Skin composition

Abstract

The present invention pertains to a film-forming skin composition that comprises (a1) an ethyl acrylate-methyl methacrylate-trimethylammonium chloride ethyl methacrylate copolymer and (a2) an ethyl acrylate-methyl methacrylate copolymer. A film formed from the composition according to the present invention has high waterproofness and / or high friction resistance. Meanwhile, this film can be easily washed off from the skin.

Description

[Technical Field]

[0001] The present invention relates to a film-forming composition, specifically to a film-forming skin protective agent and a film-forming external skin preparation. [Background technology]

[0002] Liquid bandages that form a thin film are said to be effective for symptoms of weakened skin barrier function (e.g., hangnails, abrasions, cracks, etc.) and are commercially available to protect the skin from wet work. However, while high water resistance and high abrasion resistance are desired for the film, it is also desirable that it be easy to wash off from the skin (high cleansability). This is because if the film is difficult to wash off, it cannot be quickly removed from the skin when side effects occur (as a result, administration cannot be quickly discontinued), and the old film tends to remain, reducing the amount of medicinal ingredients that can penetrate the skin through the new film that forms on top of it.

[0003] Patent Documents 1 and 2 disclose topical preparations for hands that form a flexible film when applied to the entire hand and finger, and that are quick-drying, have excellent adhesion to the skin, and can be washed off with an alkaline solution after use. Patent Document 3 discloses a film-type skin protective agent that forms a thin, transparent film, feels good to use, is water-resistant, and is easy to wash off with alkaline soap. However, all of the compositions disclosed in Patent Documents 1 to 3 have the problem that the film they form cannot be easily washed off with water (or hot water) after use. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-126796 [Patent Document 2] Japanese Patent Application Laid-Open No. 2011-126797 [Patent Document 3] Japanese Patent Application Publication No. 5-32535 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a film-forming skin composition, specifically a film-forming skin protective agent and a film-forming topical skin preparation, which are capable of forming a film that has high water resistance and / or high abrasion resistance while also having excellent cleansing properties (that is, is easily washed off from the skin). [Means for solving the problem]

[0006] As a result of extensive investigations into solving the above problems, the present inventors discovered that the above problems can be solved by combining specific polymers, and thus completed the present invention.

[0007] That is, the present invention relates to the following [1] to

[10] . [1] Two types of polymers: (a1) Ethyl acrylate-methyl methacrylate-trimethylammonium ethyl methacrylate chloride copolymer, and (a2) Ethyl acrylate-methyl methacrylate copolymer A film-forming composition for skin comprising: [2] The composition according to [1], which contains propranolol or a pharmaceutically acceptable salt thereof as an active ingredient. [3] The composition described in [2], which is used for the treatment of hemangioma. [4] The composition described in [2] or [3], which is used to treat hemangiomas in infants. [5] The composition according to any one of [1] to [4], wherein the weight ratio of the polymer (a1) to the polymer (a2) is within the range of 8:2 to 2:8. [6] The composition according to any one of [1] to [5], further comprising 36% by weight or more of water based on the total amount of the composition (excluding the propellant if the composition is an aerosol). [7] The composition according to any one of [1] to [6], further comprising a surfactant. [8] The composition according to [7], wherein the surfactant is a nonionic surfactant and / or an amphoteric surfactant. [9] The composition according to any one of [1] to [8], further comprising one or more plasticizers selected from the group consisting of ester compounds that are liquid at room temperature, aromatic alcohols that are liquid at room temperature, medium-polarity solid ester compounds, and terpenes.

[10] The composition according to any one of claims 1 to 9, which is substantially free of lower monohydric alcohols. [Effects of the Invention]

[0008] The film formed from the composition of the present invention has high water resistance and / or high abrasion resistance, while also having excellent cleansing properties. The composition of the present invention can be used as a film-forming skin protectant and a film-forming external skin preparation. DETAILED DESCRIPTION OF THE INVENTION

[0009] The composition of the present invention is characterized by containing a combination of two specific polymers, and can be used specifically as a film-forming skin protectant and a film-forming topical skin preparation.

[0010] Film-forming skin protectants (which do not contain medicinal ingredients) form a thin film when sprayed or applied to the skin, effectively protecting the skin. They can be used to prevent and treat skin diseases such as hand eczema (typically housewives' eczema), asteatosis, and atopic dermatitis. On the other hand, film-forming topical skin preparations (containing medicinal ingredients) form a film when sprayed or applied to the skin, enabling effective delivery of medicinal ingredients to the skin. Similar effects can also be expected when applied to nails, the skin around the nails, and mucous membranes.

