Pharmaceutical composition containing fexofenadine

Abstract

To provide a pharmaceutical composition having excellent anti-inflammatory action.SOLUTION: A pharmaceutical composition contains (a) fexofenadine or salt thereof; (b) glycyrrhizinic acid or a salt thereof, or belladonna or extract thereof; and (c) one or more selected from ephedrine or a derivative thereof or a salt thereof, phenylephrine or a salt thereof, and caffeine.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition having excellent anti-inflammatory effects that can be used as a general cold medicine or a medicine for rhinitis.

Background Art

[0002] A general cold medicine is a general term for pharmaceuticals used for alleviating various symptoms of a cold, such as runny nose, nasal congestion, fever, throat pain, cough, phlegm, sneezing, chill, headache, joint pain, muscle pain, etc. General cold medicines are formulated with various ingredients, such as antipyretic and analgesic components, antihistamine components, cough suppressant components, etc., to alleviate these symptoms.

[0003] A medicine for rhinitis is a general term for pharmaceuticals used for alleviating various symptoms caused by acute rhinitis, allergic rhinitis or sinusitis, such as runny nose, nasal congestion, sneezing, etc. Medicines for rhinitis are formulated with various ingredients, such as antihistamine components and anti-inflammatory components, to alleviate these symptoms.

[0004] Fexofenadine hydrochloride mainly has a selective antihistamine H1 receptor antagonistic action, and further has an inhibitory action on the production of inflammatory cytokines, an inhibitory action on eosinophil migration, and an inhibitory action on the release of chemical mediators. In Japan, its efficacy and effect on allergic rhinitis, urticaria, and itching associated with skin diseases have been recognized (for example, see Non-Patent Document 1).

[0005] Glycyrrhizic acid or its salts are components contained in licorice, and have excellent anti-inflammatory effects, and are known to have an effect of relieving throat swelling and pain.

[0006] Belladonna total alkaloids are alkaloid components extracted from the rhizomes and roots of Atropa belladonna native to Europe. Since they have an action of suppressing the function of the parasympathetic nerve and reducing the secretion of nasal discharge and lacrimal glands, they are used in rhinitis medicines (for example, see Non-Patent Document 2). In Japan, they are also formulated in general cold medicines (Non-Patent Document 3).

[0007] Currently, as a combination preparation of fexofenadine or its salts, an allergy treatment drug combining fexofenadine hydrochloride and pseudoephedrine hydrochloride is prescribed for medical use (Non-Patent Document 4). In addition, although no combination cold medicines containing fexofenadine or its salts are commercially available, tablets containing fexofenadine hydrochloride and glycyrrhizic acid (see, for example, Patent Documents 1 and 2) are known. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] Japanese Patent Publication No. 2002-212067 [Patent Document 2] Japanese Patent Publication No. 2016-222657 [Non-patent literature]

[0009] [Non-Patent Document 1] Allegra® Tablets 30mg, Allegra® Tablets 60mg, Allegra OD Tablets® 60mg - Package Insert [Non-Patent Document 2] The 17th Revised Japanese Pharmacopoeia, pages D-854 to D-857 [Non-Patent Document 3] JAPIC General Drug Compendium 2018, page 94 [Non-Patent Document 4] Pharmaceutical Interview Form: Diregra (Registered Trademark) Combination Tablets [Overview of the project] [Problems that the invention aims to solve]

[0010] The object of the present invention is to provide a pharmaceutical composition containing fexofenadine or a salt thereof that has excellent anti-inflammatory effects. [Means for solving the problem]

[0011] As a result of diligent research to solve the above problems, the present inventors have found that a combination of fexofenadine or a salt thereof with glycyrrhizic acid or a salt thereof, or belladonna or an extract thereof, further incorporating one or more of the following, such as ephedrine or a derivative thereof or a salt thereof, phenylephrine or a salt thereof, or caffeine, exhibits excellent anti-inflammatory effects, and have completed the present invention.

[0012] In other words, the present invention relates to the following. [1] (a) Fexofenadine or a salt thereof; (b) Glycyrrhizic acid or a salt thereof, or belladonna or an extract thereof; and (c) One or more selected from ephedrine or its derivatives or salts thereof, phenylephrine or its salts, and caffeine; A pharmaceutical composition containing the following: [2] The pharmaceutical composition according to [1], wherein fexofenadine or a salt thereof is fexofenadine hydrochloride. [3] The pharmaceutical composition according to [1] or [2], wherein glycyrrhizic acid or a salt thereof is glycyrrhizic acid. [4] The pharmaceutical composition according to [1] or [2], wherein belladonna or its extract is total belladonna alkaloids. [5] The pharmaceutical composition according to any one of [1] to [4], wherein ephedrine or a derivative thereof or a salt thereof is methyl ephedrine hydrochloride. [6] The pharmaceutical composition according to any one of [1] to [5], wherein phenylephrine or a salt thereof is phenylephrine hydrochloride. [7] The pharmaceutical composition according to any one of [1] to [6], wherein the caffeine is anhydrous caffeine. [8] A pharmaceutical composition according to any one of [1] to [7], which is for anti-inflammatory purposes. [9] A pharmaceutical composition according to any one of [1] to [7], for the prevention or treatment of rhinitis.

[10] A pharmaceutical composition according to any one of [1] to [7] for the relief of various symptoms of the common cold.

[11] The pharmaceutical composition according to any one of [1] to [3] and [5] to

[10] , wherein the daily dosage of fexofenadine or its salt for adults is 1 mg to 200 mg, and the daily dosage of glycyrrhizic acid or its salt for adults is 1 mg to 300 mg.

[12] The pharmaceutical composition according to any one of [1], [2] and [4] to

[10] , wherein the daily dosage of fexofenadine or its salt for adults is 1 mg to 200 mg, and the daily dosage of belladonna or its extract for adults is 0.1 mg to 10 mg.

Effects of the Invention

[0013] According to the present invention, a pharmaceutical composition having excellent anti-inflammatory effects can be provided.

