Pharmaceutical composition containing fexofenadine and tranexamic acid

Abstract

To provide a pharmaceutical composition having excellent anti-inflammatory action.SOLUTION: A pharmaceutical composition contains (a) fexofenadine or salt thereof; (b) tranexamic acid or salt thereof; and (c) one or more selected from ephedrine or a derivative thereof 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 activity, which can be used as a general cold remedy or a remedy for rhinitis. [Background technology]

[0002] A general cold medicine is a generic term for medicines used to relieve cold symptoms such as runny nose, stuffy nose, fever, sore throat, cough, phlegm, sneezing, chills, headache, joint pain, muscle pain, etc. General cold medicines contain a variety of ingredients, such as antipyretic and analgesic ingredients, antihistamine ingredients, and antitussive ingredients, to relieve these symptoms.

[0003] Rhinitis medication is a general term for medicines used to relieve symptoms caused by acute rhinitis, allergic rhinitis, or sinusitis, such as runny nose, stuffy nose, sneezing, etc. Rhinitis medications contain a variety of ingredients, including antihistamines and anti-inflammatory ingredients, to relieve these symptoms.

[0004] Fexofenadine hydrochloride has a selective antihistamine H1 receptor antagonistic effect as its main action, and further has an inhibitory effect on the production of inflammatory cytokines, eosinophil migration, and chemical mediator release, and in Japan, it has been recognized to be effective against allergic rhinitis, urticaria, and pruritus associated with skin diseases (for example, see Non-Patent Document 1).

[0005] Tranexamic acid is known to have a hemostatic effect based on its antiplasmin action, and is effective against urticaria, stomatitis, and pharyngitis based on its anti-allergic and anti-inflammatory action.

[0006] At present, as a combination drug of fexofenadine or a salt thereof, a therapeutic drug for allergies that combines fexofenadine hydrochloride and pseudoephedrine hydrochloride is prescribed for medical use (see Non-Patent Document 2). In addition, although there are no general cold medicines on the market that contain fexofenadine or a salt thereof, tablets containing fexofenadine hydrochloride and tranexamic acid are known (see, for example, Patent Documents 1 and 2). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] JP 2013-151486 A [Patent Document 2] JP 2016-88853 A [Non-patent literature]

[0008] [Non-Patent Document 1] Allegra(R) Tablets 30mg Allegra(R) Tablets 60mg Allegra OD Tablets(R) 60mg Package insert [Non-Patent Document 2] Pharmaceutical Interview Form Dilegra(R) Combination Tablets Summary of the Invention [Problem to be solved by the invention]

[0009] An object of the present invention is to solve the above problems and to provide a pharmaceutical composition containing fexofenadine or a salt thereof having excellent anti-inflammatory activity. [Means for solving the problem]

[0010] As a result of intensive research to solve the above-mentioned problems, the inventors have found that a combination of fexofenadine or a salt thereof and tranexamic acid or a salt thereof, and further containing one or more of ephedrine or a derivative thereof or a salt thereof, and caffeine, exhibits an excellent anti-inflammatory effect, and have completed the present invention.

[0011] That is, the present invention relates to the following. [1] (a) Fexofenadine or a salt thereof; (b) tranexamic acid or a salt thereof; and (c) one or more selected from ephedrine or its derivatives or salts thereof, and caffeine; A pharmaceutical composition comprising: [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 the tranexamic acid or a salt thereof is tranexamic acid. [4] The pharmaceutical composition according to any one of [1] to [3], wherein ephedrine or a derivative thereof or a salt thereof is methylephedrine hydrochloride. [5] The pharmaceutical composition according to any one of [1] to [4], wherein the caffeine is anhydrous caffeine. [6] The pharmaceutical composition described in any one of [1] to [5], which is for anti-inflammatory purposes. [7] A pharmaceutical composition described in any one of [1] to [5], for the prevention or treatment of rhinitis. [8] A pharmaceutical composition described in any one of [1] to [5] for relieving cold symptoms. [9] The pharmaceutical composition according to any one of [1] to [8], wherein the daily dose of fexofenadine or a salt thereof to an adult is 1 mg to 200 mg, and the daily dose of tranexamic acid or a salt thereof to an adult is 100 mg to 3000 mg. Effect of the Invention

[0012] According to the present invention, a pharmaceutical composition having excellent anti-inflammatory activity can be provided. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] An embodiment of the present invention will be described below. The pharmaceutical composition of the present invention comprises: (a) fexofenadine or a salt thereof; (b) tranexamic acid or a salt thereof; and (c) one or more selected from ephedrine or its derivatives or salts thereof, and caffeine; A pharmaceutical composition comprising:

[0014] In the present invention, "fexofenadine or a salt thereof" 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.