[0011] The two types of polymers used in the present invention are: (a1) Ethyl acrylate-methyl methacrylate-trimethylammonium ethyl methacrylate chloride copolymer, and (a2) Ethyl acrylate-methyl methacrylate copolymer is. The weight ratio of polymer (a1) to polymer (a2) is preferably 8:2 to 2:8, more preferably 8:2 to 5:5, particularly preferably 8:2 to 6:4, and further preferably 8:2 to 7:3.

[0012] The average molecular weight (Mw) of the ethyl acrylate-methyl methacrylate-trimethylammonium ethyl methacrylate copolymer (a1) is preferably in the range of 10,000 to 100,000, more preferably in the range of 20,000 to 50,000. Examples of commercially available products of the polymer (a1) include EUDRAGIT (登録商標) )RS type and Eudragit RL type (both manufactured by Evonik Japan Co., Ltd.). Eudragit RS type is an acrylic acid-based polymer with a composition ratio of 1:2:0.1. It has an average molecular weight (Mw) of approximately 32,000 and is insoluble in water regardless of pH. Eudragit RS type is available, for example, as Eudragit RS100, Eudragit RSPO, and Eudragit RS30D (an aqueous suspension containing 30% by weight of ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl methacrylate chloride copolymer (composition ratio 1:2:0.1)). Eudragit RL type is an acrylic acid-based polymer with a 1:2:0.2 ratio of its constituent components. It has an average molecular weight (Mw) of approximately 32,000 and is insoluble in water, regardless of pH. Eudragit RL type is available as Eudragit RL100, Eudragit RLPO, and Eudragit RL30D (an aqueous suspension containing 30% by weight of ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl methacrylate chloride copolymer (1:2:0.2 ratio)).

[0013] The average molecular weight (Mw) of the ethyl acrylate-methyl methacrylate copolymer (a2) is preferably in the range of 100,000 to 1,500,000, more preferably 500,000 to 1,000,000. An example of a commercially available polymer (a2) is Eudragit NE (Evonik Japan Co., Ltd.). Eudragit NE is an acrylic acid-based polymer with a 2:1 ratio of constituent components. It has an average molecular weight (Mw) of approximately 750,000 and is insoluble in water regardless of pH. Eudragit NE is available, for example, as Eudragit NE30D (an aqueous suspension containing 30% by weight of ethyl acrylate-methyl methacrylate copolymer (2:1 ratio)).

[0014] The content (total content) of the polymer relative to the total amount of the composition of the present invention (excluding the propellant in the case of an aerosol) is suitably 2% by weight or more, 3% by weight or more, or 4% by weight or more. For example, 6 to 35% by weight is preferred, 10 to 30% by weight is more preferred, and 12 to 20% by weight is particularly preferred. Note that, since the composition of the present invention has excellent water resistance, it does not necessarily need to contain a silicone-based polymer.

[0015] Film-forming compositions often contain lower monohydric alcohols such as ethanol and isopropanol to improve quick-drying properties, but the composition of the present invention has excellent quick-drying properties and can quickly form a film even without containing a lower monohydric alcohol (a monohydric alcohol having 1 to 3 carbon atoms, such as ethanol or isopropanol.) The composition of the present invention may contain a lower monohydric alcohol, but the content thereof is preferably 10 wt% or less, more preferably 7 wt% or less, particularly preferably 5 wt% or less, and even more preferably 3 wt% or less, based on the total amount of the composition. A preferred embodiment of the present invention is a composition that is substantially free of lower monohydric alcohols. "Substantially free" means that no lower monohydric alcohols are intentionally added during the manufacturing process. That is, the content of lower monohydric alcohols in a composition that is substantially free of lower monohydric alcohols is usually 0% by weight, and even if a small amount of lower monohydric alcohol is mixed in, the content is less than 1% by weight (more preferably less than 0.5% by weight).

[0016] Typically, in film-forming compositions, lower monohydric alcohols such as ethanol and isopropanol are used to improve the quick-drying properties and to dissolve the polymer, which is a film-forming component. However, when used to treat skin diseases with impaired barrier function, such as hand eczema and atopic dermatitis, or diseases in infants, whose skin is thinner than that of adults, it is preferable to not include lower monohydric alcohols, which can cause dry skin or irritation. The present invention can provide a composition that is substantially free of lower monohydric alcohols, and therefore can provide a composition that is highly safe for the skin and suitable for treating hand eczema, atopic dermatitis, and diseases in infants.

