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 effects that can be used as a general cold medicine or a medicine for rhinitis.

Background Art

[0002] A general cold medicine is a generic term for pharmaceuticals used for the purpose of alleviating various symptoms of a cold, such as runny nose, nasal congestion, fever, sore throat, 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, and cough suppressant components to alleviate these symptoms.

[0003] A medicine for rhinitis is a generic term for pharmaceuticals used for the purpose of 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 histamine 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 (see, for example, Non-Patent Document 1).

[0005] Tranexamic acid is known for its hemostatic effect based on its antifibrinolytic action and its effects on urticaria, stomatitis, and pharyngitis based on its anti-allergic and anti-inflammatory actions.

[0006] Currently, as a formulation containing fexofenadine or its salt, a therapeutic agent for allergic diseases combining fexofenadine hydrochloride and pseudoephedrine hydrochloride is prescribed for medical use (see Non-Patent Document 2). Moreover, although there is no over-the-counter cold medicine containing fexofenadine or its salts, tablets containing fexofenadine hydrochloride and tranexamic acid (see, for example, Patent Documents 1 and 2) are known.

Prior Art Documents

Patent Documents

[0007]

Patent Document 1

Patent Document 2

Non-Patent Documents

[0008]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0009] An object of the present invention is to provide a pharmaceutical composition containing fexofenadine or its salt having an excellent anti-inflammatory action, which solves such problems.

Means for Solving the Problems

[0010] As a result of intensive studies to solve the above problems, the present inventors have found that a combination of fexofenadine or its salt and tranexamic acid or its salt, further containing one or more of ephedrine or its derivative or their salts, or caffeine, exhibits an excellent anti-inflammatory effect, and 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 a derivative thereof or a salt thereof, and caffeine; A pharmaceutical composition containing the same. [2] The pharmaceutical composition according to [1], wherein the 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 the ephedrine or a derivative thereof or a salt thereof is methyl ephedrine hydrochloride. [5] The pharmaceutical composition according to any one of [1] to [4], wherein the caffeine is anhydrous caffeine. [6] The pharmaceutical composition according to any one of [1] to [5], which is for anti-inflammatory use. [7] The pharmaceutical composition according to any one of [1] to [5], which is for the prevention or treatment of rhinitis. [8] The pharmaceutical composition according to any one of [1] to [5], for the relief of various symptoms of a cold. [9] The pharmaceutical composition according to any one of [1] to [8], 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.

Advantages of the Invention

[0012] According to the present invention, a pharmaceutical composition having excellent anti-inflammatory effects can be provided.

Modes for Carrying Out the Invention

[0013] Embodiments of the present invention will be described below. The pharmaceutical composition of the present invention is (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 their salts, and caffeine; A pharmaceutical composition containing the same.

[0014] In the present invention, "fexofenadine or its salt" includes, for example, fexofenadine, fexofenadine hydrochloride, etc. These are known compounds, which can be produced by known methods, and commercially available products can also be used.

[0015] In the present invention, the content of "fexofenadine or its salt" is not particularly limited and may be appropriately considered and determined according to the gender, age, symptoms, etc. of the user. For example, when 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.

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

[0017] In the present invention, the content of "tranexamic acid or its salt" is not particularly limited and may be appropriately considered and determined according to the gender, age, symptoms, etc. of the user. 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, the "ephedrine or its derivative or their salts" include, for example, pseudoephedrine hydrochloride, pseudoephedrine sulfate, l-methyl ephedrine hydrochloride, dl-methyl ephedrine hydrochloride, dl-methyl ephedrine saccharin salt and the like. These are known substances and can be produced by known methods, and commercially available products can also be used.

[0019] In the present invention, the content of the "ephedrine or its derivative or their salts" is not particularly limited and may be appropriately considered and determined according to the sex, age, symptoms, etc. of the user. For example, when the ephedrine or its derivative or their salts are dl-methyl ephedrine 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. Further, when the ephedrine or its derivative or their salts 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.

[0020] In the present invention, as the caffeine, caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate can be used, anhydrous caffeine and caffeine hydrate are preferred, and anhydrous caffeine is particularly preferred. Anhydrous caffeine and caffeine hydrate are included in the 17th revised Japanese Pharmacopoeia.