[0015] In the present invention, the content of "fexofenadine or a salt thereof" is not particularly limited, and may be appropriately determined depending on the gender, age, symptoms, etc. of the recipient. For example, when the fexofenadine or a salt thereof 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.

[0016] In the present invention, "tranexamic acid or a salt thereof" means tranexamic acid or a salt of tranexamic acid. Examples of salts of tranexamic acid include mineral acid salts such as hydrochloride, nitrate, and sulfate, organic acid salts such as methanesulfonate, alkali metal salts such as sodium salt, potassium salt, calcium salt, and magnesium salt, and alkaline earth metal salts. The "tranexamic acid" used in the present invention is listed in the 17th revised Japanese Pharmacopoeia, is commercially available, and can be easily obtained.

[0017] In the present invention, the content of "tranexamic acid or a salt thereof" is not particularly limited, and may be appropriately determined depending on the gender, age, symptoms, etc. of the recipient. For example, in the case of tranexamic acid, the daily dose is usually 100 mg to 3000 mg, preferably 210 mg to 1500 mg, and more preferably 420 mg to 750 mg.

[0018] In the present invention, "ephedrine or a derivative thereof or a salt thereof" includes, for example, pseudoephedrine hydrochloride, pseudoephedrine sulfate, l-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, etc. These are known substances and can be produced by known methods, or commercially available products can be used.

[0019] In the present invention, the content of "ephedrine or its derivative or a salt thereof" is not particularly limited, and may be appropriately determined depending on the gender, age, symptoms, etc. of the person taking the drug. For example, when ephedrine or its derivative or a salt thereof is 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, when ephedrine or its derivative or a salt thereof is 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.

[0020] In the present invention, caffeine may be used in the form of caffeine hydrate, anhydrous caffeine, sodium caffeine benzoate, 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.

[0021] In the present invention, the content of "caffeine" is not particularly limited, and may be appropriately determined depending on the gender, age, symptoms, etc. of the person taking the caffeine. For example, when the caffeine is anhydrous caffeine, the daily amount is usually 1 mg to 1000 mg, preferably 75 mg to 600 mg, and more preferably 150 mg to 300 mg.

[0022] In the present invention, in addition to the above-mentioned components, other components that are usually used in general cold medicines or rhinitis medicines can be added as necessary within the scope that does not impair the effect.For example, the components described in the General Drug Manufacturing and Sales Approval Standards can be added.Specifically, one or more components selected from antipyretic analgesics, antihistamines, vasoconstrictors, antitussives, noscapines, bronchodilators, expectorants, anticholinergics, anti-inflammatory agents, vitamins, gastric mucosa protective agents, herbal medicines, hypnotics and sedatives, and Chinese herbal prescriptions can be added.

[0023] Examples of the antipyretic, anti-inflammatory, and analgesic agent that can be used include one or more components selected from aspirin, aspirin aluminum, acetaminophen, ethenzamide, sazapirin, salicylamide, lactylphenetidine, ibuprofen, isopropylantipyrine, rofecoxib sodium hydrate, prazolam, diclofenac sodium, mefenamic acid, indomethacin farnesyl, acemetacin, etodolac, naproxen, meloxicam, celecoxib, and tiaramide hydrochloride.

[0024] Examples of antihistamines include isothipendyl hydrochloride, difeterol hydrochloride, tripelennamine hydrochloride, thonzylamine hydrochloride, fenethazine hydrochloride, methdilazine hydrochloride, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, carbinoxamine diphenyldisulfonate, diphenylpyraline hydrochloride, diphenylpyraline theoclate, diphenhydramine hydrochloride, diphenhydramine salicylate, alimemazine tartrate, and tannins. One or more ingredients selected from diphenhydramine hydrochloride, triprolidine hydrochloride hydrate, mebhydroline napadisilate, promethazine methylene disalicylate, carbinoxamine maleate, difeterol phosphate, clemastine fumarate, mequitazine, ketotifen fumarate, promethazine hydrochloride, epinastine hydrochloride, emedastine fumarate, olopatadine hydrochloride, azelastine hydrochloride, and cetirizine hydrochloride may be blended.