Embodiments for Carrying Out the Invention

[0014] Embodiments of the present invention will be described below. The pharmaceutical composition of the present invention (a) fexofenadine or its salt; (b) glycyrrhizic acid or its salt, or belladonna or its extract; and (c) one or more selected from ephedrine or its derivatives or their salts, phenylephrine or its salt, and caffeine; is a pharmaceutical composition containing the above.

[0015] In the present invention, "fexofenadine or its salt" includes, for example, fexofenadine, fexofenadine hydrochloride, etc. These are known compounds and can be produced by known methods, or commercially available products can be used.

[0016] In the present invention, the content of "fexofenadine or its salt" is not particularly limited and may be determined appropriately depending on the gender, age, symptoms, etc. of the person taking the medication. For example, if fexofenadine or its salt is fexofenadine hydrochloride, the daily dose is usually 1 mg to 200 mg, preferably 30 mg to 150 mg, and most preferably 60 mg to 120 mg.

[0017] In the present invention, "glycyrrhizic acid or its salt" refers to, for example, glycyrrhizic acid, dipotassium glycyrrhizate, trisodium glycyrrhizate, diammonium glycyrrhizate, disodium glycyrrhizate, monoammonium glycyrrhizate, and the like. These are known substances and can be produced by known methods, or commercially available products can be used.

[0018] In the present invention, the content of "glycyrrhizic acid or its salt" is not particularly limited and can be appropriately determined by consideration according to the gender, age, symptoms, etc. of the person taking the medication. For example, if glycyrrhizic acid or its salt is glycyrrhizic acid, the daily dose is usually 1 mg to 300 mg, preferably 5 mg to 200 mg, and more preferably 10 to 200 mg.

[0019] In the present invention, "belladonna or its extract" refers to, for example, belladonna, belladonna cone, belladonna extract, and belladonna total alkaloids. These are known substances and can be produced by known methods, or commercially available products can be used.

[0020] In the present invention, the content of "belladonna or its extract" is not particularly limited and can be appropriately determined by consideration depending on the gender, age, symptoms, etc. of the person taking the medication. For example, if the belladonna or its extract is total belladonna alkaloids, the daily dose (preferably for adults) is usually 0.1 mg to 10 mg, preferably 0.12 mg to 0.6 mg, and more preferably 0.3 mg to 0.6 mg.

[0021] In the present invention, "ephedrine or its derivatives or salts thereof" include, for example, pseudoephedrine hydrochloride, pseudoephedrine sulfate, l-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, and dl-methylephedrine saccharin salt. These are known substances and can be produced by known methods, or commercially available products can be used.

[0022] In the present invention, the content of "ephedrine or its derivatives or salts thereof" is not particularly limited and may be appropriately determined depending on the gender, age, symptoms, etc. of the user. For example, if ephedrine or its derivatives or salts thereof are dl-methylephedrine hydrochloride, the daily dose is usually 1 mg to 300 mg, preferably 10 mg to 250 mg, and more preferably 25 mg to 200 mg. Furthermore, if ephedrine or its derivatives or salts thereof are pseudoephedrine hydrochloride, the daily dose is usually 1 mg to 1000 mg, preferably 50 mg to 500 mg, and more preferably 100 mg to 250 mg.

[0023] In the present invention, "phenylephrine or its salt" refers to, for example, phenylephrine, phenylephrine hydrochloride, etc. These are known compounds and can be manufactured by known methods, or commercially available products can be used. Phenylephrine hydrochloride is listed in the 17th edition of the Japanese Pharmacopoeia.

[0024] In the present invention, the content of "phenylephrine or its salt" is not particularly limited and may be determined appropriately depending on the gender, age, symptoms, etc. of the person taking the medication. For example, if phenylephrine or its salt is phenylephrine hydrochloride, the daily dose is usually 1 mg to 50 mg, preferably 5 mg to 30 mg, and more preferably 10 mg to 30 mg.

[0025] In the present invention, caffeine can be caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine, caffeine citrate, etc., with anhydrous caffeine and caffeine hydrate being preferred, and anhydrous caffeine being particularly preferred. Anhydrous caffeine and caffeine hydrate are listed in the 17th edition of the Japanese Pharmacopoeia.

[0026] In the present invention, the caffeine content is not particularly limited and can be determined appropriately depending on the gender, age, symptoms, etc. of the user. For example, if the caffeine is anhydrous caffeine, the daily dose is usually 1 mg to 1000 mg, preferably 75 mg to 600 mg, and more preferably 150 mg to 300 mg.

[0027] In the present invention, in addition to the above-mentioned components, other components commonly used in general cold medicines or rhinitis medicines may be added as needed, to the extent that they do not impair the effects. For example, components listed in the General Use Drug Manufacturing and Marketing Approval Standards may be added. Specifically, one or more components selected from antipyretic analgesics, antihistamines, vasoconstrictors, antitussives, noscapines, bronchodilators, expectorants, anticholinergics, anti-inflammatory agents, vitamins, gastric mucosal protectants, herbal medicines, hypnotics and sedatives, and Kampo prescriptions may be added.

[0028] As an antipyretic, anti-inflammatory, and analgesic agent, one or more components selected from, for example, aspirin, aluminum aspirin, acetaminophen, ethenzamide, sazapyrine, salicylamide, lactylphenetidine, ibuprofen, isopropylantipyrine, loxoprofen sodium hydrate, pranopufen, diclofenac sodium, mefenamic acid, indomethacin farnesil, acemetacin, etodolac, naproxen, meloxicam, celecoxib, and tiaramide hydrochloride can be included.

[0029] Examples of antihistamines include isotipendyl hydrochloride, difeterol hydrochloride, triperenamine hydrochloride, tondiamine hydrochloride, phenetazine hydrochloride, methodilazine hydrochloride, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, carbinoxamine diphenyldisulfonate, diphenylpyraline hydrochloride, diphenylpyraline theoclate, diphenhydramine hydrochloride, diphenhydramine salicylate, alimazine tartrate, and tannins. One or more ingredients selected from diphenhydramine acid, triprolidine hydrochloride hydrate, mebhydroline napadisylate, promethazine methylene disalicylate, carbinoxamine maleate, dipheterol phosphate, clemastine fumarate, mequitazine, ketotifen fumarate, promethazine hydrochloride, epinastine hydrochloride, emedastine fumarate, olopatadine hydrochloride, azelastine hydrochloride, and cetirizine hydrochloride may be included.

