Film-forming topical preparation base

Abstract

To provide a novel base for film-forming external agents that is capable of forming a film with high shape retention and reduced stickiness by using a water-based polymer emulsion containing a copolymer with a glass transition temperature of -15°C or lower, which is not easily applicable as a base for film-forming formulations.SOLUTION: This invention provides, for example, a base for film-forming external agents that contains the following components A- C. A) Methyl acrylate and 2-ethylhexyl acrylate copolymer emulsion, B) oil (e.g. liquid paraffin) and C) oil gelator (e.g. dextrin palmitate).SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention belongs to the technical field of external preparations. The present invention relates to a base for a film-forming external preparation that is liquid or gel-like before use, but when applied to the skin, the solvent of the carrier component volatilizes to form a film on the skin.

Background Art

[0002] As one of the external preparations applied to the skin, there is known a film-forming external preparation (for example, a liquid bandage) that is liquid or gel-like before use, but when applied to the skin, the solvent of the carrier component evaporates to form a film on the skin. Such a film-forming external preparation is convenient because it causes less physical irritation during peeling and can form a film according to the size and shape of the damaged area. It can also be directly applied with a container.

[0003] Conventionally, as film-forming agents for film-forming external preparations, for example, cellulose-based resins such as hydroxypropyl cellulose, water-soluble polymers such as polyvinyl alcohol and polyvinyl pyrrolidone (Patent Documents 1 to 3), (meth) acrylic acid-based polymers (Patent Document 4), and pyroxylin (Patent Document 5) are known.

[0004] An aqueous polymer emulsion is one in which polymer particles are dispersed in an aqueous solvent such as water, and when the aqueous solvent volatilizes, the polymer particles come together and fuse and deform to form a film. The aqueous polymer emulsion is used, for example, in the cosmetic field, and Patent Document 6 discloses an invention related to a composition for artificial nail coating using an aqueous polymer emulsion.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

[0006] As mentioned above, aqueous polymer emulsions are used as bases for film-forming topical agents. However, aqueous polymer emulsions in which polymer particles selected from acrylic acid copolymers with a glass transition temperature of -15°C or lower are dispersed in an aqueous medium tend to form films with poor shape retention and excessive stickiness when the medium is evaporated to form a film. Therefore, it is not easy to use such aqueous polymer emulsions as film-forming formulations.

[0007] The main objective of this invention is to provide a novel base for a film-forming topical preparation that can form a film with high shape retention while suppressing tackiness, using an aqueous polymer emulsion containing an acrylic acid copolymer with a glass transition temperature of -15°C or lower, which is not easily used as a base for such film-forming preparations. [Means for solving the problem]

[0008] To solve the above problems, the inventors conducted diligent research and found that the above problems can be solved by adding an oil and an oil gelling agent to an aqueous polymer emulsion in which polymer particles selected from copolymers containing (meth)acrylic acid polymers and (meth)acrylic acid monomers in their molecules and having a glass transition temperature of -15°C or lower are dispersed in an aqueous medium, and further adding a filler such as an inorganic powder as needed, thereby completing the present invention.

[0009] Examples of the present invention include the following embodiments. [1] A film-forming topical preparation base containing the following components A to C: A) A copolymer comprising polymer particles consisting of one or more polymers selected from copolymers containing (meth)acrylic acid polymers and (meth)acrylic acid monomers in their molecules, and having a glass transition temperature of -15°C or lower, dispersed in an aqueous medium. B) oil content, C) Oil gelling agent. [2] The film-forming topical agent base according to [1] above, wherein the copolymer is a methyl acrylate / 2-ethylhexyl acrylate copolymer, an alkyl acrylate copolymer emulsion (2), or an alkyl acrylate / vinyl acetate copolymer emulsion. [3] The film-forming topical agent base according to [1] or [2] above, wherein the average particle size of the polymer particles measured by dynamic light scattering is in the range of 10 to 600 nm. [4] The film-forming topical agent base according to [1] or [2] above, wherein the amount of polymer solids in the aqueous polymer emulsion is in the range of 20 to 80% by mass. [5] The film-forming topical preparation base according to [1] or [2] above, further comprising a filler. [6] The film-forming topical preparation base according to [1] or [2] above, wherein the oil component is one or more selected from the group consisting of fatty acids, higher alcohols, sorbitan fatty acid esters, polyglycerin fatty acid esters, paraffins, triglycerides, neopentyl glycols, silicone oils, and esters. [7] The fatty acid is palmitic acid, stearic acid, isostearic acid, or oleic acid; the higher alcohol is cetanol, stearyl alcohol, isostearyl alcohol, 2-octyldodecanol, or decyltetradecanol; the sorbitan fatty acid ester or polyglycerin fatty acid ester is sorbitan sesquioleate, sorbitan sesquiisostearate, sorbitan isostearate, or polyglyceryl diisostearate; the paraffins are isoparaffin, liquid paraffin, or squalane; the triglycerides are tri(2-ethyl The film-forming topical preparation base described in [6] above, wherein the neopentyl glycols are glyceryl hexanoate or caprylic / capric triglyceride; the neopentyl glycols are neopentyl glycol dioctanoate or neopentyl glycol dicaprate; the silicone oils are methylphenylpolysiloxane; or the esters are isononyl isononanoate, isopropyl myristate, isotridecyl myristate, isopropyl palmitate, cetyl 2-ethylhexanoate, isostearyl myristate, octyldodecyl myristate, di(2-heptylundecyl) adipate, or jojoba oil. [8] The film-forming topical preparation base according to [1] or [2] above, wherein the oil gelling agent is one or more selected from the group consisting of dextrin myristate, dextrin palmitate, (palmitic acid / ethylhexanoic acid) dextrin, and (palmitic acid / hexyldecanoic acid) dextrin. [9] The film-forming topical agent base according to [5] above, wherein the filler is an inorganic powder.