[0025] As the vasoconstrictor, one or more components selected from methoxyphenamine hydrochloride, phenylephrine or a salt thereof (such as phenylephrine hydrochloride) can be blended.

[0026] The cough suppressant may contain one or more ingredients selected from, for example, alloclamide hydrochloride, cloperastine hydrochloride, cloperastine fendizoate, codeine phosphate hydrate, dihydrocodeine phosphate, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthaline salt, tipepidine citrate, tipepidine hibenzate, dibunate sodium, pentoxyverine citrate, dimemorfan phosphate, eprazinone hydrochloride, pentoxyverine citrate, benproperine phosphate, and clofedanol hydrochloride.

[0027] As the noscapine compound, for example, one or more components selected from noscapine, noscapine hydrochloride hydrate, and the like can be blended.

[0028] The bronchodilator may contain, for example, one or more components selected from aminophylline, diprophylline, theophylline, proxyphylline, trimetoquinol hydrochloride, phenylpropanolamine hydrochloride, methoxyphenamine hydrochloride, and isoprenaline hydrochloride.

[0029] The expectorant may contain one or more components 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, ammoniacal extract, cherry bark extract, methylcysteine ​​hydrochloride, and fudosteine.

[0030] As the anticholinergic agent, for example, ingredients such as belladonna total alkaloids and isopropamide iodide can be blended.

[0031] The anti-inflammatory agent may be one or more components selected from glycyrrhizinic acid, dipotassium glycyrrhizinate, glycyrrhetinic acid, serrapeptase, bromelain, semi-alkaline proteinase, pronase, seaprose, proctase, lysozyme hydrochloride, and the like.

[0032] Examples of vitamins include vitamin B1 and its derivatives and salts thereof, such as thiamine, thiamine chloride hydrochloride, thiamine nitrate, dicethiamine hydrochloride, setotiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octotiamine, shikotiamine, thiamine disulfide, bis-ibuthiamine, bis-bentiamine, prosultiamine, and benfotiamine; vitamin B2 and its derivatives and salts thereof, such as riboflavin, riboflavin phosphate, riboflavin butyrate, and riboflavin sodium phosphate; pantothenic acid, panthenol, panthenol, and panthenol. It is possible to blend one or more ingredients selected from the group consisting of vitamin B5 and its derivatives and their salts, such as vitamin B12, cyanocobalamin and mecobalamin, vitamin B2 and its derivatives and their salts, such as vitamin B3, vitamin B4 and its derivatives and their salts, such as vitamin B5, calcium pantothenate, and sodium pantothenate, vitamin B5 and its derivatives and their salts, such as vitamin B6, pyridoxine hydrochloride and pyridoxal phosphate, vitamin B12 and its derivatives and their salts, such as vitamin B12, cyanocobalamin and mecobalamin, vitamin C and its derivatives and their salts, such as ascorbic acid, sodium ascorbate, and calcium ascorbate, and hesperidin and its derivatives and their salts.

[0033] The gastric mucosa protecting agent may contain 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, co-precipitation product of aluminum hydroxide and sodium hydrogen carbonate, mixed dried gel of aluminum hydroxide and magnesium carbonate, co-precipitation product of aluminum hydroxide, magnesium carbonate and calcium carbonate, co-precipitation 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, sofalcone, gefarnate, teprenone, rebamipide, etc.

[0034] Herbal medicines include Ephedra, Nandina, Scutellaria, Onji, Licorice, Platycodon, Coptis, Coptis Root, Garlic, Senega, Fritillaria, Fennel, Phellodendron Bark, Coptis Rhizome, Zedoary, Chamomile, Cinnamon Bark, Gentian, Beou, Animal Gall (including Yutang), Shajin, Ginger, Atractylodes Root, Clove, Tangerine Peel, Atractylodes Root, Dioscorea Root, Carrot, Mallotus Japonicus, Epilachna, Corydalis Root, Scutellaria Root, Coptis Root, Valerian, Calonin, Apricot kernel, Lycium bark, Lycium chinense, Caulerpa chinense, Gennoshoko, It is possible to blend one or more ingredients selected from herbal medicines such as Magnolia officinalis, Gomizushi, Saishin, Zanthoxylum Root, Aster Root, Jikoppi, Peony Root, Musk, Cnidium Root, Zenko, Swertia britannica, Sophora Root, Perilla Root, Taisan, Touki, Ipecac, Bakumondou, Pinellia Root, Japanese Root, Cardamom Root, Angelica Root, Byakushi, Poria Root, Peony Root, Boletus Root, and Rokujo, as well as extracts thereof (extracts, tinctures, dried extracts, etc.).

