Composition for application to nasal cavity

Abstract

To provide a composition for application to nasal cavity comprising menthol, the composition capable of suppressing an increase in irritation due to storage.SOLUTION: A composition for application to nasal cavity containing menthol is accommodated in a container in which an olefin resin is included in all or a part of a contact portion with the composition for application to nasal cavity, wherein the olefin resin is preferably polyethylene.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a menthol-containing composition to be applied to the nasal cavity, which is inhibited from being degraded by the container material. [Background technology]

[0002] Depending on the combination of pharmaceutical preparation ingredients and container materials, undesirable changes may occur in the properties of the preparation. For example, Patent Document 1 teaches that when a liquid preparation containing chlorpheniramine and / or a salt thereof and having a pH of 7.0 or higher is stored in a polyethylene container, the chlorpheniramine and / or a salt thereof is likely to be adsorbed to the container wall, but when the liquid preparation is stored in a polybutylene terephthalate container, adsorption of chlorpheniramine and / or a salt thereof to the container wall is suppressed, and the content of chlorpheniramine and / or a salt thereof in the liquid preparation can be stably maintained. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent Publication No. 2019-23231 Summary of the Invention [Problem to be solved by the invention]

[0004] The present inventors have found that a menthol-containing composition for nasal application can cause a stronger burning sensation (pain) in the nasal mucosa during storage, depending on the container material. Therefore, an object of the present invention is to provide a menthol-containing composition for nasal application in which the burning sensation (pain) felt in the nasal cavity is inhibited from increasing during storage. [Means for solving the problem]

[0005] The present inventors have conducted extensive research to solve the above-mentioned problems and have found that if a menthol-containing composition for nasal application is stored in a container containing an olefin resin in all or part of the area that comes into contact with the composition, the staining sensation on the nasal mucosa can be prevented from becoming stronger even during storage.

[0006] The present invention was completed based on the above findings, and provides the following [1] to [3]. [1] A composition for nasal application containing menthol, which is contained in a container containing an olefin resin in all or part of the area that comes into contact with the composition for nasal application. [2] The composition according to [1], wherein the olefin resin is polyethylene. [3] A method for suppressing the increase in the feeling of staining due to storage of a nasal composition containing menthol, wherein a container containing an olefin resin is used as a container for use with the nasal composition, and the container contains an olefin resin in all or part of the area that comes into contact with the nasal composition. [Effects of the Invention]

[0007] The composition for nasal application of the present invention prevents the components contained therein from deteriorating during storage due to the influence of the container material. As shown in the Examples section, when a composition for nasal application containing menthol was contained in a container whose wall surface in contact with the composition contained an olefin resin, the increase in staining sensation due to storage was less than when the composition was contained in a container whose wall surface in contact with the composition contained polyethylene terephthalate. On the other hand, there was almost no difference in the refreshing sensation, which is the original function of menthol, regardless of the container in which the composition was contained and stored. Thus, the composition for nasal application of the present invention is unlikely to degrade even during storage. DETAILED DESCRIPTION OF THE INVENTION

[0008] The present invention will be described in detail below. The composition for nasal application of the present invention contains menthol and is housed in a container in which an olefin resin is contained in all or part of the area that comes into contact with the composition. Nasal application compositions include nasal drops (also called nasal medicine), nasal washes (also called nasal irrigation solutions), etc.

[0009] container The container in which the composition for nasal application is housed may be in the form of a spray container (such as a pump container or an aerosol container), a dropper container, a dropper container, a bottle container, a tube container, a jar container, a dispenser container, a pouch bag, a cheer pack, a sponge head container, a roll-on container, or a stick container.

[0010] The container may be any packaging material having a portion (surface or wall) that comes into contact with the composition for nasal application, and may include a container body containing the composition for nasal application, a portion including an extraction port (nozzle, inner plug), a suction tube, a lid, etc. It is particularly preferred that all or part of the portion of the container body containing the composition for nasal application that comes into contact with the composition contains an olefin resin. The olefin resin may be contained as a molding component (a component that contributes to molding, excluding additives) in the portion containing the olefin resin, and this portion may contain additives such as plasticizers. This portion may also contain molding components such as plastic materials other than olefin resins, but the content of the olefin resin is preferably 50% by mass or more, 80% by mass or more, 90% by mass or more, 95% by mass or more, or 99% by mass or more of the total amount of molding components. It is particularly preferred that the total amount of molding components (100% by mass) is olefin resin.