[10] The film-forming topical agent base according to [9] above, wherein the inorganic powder is one or more selected from the group consisting of light anhydrous silicic acid, hydrated silicon dioxide, and titanium dioxide.

[0010]

[11] A non-medicinal topical preparation comprising the film-forming topical preparation base described in [1] or [2] above.

[12] A pharmaceutical external preparation comprising the film-forming external preparation base described in [1] or [2] above and a medicinal ingredient.

[13] The pharmaceutical external preparation according to

[12] above, wherein the medicinal ingredient is a medicine for fish eyes, octopus, or boils, an acne treatment agent, a bactericide, a tinea medicine (antifungal agent), an antipruritic agent, a moisturizer, an analgesic and anti-inflammatory agent, an antihistamine, an anti-inflammatory agent, a local anesthetic, a keratolytic agent, a tissue repair agent, a skin protectant, or a vitamin agent.

[14] The non-pharmaceutical external preparation according to

[11] above, enclosed in a pump-type container, a mini roll-on container, a roll-on container, a spray container, or a brush-attached container.

[15] The pharmaceutical external preparation according to

[12] above, enclosed in a pump-type container, a roll-on container, a mini roll-on container, a spray container, or a brush-attached container.

Effects of the Invention

[0011] When the film-forming external preparation base according to the present invention is used, a film-forming external preparation can be prepared that forms a film with suppressed adhesiveness and no problem in film formation, which contains an aqueous polymer emulsion in which polymer particles selected from acrylic acid copolymers having a glass transition temperature of -15°C or lower are dispersed in an aqueous medium.

Modes for Carrying Out the Invention

[0012] 1 The film-forming external preparation base according to the present invention The film-forming external preparation base according to the present invention (hereinafter referred to as "the base of the present invention") is characterized by containing the following components A to C: A) An aqueous polymer emulsion in which polymer particles composed of one or more polymers selected from copolymers containing a (meth)acrylic acid polymer and a (meth)acrylic acid monomer in the molecule and having a glass transition temperature of -15°C or lower are dispersed in an aqueous medium, B) An oil component, C) An oil gelling agent.

[0013] 1.1 Regarding Component A The base material of the present invention comprises component A. Component A is a film-forming agent comprising an aqueous polymer emulsion in which polymer particles selected from (meth)acrylic acid polymers and copolymers containing (meth)acrylic acid monomers in their molecules are dispersed in an aqueous medium, wherein the glass transition temperature (Tg) of the polymer is -15°C or lower. Preferably, the glass transition temperature is in the range of -80°C to -15°C, and more preferably, in the range of -60°C to -20°C.

[0014] As described above, an aqueous polymer emulsion is a solution in which polymer particles are dispersed in an aqueous solvent such as water. When the aqueous solvent evaporates, the polymer particles fuse together and deform, forming a film. Therefore, a film made of polymers is basically formed on the skin by component A. Furthermore, the water in which the polymer particles are dispersed basically serves as the carrier solvent for the base of the present invention. Accordingly, the base of the present invention contains water.

[0015] The glass transition temperature (Tg) is a material property well known to those skilled in the art and can be determined by conventional methods. Specifically, examples include methods that measure changes in mechanical properties and endothermic / exothermic reactions while gradually increasing or decreasing the temperature of a polymer sample (e.g., differential scanning calorimetry (DSC), differential thermal analysis (DTA)), and mechanical spectroscopy (dynamic viscoelasticity measurement). Furthermore, Tg can be calculated using the so-called Fox equation.

[0016] The polymer of the aqueous polymer emulsion relating to component A is selected from (meth)acrylic acid polymers and copolymers containing (meth)acrylic acid monomers within the molecule. Here, "(meth)acrylic acid" refers to the combined term of acrylic acid and methacrylic acid. In the present invention, polymers or copolymers ((meth)acrylate alkyl ester polymers) having alkyl ester (meth)acrylate as the main constituent monomer are preferred. These may also contain, for example, (meth)acrylic acid, or one or more hydrophobic monomers or hydrophilic monomers as constituent monomers within the molecule.

[0017] Examples of the polymerizable monomer alkyl (meth)acrylates mentioned above include methyl (meth)acrylate, ethyl (meth)acrylate, isopropyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, n-amyl (meth)acrylate, isoamyl (meth)acrylate, n-hexyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, octyl (meth)acrylate, decyl (meth)acrylate, dodecyl (meth)acrylate, octadecyl (meth)acrylate, cyclohexyl (meth)acrylate, phenyl (meth)acrylate, benzyl (meth)acrylate, and isoamyl (meth)acrylate. Among these, methyl (meth)acrylate, ethyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, and isoamyl (meth)acrylate are preferred. These may be one type or any two or more types.