[0035] As the hypnotic sedative, one or more components selected from bromvalerylurea, allylisopropylacetylurea, and the like can be blended.

[0036] The herbal prescription may contain one or more ingredients selected from Kakkonto, Kakkonto-ka-kikyo, Keishito, Kososan, Saiko-keishito, Sho-saikoto, Sho-seiryuto, Bakumondoto, Hange-koubokuto, Mao-to, and the like.

[0037] Furthermore, the pharmaceutical composition of the present invention may contain pharmaceutical additives necessary for producing the preparation, within the scope of not impairing the effects of the present invention. For example, the pharmaceutical additives may be those described in Yakushoku Shindan Hatsu 1204-1 (Pharmaceutical Affairs Administration Act), Pharmaceutical Additives Encyclopedia 2016 (edited by Japan Pharmaceutical Additives Association, Yakuji Nipposha), and the 8th Edition of Food Additives Official Specification (Japan Food Additives Association). Specifically, one or more components selected from excipients, binders, disintegrants, disintegration aids, flow agents, lubricants, plasticizers, coating agents, sugar coating agents, gloss agents, solvents, pH regulators, colorants, flavorings, sweeteners, flavorings, flavorings, and flavorings may be contained.

[0038] The excipients include candy powder, pregelatinized starch, isomalt, cacao butter, dried hydrolyzed starch, caramel, carmellose, carmellose calcium, carmellose sodium, hydrated silicon dioxide, hydrated amorphous silicon oxide, dried aluminum hydroxide gel, dried potato starch, licorice powder, dried magnesium sulfate, agar, agar powder, winter plum powder, xylitol, croscarmellose sodium, crospovidone, magnesium aluminosilicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, calcium silicate, kettle. Magnesium silicate, light anhydrous silicic acid, cinnamon powder, crystalline cellulose, crystalline cellulose / carmellose sodium, crystalline cellulose (microparticles), 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, magnesium alumina 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, white sugar, potato starch, microcrystalline cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose (2208), hypromellose (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 acetoacetate, 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, methacrylic acid copolymer LD, magnesium aluminometasilicate, methyl acrylate-methacrylic acid copolymer, methyl acrylate-methyl methacrylate, methyl cellulose, 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 blended.

[0039] Examples of binders include gum arabic, powdered gum arabic, agar, powdered agar, kanbai powder, crystalline cellulose, copolyvidone, gelatin, shellac, low-substituted hydroxypropyl cellulose, corn starch, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, vinylpyrrolidone-vinyl acetate copolymer, hypromellose (2208), hypromellose (2906), hypromellose (2910), hypromellose acetate succinate, hypromellose phthalate (200731 type), hypromellose phthalate (220824 type), It can contain one or more ingredients selected from the group consisting of methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, butyl methacrylate-methyl methacrylate copolymer, magnesium aluminometasilicate, and methylcellulose, etc., as well as polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified), polyvinyl alcohol-polyethylene glycol graft polymer, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, butyl methacrylate-methyl methacrylate copolymer, magnesium aluminometasilicate, and methylcellulose.

[0040] The disintegrant may be one or more components selected from pregelatinized starch, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, crospovidone, low-substituted sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, sodium starch glycolate, potato starch, hydroxypropyl starch, and partially pregelatinized starch.

[0041] The disintegration aid may be, for example, one or more components selected from carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, light anhydrous silicic acid, crystalline cellulose, sodium starch glycolate, and hydroxypropyl starch.

[0042] The fluidizing agent may be, for example, one or more components selected from hydrous silicon dioxide, light anhydrous silicic acid, crystalline cellulose, synthetic aluminum silicate, heavy anhydrous silicic acid, magnesium alumina hydroxide, calcium triphosphate, talc, corn starch, magnesium aluminometasilicate, and calcium hydrogen phosphate granules.