[0011] Examples of olefin resins include polyethylene and polypropylene. Polyethylene includes high-density polyethylene (HDPE), low-density polyethylene (LDPE), very low-density polyethylene, linear low-density polyethylene, and ultra-high molecular weight polyethylene. Polypropylene includes isotactic polypropylene, syndiotactic polypropylene, and atactic polypropylene. Among these, polyethylene is preferred, and high-density polyethylene is more preferred.

[0012] Composition for nasal application Formulation forms of compositions for nasal application include liquids, suspensions, emulsions, creams, emulsion ointments, ointments, gels, foams, sprays, aerosols, pump foams, and sticks.

[0013] Menthol may be in the l-, d-, or dl-form, but is preferably the l-form. These may also be used in combination. Menthol may also be contained in essential oils such as peppermint oil. The total concentration of menthol in the composition for nasal application can be 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, or 0.5% by mass or more, relative to the total amount of the composition, and can be 0.5% by mass or less, 0.1% by mass or less, 0.05% by mass or less, 0.01% by mass or less, or 0.001% by mass or less. When menthol is contained as an essential oil, the above concentration is based on the amount of menthol in the essential oil.

[0014] The nasal compositions of the present invention may include a vasoconstrictor (decongestant). Examples of vasoconstrictors include phenylethylamine decongestants such as adrenaline, epinephrine or a salt thereof (e.g., epinephrine hydrochloride, epinephrine bitartrate), ephedrine or a salt thereof (e.g., ephedrine hydrochloride), methylephedrine or a salt thereof (e.g., methylephedrine hydrochloride, particularly dl-methylephedrine hydrochloride, phenylephrine or a salt thereof (e.g., phenylephrine hydrochloride), oxymetazoline or a salt thereof (e.g., oxymetazoline hydrochloride)); and imidazoline decongestants such as tetrahydrozoline or a salt thereof (e.g., tetrahydrozoline hydrochloride, tetrahydrozoline nitrate), naphazoline or a salt thereof (e.g., naphazoline hydrochloride, naphazoline nitrate). One or more vasoconstrictors can be used.

[0015] The total concentration of the vasoconstrictor in the composition for nasal application can be 0.005% by mass or more, 0.025% by mass or more, 0.05% by mass or more, 0.1% by mass or more, or 0.25% by mass or more, relative to the total amount of the composition, and can be 1% by mass or less, 0.5% by mass or less, 0.3% by mass or less, 0.1% by mass or less, 0.05% by mass or less, 0.025% by mass or less, or 0.01% by mass or less.

[0016] The intranasal compositions of the present invention may include an antihistamine. Antihistamines include diphenhydramine or a salt thereof (e.g., diphenhydramine hydrochloride), chlorpheniramine or a salt thereof (e.g., chlorpheniramine maleate, chlorpheniramine fumarate), ketotifen or a salt thereof (e.g., ketotifen fumarate), olopatadine or a salt thereof (e.g., olopatadine hydrochloride), iproheptine or a salt thereof (e.g., iproheptine hydrochloride), and the like. One or more antihistamines can be used.

[0017] The total concentration of the antihistamine in the composition for nasal application can be 0.04% by mass or more, 0.1% by mass or more, 0.2% by mass or more, 0.25% by mass or more, or 0.5% by mass or more, relative to the total amount of the composition, and can be 1% by mass or less, 0.5% by mass or less, 0.25% by mass or less, 0.2% by mass or less, or 0.1% by mass or less.

[0018] The nasal compositions of the present invention may contain antimicrobial components (also known as preservatives). Antibacterial ingredients include acrinol hydrate, isopropylmethylphenol, phenoxyethanol, alkylpolyaminoethylglycine, boric acid, alkyldiaminoethylglycine and / or its salts (e.g., alkyldiaminoethylglycine hydrochloride), benzoic acid and / or its salts (e.g., sodium benzoate, potassium benzoate), ethanol, quaternary ammonium salts (e.g., benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride), chlorhexidine and / or its salts (e.g., guanylate ... Examples of the antibacterial agent include chlorhexidine disuccinate, chlorobutanol, sorbic acid and / or its salts (e.g., potassium sorbate), sodium dehydroacetate, parahydroxybenzoic acid esters (e.g., methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate), oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguamides such as polyhexamethylene biguanide, Gloquil (trade name, Rhodia), and polydronium chloride. In addition, sulfa-based antibacterial agents such as sulfamethoxazole or a salt thereof (e.g., sulfamethoxazole sodium, sulfamethoxazole potassium, sulfamethoxazole calcium, sulfamethoxazole magnesium), sulfisoxazole, sulfisomidine or a salt thereof (e.g., sulfisomidine sodium, sulfisomidine potassium, sulfisomidine calcium, sulfisomidine magnesium), alkylpolyaminoethylglycine, chloramphenicol, ofloxacin, norfloxacin, levofloxacin, lomefloxacin hydrochloride, and acyclovir can also be used as the antibacterial component. One or more antibacterial components can be used.