[0018] Examples of the hydrophobic monomers mentioned above include styrene monomers such as styrene, 2-methylstyrene, t-butylstyrene, and chlorostyrene; allyl monomers such as allyl acrylate; vinyl chloride monomers such as vinyl chloride; epoxy monomers such as butyl glycidyl ether, glycidyl (meth)acrylate, diglycidyl (meth)acrylate, and allyl glycidyl ether; silicone monomers such as dimethylsiloxane; and urethane monomers such as urethane.

[0019] Examples of the hydrophilic monomers mentioned above include alkyl (meth)acrylates having hydroxyl groups in the side chain, such as 2-hydroxyethyl (meth)acrylate and hydroxypropyl (meth)acrylate; amide monomers such as acrylamide, maleic acid amide, and N-methylol(meth)acrylamide; maleic acid monomers such as maleic anhydride; and vinyl monomers such as vinyl acetate.

[0020] The method for producing the aqueous polymer emulsion relating to component A is not particularly limited, but for example, the aqueous polymer emulsion can be produced by uniformly dispersing raw materials such as acrylic monomers and emulsifiers in water, micellizing the monomers with the emulsifier, adding a polymerization initiator (e.g., hydrogen peroxide, peracetic acid, t-butyl hydroperoxide, perbenzoic acid), and heating to carry out emulsion polymerization. Alternatively, it can be produced by methods such as soap-free polymerization using a reactive emulsifier or heterogeneous polymerization using an aqueous medium that does not contain an emulsifier.

[0021] Examples of the emulsifiers mentioned above include nonionic emulsifiers such as polyoxyethylene alkylphenyl ethers like polyoxyethylene nonylphenyl ether and polyoxyalkylene alkyl ethers like polyoxyethylene dodecyl ether; and anionic emulsifiers such as polyoxyalkylene alkyl ether sulfate ammonium, polyoxyethylene lauryl ether sulfate sodium, 2-ethylhexyl sulfate sodium, and dioctyl sulfosuccinate sodium.

[0022] The average particle size of polymer particles in the aqueous polymer emulsion relating to component A is not particularly limited, but when measured by dynamic light scattering (DLS), a weight-average particle size of, for example, in the range of 10 to 600 nm is appropriate, preferably in the range of 100 to 500 nm, and more preferably in the range of 200 to 400 nm. Such an average particle size can be measured using, for example, a nanoparticle size analyzer such as Nanotrac Wave II (MICROTRAC) or Zetasizer PRO (SPECTRIS).

[0023] The amount of polymer solids in the aqueous polymer emulsion relating to component A is not particularly limited, but is suitable in the range of 20 to 80% by mass, and preferably in the range of 50 to 70% by mass.

[0024] Examples of copolymers relating to preferred component A include methyl acrylate / 2-ethylhexyl acrylate copolymer and alkyl acrylate copolymer emulsion. hmm,Examples include alkyl acrylate / vinyl acetate copolymer emulsions. Some of the aqueous polymer emulsions related to component A are commercially available, and commercially available products can be used in the present invention. Specific examples include Nikazol TS-620 (manufactured by Nippon Carbide Industries Co., Ltd.), Nikazol TS-620G (manufactured by Nippon Carbide Industries Co., Ltd.), and Vinysol 1087FT (manufactured by Daido Chemical Industries Co., Ltd.). )of It can be listed.

[0025] The content of component A in the base of the present invention can be set as desired and is not particularly limited.

[0026] 1.2 About Component B Component B is an oil, and the base of the present invention contains component B. Basically, component B and component C (oil gelling agent) described later can improve the film retention and reduce the tackiness of the formed film. The oil in question is not particularly limited as long as it is a lipid-soluble organic substance that is insoluble in water, but examples include oily organic substances with a solubility in neutral water at 20°C of 100 μg / mL or less. Examples of such oils include fatty acids, higher alcohols, sorbitan fatty acid esters, polyglycerol fatty acid esters, paraffins (hydrocarbons), triglyceryl triglycerides, neopentyl glycols, silicone oils, esters, and animal and vegetable oils. Specifically, for example, fatty acids such as palmitic acid, stearic acid, isostearic acid, oleic acid, behenic acid, lauric acid, and myristic acid; higher alcohols such as cetanol, stearyl alcohol, isostearyl alcohol, 2-octyldodecanol, and decyltetradecanol; sorbitan fatty acid esters and polyglycerin fatty acid esters (surfactants) such as sorbitan sesquioleate, sorbitan sesquiisostearate, sorbitan isostearate, and polyglyceryl diisostearate; paraffins (hydrocarbons) such as isoparaffin, liquid paraffin, squalane, and petrolatum; and tri(2-ethylhexanoic acid) Triglycerides such as glyceryl tri(caprylic / capric acid) glyceryl; neopentyl glycols such as neopentyl glycol dioctanoate and neopentyl glycol dicaprate; silicone oils such as methylphenylpolysiloxane, dimethylpolysiloxane (polydimethylsiloxane), highly polymerized methylpolysiloxane, methylhydrogenpolysiloxane, octamethylcyclotetrasiloxane, octamethylcyclopentasiloxane, decamethylcyclohexasiloxane, stearoxysilicone, alkyl-modified silicones, and higher fatty acid ester-modified silicones;Isononyl isononanoate, isopropyl myristate, isotridecyl myristate, isopropyl palmitate, cetyl 2-ethylhexanoate, isostearyl myristate, octyldodecyl myristate, di(2-heptylundecyl) adipate, jojoba oil, cetyl isooctanate, glyceryl trioctanoate, diglyceryl triisostearate, glyceryl tribehenate, diisostearyl malate, cholesterol fatty acid ester, di(cholesteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamic acid Examples of animal and vegetable oils include esters such as tocopherol acetate; avocado oil, linseed oil, almond oil, olive oil, cocoa oil, beef tallow, tung oil, wheat germ oil, sesame oil, rice germ oil, rice bran oil, safflower oil, soybean oil, evening primrose oil, camellia oil, corn oil, rapeseed oil, horse fat, peach kernel oil, palm oil, palm kernel oil, castor oil, sunflower oil, lard, grape oil, jojoba oil, macadamia nut oil, mink oil, cottonseed oil, Japanese wax, beeswax, bleached beeswax, coconut oil, hydrogenated coconut oil, peanut oil, lanolin, egg yolk oil, and rosehip oil. Among these, paraffins such as isoparaffin, liquid paraffin, and squalane, esters such as octyldodecyl myristate, and silicone oils such as methylphenylpolysiloxane are preferred, with liquid paraffin and octyldodecyl myristate being more preferred. Component B may be any one of the above or any two or more in combination.