[0043] The lubricant may be one or more components selected from the group consisting of hydrated silicon dioxide, hydrated amorphous silicon oxide, glycerin fatty acid esters, magnesium silicate, light anhydrous silicic acid, hardened oil, heavy anhydrous silicic acid, sucrose fatty acid esters, stearyl alcohol, stearic acid, zinc stearate, aluminum stearate, calcium stearate, polyoxyl 40 stearate, magnesium stearate, soybean hardened oil, talc, sodium stearyl fumarate, beeswax, anhydrous silicic acid hydrate, magnesium aluminometasilicate, and glycerin monostearate.

[0044] As the plasticizer, one or more components selected from triethyl citrate, glycerin, glycerin fatty acid esters, medium-chain fatty acid triglycerides, 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, glycerin monostearate, isopropyl linoleate, and liquid paraffin can be blended.

[0045] Coating agents include ethyl acrylate-methyl methacrylate copolymer dispersion, acetyl glycerin fatty acid ester, aminoalkyl methacrylate copolymer E, gum arabic, powdered gum arabic, ammonioalkyl 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-8472, Opadry OY-S-8473 ... OY-S-9607, Opadry OY-S-22829, Opadry OY-S-22835, Opadry OY-S-22961, Opadry OY-S-28924, Opadry YS-1-7003 White, Opadry YS-1-12524-A, Opadry YS-1-14762-A, Opadry YS-1-15585-A, Opadry YS-1-19025A, Opadry YS-2-19114-A, Opadry II Yellow, Opadry Clear (YS-2-19114-A), Opadry II Grey 85F17659, Opadry 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 methacrylic acid 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 oxide,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, refined gelatin, refined shellac, refined white sugar, gelatin, shellac, D-sorbitol, D-sorbitol liquid, talc, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, concentrated glycerin, white shellac, white sugar , Paraffin, Hydroxypropylcellulose, Hydroxypropylmethylcellulose 2910-Titanium dioxide-Macrogol mixture, Hypromellose (2208), Hypromellose (2906), Hypromellose (2910), Hypromellose acetate succinate, Hypromellose phthalate (200731 type), Hypromellose phthalate (220824 type), 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, glycerin monostearate, sorbitan monostearate, sorbitan monolaurate,One or more components selected from calcium sulfate, DL-malic acid, etc. may be blended.

[0046] The sugar-coating agent may be one or more components selected from gum arabic, powdered gum arabic, ethyl cellulose, carnauba wax, carmellose sodium, crystalline cellulose, titanium oxide, stearic acid, polyoxyl 40 stearate, purified gelatin, purified shellac, refined sucrose, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, sucrose, hydroxypropyl cellulose, 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.

[0047] The glossing agent may be one or more components selected from carnauba wax, refined shellac, macrogol 400, macrogol 1500, macrogol 4000, macrogol 6000, beeswax, and the like.

[0048] As the solvent, one or more components selected from isopropanol, ethanol, glycerin, 1,3-butylene glycol, propylene glycol, macrogol, and the like can be blended.

[0049] The pH adjuster may be 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.

[0050] The coloring agent may be one or more components selected from yellow iron oxide, Yellow No. 5 premix, brown iron oxide, carbon black, caramel, β-carotene, licorice extract, black iron oxide, titanium oxide, iron sesquioxide, iron sesquioxide-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, sodium copper chlorophyllin, copper chlorophyll, riboflavin, riboflavin butyrate, riboflavin sodium phosphate, green tea powder, and rose oil.

[0051] Flavoring agents include erythritol, sodium chloride, Phellodendron bark powder, Phellodendron arborescens extract, Coptis japonica, Coptis japonica powder, Ononis root dried extract, orange, orange oil, cocoa powder, fructose, caramel, licorice, licorice extract, licorice crude 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, Japanese pepper tincture, Japanese pepper powder, tartaric acid, D-tartaric acid, potassium hydrogen tartrate, DL-sodium tartrate, ginger chinese pepper It is possible to blend one or more ingredients selected from the group consisting of ginger powder, sucralose, stevia extract, purified stevia extract, purified licorice extract powder, refined white sugar, Swertia bristle, Perilla japonica powder, D-sorbitol, Taurine, dried extract of the root and grass of Ardisia crenata, tannic acid, clove tincture, clove oil, tangerine tincture, capsicum, capsicum tincture, capsicum powder, spruce tincture, spruce powder, trehalose hydrate, bittern powder, plum extract, white sugar, fructooligosaccharides, powdered sugar, peppermint powder, maltose hydrate, D-mannitol, dl-menthol, l-menthol, menthol powder, ryunou, ryunou powder, green tea powder, DL-malic acid, DL-sodium malate, lemon oil, and rose oil.