[0021] In the present invention, the content of the "caffeine" is not particularly limited and may be appropriately considered and determined according to the sex, age, symptoms, etc. of the user. For example, when 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.

[0022] In the present invention, in addition to the above-described components, other components that are usually used in general cold medicines or nasal congestion medicines can be blended as needed within a range that does not impair the effects. For example, components described in the manufacturing and selling approval standards for general pharmaceuticals can be blended. Specifically, one or more components selected from antipyretic analgesics, antihistamines, vasoconstrictors, antitussives, noscapines, bronchodilators, expectorants, anticholinergics, anti-inflammatory agents, vitamins, gastric mucosal protectants, crude drugs, hypnotic sedatives, and Kampo prescriptions can be blended.

[0023] As the antipyretic anti-inflammatory analgesic, for example, one or more components selected from aspirin, aluminum aspirin, acetaminophen, ethenzamide, salsalate, salicylamide, lactylphenetidine, ibuprofen, isopropylantipyrine, loxoprofen sodium hydrate, pranoprofen, diclofenac sodium, mefenamic acid, indomethacin farnesyl, acemetacin, etodolac, naproxen, meloxicam, celecoxib, and tiaramide hydrochloride can be blended.

[0024] As the antihistamine, for example, one or more components selected from isothipendyl hydrochloride, diphenhydramine hydrochloride, tripelennamine hydrochloride, tonzylamine hydrochloride, phenetidine hydrochloride, methdilazine hydrochloride, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, carbinoxamine diphenyl disulfonate, diphenylpyraline hydrochloride, diphenylpyraline theoclate, diphenhydramine hydrochloride, diphenhydramine salicylate, alimemazine tartrate, diphenhydramine tannate, triprolidine hydrochloride hydrate, mebhydroline napadisilate, promethazine methylene disalicylate, carbinoxamine maleate, diphenhydramine phosphate, clemastine fumarate, mequitazine, ketotifen fumarate, promethazine hydrochloride, epinastine hydrochloride, emedastine fumarate, olopatadine hydrochloride, azelastine hydrochloride, and cetirizine hydrochloride can be blended.

[0025] As the vasoconstrictor, one or more components selected from methoxyphenamine hydrochloride, phenylephrine or its salts (such as phenylephrine hydrochloride, etc.) can be formulated.

[0026] As the antitussive agent, for example, one or more components selected from allokramide hydrochloride, cloperastine hydrochloride, cloperastine fendizoate, codeine phosphate hydrate, dihydrocodeine phosphate, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthalein salt, tipepidine citrate, tipepidine hibenzate, dibunate sodium, pentoxyverine citrate, dimemorfan phosphate, eplazinone hydrochloride, pentoxyverine citrate, benproperine phosphate, and clofedanol hydrochloride, etc. can be formulated.

[0027] As the noscapines, for example, one or more components selected from noscapine, noscapine hydrochloride hydrate, etc. can be formulated.

[0028] As the bronchodilator, for example, one or more components selected from aminophylline, diprophylline, theophylline, proxiphylline, trimethoquinol hydrochloride, phenylpropanolamine hydrochloride, methoxyphenamine hydrochloride, and isoprenaline hydrochloride, etc. can be formulated.

[0029] As the expectorant, for example, one or more components selected from guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, bromhexine hydrochloride, l-carbocysteine, l-ethylcysteine hydrochloride, l-methylcysteine hydrochloride, ambroxol hydrochloride, ammonium chloride, l-menthol, ammonia wikyo essence, cherry bark extract, methylcysteine hydrochloride, and fudosteine, etc. can be formulated.

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

[0031] As the anti-inflammatory agent, one or more components selected from glycyrrhizic acid, dipotassium glycyrrhizinate, glycyrrhetinic acid, serrapeptase, bromelain, semi-alkali protease, pronase, seaprase, proctase, and lysozyme hydrochloride can be formulated.