[0027] The content of component B in the base of the present invention can be set as desired and is not particularly limited, but a range of 5 to 40% by mass is appropriate, a range of 10 to 30% by mass is preferred, and a range of 10 to 20% by mass is more preferred. If the content is less than 5% by mass or more than 40% by mass, oil stains may occur, or sufficient form retention and reduced tackiness may not be obtained.

[0028] 1.3 About Component C The base material of the present invention contains an oil gelling agent. This oil gelling agent basically suppresses stickiness caused by the oil related to component B. Because this oil gelling agent suppresses stickiness caused by oil, it can also help maintain the formation of the formed film and reduce its tackiness. The oil gelling agent is not particularly limited as long as it is an organic substance that can gel the oil related to component B, but specifically, examples include dextrin myristate, dextrin palmitate, (palmitic acid / ethylhexanoic acid) dextrin, and (palmitic acid / hexyldecanoic acid) dextrin. Among these, dextrin palmitate is preferred. Component C may be any one of the above or any two or more in combination.

[0029] The content of component C in the base of the present invention varies depending on, for example, the type of component C and the type and amount of oil in component B, but a range of 0.1 to 20% by mass is appropriate, a range of 0.5 to 10% by mass is preferred, and a range of 1 to 10% by mass is more preferred. If the content is less than 0.1% by mass or more than 20% by mass, oil stains may occur, or sufficient form retention and reduced tackiness may not be obtained.

[0030] 1.4 Other ingredients 1.4.1 Carrier Solvent The carrier solvent of the base of the present invention is basically water, but a volatile organic solvent may be included in a proportion of less than 20% by mass of the total amount of the base of the present invention in order to facilitate the dissolution or dispersion of the active pharmaceutical ingredient. Such a volatile organic solvent does not have to be included in the base of the present invention (0% by mass), but if it is included, it is preferably 15% by mass or less to 10% by mass or less, and more preferably 5% by mass or less to 1% by mass or less. Here, "carrier solvent" refers to a medium for holding components A of the film-forming agent, component B of the oil, component C of the oil gelling agent, etc. in the base until the formulation using the base of the present invention is applied to the skin, and after skin application, it eventually evaporates and disappears.

[0031] The volatile organic solvents that may be included in the base material of the present invention are typically low-boiling point organic solvents. Specifically, examples include lower monohydric alcohols (approximately 1 to 4 carbon atoms) (e.g., methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, isobutyl alcohol), acetone, ethyl acetate, methyl ether, and ethyl ether. Generally, these are lower monohydric alcohols, specifically ethyl alcohol.

[0032] As described above, the carrier solvent is basically water, so volatile organic solvents containing lower monohydric alcohols such as ethyl alcohol do not need to be included in the base of the present invention, and from the viewpoint of irritation, it is preferable that they are not included.

[0033] 1.4.2 Polyhydric alcohols and surfactants The base of the present invention may optionally contain polyhydric alcohols or surfactants in a proportion of 50% by mass or less, preferably 30% by mass or less to 20% by mass or less, and more preferably 10% by mass or less to 5% by mass or less, of the total amount of the base of the present invention, for purposes such as assisting in the dissolution of the pharmaceutically active ingredient.

[0034] The polyhydric alcohols that may be included in the base of the present invention are typically alcohols having two or more hydroxyl groups in their molecule. Specifically, examples include glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, and macrogol 400. Specific examples of surfactants that may be included in the base of the present invention include polyglycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ethers, and polyethylene glycol fatty acid esters.

[0035] 1.4.3 Other Additives Other additives may be added to the base material of the present invention as desired, provided that they do not impair the effects of the present invention. Examples of such additives include stabilizers, solubilizers, antioxidants, wetting agents, cooling agents, colorants, flavoring agents (fragrances), emulsifiers, adhesives, viscosity enhancers, viscosity modifiers, pH adjusters, preservatives, solvents, astringents, chelating agents, thickeners, and irritation reducers.