[0052] The sweetening agent may be one or more components 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, saccharin sodium hydrate, sucralose, stevia extract, purified stevia extract, refined sucrose, refined sucrose spherical granules, sucrose, powdered reduced maltose syrup, maltitol, D-mannitol, and erythritol.

[0053] The flavoring may be one or more ingredients selected from orange flavor, orange flavor powder SH-1171-A, orange micron H-800092, guarana extract, flavor (sweet orange), flavor (strawberry), flavor (lemon), brown sugar flavor, strawberry essence, strawberry flavor B86173, cherry flavor 181612, dent mint 1148J, banana powder flavor, peach essence, cypress 6E-84211, black current flavor 290012SYM, fruit essence, peppermint NAEFCOPO551957685, peppermint micron H-81550, mixed flavor powder, melon powder flavor, l-menthol, and menthol L163592SYM.

[0054] Flavoring agents and fragrances 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, Himalayan. It is possible to blend one or more ingredients selected from the group consisting of ginger 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, ryunou, ryunou powder, lemon powder, lemon oil, rose water, rose oil, locust oil, and Roman chamomile oil.

[0055] The dosage form of the pharmaceutical composition of the present invention is not particularly limited, and examples thereof include oral preparations such as capsules, pills, granules, fine granules, powders, tablets, liquids, syrups, jellies, and lozenges, and parenteral preparations such as external liquids, ointments, creams, gel creams, poultices, transdermal preparations, patches, liniments, lotions, suppositories, eye drops, and nasal drops. Oral preparations, nasal drops, and eye drops are preferred, and oral preparations are more preferred, and solid preparations such as capsules, pills, granules, fine granules, powders, and tablets are even more preferred. These solid preparations may be coated with sugar coating, film coating, or the like by a known method, if necessary.

[0056] The pharmaceutical composition of the present invention can be prepared into the above-mentioned dosage form according to the method described in the 17th edition of the Japanese Pharmacopoeia, etc. For example, when the pharmaceutical composition of the present invention is in the form of a tablet, it can be manufactured in accordance with the section on "tablets" in the General Provisions of the Japanese Pharmacopoeia. When the pharmaceutical composition of the present invention is in the form of a granule, it can be manufactured in accordance with the section on "granules" in the General Provisions of the Japanese Pharmacopoeia. When the pharmaceutical composition of the present invention is a solid preparation, if the components specified in the present invention and other components and additives in such a solid preparation have problems with storage stability due to incompatibility with each other, the components can be appropriately prepared by dividing the components into granules, multi-layering, etc. so that they do not come into contact with each other.

[0057] When the dosage form of the pharmaceutical composition of the present invention is a solid preparation, it may be once packaged in SP packaging, PTP packaging, stick packaging, bottle packaging, etc. and then airtightly stored. Furthermore, these may be pillow-packaged, and these may be stored in a box or the like. The material used for the pillow packaging is not particularly limited, and for example, a resin film such as a polypropylene film, a polyethylene terephthalate film, a polyethylene film, or a resin film with aluminum foil attached thereto may be used. In addition, when hygroscopicity is a concern, a desiccant or the like may be stored simultaneously in the bottle packaging or pillow packaging.

[0058] The pharmaceutical composition of the present invention can be administered for anti-inflammatory purposes. Examples of diseases to which the anti-inflammatory pharmaceutical composition is applied include cold, rhinitis, eczema, urticaria, tonsillitis, pharyngitis, hemorrhoids, stomatitis, and relief of various symptoms associated with these diseases. That is, it can be used as a cold medicine, a nasal drop for rhinitis (allergic rhinitis, sinusitis, etc.), an insect bite, an anti-itching agent, a preventive and / or therapeutic agent for dermatitis, a medicine for athlete's foot and ringworm, and a preventive and / or therapeutic agent for symptoms such as itching in hemorrhoids, and a preventive and / or therapeutic agent for throat irritation, pain, etc. due to throat inflammation.

[0059] The pharmaceutical compositions of the present invention can be administered to relieve cold symptoms (fever, chills, headache, sore throat, runny nose, stuffy nose, cough, phlegm, joint pain, muscle pain, sneezing).