[0019] The total concentration of the antibacterial components in the composition for nasal application can be 0.0005% by mass or more, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.02% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 1% by mass or more, relative to the total amount of the composition, and can be 5% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less, 0.05% by mass or less, 0.02% by mass or less, 0.01% by mass or less, 0.005% by mass or less, or 0.001% by mass or less.

[0020] The nasal compositions of the present invention may include a solubilizing agent. The solubilizer is preferably a nonionic surfactant. Examples of nonionic surfactants include POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate 40), POE (20) sorbitan monostearate (polysorbate 60), POE (20) sorbitan tristearate (polysorbate 65), and POE (20) sorbitan monooleate (polysorbate 80) fatty acid esters; poloxamer 407, poloxamer 235, poloxamer 188, poloxamer 403, and poloxamer 188. POE-POP block copolymers such as Poloxamer 237 and Poloxamer 124; POE hydrogenated castor oils such as POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, and POE hydrogenated castor oil 80; POE castor oils such as POE castor oil 3, POE castor oil 4, POE castor oil 6, POE castor oil 7, POE castor oil 10, POE castor oil 13.5, POE castor oil 17, POE castor oil 20, POE castor oil 25, POE castor oil 30, POE castor oil 35, and POE castor oil 50; polyethylene monostearate Polyethylene glycol (2 E.O.), polyethylene glycol monostearate (4 E.O.), polyethylene glycol monostearate (9 E.O.), polyethylene glycol monostearate (10 E.O.), polyethylene glycol monostearate (23 E.O.), polyethylene glycol monostearate (25 E.O.), polyethylene glycol monostearate (32 E.O.), polyethylene glycol monostearate (40 E.O., Polyoxyl 40 stearate), polyethylene monostearate polyethylene glycol monostearate such as polyethylene glycol (45 E.O.), polyethylene glycol monostearate (55 E.O.), polyethylene glycol monostearate (75 E.O.), and polyethylene glycol monostearate (140 E.O.); POE alkyl ethers such as POE (9) lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether; and POE alkyl phenyl ethers such as POE (10) nonylphenyl ether.In the compounds exemplified above, POE stands for polyoxyethylene, POP stands for polyoxypropylene, and the numbers in parentheses stand for the number of moles added.

[0021] Other amphoteric surfactants that can be used include glycine-type amphoteric surfactants (e.g., alkyldiaminoethylglycine, alkylpolyaminoethylglycine) and betaine-type amphoteric surfactants (e.g., lauryldimethylaminoacetic acid betaine, imidazolinium betaine). One or more solubilizers can be used.

[0022] The total concentration of the solubilizer in the composition for nasal application can be 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 3% by mass or more, or 5% by mass or more, relative to the total amount of the composition, and can be 10% by mass or less, 5% by mass or less, 3% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less, or 0.01% by mass or less.

[0023] The nasal compositions of the present invention may include a humectant. Examples of the humectant include polyhydric alcohols such as polyethylene glycol, propylene glycol, butylene glycol, and glycerin; and sugar alcohols such as erythritol, xylitol, sorbitol, mannitol, and lactitol. One or more types of wetting agents can be used.

[0024] The total concentration of the humectant in the composition for nasal application can be 0.01% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 2% by mass or more, 4% by mass or more, 8% by mass or more, or 10% by mass or more, relative to the total amount of the composition, and can be 15% by mass or less, 10% by mass or less, 8% by mass or less, 4% by mass or less, 2% by mass or less, 1% by mass or less, 0.5% by mass or less, or 0.1% by mass or less.