[0036] Examples of the stabilizers mentioned above include ascorbic acid, sodium edetate hydrate, sodium chloride, and magnesium chloride.

[0037] Examples of the solubilizing agents mentioned above include triacetin, D-mannitol, D-sorbitol, benzyl benzoate, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, and sodium citrate.

[0038] Examples of the above antioxidants include butylhydroxyanisole, sodium sulfite, ascorbic acid and its salts, sodium bisulfite, sodium sulfite, sodium pyrosulfite, benzotriazole, cysteine ​​hydrochloride, and citric acid.

[0039] Examples of humectants include methylcellulose and sodium lauryl sulfate.

[0040] Examples of cooling agents include menthol (l-menthol, dl-menthol, etc.), camphor (d-camphor, dl-camphor, etc.), terpenoids such as chlorobutanol, geraniol, cineole, anethole, limonene, and borneol, and essential oils containing terpenoids (peppermint oil).

[0041] Examples of the above-mentioned coloring agents include synthetic or naturally derived pigments such as tar dyes (Brown No. 201, Blue No. 201, Yellow No. 4, Yellow No. 403, etc.), caramel, copper chlorophyll sodium, methylene blue, gardenia pigment, marigold pigment, carotene pigment, anthocyanin pigment, fruit juice pigment, vegetable pigment, and iron oxide.

[0042] Examples of the above-mentioned fragrances include clove oil, hyperonal, and d-borneol.

[0043] Examples of the emulsifiers mentioned above include sucrose fatty acid esters and hydrogenated soybean phospholipids.

[0044] Examples of the adhesives mentioned above include carboxyvinyl polymer and carboxymethylcellulose sodium. Examples of the tack enhancers mentioned above include xanthan gum and polyethylene glycol (macrogol) 6000. Examples of the viscosity-reducing agents mentioned above include magnesium aluminum silicate and polyvinyl alcohol.

[0045] Examples of the pH adjusting agents mentioned above include organic acids or their salts, such as citric acid, sodium citrate, anhydrous citric acid, malic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, sodium tartrate, lactic acid, calcium lactate, sodium lactate, acetic acid, sodium acetate, and glacial acetic acid; inorganic acids or their salts, such as hydrochloric acid, sulfuric acid, phosphoric acid, boric acid, sodium hydrogen phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, sodium carbonate, and sodium bicarbonate; alkali hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, and borax; and amines such as monoethanolamine, triethanolamine, diethanolamine, diisopropanolamine, and triisopropanolamine.

[0046] Examples of the above-mentioned preservatives include methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, isobutyl parahydroxybenzoate, benzyl parahydroxybenzoate, benzoic acid, sodium benzoate, benzoic acid, benzyl benzoate, sodium dehydroacetate, benzalkonium chloride, cetylpyridinium chloride, benzethonium chloride, aminoethylsulfonic acid, phenoxyethanol, chlorobutanol, benzyl alcohol, phenethyl alcohol, thymol, sorbic acid and its salts. Examples of the solvents mentioned above include concentrated glycerin, propylene glycol, and benzyl alcohol.

[0047] Examples of the astringent agents mentioned above include metal salts such as alum, zinc sulfate, potassium aluminum sulfate, and basic zinc aluminum lactate; organic acids such as tannic acid, citric acid, lactic acid, and succinic acid; and components derived from plants (for example, seaweed, thyme, black tea, oolong tea, green tea, St. John's wort, witch hazel, loquat, peony root, saxifrage, rooibos, astragalus, artichoke, chamomile, eucalyptus, lemon, rosemary, burnet, salvia, etc.).

[0048] Examples of the chelating agents mentioned above include ethylenediaminetetraacetic acid (EDTA), ethylenediaminetetraacetic acid salts (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, gluconic acid, polyphosphate, and metaphosphate.

[0049] Examples of the thickening agents mentioned above include guar gum, pectin, pullulan, gelatin, locust bean gum, carrageenan, agar, glucomannan, curdlan, gellan gum, xanthan gum, polyethylene glycol, bentonite, alginic acid, propylene glycol alginate, macrogol, sodium chondroitin sulfate, hyaluronic acid, and sodium hyaluronate.

[0050] Examples of the irritation-reducing agents mentioned above include gelatin, acacia gum, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol alginate, licorice extract, and 2-methacryloyloxyethyl phosphorylcholine. The above additives may be used individually or in combination of any two or more, as desired.

[0051] The base material of the present invention typically has a pH of 2 to 9, but from the viewpoint of skin irritation and skin feel, a pH of 3 to 8 is preferred, and a pH of 4 to 8 is particularly preferred. This pH can be adjusted as appropriate by using the above-mentioned pH adjusting agent.

[0052] The base material of the present invention may have a viscosity in the range of 1 to 10,000 mPa·s, but from the viewpoint of ease of handling and application, it is preferably in the range of 3 to 5,000 mPa·s, and more preferably in the range of 5 to 3,000 mPa·s.

[0053] The method for producing the base material of the present invention is not particularly limited. The base material of the present invention can be produced by appropriately selecting and blending various components necessary for the preparation of the base material of the present invention, and stirring by a conventional method using a suitable stirrer.