[0060] Furthermore, the pharmaceutical composition of the present invention can be administered for the prevention or treatment of rhinitis, particularly for the relief of various symptoms (runny nose, stuffy nose, sneezing) caused by acute rhinitis, allergic rhinitis caused by pollen, house dust (indoor dust), etc., or sinusitis.

[0061] Furthermore, the pharmaceutical composition of the present invention can be administered for the prevention and / or treatment of dermatitis, particularly for the prevention and / or treatment of skin itch, eczema, hives, dermatitis, and rash.

[0062] Examples and production examples are shown below, but the present invention is not limited to the following examples. EXAMPLES

[0063] (Test Example) Anti-inflammatory test for bradykinin-plasmin paw edema in rats 1-1. Test substances and inflammatory reagents In this test, methylcellulose manufactured by Shin-Etsu Chemical Co., Ltd., fexofenadine hydrochloride (hereinafter, fexofenadine) manufactured by Dipharma Inc., tranexamic acid manufactured by Daiichi Fine Chemical Co., Ltd., dl-methylephedrine hydrochloride (hereinafter, methylephedrine) manufactured by Alps Pharmaceutical Co., Ltd., and anhydrous caffeine (hereinafter, caffeine) manufactured by Shizuoka Caffeine Co., Ltd. were used. Bradykinin manufactured by Wako Pure Chemical Industries, Ltd., and Human Plasmin (hereinafter, plasmin) manufactured by Haemagtologic Technology Inc. were used. Each specimen was prepared by dissolving or suspending each test substance in 0.5% aqueous methylcellulose solution.

[0064] (Specimen) Group 0: Vehicle (0.5% methylcellulose) *Inflammatory control group Group 1: fexofenadine 0.3 mg / kg Group 2: tranexamic acid 100mg / kg Group 3: methylephedrine 110 mg / kg Group 4: caffeine 150mg / kg Group 5: fexofenadine 0.3 mg / kg + tranexamic acid 100 mg / kg + methylephedrine 110 mg / kg Group 6: fexofenadine 0.3 mg / kg + tranexamic acid 100 mg / kg + caffeine 150 mg / kg

[0065] (Inflammatory agent) 1 mg of bradykinin and 0.5 U of plasmin were dissolved in physiological saline to make up 20 mL.

[0066] 1-2. Test method Five-week-old male Crij:WI rats (Charles River Japan, Inc.) were quarantined for five days, and then allowed to acclimate for two to four days. After acclimatization, the rats were divided into groups (five rats per group) based on their body weights, and the test substance was orally administered using a probe. Thirty minutes later, 0.1 ml of bradykinin-plasmin solution was subcutaneously injected into the right hind footpad as an inflammation inducer to induce inflammation. The footpad volume of each rat was measured before grouping and 60 minutes after inflammation induction, and the edema rate, area under the curve, and inhibition rate were calculated using the formula described below.

[0067] 1-3. Measurement of paw volume and calculation of edema rate, area under the curve (AUC) and inhibition rate Before grouping, and 15, 30, 45, and 60 minutes after the onset of inflammation, the right hind paw volume (mL) was measured using a mouse / rat hind paw edema volume measuring device (TK-101CMP, Unicom Co., Ltd.). The edema rate was calculated for each individual from the paw volume before grouping and the paw volume at each measurement time using the following formula.

[0068]

number

[0069] In addition, for each individual, the area under the curve (AUC 0-1hr ) was calculated.

[0070]

number

[0071] a: Edema rate 15 minutes after onset b: Edema rate 30 minutes after the onset of inflammation c: Edema rate 45 minutes after the onset of inflammation d: Edema rate 60 minutes after onset

[0072] Furthermore, the AUC 0-1hr and AUC for each drug group (groups 1 to 6) 0-1hr From the values, the inhibition rate of each drug group was calculated using the following formula.

[0073]

number

[0074] 2. Test Results The test results are shown in Table 1. [Table 1]

[0075] In Table 1, compared with groups 1 to 4 in which fexofenadine, tranexamic acid, methylephedrine, and caffeine were administered alone, group 5 in which fexofenadine, tranexamic acid, and methylephedrine were administered in combination, and group 6 in which fexofenadine, tranexamic acid, and caffeine were administered in combination, the edema inhibition rate was significantly improved and a high anti-inflammatory effect was demonstrated.