[0025] The nasal compositions of the present invention may include a thickening agent. Examples of thickeners include guar gum, locust bean gum, carrageenan, xanthan gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, acrylic acid alkyl methacrylate copolymer, polyethylene glycol, bentonite, alginic acid, macrogol, and cellulose-based thickeners (methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, and salts thereof (e.g., sodium salts, potassium salts), etc.). One or more types of thickeners can be used.

[0026] The total concentration of the thickener in the composition for nasal application can be 0.05% by mass or more, 0.1% by mass or more, 0.3% by mass or more, 0.5% by mass or more, 0.8% by mass or more, or 1% by mass or more, and can be 1% by mass or less, 0.8% by mass or less, 0.5% by mass or less, 0.3% by mass or less, or 0.1% by mass or less, based on the total amount of the composition.

[0027] The nasal compositions of the present invention may include a buffering agent. Examples of buffers include borate buffers, phosphate buffers, carbonate buffers, citrate buffers, acetate buffers, epsilon-aminocaproic acid buffers, and aspartate buffers. Examples of borate buffer components include boric acid and borate salts (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.). Borates may be hydrates. Examples of phosphate buffer components include phosphoric acid and phosphate salts (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.). Phosphates may be hydrates. Examples of carbonate buffer components include carbonic acid and carbonate salts (potassium carbonate, sodium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, magnesium carbonate, etc.). Components of citrate buffers include citric acid and citrate salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.). Components of acetate buffers include acetic acid and acetate salts (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.). Components of aspartic acid buffers include aspartic acid and salts of aspartic acid (sodium aspartate, magnesium aspartate, potassium aspartate, etc.). One or more buffers can be used.

[0028] The total concentration of the buffer in the composition for nasal application can be 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 2% by mass or more, or 4% by mass or more, and can be 8% by mass or less, 4% by mass or less, 2% by mass or less, 1% by mass or less, 0.5% by mass or less, or 0.1% by mass or less, based on the total amount of the composition.

[0029] The nasal compositions of the present invention may contain a tonicity agent. The tonicity agent includes sodium chloride, potassium chloride, calcium chloride, magnesium chloride, potassium acetate, sodium acetate, magnesium sulfate, and the like. One or more isotonicity agents can be used.

[0030] The total concentration of the isotonic agent in the composition for nasal application can be 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 1% by mass or more, and can be 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less, 0.05% by mass or less, or 0.01% by mass or less, relative to the total amount of the composition.

[0031] In addition to the above components, the composition for nasal application may contain one or more additives and physiologically or pharmacologically active ingredients that can be used in compositions for nasal application, provided that the effects of the present invention are not impaired. Among the additives and physiologically or pharmacologically active ingredients exemplified below, some have multiple functions or serve multiple purposes.

[0032] Examples of additives include bases, antioxidants, pH adjusters, stabilizers, chelating agents, irritation reducers, colorants, and fragrances.

[0033] The base includes an oily base and an aqueous base. Oily bases include hydrocarbons such as petrolatum (white petrolatum, yellow petrolatum), gelling hydrocarbons (such as Plastibase), ozokerite, ceresin, microcrystalline wax, squalene, squalane, α-olefin oligomers, paraffin, liquid paraffin, and light liquid paraffin; higher alcohols such as cetyl alcohol, cetostearyl alcohol, stearyl alcohol, and behenyl alcohol; sterols such as cholesterol, phytosterol, and phytosteryl hydroxystearate; shea butter, Vegetable fats such as carnauba wax, cocoa butter, and candelilla wax; vegetable oils such as avocado oil, olive oil, camellia oil, macadamia nut oil, evening primrose oil, jojoba oil, rapeseed oil, egg yolk oil, sesame oil, castor oil, safflower oil, cottonseed oil, soybean oil, tea seed oil, rice bran oil, rice germ oil, wheat germ oil, peanut oil, sunflower oil, almond oil, corn oil, coconut oil, orange oil, sage oil, palm oil, mink oil, meadowfoam oil, lavender oil, rosemary oil, and rosehip oil; lanolin, orange roughy oil, squalane, horse oil, spermaceti, and and animal fats and oils such as beeswax; hydrogenated oils; silicone oils such as methylpolysiloxane, crosslinked methylpolysiloxane, highly polymerized methylpolysiloxane, cyclic silicone, alkyl-modified silicone, crosslinked alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, crosslinked polyether-modified silicone, crosslinked alkylpolyether-modified silicone, silicone-alkyl chain co-modified polyether-modified silicone, silicone-alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, and silicone resin; natural polymer derivatives such as ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, and cationized guar gum; synthetic polymers such as polyvinylpyrrolidone, carboxyvinyl polymer, and alkyl acrylate methacrylate copolymer; natural polymers such as carrageenan, alginic acid, cellulose, guar gum, quince seed, dextran, and gellan gum;Esters such as diethylhexyl succinate, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerythrityl tetra-2-ethylhexanoate, and caprylic / capric triglyceride; polysaccharides such as dextrin and maltodextrin; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; Examples of aqueous bases include water; lower alcohols such as ethanol and isopropanol; and the like.