[0054] 2. Uses of the base material of the present invention The base material of the present invention can be used as a base for non-pharmaceutical film-forming topical preparations, or as a base for film-forming topical preparations containing pharmacoactive ingredients related to pharmaceuticals. The present invention can include non-pharmaceutical topical preparations such as general merchandise and cosmetics that contain the base material of the present invention but do not contain pharmacoactive ingredients, and pharmaceutical topical preparations that contain the base material of the present invention and pharmacoactive ingredients. Hereinafter, these non-pharmaceutical topical preparations and pharmaceutical topical preparations will be simply referred to as "topical preparations of the present invention."

[0055] In the topical preparation of the present invention for pharmaceutical use, a wide range of pharmacoactive ingredients can be incorporated, from hydrophilic to hydrophobic drugs. Examples of such drugs (pharmacoactive ingredients) include medications for corns, calluses, and warts, acne treatments, antiseptics, antifungal agents for athlete's foot, antipruritics, moisturizers, analgesics and anti-inflammatory agents, antihistamines, anti-inflammatory agents, local anesthetics, keratolytics, tissue repair agents, skin protectants, and vitamins. These can be used individually or in combination of any two or more.

[0056] The method for producing the topical preparation of the present invention for pharmaceutical use is not particularly limited, but for example, it can be produced by stirring and mixing the base of the present invention, a desired pharmaceutically active ingredient, and additives as needed using a conventional method with a stirrer or the like. More specifically, for example, the topical preparation of the present invention for pharmaceutical use can be produced by a method including the following steps. In the case of the topical preparation of the present invention for non-pharmaceutical use, it can be produced in the same manner except for step 1 below.

[0057] Step 1: Dissolve or disperse the drug (active ingredient) (drug phase). Step 2: Various additives are added to the aqueous emulsion according to the present invention and stirred with a stirrer to prepare the base material of the present invention (base phase). Step 3: Add the drug phase to the base phase and stir with a stirrer (bulk formulation). Step 4: The bulk formulation is filled into containers of choice using a filling machine.

[0058] The topical preparation of the present invention can be sealed in any sealed container, such as a foamed rubber stopper application container, a (mini) roll-on container, a spray container, a dropper container, an emulsion container, an aluminum tube, or a pin-push type container. It can be applied directly to the skin from the container. From the viewpoint of suppressing drying of the application area, it is preferable to seal it in a pin-push type container, a roll-on container, a mini roll-on container, a spray container, or a container with a brush. Examples of materials for the container include general plastics such as polyethylene, polypropylene, and polyethylene terephthalate.

[0059] The method of applying the topical preparation of the present invention for pharmaceutical use varies depending on the disease, active ingredient, affected area, gender, age, etc., and is not particularly limited. However, it can usually be used by applying an appropriate amount to the area including the affected area on the skin or other external surface, once to several times a day. After application, the topical preparation of the present invention dries quickly, and a film is formed on the skin to which the topical preparation of the present invention has been applied. This film does not swell easily even when exposed to water and can remain on the skin for a relatively long period of time if no force is applied. [Examples]

[0060] The present invention will be described in more detail below with reference to examples and test cases. However, the present invention is not limited in any way to the following examples.

[0061] [Reference Examples 1-18] Screening of additives to improve film formation 9.5 g of methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion (Nikazol TS-620, manufactured by Nippon Carbide Industries, Ltd., glass transition temperature -50°C; the same applies hereafter) was mixed with 0.5 g of each additive shown in Table 1 (Reference Example 1 is unadded) and stirred well. After stirring, 0.5 g of each liquid was mixed into a 3 cm diameter (approximately 7 cm area) solution. 2 It was placed in a polypropylene container and dried at 50°C for 6 hours. After drying, the film formation status of the formed film was evaluated according to the following criteria. The results are shown on the far right of Table 1.

[0062] <Evaluation Criteria> ○: Good film-forming and shape-retention properties. △: Film-forming or shape-retention properties are moderately good. ×: Poor shape retention

[0063] [Table 1]

[0064] Without additives (Reference Example 1), the material was extremely sticky and had poor shape retention, resulting in no film being formed. Adding liquid paraffin or dimethylsiloxane allowed for the formation of a water-insoluble film, but it was considerably sticky.

[0065] [Examples 1-4] 0.025 g of dextrin palmitate (Leopal KL2 or TL2, manufactured by Chiba Flour Milling Co., Ltd.; the same applies hereafter) was added to 0.475 g of liquid paraffin (Hycol M172 (viscosity: 165 SUS) or M352 (viscosity: 360 SUS), manufactured by Kaneda Co., Ltd.; the same applies hereafter) and dissolved at 80°C. This solution was added to 9.5 g of methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion (Nicazole TS-620) and thoroughly mixed. After mixing, 0.5 g of each solution was added to a 3 cm diameter (approximately 7 cm area) 2 It was placed in a polypropylene container and dried at 50°C for 6 hours.

[0066] [Table 2]

[0067] As a result, the bases manufactured using the formulations shown in Table 2 all produced coatings with good film-forming and shape-retention properties, and with almost no stickiness.

[0068] [Examples 5-13] According to the formulation shown in Table 3, dextrin palmitate (Leopal TL2) was added to liquid paraffin (Hycol M352) and dissolved at 80°C. This solution was added to methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion (Nicazole TS-620) and thoroughly mixed. After mixing, 0.5 g of each solution was added to a 3 cm diameter (approximately 7 cm area) sample. 2 It was placed in a polypropylene container and dried at 50°C for 6 hours.