[0030] As a vasoconstrictor, one or more components selected from methoxyphenamine hydrochloride, etc., may be included.

[0031] As a cough suppressant, one or more ingredients selected from, for example, alloclamide hydrochloride, cloperastine hydrochloride, cloperastine fendizoate, codeine phosphate hydrate, dihydrocodeine phosphate, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthalein salt, tipepidine citrate, tipepidine hibenzate, dibnate sodium, pentoxyverin citrate, dimemorphan phosphate, eprazinon hydrochloride, pentoxyverin citrate, benproperine phosphate, and clofedanol hydrochloride may be included.

[0032] As for noscapines, for example, one or more components selected from noscapine and noscapine hydrochloride hydrate may be included.

[0033] As a bronchodilator, one or more components selected from, for example, aminophylline, diprophylline, theophylline, proxyphylline, trimethoquinol hydrochloride, phenylpropanolamine hydrochloride, methoxyphenamine hydrochloride, and isoprenaline hydrochloride may be included.

[0034] As an expectorant, one or more ingredients selected from, for example, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, bromhexine hydrochloride, l-carbocysteine, l-ethylcysteine ​​hydrochloride, l-methylcysteine ​​hydrochloride, ambroxol hydrochloride, ammonium chloride, l-menthol, ammonia / fennel extract, cherry bark extract, methylcysteine ​​hydrochloride, and fudosteine ​​can be included.

[0035] Anticholinergic agents such as isopropamide iodide can be incorporated into the formulation.

[0036] As an anti-inflammatory agent, one or more components selected from tranexamic acid, serrapeptase, bromelain, semi-alkaline proteinase, pronase, cearprose, productase, and lysozyme hydrochloride may be included.

[0037] Examples of vitamins include vitamin B1 and its derivatives and their salts, such as thiamine, thiamine chloride hydrochloride, thiamine nitrate, dicethiamine hydrochloride, cetothiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octothiamine, shikothiamine, thiamine disulfide, bis-ibthiamine, bis-bentiamine, prosultiamine, and benfotiamine; vitamin B2 and its derivatives and their salts, such as riboflavin, riboflavin phosphate, riboflavin butyrate, and riboflavin sodium phosphate; pantothenic acid, panthenol, panthenol One or more components selected from the following may be included: vitamin B5 and its derivatives such as tin, calcium pantothenate, and sodium pantothenate, and their salts; vitamin B6 and its derivatives such as pyridoxine hydrochloride and pyridoxal phosphate, and their salts; vitamin B12 and its derivatives such as cyanocobalamin and mecobalamin, and their salts; vitamin C and its derivatives such as ascorbic acid, sodium ascorbate, and calcium ascorbate, and their salts; and hesperidin and its derivatives, and their salts.

[0038] As a gastric mucosal protective agent, one or more components selected from glycine, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum alnoacetate (aluminum glycinate), aluminum hydroxide gel, dried aluminum hydroxide gel, coprecipitation product of aluminum hydroxide and sodium bicarbonate, mixed dried gel of aluminum hydroxide and magnesium carbonate, coprecipitation product of aluminum hydroxide, magnesium carbonate and calcium carbonate, coprecipitation product of magnesium hydroxide and aluminum potassium sulfate, magnesium carbonate, magnesium aluminometasilicate, aldioxa, sodium copper chlorophyllin, potassium copper chlorophyllin, methylmethionine sulfonium chloride, sucralfate, cetraxate hydrochloride, solfalkone, gefarnate, teprenone, and rebamipide may be included.

[0039] As for crude drugs, these include ephedra, nandina fruit, oyster shell, yam, licorice, balloon flower, plant star, plant star, sekisan (stone garlic), senega, fritillary, fennel, phellodendron bark, cow's rhizome, turmeric, chamomile, cinnamon bark, gentian, ox gall, animal bile (including bear bile), adenophora, ginger, lanceolata, clove, citrus peel, atractylodes, zerria, bamboo shoot ginseng, ginseng, red oak, catechu, edamame, corydalis, scutellaria, oleander, valerian, carotenoides, apricot kernel, goji berry, goji leucocarpa, schizonepeta, cassia seed, geranium, One or more ingredients selected from crude drugs such as Cyperus rotundus, Schisandra chinensis, Asarum sieboldii, Zanthoxylum piperitum, Aster tataricus, Dicranopteris erythrosora, Paeonia lactiflora, Musk, Magnolia bark, Ligusticum chuanxiong, Zenia japonica, Swertia japonica, Morus alba, Perilla frutescens, Southern laurel, Angelica acutiloba, Gloucestershire, Ophiopogon japonicus, Pinellia ternata, Banka japonica, Deer antler, Angelica dahurica, Poria cocos, Paeonia lactiflora, Oyster shell, and Deer antler, as well as extracts (extracts, tinctures, dried extracts, etc.) of these, may be included.

[0040] As a hypnotic sedative, one or more components selected from bromovalerylurea and allyl isopropylacetylurea may be included.

[0041] As a Kampo prescription, one or more ingredients selected from Kakkonto, Kakkonto-ka-kikyo, Keishito, Kososan, Saiko-keishito, Sho-saikoto, Sho-seiryuto, Bakumondoto, Hange-kobokuto, Maoto, etc. may be combined.

[0042] Furthermore, the pharmaceutical composition of the present invention may contain pharmaceutical additives necessary for manufacturing the formulation, to the extent that they do not impair the effects of the present invention. For example, the pharmaceutical additives may be those listed in Pharmaceutical and Food Safety Bureau Notification No. 1204-1 (Pharmaceutical Administration Laws and Regulations), the 2016 Dictionary of Pharmaceutical Additives (edited by the Japan Pharmaceutical Additives Association, Yakuji Nippo Co., Ltd.), and the 8th edition of the Official Compendium of Food Additives (Japan Food Additives Association), etc. Specifically, one or more components selected from excipients, binders, disintegrants, disintegration aids, fluidizers, lubricants, plasticizers, coating agents, sugar coating agents, glossing agents, solvents, pH adjusters, colorants, flavoring agents, sweeteners, fragrances, and flavoring agents may be included.