[0032] As the vitamins, for example, vitamin B1 and its derivatives and their salts such as thiamine, thiamine chloride hydrochloride, thiamine nitrate, dithiothiamine hydrochloride, cetotiamine hydrochloride, furfurylthiamine, furfurylthiamine hydrochloride, octotiamine, ciclotiamine, thiamine disulfide, bisibuthiamine, bisbentiamine, prosultiamine, and benfotiamine; vitamin B2 and its derivatives and their salts such as riboflavin, riboflavin phosphate ester, riboflavin butyrate ester, and sodium riboflavin phosphate; vitamin B5 and its derivatives and their salts such as pantothenic acid, panthenol, pantethine, calcium pantothenate, and sodium pantothenate; vitamin B6 and its derivatives and their salts such as pyridoxine hydrochloride and pyridoxal phosphate ester; vitamin B12 and its derivatives and their salts such as 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, etc. One or more components selected therefrom can be formulated.

[0033] As gastric mucosal protectants, one or more components selected from glycine, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate (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, coprecipitate of aluminum hydroxide, magnesium carbonate and calcium carbonate, coprecipitation product of magnesium hydroxide and potassium aluminum sulfate, magnesium carbonate, magnesium aluminometasilicate, aldioxa, sodium copper chlorophyllin, potassium copper chlorophyllin, methylmethionium sulfonium chloride, sucralfate, cetraxate hydrochloride, sophorae flavescentis radix, gefarnate, teprenone, and rebamipide, etc. can be formulated.

[0034] As crude drugs, one or more components selected from Cortex Phellodendri, Nantenjitsu, Cinnamomi Ramulus, Angelicae Gigantis Radix, Glycyrrhizae Radix, Platycodonis Radix, Schizonepetae Herba, Schizonepetae Spica, Lycoris radiata Herb, Senega Root, Baimo, Wikyō, Oubaku, Ouren, Gajutsu, Chamomillae Flos, Cinnamomi Cortex, Gentianae Radix, Gōō, Fel Ursi (including Yutan), Shajin, Zingiberis Rhizoma, Sōjutsu, Caryophylli Flos, Chinpi, Byakujutsu, Jiryū, Ginseng Radix, Carotae Radix, Aceris Cortex, Aconiti Radix, Rhizoma Alismatis, Polygonati Rhizoma, Ougon, Ousei, Canocoso, Karonin, Kyōnin, Kukoshi, Kukoyō, Keigai, Ketsumeishi, Gen'noshōko, Kōbushi, Gomishi, Saishin, Sanshō, Shion, Dikoppi, Paeoniae Radix Alba, Jakō, Shin'i, Senkyū, Zenkō, Senburi, Sōhakuhi, Soyo, Taisan, Toki, Tokon, Bakumondō, Hangē, Bunkōka, Hanpi, Byakushi, Bukuryō, Botampi, Borei, Rokujō, etc. crude drugs and extracts (extracts, tinctures, dried extracts, etc.) thereof can be formulated.

[0035] As hypnotics and sedatives, one or more components selected from bromovalerylurea, and allylisopropylacetylurea, etc. can be formulated.

[0036] As a Kampo prescription, one or more components selected from the group consisting of Keishito, Keishito plus Kikyo, Keishi-to, Kososhisan, Saiko-Keishi-to, Sho-saikoto, Shokeishuto, Baikamuto, Hanpeito, and Ephedra Decoction can be formulated.

[0037] Furthermore, in the pharmaceutical composition of the present invention, pharmaceutical additives necessary for manufacturing the preparation can be formulated within a range that does not impair the effects of the present invention. For example, the pharmaceutical additives can be those described in Pharmaceutical and Food Sanitation Council Notice No. 1204 (Pharmaceutical Affairs Administrative Ordinance), Pharmaceutical Additive Dictionary 2016 (edited by the Japan Pharmaceutical Additives Association, Yakujitsu Shimbunsha), and the 8th Edition of the Official Monograph on Food Additives (Japan Food Additives Association). Specifically, one or more components selected from the group consisting of excipients, binders, disintegrants, disintegration aids, fluidizing agents, lubricants, plasticizers, coating agents, sugar coating agents, polishing agents, solvents, pH adjusters, colorants, flavor correctives, sweeteners, fragrances, flavoring agents, and perfumes can be formulated.