[0017] The composition of the present invention preferably contains at least one surfactant (emulsifier). Adding a surfactant to the composition can reduce the amount of film remaining after washing and / or improve the visibility of the film. By improving the visibility of the film, it becomes easier to confirm whether the film has been removed after washing. The surfactant is selected from the group consisting of nonionic surfactants, cationic surfactants, anionic surfactants, and amphoteric surfactants. Nonionic surfactants and amphoteric surfactants are more preferred, and nonionic surfactants are particularly preferred. The content of the surfactant relative to the total amount of the composition (excluding the propellant in the case of an aerosol) is preferably 0.1 to 5 wt %, more preferably 0.3 to 4 wt %, and particularly preferably 0.5 to 3 wt %. Suitable compositions include, for example, compositions containing 0.8 wt % or more or 1 wt % or more of the surfactant. A single surfactant may be used, or multiple surfactants may be used in combination.

[0018] Examples of the nonionic surfactant include polyoxyethylene alkyl ethers such as polyoxyethylene oleyl ether, polyoxyethylene octyldodecyl ether, and polyoxyethylene lauryl ether; polyoxyethylene alkylphenol ethers; polyoxyethylene hydrogenated castor oil; polyoxyl stearate; glycerin fatty acid esters such as glyceryl monostearate, self-emulsifying glyceryl monostearate, glyceryl monoisostearate, glyceryl palmitate, glyceryl myristate, glyceryl oleate, and glyceryl triisooctanoate; diglycerin fatty acid esters such as diglyceryl laurate, diglyceryl stearate, and diglyceryl oleate; and monolaurin. Examples of suitable fatty acid esters include polyglycerol fatty acid esters such as decaglyceryl monostearate; polyoxyethylene glycerol fatty acid esters such as polyoxyethylene glyceryl monostearate; sorbitan fatty acid esters such as sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, sorbitan coconut oil fatty acid, sorbitan tristearate, and sorbitan trioleate; polyethylene glycol fatty acid esters such as polyethylene glycol monolaurate, polyethylene glycol monostearate, and polyethylene glycol monooleate; and polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan tristearate and polyoxyethylene sorbitan coconut oil fatty acid. Particularly preferred are polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan tristearate, polyoxyethylene lauryl ether, polyoxyethylene sorbitan coconut oil fatty acid, polyethylene glycol monooleate, decaglyceryl monolaurate, diglyceryl monooleate, and polyoxyethylene glyceryl monostearate.

[0019] Specific examples of the cationic surfactant include cetyltrimethylammonium chloride, lauryldimethylbenzylammonium chloride, tetrabutylammonium chloride, and dioctadecyldimethylammonium chloride.

[0020] Examples of the anionic surfactant include sodium alkylbenzenesulfonate, sodium dodecyl sulfate, sodium coconut alcohol ethoxy sulfate, sodium α-olefinsulfonate, emulsified cetostearyl alcohol, sodium lauroyl sarcosinate, and potassium myristate.

[0021] Examples of the amphoteric surfactant include N-alkyl-N,N-dimethylammonium betaine, lauryl dimethylaminoacetic acid betaine, coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine, and imidazoline-type amphoteric surfactants.

[0022] The composition of the present invention may contain a plasticizer. Examples of plasticizers include ester compounds that are liquid at room temperature (25°C; the same applies hereinafter), aromatic alcohols that are liquid at room temperature, medium-polarity solid ester compounds, and terpenes. These may be used alone or in combination. The use of such plasticizers shortens the film formation time (i.e., improves quick-drying properties).

[0023] Preferred examples of the ester compound that is liquid at room temperature include triethyl citrate, triacetin, dibutyl phthalate, diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, and medium-chain fatty acid triglycerides (e.g., glyceryl triisooctanoate and tri(caprylic / capric) acid)glyceryl). Fatty acid esters that are liquid at room temperature and selected from diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, and medium-chain fatty acid triglycerides are more preferred, and among these, diethyl sebacate and diisopropyl adipate are even more preferred, with diisopropyl adipate being particularly preferred.

[0024] Preferred examples of the aromatic alcohol that is liquid at room temperature include ethylene glycol salicylate and phenoxyethanol, with phenoxyethanol being particularly preferred.

[0025] Examples of the medium-polarity solid ester compound include phospholipids (e.g., lecithin, particularly hydrogenated lecithin) and ester compounds that are solid at room temperature, such as parahydroxybenzoates. In this specification, medium polarity refers to an α value of 35° to 55° according to the organic conceptual diagram. The organic conceptual diagram was proposed by Atsushi Fujita, and its details are explained in "Pharmaceutical Bulletin," 1954, Vol. 2, pp. 163-173; "Chemical Domain," 1957, Vol. 11, pp. 719-725; and "Fragrance Journal," 1981, Vol. 50, pp. 79-82. Specifically, all organic compounds are considered to be derived from methane (CH4), and all other compounds are considered to be derivatives of methane. The carbon number, substituents, modification sites, rings, and other parameters are assigned specific values, and the organic and inorganic values ​​are calculated by adding up the scores. When this value is plotted on a graph with organic values ​​on the X axis and inorganic values ​​on the Y axis, the slope or angle is the α value.