[0034] Examples of antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, p-hydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivatives (ascorbic acid stearate, ascorbic acid palmitate, ascorbyl dipalmitate, ascorbic acid monophosphate, ascorbic acid diphosphate, ascorbic acid triphosphate, ascorbic acid sulfate, etc.), tocopherol, tocopherol derivatives (tocopherol acetate, tocopherol succinate, tocopherol calcium succinate, etc.), erythorbic acid, L-cysteine ​​hydrochloride, lycopene, glutathione, propyl gallate, tannic acid, epigallocatechin, anthocyanin, hydroxytyrosol, nordihydroguaiaretic acid, caffeic acid, and enzymes (catalase, superoxide dismutase, glutathione peroxidase, elastase, etc.).

[0035] Examples of pH adjusters include inorganic acids (such as hydrochloric acid and sulfuric acid), organic acids (such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, and sodium succinate), inorganic bases (such as potassium hydroxide and sodium hydroxide), and organic bases (such as triethanolamine, diisopropanolamine, and triisopropanolamine).

[0036] The stabilizer may include sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole, and the like.

[0037] Chelating agents include EDTA disodium salt and EDTA calcium disodium salt.

[0038] Irritation reducers include licorice extract and sodium alginate.

[0039] Examples of colorants include those listed in the Legal Dyes Handbook (edited by the Japan Cosmetic Industry Association (2004)).

[0040] Examples of physiologically active or pharmacologically active ingredients include antiallergic drugs, anti-inflammatory agents, local anesthetics (soothing agents), antipruritics other than antihistamines, moisturizing ingredients, vitamins, cooling agents other than menthol, mucopolysaccharides, amino acids, proteins, etc.

[0041] Antiallergic drugs include cromoglycic acid or a salt thereof (for example, sodium cromoglycate, potassium cromoglycate, calcium cromoglycate, magnesium cromoglycate), ashitazanolast, amlexanox, ibudilast, tranilast, pemirolast potassium, ketotifen, etc.

[0042] The anti-inflammatory agent may be either a non-steroidal or a steroidal agent. Non-steroidal anti-inflammatory agents include allantoin, glycyrrhizinic acid, glycyrrhetinic acid, acetaminophen, epsilon-aminocaproic acid, berberine, azulene, bromelain, zinc, and methyl salicylate; plant extracts such as licorice extract, sage extract, and rosemary extract; enzyme-based anti-inflammatory agents such as lysozyme, serrapeptase, and semi-alkaline proteinase; fenamic acid-based anti-inflammatory agents such as mefenamic acid, tolfenamic acid, and flufenamic acid; acemetacin, indomethacin, indomethacin farnesyl, etodolac, diclofenac, and sulindac. arylacetic acid anti-inflammatory agents such as nabumetone, fenbufen, proglumetacin, and mofezolac; propionic acid anti-inflammatory agents such as aminoprofen, ibuprofen, oxaprozin, ketoprofen, zaltoprofen, tiaprofenic acid, naproxen, flurbiprofen, zaltoprofen, ibuprofen piconol, flurbiprofen axetil, fenoprofen, pranoprofen, and loxoprofen; and oxicam anti-inflammatory agents such as ampiroxicam, tenoxicam, piroxicam, meloxicam, and lornoxicam. These may be salts, such as dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, stearyl glycyrrhizinate, stearyl glycyrrhetinate, indomethacin hydrochloride, diclofenac sodium salt, bromfenac sodium salt, berberine sulfate, berberine hydrochloride, berberine tannate, azulene sulfonate sodium salt, zinc sulfate, zinc lactate, lysozyme hydrochloride, ufenamate (butyl flufenamate), proglumetacin maleate, fenoprofen calcium salt, and loxoprofen sodium salt.