[0043] Excipients include: syrup powder, pregelatinized starch, isomalt, cocoa butter, hydrolyzed starch dry product, caramel, carmellose, carmellose calcium, carmellose sodium, hydrated silicon dioxide, hydrated amorphous silicon dioxide, dried aluminum hydroxide gel, dried potato starch, licorice powder, dried magnesium sulfate, agar, agar powder, kanbai powder, xylitol, croscarmellose sodium, crospovidone, magnesium aluminosilicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, calcium silicate, ke Magnesium silicate, light anhydrous silicic acid, cinnamon powder, crystalline cellulose, crystalline cellulose / carmellose sodium, crystalline cellulose (fine particles), crystalline cellulose (granules), synthetic aluminum silicate, synthetic aluminum silicate / hydroxypropyl starch / crystalline cellulose, synthetic hydrotalcite, wheat starch, rice flour, rice starch, β-cyclodextrin, heavy anhydrous silicic acid, aluminum magnesium hydroxide, aluminum hydroxide gel, aluminum hydroxide / sodium bicarbonate coprecipitate, aluminum hydroxide / magnesium carbonate / calcium carbonate Co-precipitate, magnesium hydroxide, D-sorbitol, talc, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low-substituted sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, sodium starch glycolate, corn starch, corn starch granules, trehalose hydrate, silicon dioxide, lactose hydrate, lactose granules, nonpareil, sucrose, potato starch, microcrystalline cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose (2208), hypromellose Calcium (2906), hypromellose (2910), hypromellose phthalate (200731 type), hypromellose phthalate (220824 type), fine silicon dioxide, partially pregelatinized starch, pullulan, powdered sugar, powdered reduced maltose syrup, powdered cellulose, powdered cellulose (average degree of polymerization: 800~1100), povidone (K25), povidone (K30), povidone (K90), polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene (105) polyoxypropylene (5) glycol,One or more components selected from polyoxyethylene (160) polyoxypropylene (30) glycol, sodium polystyrene sulfonate, polysorbate 80, polyvinyl acetal diethyl acetate, polyvinyl alcohol / diethylene glycol mixture, maltitol, maltose hydrate, D-mannitol, D-mannitol / crospovidone / D-sorbitol / hydrated silicon dioxide mixture, anhydrous silicic acid hydrate, anhydrous lactose, anhydrous calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate granules, methacrylate copolymer LD, magnesium aluminometasilicate, methyl acrylate / methacrylate copolymer, methyl acrylate / methyl methacrylate, methylcellulose, calcium hydrogen phosphate hydrate, calcium hydrogen phosphate granules, sodium hydrogen phosphate hydrate, potassium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, sodium dihydrogen phosphate, and erythritol may be included.

[0044] Examples of binders include gum arabic, gum arabic powder, agar, agar powder, kanbai flour, crystalline cellulose, copolyvidone, gelatin, shellac, low-substituted hydroxypropyl cellulose, corn starch, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl starch, hydroxypropyl cellulose, vinylpyrrolidone / vinyl acetate copolymer, hypromellose (2208), hypromellose (2906), hypromellose (2910), hypromellose acetate succinate, hypromellose phthalate (type 200731), and hypromellose phthalate (type 220824). One or more components selected from the following may be included: (type), fumaric acid / stearic acid / polyvinyl acetal diethylaminoacetate / hydroxypropylcellulose 2910 mixture, pullulan, povidone (K25), povidone (K30), povidone (K90), polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified), polyvinyl alcohol / polyethylene glycol / graft polymer, methacrylate copolymer L, methacrylate copolymer LD, methacrylate copolymer S, butyl methacrylate / methyl methacrylate copolymer, magnesium aluminometasilicate, and methylcellulose.

[0045] As a disintegrant, one or more components selected from, for example, pregelatinized starch, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, crospovidone, low-substituted carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, sodium starch glycolate, potato starch, hydroxypropyl starch, and partially pregelatinized starch may be included.

[0046] As disintegration aids, one or more components selected from, for example, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, light anhydrous silicic acid, crystalline cellulose, sodium starch glycolate, and hydroxypropyl starch can be included.

[0047] As a fluidizing agent, one or more components selected from, for example, hydrated silicon dioxide, light anhydrous silicic acid, crystalline cellulose, synthetic aluminum silicate, heavy anhydrous silicic acid, magnesium aluminum hydroxide, tricalcium phosphate, talc, corn starch, magnesium aluminometasilicate, and calcium hydrogen phosphate granules can be blended.

[0048] As a lubricant, one or more components selected from, for example, hydrated silicon dioxide, hydrated amorphous silicon dioxide, glycerin fatty acid ester, magnesium silicate, light anhydrous silicic acid, hydrogenated oil, heavy anhydrous silicic acid, sucrose fatty acid ester, stearyl alcohol, stearic acid, zinc stearate, aluminum stearate, calcium stearate, polyoxyl 40 stearate, magnesium stearate, hydrogenated soybean oil, talc, sodium stearyl fumarate, beeswax, anhydrous silicic acid hydrate, magnesium aluminometasilicate, and glyceryl monostearate can be incorporated.

[0049] As plasticizers, one or more components selected from triethyl citrate, glycerin, glycerin fatty acid ester, medium-chain triglyceride, triacetin, concentrated glycerin, castor oil, propylene glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polysorbate 80, macrogol 400, macrogol 600, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, glyceryl monostearate, isopropyl linoleate, and liquid paraffin may be incorporated.