[0076] A manufacturing example is shown below. The values ​​indicate the daily blend amount of the ingredients contained in the formulation.

[0077] (Formulation Example 1) The ingredients listed below were mixed with the ingredients other than magnesium stearate, and then granulated to produce granules. Magnesium stearate was then added to the granules, which were then filled into hard capsules to produce capsules. Pseudoephedrine hydrochloride 180mg Phenylephrine hydrochloride 30mg Fexofenadine hydrochloride 120mg Tranexamic acid 420mg Glycyrrhizic acid 45mg Caffeine anhydrous 100mg Benfotiamine 24mg Corn starch (as needed) Lactose in moderation Crystalline cellulose (appropriate amount) ECG505 Carmellose calcium 10mg Povidone (K30) 10mg Magnesium stearate trace amount

[0078] (Production Example 2) The following ingredients are used to prepare film-coated tablets in accordance with the "Tablets" section of the Japanese Pharmacopoeia General Provisions for Preparations. Loxoprofen sodium (as anhydrous) 180mg Tranexamic acid 750mg Fexofenadine hydrochloride 120mg Dextromethorphan hydrobromide hydrate 48mg dl-Methylephedrine hydrochloride 60mg Ambroxol hydrochloride 48mg Glycyrrhizic acid 39mg Caffeine anhydrous 60mg Benfotiamine 24mg Crystalline cellulose (appropriate amount) Crospovidone 15mg Hydroxypropyl cellulose 20mg Magnesium stearate trace amount Hypromellose 10mg Macrogol 6mg Titanium dioxide 10mg Carnauba wax 5mg

[0079] (Production Example 3) The following ingredients are used to prepare film-coated tablets in accordance with the "Tablets" section of the Japanese Pharmacopoeia General Provisions for Preparations. Ibuprofen 450mg Tranexamic acid 420mg Dihydrocodeine phosphate 24mg Methylephedrine hydrochloride 60mg Bromhexine hydrochloride 12mg Fexofenadine hydrochloride 120mg Belladonna total alkaloids 0.3mg Caffeine anhydrous 75mg Crystalline cellulose (appropriate amount) Croscarmellose sodium 20mg D-mannitol (appropriate amount) Hydroxypropyl cellulose 10mg Magnesium stearate 5mg Hypromellose 9mg Macrogol 5mg Titanium dioxide 7mg Talc 10mg

[0080] (Production Example 4) The following ingredients are used to prepare film-coated tablets in accordance with the "Tablets" section of the Japanese Pharmacopoeia General Provisions for Preparations. Fexofenadine hydrochloride 120mg Tranexamic acid 420mg Caffeine anhydrous 100mg Crystalline cellulose 150mg Croscarmellose sodium 20mg Hydroxypropyl cellulose 5mg Magnesium stearate 10mg Hypromellose 20mg Titanium dioxide 4mg Macrogol 2mg Talc 2mg

[0081] (Reference example 1) The following ingredients are used to prepare film-coated tablets in accordance with the "Tablets" section of the Japanese Pharmacopoeia General Provisions for Preparations. Fexofenadine hydrochloride 120mg Tranexamic acid 420mg Crystalline cellulose 120mg Croscarmellose sodium 15mg Hydroxypropyl cellulose 10mg Magnesium stearate 8mg Hypromellose 20mg Titanium dioxide 4mg Macrogol 2mg Talc 2mg

Claims

1. (a) fexofenadine or a salt thereof; (b) tranexamic acid or a salt thereof; and (c) caffeine; An anti-inflammatory pharmaceutical composition comprising The following components (A) and (B): (A) one or more selected from the group consisting of fexofenadine and solvates thereof; (B) one or more selected from the group consisting of the following components (B-1) to (B-2): (B-1) Phenethylamines (B-2) Tropane alkaloids The present invention excludes a pharmaceutical product in which a pharmaceutical composition containing the above is contained in an airtight package.

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

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

4. 4. The pharmaceutical composition according to claim 1, wherein the caffeine is anhydrous caffeine.

5. The pharmaceutical composition according to any one of claims 1 to 4, which is for the prevention or treatment of rhinitis.

6. A pharmaceutical composition according to any one of claims 1 to 4 for relieving cold symptoms.

7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the daily dose of fexofenadine or a salt thereof for an adult is 1 mg to 200 mg, and the daily dose of tranexamic acid or a salt thereof for an adult is 100 mg to 3000 mg.

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