 mL capacity, PET-vial hole cap, manufactured by Maruem), polypropylene (PP) container (main body maximum inner diameter 10.8 mm , 1.5 mL capacity, Violamo microtube, manufactured by Violamo), or a container containing cyclic olefin copolymer (COC) (longer diameter 10 mm, minor diameter 8 mm, 2.5 mL capacity, COC 70 w / w% and LLDPE 30 w / w %, and hermetically sealed in an integrally molded container). In addition, 0.5 mL of the prepared test solution was hermetically stored in a polyethylene (LDPE) container (outer diameter of 8 mm, capacity of 1 mL, sample bottle, manufactured by Kartell). Each container in which the test solution was hermetically stored was vertically shaken 10 times over a distance of 20 cm within 4 seconds in a vertical state with the opening facing upward. Immediately after shaking, the container was placed vertically, and the time (seconds) until the bubbles formed on the liquid interface disappeared was measured. Five measurements were made for one test solution. The average of the three measured values excluding the maximum and minimum measured values was calculated and used as the defoaming time of the test solution. A value of 30 was given if the foam did not disappear after 30 seconds. The change rate of defoaming speed was calculated according to the following [Formula 1]. The calculated results are shown in Tables 1-5.
[Formula 1] Rate of change in defoaming speed (%) = {(defoaming time of corresponding test liquid/defoaming time of each test liquid) -1} x 100
The corresponding test liquids are Comparative Example 1-1 for Examples 1-1 to 1-22, Example 1-23 for Examples 1-24 to 1-27, and Examples 1-28 to 1. -34 is Example 1-15, Examples 1-36 to 1-40 are Example 1-35, and Examples 1-42 to 1-44 are Example 1-41.

The defoaming speed of the topical compositions of Examples 1-1 to 1-22 containing minoxidil and a pH adjuster was remarkably improved compared to the topical composition of Comparative Example 1-1 containing only minoxidil. was confirmed. In addition, it was confirmed that the addition of a monohydric alcohol or a polyhydric alcohol to an external composition containing minoxidil and a pH adjuster further improved the defoaming rate (for the monohydric alcohol, Example 1-4 Examples 1-5 to 1-6, Examples 1-20 and 1-21 to 1-22, Examples 1-15 and 1-33 to 1-34; and Example 1-24, Example 1-15 and Examples 1-29 to 1-32). Furthermore, when glycyrrhetinic acid and dipotassium glycyrrhizinate were further added to an external composition containing minoxidil and a pH adjuster, to an external composition containing minoxidil, a pH adjuster and a monohydric alcohol (Examples 1-23 and Examples 1-26 to 1-27), when pantothenyl ethyl ether, panthenol, pyridoxine hydrochloride, diphenhydramine hydrochloride or carpronium chloride was added to an external composition containing minoxidil, a pH adjuster and a polyhydric alcohol (implementation Examples 1-35 and Examples 1-36 to 1-40), and when pantothenyl ethyl ether, panthenol or pyridoxine hydrochloride was added to an external composition containing minoxidil and a pH adjuster (Example 1- 41 and Examples 1-42 to 1-44), it was confirmed that the defoaming rate was further improved compared to the case where these components were not added. Thus, it was confirmed that the test liquid of each example causes bubbles to disappear faster than the corresponding test liquid, making it easier for the bubbles in the container to disappear.

[Test Example 2-1: Defoaming Evaluation]
Test solutions shown in Tables 6 to 8 were prepared in a conventional manner. Immediately after preparation, the test solution was sealed in a container made of polyethylene terephthalate, a container made of polypropylene, a container containing a cyclic olefin copolymer, or a container made of polyethylene. The container and capacity used are the same as in Test Example 1-1. In the same manner as in Test Example 1-1, the time until bubbles formed at the liquid interface disappeared was measured (defoaming time immediately after preparation). 1 mL of the test solution immediately after preparation was placed in a glass vial bottle (2 mL capacity, manufactured by Maruem), sealed, and left to stand at 60 ° C. for 3 days for heat treatment. It was hermetically housed in a terephthalate container, a polypropylene container, a cyclic olefin copolymer-containing container, or a polyethylene container. The container and capacity used are the same as in Test Example 1-1. With respect to the test liquid after heat treatment, the time until bubbles formed at the liquid interface disappeared was measured in the same manner as in Test Example 1-1 (defoaming time after heat treatment). The change rate of defoaming speed was calculated according to the following [Formula 2]. The calculated results are shown in Tables 6-8.
[Formula 2] Rate of change in defoaming speed (%) = {1-(defoaming time after heat treatment/defoaming time immediately after preparation)} x 100

The defoaming speed of the topical compositions of Examples 2-1 to 2-29 containing minoxidil and a pH adjuster was remarkably improved compared to the topical composition of Comparative Example 2-1 containing only minoxidil. was confirmed. Further, it was confirmed that the addition of a polyhydric alcohol to an external composition containing minoxidil and a pH adjuster further improved the defoaming speed (Example 2-2 and Examples 2-3 to 2- 4, Examples 2-15 and 2-17 to 2-21, and Examples 2-22 and 2-23). Furthermore, it was confirmed that the addition of pantothenyl ethyl ether, panthenol, pyridoxine hydrochloride, diphenhydramine hydrochloride, or carpronium chloride to an external composition containing minoxidil and a pH adjuster further improved the defoaming rate (implementation Example 2-24 and Examples 2-25 to 2-29). Thus, it was confirmed that the test liquid of each example causes bubbles to disappear faster than the corresponding test liquid, making it easier for the bubbles in the container to disappear. In addition, for Examples 2-2, 2-15 and 2-24, 0.5 mL was accommodated in a polyethylene (LDPE) integrally molded container (accommodating length 8 mm, accommodating part minor diameter 6 mm, 1 mL capacity). It was confirmed that the defoaming rate was further improved even when the