[0050] The coating agents include ethyl acrylate / methyl methacrylate copolymer dispersion, acetylglycerin fatty acid ester, aminoalkyl methacrylate copolymer E, gum arabic, gum arabic powder, ammonia alkyl methacrylate copolymer, ethyl cellulose, ethyl cellulose aqueous dispersion, octyldecyl triglyceride, Opadry OY-6950, Opadry OY-L-28900, Opadry OY-LS-20291, Opadry OY-LS-23016, Opadry OY-S-7135, Opadry OY-S-8471, Opadry OY-S-9607, OPA-DRY OY-S-22829, OPA-DRY OY-S-22835, OPA-DRY OY-S-22961, OPA-DRY OY-S-28924, OPA-DRY YS-1-7003 White, OPA-DRY YS-1-12524-A, OPA-DRY YS-1-14762-A, OPA-DRY YS-1-15585-A, OPA-DRY YS-1-19025A, OPA-DRY YS-2-19114-A, OPA-DRY II Yellow, OPA-DRY Clear (YS-2-19114-A), OPA-DRY II Gray 85F17659, OPA-DRY White 03K2800 00, OpaDry Pink (02F34337), OpaDry II Pink, OpaDry II Pink 85F97191, OpaDry II Blue (85G20427), OpaDry II Beige 85F17438, OpaDry White (15B180002), OpaDry White OY-LS-28914, OpaDry White YS-1-18177-A, OpaDry White (YS-1-18202-A), OpaDry II White (33G28523), OpaDry II White (85F28751), OpaDry II White (OY-LS-28914) ), OpaDry II Light Blue (85G20426), OpaDry II Light Beige 85F17498, OpaDry II Red (32K15441), Carnauba wax, Carmellose calcium, Carmellose sodium, Hydrated silicon dioxide, Dried aluminum hydroxide gel, Dried methacrylate copolymer LD, Triethyl citrate, Glycerin, Glycerin fatty acid ester, Magnesium silicate, Light anhydrous silicic acid, Light anhydrous silicic acid-containing hydroxypropyl cellulose, Crystalline cellulose, Synthetic aluminum silicate, Synthetic hydrotalcite, Titanium dioxide,Magnesium oxide, dimethylaminoethyl methacrylate / methyl methacrylate copolymer, sucrose fatty acid ester, aluminum hydroxide gel, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyoxyl 40 stearate, magnesium stearate, purified gelatin, purified shellac, purified sucrose, gelatin, shellac, D-sorbitol, D-sorbitol solution, talc, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, concentrated glycerin, white shellac, sucrose Paraffin, hydroxypropylcellulose, hydroxypropylmethylcellulose 2910, titanium dioxide, macrogol mixture, hypromellose (2208), hypromellose (2906), hypromellose (2910), hypromellose acetate succinate, hypromellose phthalate (type 200731), hypromellose phthalate (type 220824), fumaric acid, stearic acid, polyvinyl acetal diethylaminoacetate, hydroxypropylmethylcellulose 2910 mixture, pullulan, premix additive Opadry White, Bentonite, Polyoxyethylene Hydrogenated Castor Oil 40, Polyoxyethylene Hydrogenated Castor Oil 60, Polyoxyethylene (105) Polyoxypropylene (5) Glycol, Polyoxyethylene (160) Polyoxypropylene (30) Glycol, Sodium Polystyrene Sulfonate, Polysorbate 80, Polyvinyl Acetal Diethyl Acetoacetate, Polyvinyl Alcohol (Partially Saponified), Macrogol 300, Macrogol 400, Macrogol 600, Macrogol 1500, Macrogol 1540, Macrogol 40 00, Macrogol 6000, Macrogol 6000EP, Macrogol 20000, Macrogol 35000, D-mannitol, Anhydrous citric acid, Anhydrous silicic acid hydrate, Anhydrous phthalic acid, Anhydrous calcium hydrogen phosphate, Methacrylic acid copolymer L, Methacrylic acid copolymer LD, Methacrylic acid copolymer S, Magnesium aluminometasilicate, Methyl methacrylate / methacrylic acid / methyl methacrylate copolymer, Aluminum monostearate, Glyceryl monostearate, Sorbitan monostearate, Sorbitan monolaurate,It may contain one or more components selected from calcium sulfate and DL-malic acid, etc.

[0051] As a sugar coating agent, one or more components selected from gum arabic, gum arabic powder, ethylcellulose, carnauba wax, carboxymethylcellulose sodium, crystalline cellulose, titanium dioxide, stearic acid, polyoxyl 40 stearate, purified gelatin, purified shellac, purified sucrose, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, sucrose, hydroxypropylcellulose, hypromellose (2208), hypromellose (2910), pullulan, povidone (K25), povidone (K30), povidone (K90), polyoxyethylene (105) polyoxypropylene (5) glycol, polyvinyl alcohol (partially saponified), macrogol 1500, macrogol 4000, macrogol 6000, and D-mannitol may be incorporated.

[0052] As a glossing agent, one or more components selected from carnauba wax, refined shellac, macrogol 400, macrogol 1500, macrogol 4000, macrogol 6000, and beeswax may be included.

[0053] As a solvent, one or more components selected from isopropanol, ethanol, glycerin, 1,3-butylene glycol, propylene glycol, and macrogol may be included.

[0054] As a pH adjuster, one or more components selected from hydrochloric acid, acetic acid, phosphoric acid, lactic acid, citric acid, succinic acid, tartaric acid, sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, and triethanolamine may be included.

[0055] As coloring agents, one or more ingredients selected from yellow iron oxide, Yellow No. 5 premix, brown iron oxide, carbon black, caramel, β-carotene, licorice extract, black iron oxide, titanium dioxide, ferric oxide, ferric oxide / glycerin suspension, Food Blue No. 1, Food Blue No. 2 aluminum lake, Food Yellow No. 4, Food Yellow No. 4 aluminum lake, Food Yellow No. 5, Food Red No. 2, Food Red No. 3, Food Red No. 102, copper chlorophyllin sodium, copper chlorophyll, riboflavin, riboflavin butyrate, riboflavin phosphate sodium, green tea powder, and rose oil may be included.