[0026] Examples of combinations of ester compounds that are liquid at room temperature include combinations of medium-chain fatty acid triglycerides (e.g., glyceryl triisooctanoate and tri(caprylic / capric)glyceryl) with triethyl citrate, triacetin, dibutyl phthalate, diethyl sebacate, diisopropyl sebacate, or diisopropyl adipate.

[0027] An example of a combination of an ester compound that is liquid at room temperature with an aromatic alcohol that is liquid at room temperature is a combination of a medium-chain fatty acid triglyceride (e.g., glyceryl triisooctanoate and tri(caprylic / capric acid)glyceryl) with ethylene glycol salicylate or phenoxyethanol.

[0028] Preferred examples of terpenes include limonene and menthol.

[0029] The content of the plasticizer relative to the total amount of the composition of the present invention (excluding the propellant in the case of an aerosol) may be 0.5% by weight or more, or 1% by weight or more, and is, for example, preferably 1.3 to 35% by weight, more preferably 1.5 to 20% by weight, particularly preferably 1.7 to 12% by weight, and even more preferably 2 to 8% by weight. If the amount of plasticizer is less than 1.3% by weight, film-forming properties and water resistance will decrease, and if it exceeds 35% by weight, the film will tend to become sticky, which is undesirable.

[0030] The composition of the present invention may contain water. Purified water is particularly preferred as the water used in the present invention. The water content of the composition of the present invention (excluding the propellant in the case of an aerosol) is preferably 36% by weight or more, more preferably 50% by weight or more. More specifically, the water content is preferably 36 to 92% by weight, more preferably 43 to 89% by weight, particularly preferably 50 to 87% by weight, and even more preferably 64 to 85% by weight. Compositions containing a large amount of water (36% by weight or more) provide a refreshing feel when used. Eudragit RS30D, RL30D, and NE30D are all provided as aqueous suspensions containing 30% by weight of an acrylic polymer. The water contained in these aqueous suspensions (equivalent to 70% by weight of the aqueous suspension) also falls under the category of water used in the present invention.

[0031] The composition of the present invention may contain one or more substances selected from the group consisting of light anhydrous silicic acid, titanium oxide, talc, and calcium carbonate to reduce the shine of the coating. The content of these substances relative to the total amount of the composition of the present invention (excluding the propellant in the case of an aerosol) is preferably 0.8 to 3 wt %, particularly preferably 1 to 3 wt %.

[0032] The composition of the present invention may contain a pH adjuster in addition to the above components. Examples of the pH adjuster include phosphates, citrates, hydroxides, and hydrochloric acid. One or more of the pH adjusters may be used alone or in combination. The content of the pH adjuster relative to the total amount of the composition of the present invention (excluding the propellant in the case of an aerosol) is preferably 0.01 to 1 wt %, and particularly preferably 0.1 to 0.5 wt %. In particular, it is preferable for the pH of the composition to be 4 or higher, since this improves the water resistance of the film. The preferred pH range is 5-9, and more preferably 6-8.

[0033] The composition of the present invention may further contain additives such as thickeners (e.g., hydrophobized hydroxypropyl methylcellulose [also known as hydroxypropyl methylcellulose stearoxy ether], gelatin, polyoxyethylene glycol, etc.), preservatives (e.g., parahydroxybenzoates, benzalkonium chloride, benzethonium chloride, phenoxyethanol, etc.), and stabilizers (e.g., dibutylhydroxytoluene, sodium citrate, citric acid, ascorbic acid, mannitol, sorbic acid, sorbitol, sodium edetate, cyclodextrins, etc.). The content of each of the additives relative to the total amount of the composition of the present invention (excluding the propellant in the case of an aerosol) is preferably 0.01 to 2 wt%, more preferably 0.05 to 1 wt%, and the total content of the additives is preferably 5 wt% or less, more preferably 4 wt% or less, and particularly preferably 3 wt% or less.