[0043] Steroidal anti-inflammatory agents include prednisolone, hydrocortisone, cortisone, dexamethasone, triamcinolone, triamcinolone acetonide, difluprednate, mometasone, diflucortolone, fluocinside, beclomethasone, deprodone, alclometasone, flumethasone, amcinonide, clobetasone, diflorasone, and derivatives thereof. Derivatives include prednisolone esters such as prednisolone valerate acetate, prednisolone succinate, prednisolone acetate, and prednisolone phosphate; dexamethasone esters such as dexamethasone valerate, dexamethasone propionate, dexamethasone acetate, dexamethasone phosphate, dexamethasone metasulfobenzoate, dexamethasone cipesilate, and dexamethasone palmitate; hydrocortisone butyrate (especially hydrocortisone-17-butyrate); and hydrocortisone. Examples of hydrocortisone esters include acetate, hydrocortisone succinate, hydrocortisone butyrate propionate, and hydrocortisone phosphate, mometasone furoate, diflucortolone valerate, beclomethasone propionate, beclomethasone dipropionate, clobetasone butyrate, deprodone propionate, alclometasone propionate, flumethasone pivalate, clobetasone propionate, clobetasone butyrate, and diflorasone acetate.

[0044] Local anesthetics (analgesics) include chlorobutanol, oxybuprocaine hydrochloride, cocaine hydrochloride, cornecaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, diethylaminoethyl parabutylaminobenzoate hydrochloride, piperocaine hydrochloride, procaine hydrochloride, proparacaine hydrochloride, hexothiocaine hydrochloride, lidocaine, and lidocaine hydrochloride.

[0045] Examples of antipruritic agents other than antihistamines include crotamiton, ichthammol, moctal, and thymol.

[0046] Examples of moisturizing ingredients include polyhydric alcohols such as glycerin, dipropylene glycol, 1,3-butylene glycol, propylene glycol, polyethylene glycol, diglycerin, pentanediol, hexanediol, and octanediol; sugars such as trehalose, xylitol, and sorbitol; polymeric compounds such as keratin, chitin, and chitosan; lipids such as ceramide, cholesterol, and phospholipids; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and aloe extract.

[0047] Vitamins include retinol derivatives such as retinol, retinol acetate, and retinol palmitate, retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoate, vitamin A such as d-δ-tocopheryl retinoate, α-tocopheryl retinoate, and β-tocopheryl retinoate; β-carotene, α-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, and cryptoxanthin. Provitamins A such as dl-α-tocopherol, echinenone, etc.; Vitamin E such as δ-tocopherol, dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, and tocopherol nicotinate; Riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, and riboflavin 5'-phosphate ester. Vitamin B2 compounds such as sodium nicotinate and riboflavin tetranicotinate; nicotinic acids such as dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, and 1-(4-methylphenyl)ethyl nicotinate; vitamin C compounds such as ascorbyl stearate, L-ascorbyl dipalmitate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl glucoside, ascorbigen-A, ascorbyl stearate, and ascorbyl palmitate; vitamin D compounds such as methylhesperidin, ergocalciferol, and cholecalciferol; vitamin K compounds such as phylloquinone and farnoquinone;Vitamin B1 compounds such as dibenzoyl thiamine, dibenzoyl thiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate ester, thiamine diphosphate ester, thiamine diphosphate ester hydrochloride, thiamine triphosphate, thiamine triphosphate monophosphate; pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, pyridoxal 5'-phosphate, pyridoxal hydrochloride Vitamin B6 compounds such as cyanocobalamin, hydroxocobalamin, and deoxyadenosylcobalamin; folic acids such as folic acid and pteroylglutamic acid; nicotinic acids such as nicotinic acid and nicotinamide; pantothenic acids such as pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantethine, D-pantethine, coenzyme A, and pantothenyl ethyl ether; biotins such as bioticin; vitamin-like factors such as gamma-oryzanol, carnitine, ferulic acid, alpha-lipoic acid, and orotic acid;

[0048] Examples of cooling agents other than menthol include terpenoids such as camphor, borneol, geraniol, cineole, linalool, citronellol, anethole, limonene, and eugenol. Terpenoids may be in the d-, l-, or dl-form. Other examples include essential oils such as cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, and rose oil.