[0069] [Table 3]

[0070] The film-forming properties, oil stain resistance, and shape retention of the films formed from the base materials of each example were evaluated visually and by touch, and the results shown in Table 3 were obtained. Each evaluation was performed according to the following criteria.

[0071] <Film forming properties> ○: Forms a good film △: Forms a moderately good film. ×: Does not form a film or aggregates.

[0072] <Oil stains on the surface> ○: Almost none △: Somewhat present ×: Yes

[0073] <Shape retention> ○: Good △: Fairly good ×: Weak or brittle

[0074] As a result, the bases manufactured using the formulations shown in Table 3 all exhibited good or moderately good film-forming and shape-retention properties, and produced a film with almost no or moderate oil stains on the surface.

[0075] [Examples 14-16] Formulation of inorganic powders According to the formulation shown in Table 4, dextrin palmitate (Leopal TL2) was added to liquid paraffin (Hycol M352) and dissolved at 80°C. This solution, or this solution and light anhydrous silicic acid (Adsolida-101, manufactured by Freund Industrial Co., Ltd.), was added to methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion (Nicazole TS-620) and thoroughly mixed. After mixing, 0.5 g of each solution was added to a 3 cm diameter (approximately 7 cm area) sample. 2 It was placed in a polypropylene container and dried at 50°C for 6 hours.

[0076] [Table 4]

[0077] The film-forming properties, oil stain resistance, and shape retention of the films formed from the base materials of each example were evaluated visually and by touch, and the results shown in Table 4 were obtained. Each evaluation was performed according to the following criteria.

[0078] <Film forming properties> ◎: Forms a tough membrane ○: Forms a good film △: Forms a moderately good film. ×: Does not form a film or aggregates.

[0079] <Oil stains on the surface> ◎: Not at all ○: Almost none △: Somewhat present ×: Yes

[0080] <Shape retention> ◎: Robust ○: Good △: Fairly good ×: Weak or brittle

[0081] As a result, the base material produced using the formulation shown in Table 4 yielded a tough, robust film with absolutely no oil stains on the surface.

[0082] [Examples 17-19] Formulation of inorganic powders The procedure was carried out in the same manner as in Examples 14-16, using hydrated silicon dioxide (Adsolida-102, manufactured by Freund Industrial Co.) instead of light anhydrous silicic acid, according to the formulations shown in Table 5.

[0083] [Table 5]

[0084] The film-forming properties, oil stain resistance, and shape retention of the films formed from the base materials of each example were evaluated visually and by touch, and the results shown in Table 5 were obtained. The evaluations were performed in the same manner as described above. As a result, a tough, robust coating with no oil stains on the surface was obtained from the base material manufactured using the formulation shown in Table 5.

[0085] [Examples 20-22] The procedure was carried out in the same manner as in Examples 14-16, using titanium dioxide instead of light anhydrous silicic acid, according to the formulations shown in Table 6.

[0086] [Table 6]

[0087] The films formed from the base materials of each example were evaluated visually and by touch for film-forming properties, oil stain resistance, and shape retention, and the results shown in Table 6 were obtained. The evaluations were performed in the same manner as described above. As a result, a tough, robust film with no oil stains on the surface was obtained from the base material manufactured using the formulation shown in Table 6.

[0088] [Examples 23-33] According to the formulations shown in Table 7 or Table 8, dextrin palmitate (Leopal KL2) was added to octyldodecyl myristate (Nikko ODM-100, manufactured by Nikko Chemicals Co., Ltd.; the same applies hereafter) and dissolved at 80°C. This solution was added to methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion (Nikazol TS-620G, manufactured by Nippon Carbide Industries Co., Ltd., glass transition temperature: -20°C; the same applies hereafter) and thoroughly stirred. After stirring, 0.5 g of each solution was added to a 3 cm diameter (approximately 7 cm area) 2 It was placed in a polypropylene container and dried at 50°C for 6 hours.

[0089] [Table 7]

[0090] [Table 8]

[0091] The films formed from the base materials of each example were evaluated for oil staining, bubbles, transparency, flexibility, elasticity, strength, and interfilm adhesion, and the results shown in Tables 7 and 8 were obtained. Each evaluation was performed according to the following criteria. Interfilm adhesion is the degree of adhesion between two identical films when they are pressed together for 30 seconds and then peeled apart; the lower the adhesion, the better the film formulation.

[0092] <Oil stains on the surface> ◎: Not at all ○: Almost none △: Somewhat present ×: Yes

[0093] <bubbles> ◎: Not at all ○: Almost none △: Slightly present ×: Yes

[0094] <Transparency> ◎: Extremely transparent ○:Transparent △: Translucent ×: Milky white

[0095] <Flexibility> ◎: Extremely high ○: High △: Slightly expensive ×: Not available

[0096] <Stretchability> ◎: Extremely high ○: High △: Slightly expensive ×: Not available

[0097] <Strength> ◎: Extremely high ○: High △: Slightly expensive ×: Not available

[0098] <Intermembrane adhesion> ◎: None ○: Slightly present △: Yes ×: There is plenty

[0099] As a result, the base materials manufactured using the formulations in Tables 7 and 8 yielded films that were transparent, had almost no surface oil stains or bubbles, exhibited excellent flexibility, elasticity, and strength, and had almost no interfilm adhesion.