[Test Example 3-1: Defoaming evaluation]
Test solutions shown in Tables 9 and 10 were prepared by a conventional method, and 1 mL of each was sealed in a container made of polyethylene terephthalate or polypropylene. The container and capacity used are the same as in Test Example 1-1. The container containing the test liquid was shaken in the same manner as in Test Example 1-1 except that it was shaken back and forth 60 times. The height of the foam was measured at an arbitrary point and the other end point of the diameter with that point as the end point, and the average value was obtained. One test liquid was measured three times, and the average value was taken as the foam height of the test liquid (height of foam immediately after shaking). After shaking, the sample was allowed to stand still for 30 minutes, and the height of foam in each test solution was measured (height of foam after 30 minutes of shaking). The defoaming rate was calculated according to the following [Formula 3-1]. Next, according to the following [Formula 3-2], the defoaming degree for the corresponding test solution was calculated. The calculated results are shown in Tables 9-10.
[Formula 3-1] Defoaming rate (%) = {1-(height of foam after 30 minutes of shaking/height of foam immediately after shaking)} x 100
[Formula 3-2] Defoaming degree = Defoaming rate of test liquid/Defoaming rate of corresponding test liquid The corresponding test liquid is Example 3-1 for Examples 3-2 to 3-6. , Example 3-7 for Examples 3-8 to 3-11, Example 3-12 for Examples 3-13 to 3-15, Example 3- for Examples 3-17 to 3-20 is 16.

It was confirmed that the defoaming rate was further improved by further adding an antioxidant, a higher fatty acid, a monohydric alcohol or a surfactant to the topical composition containing minoxidil and a pH adjuster (Example 3-1 and Examples 3-2 to 3-11). Further, it was confirmed that when menthol, hinokitiol, salicylic acid or tocopherol acetate was further added to the composition for external use containing minoxidil, a pH adjuster and a surfactant, the defoaming rate was further improved (Example 3-12). and Examples 3-13 to 3-20). Thus, it was confirmed that the test liquid of each example causes bubbles to disappear faster than the corresponding test liquid, making it easier for the bubbles in the container to disappear.

[Test Example 4-1: Defoaming evaluation]
A test solution shown in Table 11 was prepared by a conventional method, and 1 mL of the solution was placed in a glass vial bottle (2 mL capacity, manufactured by Maruem Co., Ltd.) and sealed. Heat treatment was performed by standing at 60° C. for 3 days, and 1 mL of the obtained test solution after heat treatment was sealed and contained in a container made of polyethylene terephthalate or polypropylene. The container and capacity used are the same as in Test Example 1-1. The test solution was shaken in the same manner as in Test Example 3-1, and the foam height (mm) was measured immediately after shaking and 30 minutes after shaking. Next, the defoaming degree for the corresponding test solution was calculated in the same manner as in Test Example 3-1. The calculated results are shown in Table 11.
The corresponding test liquid is Example 4-1 for Examples 4-2 to 4-4.

It was confirmed that the defoaming speed was further improved by further adding a thickener to the external composition containing minoxidil and a pH adjuster (Example 4-1 and Examples 4-2 to 4-4). . Thus, it was confirmed that the test liquid of each example causes bubbles to disappear faster than the corresponding test liquid, making it easier for the bubbles in the container to disappear.

[Formulation example]
A composition for external use as described in Tables 12 and 13 below is prepared. 1 mL of each of Formulation Examples 1 to 14 was placed in a PET-containing resin container and covered with a PP-containing resin lid. 1 mL of Formulation Examples 1 to 14 was placed in a PP-containing resin container, and the PP-containing resin was capped. 1 mL of Formulation Examples 1 to 14 was placed in a PE (HDPE)-containing resin container, and a PS-containing resin lid was placed on the container. 1 mL of each of Formulation Examples 1 to 14 was contained in a container integrally molded with PE (LDPE)-containing resin. 1 mL of Formulation Examples 1 to 14 was contained in a container integrally molded with a COC-containing resin. The unit of numerical values in the formulation examples is "w/v %". The pHs of the external compositions of Formulation Examples 10, 11, 12 and 14 are 6.0, 6.1, 7.1 and 5.9, respectively.

Claims (5)

An external composition comprising (A) minoxidil and (B) a pH adjuster, wherein 0.1 to 2 mL of the external composition is contained in a single-use container. 2. The composition for external use according to claim 1, further comprising (C) one or more selected from the group consisting of monohydric alcohols, polyhydric alcohols, higher fatty acids, surfactants, antioxidants, and thickeners. . pantothenyl ethyl ether, panthenol, pyridoxine, tocopherol, menthol, hinokitiol, diphenhydramine, salicylic acid, glycyrrhetinic acid, glycyrrhizic acid, and carpronium chloride, and at least one selected from the group consisting of salts thereof. Item 3. The composition for external use according to Item 1 or 2. A topical composition according to any preceding claim, wherein the material comprising the single-use container comprises a resin. Improving defoaming speed in an external composition, comprising incorporating (A) minoxidil and (B) a pH adjuster in the external composition, and storing 0.1 to 2 mL of the external composition in a single-use container. how to let