[0034] The composition of the present invention can contain, for example, a medicinal ingredient that is effective in treating various skin diseases, including chronic skin diseases such as atopic dermatitis. Examples of the medicinal ingredients include, but are not limited to, the following ingredients: Steroidal anti-inflammatory drugs such as hydrocortisone, dexamethasone, clobetasol 17-propionate, dexamethasone 17-valerate, fluocinonide, halcinonide, amcinonide, difluprednate, and betamethasone butyrate propionate; Nonsteroidal anti-inflammatory drugs such as indomethacin, ketoprofen, flurbiprofen, felbinac, piroxicam, ibuprofen piconol, benzadacu, butyl flufenamate, and bufexamac; Antifungal drugs such as lanoconazole, tolnaftate, clotrimazole, bifonazole, miconazole nitrate, econazole nitrate, ketoconazole nitrate, omoconazole nitrate, oxiconazole nitrate, exalamide, tricyclate, and siccanin; Antibacterial drugs such as ozenoxacin and clindamycin; Antiallergic drugs such as ketotifen, azelastine and their salts, chrompheniramine maleate, oxitamide, tranilast, and sodium cromoglycolate; Local anesthetics such as lidocaine and propitocaine; Antiviral drugs such as acyclovir, valacyclovir, famciclovir, amenamevir, vidarabine, etc. and their salts; · Moisturizing agents such as heparinoids, hyaluronic acid, and urea; · Fibroblast growth factors and wound care drugs such as bucladesine sodium; Acne medications such as benzoyl peroxide and adapalene; ·Medications for treating psoriasis vulgaris isokeratosis, such as maxacalcitol; Beta-blockers and other drugs for treating arrhythmia, hypertension, myocardial infarction, angina, migraine, and hemangiomas; -Medicines for treating common warts, such as salicylic acid, mono- and trichloroacetic acid, glutaraldehyde, phenol, tacalcitol, calcipotriol, maxacalcitol, calcitriol, alfacalcidol, eldecalcitol, bleomycin, 5-FU, podophyllin, retinoids, coix seed extract, imiquimod, cimetidine, and interferon; Drugs for the treatment of postherpetic neuralgia, such as acyclovir, valacyclovir, famciclovir, amenamevir, vidarabine, pregabalin, gabapentin, duloxetine, amitriptyline, nortriptyline, imipramine, extract of inflamed skin of rabbits inoculated with vaccinia virus, tramadol, tramadol-acetaminophen, fentanyl, oxycodone, buprenorphine, mexiletine, epalrestat, and morphine.

[0035] Examples of β-blockers include acebutolol, betaxolol, carteolol, carvedilol, labetalol, oxprenolol, penbutolol, pindolol, and propranolol. The composition of the present invention containing such a β-blocker can be used as a therapeutic agent for arrhythmia, hypertension, migraine, hemangioma, and the like.

[0036] When a beta-blocker is used, the compositions of the present invention can be used to treat hemangiomas (particularly infantile hemangiomas), such as, but not limited to, vascular tumors selected from the group consisting of capillary hemangiomas, epithelioid hemangiomas, sinusoidal hemangiomas, spindle cell hemangiomas, tufted hemangiomas, hemangioendotheliomas (i.e., Kaposi-like hemangioendotheliomas), hemangiomas in von Hippel-Lindau syndrome, fibroangiomas and angiolipomas in Bretaville disease, pyogenic granulomas, angiosarcomas, e.g., Kaposi's sarcoma, proliferating arteriovenous malformations, and tumor-associated vascular proliferation. When the compositions of the present invention are used to treat hemangiomas, they are preferably used during the proliferative phase.

[0037] A preferred example of the composition of the present invention is a composition containing propranolol or a pharmaceutically acceptable salt thereof. Pharmaceutically acceptable salts include salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, and salts formed with organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, andelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid. Compositions containing propranolol hydrochloride (propranolol hydrochloride) are particularly preferred. A preferred indication for the composition of the present invention containing propranolol or a pharmaceutically acceptable salt thereof (particularly propranolol hydrochloride) is hemangioma (e.g., infantile hemangioma).

[0038] The composition of the present invention not only has high water resistance and / or high abrasion resistance but also excellent cleansing properties, so that if side effects due to the medicinal ingredients contained in the coating occur, the use of the medicinal ingredients can be discontinued by quickly removing the coating from the skin. Therefore, the composition of the present invention is particularly suitable as a therapeutic drug for diseases of infants and young children, for which high safety is required.

[0039] The composition according to the present invention can be used in the form of, but is not limited to, a liquid, a lotion, a gel, a cream, an aerosol, or the like.

[0040] The content of the medicinal ingredient in the total amount of the composition of the present invention (excluding the propellant in the case of an aerosol) is preferably 0.01 to 5 wt %, more preferably 0.1 to 1 wt %, and particularly preferably 0.1 to 0.5 wt %.

[0041] The composition of the present invention may contain other components in addition to the above-mentioned polymer, medicinal ingredient, plasticizer, surfactant, light anhydrous silicic acid, titanium oxide, talc, calcium carbonate, pH adjuster, additive, and water, but the total content of other components relative to the total amount of the composition of the present invention (excluding the propellant in the case of an aerosol) is preferably 5 wt % or less, more preferably 3 wt % or less, and particularly preferably 1 wt % or less.