[0038] Excipients include: maltose powder, pregelatinized starch, isomalt, cocoa butter, hydrolyzed starch dried product, caramel, carmellose, calcium carmellose, sodium carmellose, hydrated silicon dioxide, hydrated amorphous silicon dioxide, dried aluminum hydroxide gel, dried potato starch, licorice powder, dried magnesium sulfate, agar, agar powder, ume powder, xylitol, croscarmellose sodium, crospovidone, magnesium aluminum silicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, calcium silicate, magnesium silicate, light anhydrous silicic acid, cinnamon powder, crystalline cellulose, crystalline cellulose - sodium carmellose, crystalline cellulose (fine particles), crystalline cellulose (granules), synthetic aluminum silicate, synthetic aluminum silicate - hydroxypropyl starch - crystalline cellulose, synthetic hydrotalcite, wheat starch, rice flour, glutinous rice starch, β - cyclodextrin, heavy anhydrous silicic acid, magnesium aluminum hydroxide, aluminum hydroxide gel, aluminum hydroxide - sodium hydrogen carbonate coprecipitate, aluminum hydroxide - magnesium carbonate - calcium carbonate coprecipitate, magnesium hydroxide, D - sorbitol, talc, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, sodium carboxymethyl starch of low substitution degree, hydroxypropyl cellulose of low substitution degree, sodium starch glycolate, corn starch, granulated corn starch, trehalose hydrate, silicon dioxide, lactose hydrate, granulated lactose, nonpareil, granulated sugar, potato starch, microcrystalline cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose (2208), hypromellose (2906), hypromellose (2910), hypromellose phthalate (type 200731), hypromellose phthalate (type 220824), fine particle silicon dioxide, partial 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-silica hydrate mixture, silicic anhydride 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, etc. can be formulated.

[0039] As the binder, for example, one or more components selected from gum arabic, powdered gum arabic, agar, powdered agar, loquat powder, crystalline cellulose, copovidone, gelatin, shellac, low-substituted hydroxypropyl cellulose, corn starch, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, vinyl pyrrolidone-vinyl acetate copolymer, hypromellose (2208), hypromellose (2906), hypromellose (2910), hypromellose acetate succinate, hypromellose phthalate (type 200731), hypromellose phthalate (type 220824), fumaric acid-stearic acid-polyvinyl acetal diethylaminoacetate-hydroxypropyl cellulose 2910 mixture, pullulan, povidone (K25), povidone (K30), povidone (K90), 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 methyl cellulose, etc. can be blended.

[0040] As the disintegrant, for example, 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, etc. can be blended.

[0041] As the disintegration aid, 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, etc. can be blended.

[0042] As fluidizing agents, for example, one or more components selected from hydrated silicon dioxide, light anhydrous silicic acid, crystalline cellulose, synthetic aluminum silicate, heavy anhydrous silicic acid, aluminum magnesium hydroxide, tricalcium phosphate, talc, corn starch, magnesium aluminometasilicate, and calcium hydrogen phosphate granules can be blended.

[0043] As lubricants, for example, one or more components selected from hydrated silicon dioxide, hydrated amorphous silicon oxide, glycerin fatty acid ester, magnesium silicate, light anhydrous silicic acid, hardened 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 glycerin monostearate can be blended.

[0044] As plasticizers, for example, one or more components selected from triethyl citrate, glycerin, glycerin fatty acid ester, medium-chain fatty acid 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, glycerin monostearate, isopropyl linoleate, and liquid paraffin can be blended.

[0045] Examples of coating agents include ethyl acrylate-methyl methacrylate copolymer dispersion, acetyl glycerin fatty acid ester, aminoalkyl methacrylate copolymer E, gum arabic, gum arabic powder, 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-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 gray 85F17659, Opadry white 03K280000, 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, hydrous silicon dioxide, dry aluminum hydroxide gel, dry methacrylic acid copolymer LD, triethyl citrate, glycerin, glycerin fatty acid ester, magnesium silicate, light anhydrous silicic acid, hydroxypropyl cellulose containing light anhydrous silicic acid, 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, 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, Hydroxypropyl Cellulose, Hydroxypropyl Methylcellulose 2910-Titanium Oxide-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-Hydroxypropyl Methylcellulose 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 4000, Macrogol 6000, Macrogol 6000 EP, Macrogol 20000, Macrogol 35000, D-Mannitol, Anhydrous Citric Acid, Anhydrous Silica 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, Glycerol Monostearate, Sorbitan Monostearate, Sorbitan Monolaurate,One or more components selected from calcium sulfate, DL-malic acid, etc. can be blended.