[0056] The flavoring agents include erythritol, sodium chloride, Phellodendron bark powder, Parmesan extract, Coptis japonica, Coptis japonica powder, Ononis root dry extract, orange, orange oil, cocoa powder, fructose, caramel, licorice, licorice extract, crude licorice extract, licorice powder, xylitol, calcium citrate, citric acid hydrate, sodium citrate hydrate, L-glutamic acid, L-arginine glutamate, L-glutamic acid hydrochloride, sodium L-glutamate, grapefruit extract, brown sugar, cinnamon tincture, cinnamon powder, cinnamon oil, kelp powder, saccharin, sodium saccharin hydrate, saffron, saffron tincture, sansho tincture, sansho powder, tartaric acid, D-tartaric acid, potassium bitartrate, DL-sodium tartrate, and ginger tincture. One or more ingredients selected from the following may be included: ginger powder, sucralose, stevia extract, stevia extract, refined licorice extract powder, refined sucrose, swertia japonica, hibiscus powder, D-sorbitol, jujube powder, taurine, taraxacum root / grass dry extract, tannic acid, clove tincture, clove oil, citrus peel tincture, chili pepper, chili pepper tincture, chili pepper powder, spruce tincture, spruce powder, trehalose hydrate, pisiflora powder, plum extract, sucrose, fructooligosaccharides, powdered sugar, peppermint powder, maltose hydrate, D-mannitol, dl-menthol, l-menthol, menthol powder, bonito flakes, bonito flakes powder, green tea powder, DL-malic acid, DL-sodium malate, lemon oil, and rose oil.

[0057] As a sweetener, one or more ingredients selected from aspartame, acesulfame potassium, amacha, amacha powder, reduced maltose syrup, licorice, licorice extract, licorice powder, xylitol, dipotassium glycyrrhizinate, disodium glycyrrhizinate, monoammonium glycyrrhizinate, monopotassium glycyrrhizinate, saccharin, sodium saccharin hydrate, sucralose, stevia extract, stevia extract, refined sucrose, refined sucrose granules, sucrose, powdered reduced maltose syrup, maltitol, D-mannitol, and erythritol may be included.

[0058] As for flavorings, one or more ingredients selected from orange flavor, orange flavor powder SH-1171-A, orange micron H-800092, guarana extract, sweet orange flavor, strawberry flavor, lemon flavor, brown sugar flavor, strawberry essence, strawberry flavor B86173, cherry flavor 181612, dentmint 1148J, banana powder flavor, peach essence, cypress 6E-84211, blackcurrant flavor 290012SYM, fruit essence, peppermint NAEFCOPO551957685, peppermint micron H-81550, mixed flavor powder, melon powder flavor, l-menthol, and menthol L163592SYM may be included.

[0059] The fragrances and scentings include fennel powder, fennel oil, ethyl vanillin, orange, orange extract, orange essence, orange oil, chamomile oil, caramel, licorice powder, d-camphor, dl-camphor, cinnamon powder, cinnamon oil, citronella oil, sugar flavor, spearmint oil, cherry flavor, clove oil, chili flavor, spruce tincture, spruce oil, pine oil, peppermint oil, vanilla flavor, vanillin, bitter essence, Vitabase, and Himalayan spice. One or more ingredients selected from the following may be included: gypsum oil, fruit flavor, flavor G1, hesperidin peppermint essence, bergamot oil, vermouth flavor, d-borneol, dl-borneol, matcha, mixed flavor, mint flavor, dl-menthol, l-menthol, eucalyptus oil, lavender oil, bonito flakes, bonito flakes powder, lemon powder, lemon oil, rose water, rose oil, belladonna oil, and Roman chamomile oil.

[0060] The dosage form of the pharmaceutical composition of the present invention is not particularly limited and includes, for example, oral preparations such as capsules, pills, granules, fine granules, powders, tablets, liquids, syrups, jellies, and lozenges, and parenteral preparations such as topical liquids, ointments, creams, gel creams, poultices, transdermal preparations, patches, liniments, lotions, suppositories, eye drops, and nasal drops. Preferably, it is an oral preparation, a nasal drop, or an eye drop, more preferably an oral preparation, and even more preferably a solid preparation such as a capsule, pill, granule, fine granule, powder, or tablet. These solid preparations may be coated with sugar coating, film coating, or the like by known methods as needed.

[0061] The pharmaceutical composition of the present invention can be prepared in the dosage forms listed above, in accordance with the methods described in the 17th edition of the Japanese Pharmacopoeia, etc. For example, if the dosage form of the pharmaceutical composition of the present invention is a tablet, it can be manufactured in accordance with the section on "Tablets" in the General Provisions of the Japanese Pharmacopoeia. If the dosage form of the pharmaceutical composition of the present invention is a granule, it can be manufactured in accordance with the section on "Granules" in the General Provisions of the Japanese Pharmacopoeia. In the case of a solid dosage form of the pharmaceutical composition of the present invention, if the components specified in the present invention and other components / additives in such a solid dosage form cause problems with storage stability, etc., due to incompatibility or other issues, the formulation can be appropriately prepared so that they do not come into contact with each other, such as by dividing into granules or multilayering.

[0062] If the pharmaceutical composition of the present invention is in the form of a solid dosage form, it may be initially packaged in SP packaging, PTP packaging, stick packaging, bottle packaging, etc., and stored airtight. Furthermore, these may be pillow-packaged, and they may be stored in boxes or the like. The material used for pillow packaging is not particularly limited, and for example, resin films such as polypropylene film, polyethylene terephthalate film, polyethylene film, or these resin films with aluminum foil attached can be used. If hygroscopicity is a concern, a desiccant may be stored simultaneously in the bottle packaging or pillow packaging.

[0063] The pharmaceutical composition of the present invention can be administered for anti-inflammatory purposes. Diseases to which the anti-inflammatory pharmaceutical composition is applied include the common cold, rhinitis, eczema, urticaria, tonsillitis, pharyngitis, hemorrhoids, stomatitis, and the relief of various symptoms associated with these diseases. Specifically, it can be used as a cold medicine, a nasal spray for rhinitis (allergic rhinitis, sinusitis, etc.), an insect bite remedy, an antipruritic, a preventive and / or therapeutic agent for dermatitis, a medicine for athlete's foot and ringworm, a preventive and / or therapeutic agent for symptoms such as itching in hemorrhoids, and a preventive and / or therapeutic agent for sore throat and pain caused by throat inflammation.