[0042] The composition of the present invention may be an aerosol containing a propellant. Examples of the propellant include dimethyl ether (DME) and a mixture of DME and liquefied natural gas (LPG). A more preferred example of the propellant is DME. The content of the propellant in the aerosol of the present invention is preferably 30 to 50 parts by weight, more preferably 35 to 50 parts by weight, and particularly preferably 40 to 46 parts by weight, per 100 parts by weight of the composition excluding the propellant.

[0043] The amount and frequency of application of the composition of the present invention to the skin may be adjusted appropriately depending on the skin condition, the drug concentration in the composition, the age of the patient, etc. Usually, application once to several times a day is appropriate.

[0044] In the preceding paragraph, preferred compound names of the essential components and optional components used in the composition of the present invention have been described, but the composition of the present invention also includes compositions obtained by arbitrarily combining these and compositions obtained by arbitrarily combining the concentration ranges of each component. In addition, the numerical ranges of the concentrations, etc., described above can also be arbitrarily combined, and when multiple numerical ranges are described, the upper and lower limits of each numerical range can also be arbitrarily combined.

[0045] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. <Polymers used> (a1) Ethyl acrylate-methyl methacrylate-trimethylammonium ethyl methacrylate chloride copolymer (composition ratio of components: 1:2:0.1, average molecular weight (Mw): approximately 32,000, insoluble in water regardless of pH) (a2) Ethyl acrylate-methyl methacrylate copolymer (composition ratio of constituent components: 2:1, average molecular weight (Mw): approximately 750,000, insoluble in water regardless of pH)

[0046] <Plasticizers used> Diisopropyl adipate (DID), triethyl citrate, triacetin, diethyl sebacate, diisopropyl sebacate, medium-chain triglyceride, ethylene glycol salicylate, phenoxyethanol <Surfactants used> Polyoxyethylene hydrogenated castor oil (NIKKOL HCO-60) Polyoxyethylene (20) sorbitan tristearate (NIKKOL TS-30V, Polysorbate 65 / PS65) Polyoxyethylene lauryl ether (4.2EO) (NIKKOL BL-4.2) Polyoxyethylene coconut oil fatty acid sorbitan (20E.O) (NIKKOL TL-10) Polyethylene glycol monooleate (10E.O.) (NIKKOL MYO-10V) Decaglyceryl monolaurate (NIKKOL Decaglyn 1-L) Diglyceryl monooleate (NIKKOL DGMO-90V) Polyoxyethylene glyceryl monostearate (PEG-5) (NIKKOL TMGS-5V) Polyoxyethylene glyceryl monostearate (PEG-15) (NIKKOL TMGS-15V) Sodium lauroyl sarcosinate (NIKKOL Sarcosinate LN) Potassium myristate (NonSal MK-1) Lauryl dimethylaminoacetic acid betaine (NIKKOL AM-301) Coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine (NIKKOL AM-3130N) <Thickeners used> Hydrophobized hydroxypropyl methylcellulose (hydrophobized HPMC) <Medicinal ingredients used> Propranolol Hydrochloride

[0047] <Preparation method> Each polymer and purified water were weighed out, and optionally, a plasticizer, surfactant, thickener, or active ingredient was added and stirred until uniform. The compositions of each formulation example (Formulation Examples 1 to 58) are shown in Tables 2, 4 to 11 (the numerical values ​​for each component in the tables indicate weight percent). The polymer and surfactant contents shown in the tables are the solid content, and the purified water content shown in the tables is the total amount of water contained in the aqueous suspension or aqueous solution of the polymer and / or surfactant, when an aqueous suspension (aqueous dispersion) or solution of the polymer and / or surfactant is used, and the purified water added.

[0048] [Example 1] 15 μL of the preparation was spread on the back of each panelist's hand to a size of about 25 mm in diameter to form a film, and the visibility of the film was evaluated. After the film had completely dried, the hands were immersed in 37°C hot water for 30 seconds, and after removing the hands, the film was rubbed for 2 minutes, and the following two cleansing items were evaluated and scored (14 panelists evaluated both cleansing and visibility). The total score shown in Table 2 is the sum of the values ​​obtained by multiplying each score by the number of people who judged that score.