[0046] As the sugar coating agent, one or more components selected from gum arabic, powdered gum arabic, ethyl cellulose, carnauba wax, sodium carboxymethyl cellulose, crystalline cellulose, titanium oxide, stearic acid, polyoxyl 40 stearate, purified gelatin, purified shellac, purified 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, etc. can be blended.

[0047] As the brightening agent, one or more components selected from carnauba wax, purified shellac, macrogol 400, macrogol 1500, macrogol 4000, macrogol 6000, and beeswax, etc. can be blended.

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

[0049] As the pH adjuster, one or more components selected from hydrochloric acid, acetic acid, phosphoric acid, lactic acid, citric acid, succinic acid, tartaric acid, sodium hydrogen carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, and triethanolamine, etc. can be blended.

[0050] As the coloring agent, one or more components selected from iron oxide yellow, Yellow No. 5 premix, iron oxide brown, carbon black, caramel, β-carotene, licorice extract, iron oxide black, 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, sodium riboflavin phosphate, green tea powder, and rose oil, etc. can be blended.

[0051] As the flavoring agent, one or more components selected from erythritol, sodium chloride, cinnamon powder, aconite extract, magnolia bark, magnolia bark powder, dried extract of ononis root, 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-glutamic acid L-arginine, L-glutamic acid hydrochloride, sodium L-glutamate, grapefruit extract, brown sugar, cinnamon tincture, cinnamon powder, cinnamon oil, kombu powder, saccharin, sodium saccharin hydrate, saffron, saffron tincture, sansho tincture, sansho powder, tartaric acid, D-tartaric acid, potassium hydrogen tartrate, DL-sodium tartrate, ginger tincture, ginger powder, sucralose, stevia extract, purified stevia extract, purified licorice extract powder, refined sugar, assemblage, perilla powder, D-sorbitol, taiso powder, taurine, dried extract of taraxacum root and herb, tannic acid, clove tincture, clove oil, chinpi tincture, capsicum, capsicum tincture, capsicum powder, torreya tincture, torreya powder, trehalose hydrate, bitter orange powder, ume flesh extract, granulated sugar, fructooligosaccharide, powdered sugar, peppermint powder, maltose hydrate, D-mannitol, dl-menthol, l-menthol, menthol powder, borneol, borneol powder, green tea powder, DL-malic acid, DL-sodium malate, lemon oil, and rose oil, etc. can be blended.

[0052] As sweeteners, 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, sodium saccharin hydrate, sucralose, stevia extract, purified stevia extract, refined sugar, refined sugar spherical granules, granulated sugar, powdered reduced maltose syrup, maltitol, D-mannitol, and erythritol, etc. can be blended.

[0053] As flavors, one or more components 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, hinoki 6E-84211, blackcurrant flavor 290012SYM, fruit essence, peppermint NAEFCOPO551957685, peppermint micron H-81550, mixed flavor powder, melon powder flavor, l-menthol, and menthol L163592SYM, etc. can be blended.

[0054] As the fragrance agent and perfume, one or more components selected from the group consisting of wikyo powder, wikyo 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, torreya tincture, torreya oil, pine oil, peppermint oil, vanilla flavor, vanilla, bitter essence, vita base, Himalayan cedar oil, fruit flavor, flavor G1, hesperidin peppermint essence, bergamot oil, bergamot flavor, d-borneol, dl-borneol, matcha, mixed flavor, mint flavor, dl-menthol, l-menthol, eucalyptus oil, lavender oil, dragon's blood, dragon's blood powder, lemon powder, lemon oil, rose water, rose oil, carrot oil, and Roman chamomile oil can be blended.

[0055] The dosage form of the pharmaceutical composition of the present invention is not particularly limited. For example, oral administration preparations such as capsules, pills, granules, fine granules, powders, tablets, liquids, syrups, jellies, and troches, and parenteral administration preparations such as external liquids, ointments, creams, gel creams, poultices, transdermal absorption type preparations, patches, liniments, lotions, suppositories, eye drops, and nasal drops can be mentioned. Oral administration preparations, nasal drops or eye drops are preferred, oral administration 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, etc. by known methods if necessary.