[0064] The pharmaceutical composition of the present invention can be administered to relieve various symptoms of the common cold (fever, chills, headache, sore throat, runny nose, nasal congestion, cough, phlegm, joint pain, muscle pain, sneezing).

[0065] Furthermore, the pharmaceutical composition of the present invention can be administered for the prevention or treatment of rhinitis, and in particular for the relief of symptoms (runny nose, nasal congestion, sneezing) caused by acute rhinitis, allergic rhinitis caused by pollen or house dust, or sinusitis.

[0066] Furthermore, the pharmaceutical composition of the present invention can be administered for the prevention and / or treatment of dermatitis, and in particular for the prevention and / or treatment of itching, eczema, hives, dermatitis, and rashes.

[0067] Examples and manufacturing examples are shown below, but the present invention is not limited to the following examples. [Examples]

[0068] (Example of test) Anti-inflammatory test on bradykinin-plasmin paw edema using rats 1-1. Test substance and inflammatory reagent In this study, methylcellulose was manufactured by Shin-Etsu Chemical Co., Ltd., fexofenadine hydrochloride (hereinafter, fexofenadine) was manufactured by Dipharma Inc., glycyrrhizic acid was manufactured by Alps Pharmaceutical Co., Ltd., belladonna total alkaloids (hereinafter, belladonna) was manufactured by Alps Pharmaceutical Co., Ltd., phenylephrine hydrochloride (hereinafter, phenylephrine) was manufactured by Wako Pure Chemical Industries, Ltd., dl-methylephedrine hydrochloride (hereinafter, methylephedrine) was manufactured by Alps Pharmaceutical Co., Ltd., and anhydrous caffeine (hereinafter, caffeine) was manufactured by Shizuoka Caffeine Industry Co., Ltd. In addition, bradykinin was manufactured by Wako Pure Chemical Industries, Ltd., and human plasmin (hereinafter, plasmin) was manufactured by Haemagtologic Technology Inc. Each sample was prepared by dissolving or suspending each test substance in a 0.5% aqueous methylcellulose solution.

[0069] (Specimen) Group 0: Vessel (0.5% methylcellulose) *Inflammation control group Group 1: Fexofenadine 0.3 mg / kg Group 2: Fexofenadine 0.3 mg / kg + Glycyrrhizic acid 200 mg / kg Group 3: Methyl ephedrine 110 mg / kg Group 4: Phenylephrine 30 mg / kg Group 5: Caffeine 150 mg / kg Group 6: Fexofenadine 0.3 mg / kg + Glycyrrhizic acid 200 mg / kg + Methyl ephedrine 110 mg / kg Group 7: Fexofenadine 0.3 mg / kg + Glycyrrhizic acid 200 mg / kg + Phenylephrine 30 mg / kg Group 8: Fexofenadine 0.3 mg / kg + Glycyrrhizic acid 200 mg / kg + Caffeine 150 mg / kg Group 9: Fexofenadine 0.3 mg / kg + Belladonna 0.6 mg / kg Group 10: Fexofenadine 0.3 mg / kg + Belladonna 0.6 mg / kg + Methylephedrine 110 mg / kg Group 11: Fexofenadine 0.3 mg / kg + Belladonna 0.6 mg / kg + Phenylephrine 30 mg / kg Group 12: Fexofenadine 0.3 mg / kg + Belladonna 0.6 mg / kg + Caffeine 150 mg / kg

[0070] (Inflammatory agent) Bradykinin 1 mg and plasmin 0.5 U were dissolved in physiological saline to make 20 mL.

[0071] 1-2. Test Method Five-week-old male Crij:WI rats [Charles River Co., Ltd.] were quarantined for five days, followed by acclimatization for 2-4 days. After acclimatization, the rats were divided into groups of five based on their body weight, and the test substance was administered orally using a tube. Thirty minutes later, 0.1 ml of bradykinin-plasmin solution was subcutaneously injected into the right hind paw to induce inflammation. Paw volume was measured for each individual before group division and 60 minutes after inflammation, and the edema rate, area under the curve, and suppression rate were calculated using the formulas described later.

[0072] 1-3. Measurement of plantar volume and calculation of edema rate, area under the curve (AUC), and suppression rate. The right hind limb paw volume (mL) was measured using a mouse / rat hind limb paw volume analyzer (TK-101CMP, Unicom Co., Ltd.) before group division, after inflammation, and at 15, 30, 45, and 60 minutes. For each individual, the edema rate was calculated using the following formula based on the paw volume before group division and the paw volume at each measurement time.

[0073]

number

[0074] Furthermore, for each individual, the area under the curve (AUC) is calculated using the following formula based on the edema rate at each time point. 0-1hr ) was calculated.

[0075]

number

[0076] a: Edema rate 15 minutes after inflammation onset b: Edema rate 30 minutes after inflammation onset c: Edema rate 45 minutes after inflammation onset d: Edema rate 60 minutes after inflammation onset

[0077] Furthermore, the AUC of the inflammation control group (group 0) 0-1hr The values ​​and the AUC for each drug group (groups 1-12) 0-1hr Based on the values, the inhibition rate for each drug group was calculated using the following formula.

[0078]

number

[0079] 2. Test Results The test results are shown in Table 1. [Table 1]

[0080] In Table 1, compared to Group 1, which received fexofenadine alone, Group 2, which received fexofenadine in combination with glycyrrhizic acid, showed a lower rate of edema suppression. However, Group 6, which received fexofenadine and glycyrrhizic acid in combination with methyl ephedrine, Group 7, which received fexofenadine and glycyrrhizic acid in combination with phenylephrine, and Group 8, which received fexofenadine and glycyrrhizic acid in combination with caffeine, showed a significantly improved rate of edema suppression compared to Group 1, which received fexofenadine alone, Group 3, which received methyl ephedrine alone, Group 4, which received phenylephrine alone, and Group 2, which received fexofenadine and glycyrrhizic acid in combination, confirming a high anti-inflammatory effect.