[0049] [Table 1] [Table 2]

[0050] As shown in Table 2, compared to Formulation Example 1, which used only polymer (a1) as the polymer, Formulation Examples 2 to 4, which mixed polymers (a1) and (a2), resulted in shorter washing times and less residue. Furthermore, when Formulation Examples 2 to 4 were compared, the residue was less when surfactant (HCO-60) was added. In particular, Formulation Example 4, which had a high surfactant concentration, was evaluated by 11 of 14 panelists as having no residue (score 4). Visibility was confirmed to increase depending on the surfactant concentration. Meanwhile, the films formed on slides using Formulation Examples 2 to 4 did not peel off even after immersion in water for 10 minutes, demonstrating high water resistance. This confirms that the present invention can form films that have both high water resistance and high washability.

[0051] [Example 2] Formulations (Formulation Examples 5 to 8) were prepared in which the mixing ratio of polymers (a1) and (a2) was 9:1, 8:2, 7:3, and 6:4, and their cleaning properties were compared with that of Formulation Example 9, in which the mixing ratio of polymers (a1) and (a2) was 5:5. Formulation Example 9, used as a comparison standard, is prepared by adding a medicinal ingredient and a thickener to Formulation Example 4, which was confirmed to exhibit high cleaning properties in Example 1, and shows high cleaning properties similar to those of Formulation Example 4.

[0052] <How to evaluate cleaning performance> 15 μL of the preparation was spread on the back of each panelist's hand to a size of about 25 mm in diameter and allowed to dry for 5 minutes or more. After the film had dried, it was gently rubbed with a body wipe for 30 seconds and evaluated and scored according to the following criteria (n=4).

[0053] [Table 3]

[0054] The composition of each formulation example and the evaluation by each panelist are shown in the table below. [Table 4]

[0055] As shown in Table 4, the cleaning performance of the formulation in which the ratio of polymers (a1) to (a2) was 9:1 (Formulation Example 5) was not as high as that of Formulation Example 9, but met the required cleaning performance criteria. The formulation in which the ratio of polymers (a1) to (a2) was 8:2 (Formulation Example 6) exhibited higher cleaning performance than Formulation Example 5, and the formulations in which the ratio of polymers (a1) to (a2) was 7:3 (Formulation Example 7) and 6:4 (Formulation Example 8) exhibited cleaning performance equivalent to that of Formulation Example 9 in which the ratio was 5:5.

[0056] [Example 3] Preparations containing only polymer (a1) or polymers (a1) and (a2) in a ratio of 7:3 or 5:5 were prepared, and the abrasion resistance was evaluated according to the following criteria. <Evaluation of abrasion resistance> The mass (A) of the glass slide is measured. 100 μL of the formulation is evenly applied to the entire surface of a glass slide using a spatula and dried for 5 minutes in a mini-jet oven set to 30°C. The slide is then removed from the mini-jet oven and its mass (B) is measured. Next, a dry paper towel is placed on the formulation-coated surface of the glass slide, and a 100 g weight is placed on top of that. The slide is wiped 20 times so that the force is applied evenly across the entire slide, and then the mass (C) of the slide is measured. The formulation residual rate after wiping is calculated from each mass using the following formula. The test is repeated three times, and the average and standard deviation of the formulation residual rate are calculated.

number

[0057] The composition of each formulation and the evaluation of its abrasion resistance are shown in Table 5. [Table 5]

[0058] As shown in Table 5, the formulations containing polymers (a1) and (a2) at a ratio of 7:3 (Formulation Example 11) and 5:5 (Formulation Example 12) showed higher abrasion resistance than the formulation containing polymer (a1) alone (Formulation Example 10). This confirmed that the compositions containing polymers (a1) and (a2) have excellent cleansing properties, as well as high resistance to abrasion and are difficult to remove from the skin.

[0059] [Example 4] Formulations were prepared with varying amounts of plasticizer (DID), and the cleaning properties and abrasion resistance were evaluated using the cleaning property evaluation method described in Example 2 and the abrasion resistance evaluation method described in Example 3. The composition and evaluation results of each formulation are shown in Table 6. "Not estimable" in Table 6 indicates that evaluation was difficult because the way film residue was produced during cleaning was different from that of Formulation Example 9. [Table 6]

[0060] As shown in Table 6, all formulations had good abrasion resistance. All formulations also met the required standards for cleansing performance, with Formulation Examples 16 to 21, which contained 3 to 10% by weight of plasticizer, showing particularly good cleansing performance. As the amount of plasticizer increased, the film formation time tended to shorten (faster drying), but Formulation Example 22, which contained 20% by weight of plasticizer, immediately formed a film upon application to the skin, making it difficult to form a uniform film.

[0061] [Example 5] Formulations were prepared using different types of plasticizer, and the cleaning properties and abrasion resistance were evaluated in the same manner as in Example 4. The composition of each formulation and the evaluation results are shown in Table 7. [Table 7]

[0062] As shown in Table 7, when triethyl citrate, triacetin, or ethylene glycol salicylate was used as the plasticizer, abrasion resistance tended to decrease. When diethyl sebacate, diisopropyl sebacate, medium-chain fatty acid triglyceride, or phenoxyethanol was used as the plasticizer, abrasion resistance and cleanability were good.