[0049] Examples of mucopolysaccharides include heparin-like substances; chondroitin sulfates or salts thereof such as chondroitin sulfate and sodium chondroitin sulfate; dermatan sulfates or salts thereof such as dermatan sulfate and sodium dermatan sulfate; hyaluronic acid or salts thereof such as hyaluronic acid, sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, and calcium hyaluronate; hyaluronic acid derivatives or salts thereof such as acetylated hyaluronic acid, sodium acetylated hyaluronate, potassium acetylated hyaluronate, magnesium acetylated hyaluronate, and calcium acetylated hyaluronate; heparan sulfate; heparin; keratan sulfate I and II.

[0050] The pH of the composition for nasal application can be 4 or more, or 4.5 or more, and 9 or less, 7.5 or less, 7 or less, or 6.5 or less. If the pH is within this range, unpleasant irritation is unlikely to be felt when applied to the nasal mucosa, and the effects of the present invention can be fully obtained.

[0051] How to prevent the appearance of dark spots The present invention provides a method for suppressing an increase in the sensation of burning (pain) caused by storage of a menthol-containing composition for nasal application, using a container containing an olefin resin in all or part of the area that comes into contact with the composition for nasal application. The composition and container for the composition for nasal application are as described above. [Example]

[0052] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0053] Evaluation of the effect of container materials A spray container in which the molding material of the container body was high density polyethylene (HDPE) (Example 1) and a spray container in which the molding material of the container body was polyethylene terephthalate (PET) (Comparative Example 1) were used. The test formulation used was a composition for nasal application whose composition is shown in Table 1. [Table 1]

[0054] The test formulations were filled into containers of Example 1 and Comparative Example 1, and left to stand for 3 months in a thermostatic chamber at 40°C and 75% RH. After standing, nine subjects applied the test formulations to their nasal cavities and evaluated the cooling sensation and the feeling of burning. For the application of the test formulations to the nasal cavities, one subject sprayed one push of the formulation of Example 1 into the right nostril and one push of the formulation of Comparative Example 1 into the left nostril, and immediately evaluated the cooling sensation and the feeling of burning. After 3 hours, one push of the formulation of Example 1 into the left nostril and one push of the formulation of Comparative Example 1 into the right nostril, and immediately evaluated the cooling sensation and the feeling of burning. Then, for the cooling sensation and the feeling of dark spots, if there was no difference between Example 1 and Comparative Example 1, it was evaluated as 0, if either was slightly strong, it was evaluated as 1, and if either was strong, it was evaluated as 2. For the cooling sensation, if one of the preparations was felt to be slightly strong, 1 point was counted for the test preparation that was felt to be slightly strong, and if one of the preparations was felt to be strong, 2 points were counted for the test preparation that was felt to be strongly. For the feeling of dark spots, if one of the preparations was felt to be slightly strong, 1 point was counted for the test preparation that was felt to be slightly strong, and if one of the preparations was felt to be strong, 2 points were counted for the test preparation that was felt to be strongly. If both the cooling sensation and the feeling of dark spots were the same for both preparations, 0 points were counted. The total scores of the 9 subjects are shown in Table 2.

[0055] [Table 2] There was no difference in the cooling sensation between the test preparation containing menthol stored in an HDPE container (Example 1) and the test preparation stored in a PET container (Comparative Example 1), but the staining sensation was weaker when the test preparation containing menthol was stored in an HDPE container (Example 1) than when it was stored in a PET container (Comparative Example 1). Of the test formulation's ingredients, only l-menthol has a cooling sensation and a burning sensation. Therefore, storing the product in an HDPE container prevented the burning sensation from increasing during storage. This is thought to be due to the good compatibility between l-menthol and HDPE. Furthermore, the cooling sensation that l-menthol provides did not decrease even during storage. This demonstrates that olefin resin containers are suitable for use in nasal compositions containing menthol. [Industrial Applicability]

[0056] The composition for nasal application of the present invention is housed in a container suitable for menthol, and therefore is prevented from deteriorating during storage.

Claims

1. A nasal composition containing menthol, which is contained in a container containing an olefin resin in all or part of the area that comes into contact with the nasal composition.

2. 10. The composition of claim 1, wherein the olefin resin is polyethylene.

3. A method for suppressing an increase in the feeling of staining due to storage of a nasal composition containing menthol, wherein a container containing an olefin resin is used as a container for use with the nasal composition, and the entire or part of the area that comes into contact with the nasal composition contains the olefin resin.

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