[0081] Furthermore, compared to group 1, which received fexofenadine alone, group 9, which received fexofenadine in combination with belladonna, showed a lower rate of edema suppression. However, groups 10, which received fexofenadine and belladonna in combination with methyl ephedrine, group 11, which received fexofenadine and belladonna in combination with phenylephrine, and group 12, which received fexofenadine and belladonna in combination with caffeine, showed a significantly improved rate of edema suppression compared to group 1 (fexofenadine alone), group 4 (phenylephrine alone), group 5 (caffeine alone), and group 9 (fexofenadine and belladonna in combination), confirming a high anti-inflammatory effect.

[0082] The following is an example of a manufacturing process. The numerical values ​​indicate the daily amount of each ingredient contained in the formulation. (Manufacturing Example 1) The following ingredients are used to manufacture the product in accordance with the "Tablets" section of the General Provisions of the Japanese Pharmacopoeia, and the product is made into tablets. Acetaminophen 900mg Fexofenadine hydrochloride 120 mg Dextromethorphan hydrobromide hydrate 48 mg dl-Methylephedrine hydrochloride 60mg Bromhexine hydrochloride 12 mg Belladonna total alkaloids 0.3 mg Glycyrrhizic acid 39mg Anhydrous caffeine 60mg Benfotiamine 24mg Appropriate amount of crystalline cellulose Carmellose calcium 10mg Hydroxypropylcellulose 5mg Magnesium stearate (trace amount)

[0083] (Formulation Example 2) Using the ingredients listed below, all ingredients except magnesium stearate were mixed, and then granulated to produce granules. Magnesium stearate was then added to these granules and enclosed in hard capsules to produce capsules. Pseudoephedrine hydrochloride 180 mg Phenylephrine hydrochloride 30mg Fexofenadine hydrochloride 120 mg Belladonna total alkaloids 0.3 mg Glycyrrhizic acid 45mg Anhydrous caffeine 100mg Benfotiamine 24mg Corn starch (appropriate amount) Lactose in moderation Appropriate amount of crystalline cellulose Carmellose calcium 20mg Hydroxypropylcellulose 15mg Magnesium stearate (trace amount)

[0084] (Manufacturing Example 3) The following ingredients are used to manufacture film-coated tablets in accordance with the "Tablets" section of the General Provisions of the Japanese Pharmacopoeia. Ibuprofen 600mg Fexofenadine hydrochloride 120 mg Dihydrocodeine phosphate 24 mg dl-Methylephedrine hydrochloride 60mg Ambroxol hydrochloride 48mg Belladonna total alkaloids 0.3 mg Glycyrrhizic acid 39mg Anhydrous caffeine 60mg Benfotiamine 24mg Appropriate amount of crystalline cellulose Carmellose calcium 20mg Hydroxypropylcellulose 15mg Magnesium stearate (trace amount) Hypromellose 20mg Macrogol 10mg Titanium dioxide 10mg Carnauba wax 7mg

[0085] (Formulation example 4) Using the ingredients listed below, all ingredients except magnesium stearate were mixed, and then granulated to produce granules. Magnesium stearate was then added to these granules and enclosed in hard capsules to produce capsules. Pseudoephedrine hydrochloride 180 mg Phenylephrine hydrochloride 30mg Fexofenadine hydrochloride 120 mg Tranexamic acid 420mg Glycyrrhizic acid 45mg Anhydrous caffeine 100mg Benfotiamine 24mg Corn starch (appropriate amount) Lactose in moderation Appropriate amount of crystalline cellulose Carmellose calcium 10mg Povidone (K30) 10mg Magnesium stearate (trace amount)

[0086] (Manufacturing example 5) The following ingredients are used to manufacture film-coated tablets in accordance with the "Tablets" section of the General Provisions of the Japanese Pharmacopoeia. Loxoprofen sodium (as anhydrous) 180 mg Tranexamic acid 750mg Fexofenadine hydrochloride 120 mg Dextromethorphan hydrobromide hydrate 48 mg dl-Methylephedrine hydrochloride 60mg Dihydrocodeine phosphate 24 mg Ambroxol hydrochloride 48mg Glycyrrhizic acid 39mg Anhydrous caffeine 60mg Benfotiamine 24mg Appropriate amount of crystalline cellulose Crospovidone 15mg Hydroxypropylcellulose 20mg Magnesium stearate (trace amount) Hypromellose 10mg Macrogol 6mg Titanium dioxide 10mg

[0087] (Manufacturing example 6) The following ingredients are used to manufacture film-coated tablets in accordance with the "Tablets" section of the General Provisions of the Japanese Pharmacopoeia. Ibuprofen 450mg Tranexamic acid 420mg Dihydrocodeine phosphate 24 mg Methyl ephedrine hydrochloride 60 mg Bromhexine hydrochloride 12 mg Fexofenadine hydrochloride 120 mg Belladonna total alkaloids 0.3 mg Anhydrous caffeine 75mg Appropriate amount of crystalline cellulose Croscarmellose sodium 20mg D-mannitol (appropriate amount) Hydroxypropylcellulose 10mg Magnesium stearate (trace amount) Hypromellose 9mg Macrogol 5mg Titanium dioxide 7mg Talc 10mg Carnauba wax 5mg

Claims

1. (a) Fexofenadine or a salt thereof; (b) Glycyrrhizic acid or a salt thereof; and (c) One or more selected from pseudoephedrine hydrochloride, pseudoephedrine sulfate, l-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, and dl-methylephedrine saccharin; Anti-inflammatory pharmaceutical compositions containing the above, excluding compositions containing phenylephrine hydrochloride and total belladonna alkaloids.

2. The pharmaceutical composition according to claim 1, wherein fexofenadine or a salt thereof is fexofenadine hydrochloride.

3. The pharmaceutical composition according to claim 1 or 2, wherein glycyrrhizic acid or a salt thereof is glycyrrhizic acid.

4. A pharmaceutical composition according to any one of claims 1 to 3, for the prevention or treatment of rhinitis.

5. A pharmaceutical composition according to any one of claims 1 to 3 for the relief of various symptoms of the common cold.

6. The pharmaceutical composition according to any one of claims 1 to 5, wherein the daily dose for adults of fexofenadine or a salt thereof is 1 mg to 200 mg, and the daily dose for adults of glycyrrhizic acid or a salt thereof is 1 mg to 300 mg.

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