[0063] [Example 6] Formulations were prepared with varying amounts of surfactant (PS65), and the cleaning properties and abrasion resistance were evaluated in the same manner as in Example 4. The composition of each formulation and the evaluation results are shown in Table 8. [Table 8]

[0064] As shown in Table 8, the cleaning ability of Formulation Example 30, which does not contain a surfactant, was not as high as that of Formulation Example 9, but it was confirmed that it met the required cleaning ability standard. Formulation Examples 32 to 36, which contained 1% by weight or more of a surfactant, showed good cleaning ability.

[0065] [Example 7] Formulations were prepared with different surfactant types, and the cleaning properties and abrasion resistance were evaluated in the same manner as in Example 4. The composition of each formulation and the evaluation results are shown in Tables 9 and 10. [Table 9] [Table 10]

[0066] As shown in Table 9, Formulation Examples 37 to 43, which contained a nonionic surfactant, exhibited good cleansing properties and abrasion resistance. As shown in Table 10, abrasion resistance was good whether an anionic surfactant or an amphoteric surfactant was used. Regarding cleansing performance, as indicated by "Not Evaluable" in Table 10, when an anionic surfactant was used, the film dissolved during cleansing, making it difficult to determine whether the film was washed off the skin. Panelists 1 and 2 also judged the use of an amphoteric surfactant to be ineligible for evaluation. However, a test on cleansing performance (residue on skin) as shown in Table 1 was conducted on three panelists. For Formulation Examples 46 and 47, two panelists scored 4 (no residue) and one panelist scored 3 (less than 30% remained), demonstrating that formulations with satisfactory cleansing performance could be prepared even when an amphoteric surfactant was used. The results of Example 7 show that when a nonionic surfactant or an amphoteric surfactant is used as the surfactant, it becomes easier to visually confirm the removal of the coating.

[0067] [Example 8] Formulations were prepared with different amounts of polymers (a1) and (a2), and the cleaning properties and rub resistance were evaluated in the same manner as in Example 4. The composition of each formulation and the evaluation results are shown in Table 11. [Table 11]

[0068] As shown in Table 9, Formulation Example 48, in which the total amount of polymers (a1) and (a2) was 1.2 wt%, had poor abrasion resistance compared to the other formulations. In contrast, Formulation Examples 49 to 58, in which the total amount of polymers (a1) and (a2) was 2.4 wt% to 24 wt%, showed good cleansing properties and abrasion resistance.

Claims

1. - The following two types of polymers: (a1) ethyl acrylate, methyl methacrylate, and trimethylammonium ethyl methacrylate chloride copolymer, and (a2) Ethyl acrylate / methyl methacrylate copolymer 1.3 to 12 wt. % of a plasticizer selected from the group consisting of triethyl citrate, triacetin, dibutyl phthalate, diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, medium-chain triglycerides, ethylene glycol salicylate, phenoxyethanol, phospholipids, parahydroxybenzoates, limonene, and menthol; and 0.8% by weight or more of surfactant (Here, the weight percentages are based on the total weight of the composition (excluding the propellant in the case of an aerosol).) A film-forming composition for skin comprising:

2. The composition of claim 1 further comprising a medicinal ingredient.

3. The composition of claim 2 , wherein the active ingredient is a beta-blocker.

4. 3. The composition of claim 2, wherein the active ingredient is propranolol or a pharmaceutically acceptable salt thereof.

5. The composition according to claim 3 or 4, which is used for the treatment of hemangioma.

6. The composition according to claim 3 or 4, which is used to treat infantile hemangiomas.

7. The composition according to any one of claims 1 to 6, wherein the weight ratio of polymer (a1) to polymer (a2) is in the range of 8:2 to 2:

8.

8. The composition according to any one of claims 1 to 7, further comprising 36% by weight or more of water based on the total amount of the composition (excluding the propellant when the composition is an aerosol).

9. A composition described in any one of claims 1 to 8, comprising 1 to 5 wt% of a surfactant and 3 to 10 wt% of a plasticizer, based on the total amount of the composition (excluding the propellant if the composition is an aerosol).

10. The composition of claim 9, wherein the surfactant is a nonionic surfactant and / or an amphoteric surfactant.

11. A composition described in any one of claims 1 to 10, containing one or more plasticizers selected from the group consisting of diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, medium-chain fatty acid triglycerides, and phenoxyethanol.

12. The composition according to any one of claims 1 to 11, which is substantially free of lower monohydric alcohols.

Images