[0056] The pharmaceutical composition of the present invention can be formulated into the dosage forms mentioned above according to the methods described in the 17th revised Japanese Pharmacopoeia and the like. For example, when the dosage form of the pharmaceutical composition of the present invention is a tablet, it can be manufactured according to the section on "Tablets" in the General Rules for Pharmaceutical Preparations of the Japanese Pharmacopoeia. Also, when the dosage form of the pharmaceutical composition of the present invention is a granule, it can be manufactured according to the section on "Granules" in the General Rules for Pharmaceutical Preparations of the Japanese Pharmacopoeia. In addition, when the pharmaceutical composition of the present invention is a solid preparation, if there are problems with storage stability, etc. due to issues such as incompatibility between the components defined in the present invention and other components / additives in such solid preparations, it can be formulated so that they do not come into contact with each other by appropriate granulation, multi-layer formation, etc.

[0057] When the dosage form of the pharmaceutical composition of the present invention is a solid preparation, it may be once packaged by SP packaging, PTP packaging, stick packaging, bottle packaging, etc. and stored airtight. Furthermore, they may be pillow-packaged, and they may be stored in a box 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 those with an aluminum foil attached to these resin films can be used. In addition, when there are concerns about hygroscopicity, a desiccant or the like may be stored simultaneously inside the bottle packaging or the pillow packaging.

[0058] 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 colds, rhinitis, eczema, urticaria, tonsillitis, pharyngitis, hemorrhoid diseases, stomatitis, and alleviation of various symptoms associated with these diseases. That is, it can be used as a cold medicine, a nasal drop for rhinitis (such as allergic rhinitis, sinusitis, etc.), a medicine for mosquito bites and itching, a preventive and / or therapeutic medicine for dermatitis, a medicine for athlete's foot and scabies, a preventive and / or therapeutic medicine for symptoms such as itching in hemorrhoid diseases, and a preventive and / or therapeutic medicine for symptoms such as throat soreness and pain due to throat inflammation.

[0059] The pharmaceutical composition of the present invention can be administered to relieve various symptoms of a cold (fever, chill, headache, throat pain, runny nose, nasal congestion, 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, and in particular, for the alleviation of various symptoms (runny nose, nasal congestion, sneezing) caused by allergic rhinitis or sinusitis due to acute rhinitis, pollen, house dust (indoor dust), etc.

[0061] 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 skin itching, eczema, urticaria, dermatitis, and burns.

[0062] Hereinafter, examples and production examples will be shown, but the present invention is not limited to the following examples.

Examples

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

[0064] (Specimen) Group 0: Vehicle (0.5% methylcellulose) ※ Inflammation induction control group Group 1: Fexofenadine 0.3 mg / kg Group 2: Tranexamic acid 100 mg / kg Group 3: Methylphentermine 110 mg / kg Group 4: Caffeine 150 mg / kg Group 5: Fexofenadine 0.3 mg / kg + Tranexamic acid 100 mg / kg + Methylphentermine 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 20 mL.

[0066] 1-2. Test method Five-week-old Crij:WI male rats [Charles River Laboratories Japan, Inc.] were given a 5-day quarantine period and then acclimated for 2 to 4 days. After acclimation, they were grouped (5 rats per group) using the body weight measurement results, and the test substance was orally administered using a probe. Thirty minutes later, 0.1 mL of a bradykinin-plasmin solution as an inflammatory agent was subcutaneously injected into the right hind paw to induce inflammation. The paw volume was measured for each individual before grouping and 60 minutes after inflammation induction, and the edema rate, area under the curve, and inhibition rate were calculated using the following formulas.

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

[0068] [Equation]

[0069] Furthermore, for each individual, the area under the curve (AUC 0-1hr ) was calculated from the edema rate at each time using the following formula.

[0070]

Number

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

[0072] Furthermore, the AUC 0-1hr value of the inflammation control group (Group 0) and the AUC 0-1hr values of each drug group (Groups 1 - 6) were used to calculate the inhibition rate of each drug group 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 - 4 in which pheniramine, tranexamic acid, methyl ephedrine, and caffeine were administered alone, Group 5 in which methyl ephedrine was combined with pheniramine and tranexamic acid, and Group 6 in which caffeine was combined with pheniramine and tranexamic acid showed a significantly improved inhibition rate of edema and exhibited a high anti - inflammatory effect.