[0100] [Examples 34-37] Topical preparation of the present invention for pharmaceutical use A topical preparation of the present invention was prepared containing isoprofen piconol, an acne treatment agent, and isopropylmethylphenol, an antiseptic agent.

[0101] Isoprofen piconol was dissolved in octyldodecyl myristate according to the formulation shown in Table 9. This mixture and isopropylmethylphenol were added to a methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion (Nicazole TS-620G) and thoroughly mixed. After mixing, 0.5 g of this solution was added to a 3 cm diameter (approximately 7 cm area) area. 2 It was placed in a polypropylene container and dried at 50°C for 6 hours.

[0102] [Table 9]

[0103] The films formed from the base materials of each example were evaluated for oil stain resistance, bubbles, transparency, flexibility, elasticity, strength, and interfilm adhesion, and the results are shown in Table 9. Each evaluation was performed according to the criteria described above.

[0104] As a result, the topical preparations manufactured using the formulations shown in Table 9 produced a film that was virtually free of surface oil stains, completely free of air bubbles, transparent, extremely flexible and elastic, strong, and exhibited suppressed interfilm adhesion. [Industrial applicability]

[0105] The base material of the present invention is useful as a base for non-medicinal topical preparations or medicinal topical preparations. Therefore, the base material of the present invention can be used in industries related to daily life and the pharmaceutical field.

Claims

1. A film-forming topical preparation base containing the following components A to C: A) An aqueous polymer emulsion in which polymer particles consisting of one or more polymers selected from alkyl acrylate copolymers containing (meth)acrylic acid monomers in the molecule and having a glass transition temperature of -15°C or lower are dispersed in an aqueous medium. B) oil content, C) Oil-based gelling agent.

2. The film-forming topical agent base according to claim 1, wherein the above-mentioned aqueous polymer emulsion is a methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion.

3. The film-forming topical agent base according to claim 1 or 2, wherein the average particle size of the polymer particles measured by dynamic light scattering is in the range of 10 to 600 nm.

4. The film-forming topical agent base according to claim 1 or 2, wherein the amount of polymer solids in the above-mentioned aqueous polymer emulsion is in the range of 20 to 80% by mass.

5. Furthermore, the film-forming topical agent base according to claim 1 or 2, comprising a filler.

6. The film-forming topical preparation base according to claim 1 or 2, wherein the above oil component is one or more selected from the group consisting of fatty acids, higher alcohols, sorbitan fatty acid esters, polyglycerin fatty acid esters, paraffins, triglycerides, neopentyl glycols, silicone oils, and esters.

7. The above fatty acids are palmitic acid, stearic acid, isostearic acid, or oleic acid; the above higher alcohols are cetanol, stearyl alcohol, isostearyl alcohol, 2-octyldodecanol, or decyltetradecanol; the above sorbitan fatty acid esters or polyglycerin fatty acid esters are sorbitan sesquioleate, sorbitan sesquiisostearate, sorbitan isostearate, or polyglyceryl diisostearate; the above paraffins are isoparaffin, liquid paraffin, or squalane; the above triglycerides are tri(2-ethylhe The film-forming topical preparation base according to claim 6, wherein the neopentyl glycols are neopentyl glycol dioctanoate or neopentyl glycol dicaprate; the silicone oils are methylphenylpolysiloxane; or the esters are isononyl isononanoate, isopropyl myristate, isotridecyl myristate, isopropyl palmitate, cetyl 2-ethylhexanoate, isostearyl myristate, octyldodecyl myristate, di(2-heptylundecyl) adipate, or jojoba oil.

8. The film-forming topical preparation base according to claim 1 or 2, wherein the oil gelling agent is one or more selected from the group consisting of dextrin myristate, dextrin palmitate, (palmitic acid / ethylhexanoic acid) dextrin, and (palmitic acid / hexyldecanoic acid) dextrin.

9. The film-forming topical agent base according to claim 5, wherein the filler is an inorganic powder.

10. The film-forming topical agent base according to claim 9, wherein the inorganic powder is one or more selected from the group consisting of light anhydrous silicic acid, hydrated silicon dioxide, and titanium dioxide.

11. A non-medicinal topical preparation comprising the film-forming topical preparation base described in claim 1 or 2.

12. A topical pharmaceutical preparation comprising a film-forming topical preparation base and a pharmacoactive ingredient as described in claim 1 or 2.

13. The topical medicinal preparation according to claim 12, wherein the above-mentioned active ingredient is a medicine for corns, calluses, and warts, an acne treatment, a disinfectant, a fungal agent for athlete's foot (antifungal agent), an antipruritic, a moisturizer, an analgesic and anti-inflammatory agent, an antihistamine, an anti-inflammatory agent, a local anesthetic, a keratolytic agent, a tissue repair agent, a skin protectant, or a vitamin.

14. A non-medicinal topical preparation according to claim 11, enclosed in a pin-push type container, a roll-on container or a mini roll-on container, a spray container, or a container with a brush.

15. A topical medicinal preparation according to claim 12, enclosed in a pin-push type container, a roll-on container or a mini roll-on container, a spray container, or a container with a brush.

Images