[0076] Manufacturing examples are shown below. Note that the numerical values indicate the daily dosage of the components contained in the preparation.

[0077] (Formulation Example 1) Using the following components, the components other than magnesium stearate were mixed and then granulated to produce granules. Further, magnesium stearate was added to the granules and encapsulated in hard capsules to produce a capsule preparation. Pseudoephedrine hydrochloride 180 mg 30 mg of phenylpropanolamine hydrochloride 120 mg of pheniramine maleate 420 mg of tranexamic acid 45 mg of glycyrrhizic acid 100 mg of anhydrous caffeine 24 mg of benfotiamine Appropriate amount of corn starch Appropriate amount of lactose Appropriate amount of crystalline cellulose 10 mg of croscarmellose calcium (ECG505) 10 mg of povidone (K30) Trace amount of magnesium stearate

[0078] (Production Example 2) Using the following components, it is manufactured according to the section "Tablets" of the General Rules for Pharmaceutical Preparations of the Japanese Pharmacopoeia to obtain film-coated tablets. 180 mg of loxoprofen sodium (as anhydrous) 750 mg of tranexamic acid 120 mg of pheniramine maleate 48 mg of dextromethorphan hydrobromide hydrate 60 mg of dl-methylephedrine hydrochloride 48 mg of ambroxol hydrochloride 39 mg of glycyrrhizic acid 60 mg of anhydrous caffeine 24 mg of benfotiamine Appropriate amount of crystalline cellulose 15 mg of crospovidone 20 mg of hydroxypropyl cellulose Trace amount of magnesium stearate 10 mg of hypromellose 6 mg of macrogol 10 mg of titanium oxide 5 mg of carnauba wax

[0079] (Production Example 3) Using the following components, it is manufactured according to the section "Tablets" of the General Rules for Pharmaceutical Preparations of the Japanese Pharmacopoeia to obtain film-coated tablets. Ibuprofen 450 mg Tranexamic acid 420 mg Dihydrocodeine phosphate 24 mg Methylephedrine hydrochloride 60 mg Bromhexine hydrochloride 12 mg Fexofenadine hydrochloride 120 mg Belladonna total alkaloids 0.3 mg Caffeine anhydrous 75 mg Crystalline cellulose q.s. Croscarmellose sodium 20 mg D-Mannitol q.s. Hydroxypropyl cellulose 10 mg Magnesium stearate 5 mg Hypromellose 9 mg Macrogol 5 mg Titanium oxide 7 mg Talc 10 mg

[0080] (Production Example 4) Using the following components, manufacture according to the section "Tablets" in the General Rules of Japanese Pharmacopoeia Preparations to obtain film-coated tablets. Fexofenadine hydrochloride 120 mg Tranexamic acid 420 mg Caffeine anhydrous 100 mg Crystalline cellulose 150 mg Croscarmellose sodium 20 mg Hydroxypropyl cellulose 5 mg Magnesium stearate 10 mg Hypromellose 20 mg Titanium oxide 4 mg Macrogol 2 mg Talc 2 mg

[0081] (Reference Example 1) Using the following components, manufacture according to the section "Tablets" in the General Rules of Japanese Pharmacopoeia Preparations to obtain film-coated tablets. Fexofenadine hydrochloride 120 mg Tranexamic acid 420 mg Crystalline cellulose 120 mg Croscarmellose sodium 15 mg Hydroxypropyl cellulose 10 mg Magnesium stearate 8 mg Hypromellose 20 mg Titanium dioxide 4 mg Macrogol 2 mg Talc 2 mg

Claims

1. (a) fexofenadine or a salt thereof; (b) tranexamic 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; 2. An anti-inflammatory pharmaceutical composition comprising the compound, except for a pharmaceutical composition comprising Datura extract, 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. The pharmaceutical composition according to any one of claims 1 to 3, which is for the prevention or treatment of rhinitis.

5. A pharmaceutical composition according to any one of claims 1 to 3 for relieving cold symptoms.

6. The pharmaceutical composition according to any one of claims 1 to 5, 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.

Images