Pharmaceutical composition

Abstract

To provide a pharmaceutical composition containing tranexamic acid or a salt thereof, with masked bitterness.SOLUTION: A pharmaceutical composition comprises the following components (A) and (B): (A) tranexamic acid or a salt thereof and (B) a nonionic surfactant.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a pharmaceutical composition. [Background technology]

[0002] Tranexamic acid is known to be effective against tonsillitis and pharyngitis, and is contained in tablets, oral liquids, etc.

[0003] Since tranexamic acid has a bitter taste, there are known methods for masking the bitter taste when taken in dosage forms such as oral liquids. For example, Patent Document 1 discloses an invention relating to an oral liquid formulation in which tranexamic acid, reduced maltose syrup, and sucralose are combined to mask the bitter taste of tranexamic acid.

[0004] However, it cannot be said that sufficient research has been conducted on the effects of additives used to mask the bitterness derived from tranexamic acid on the bitterness, etc. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 5249558 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a pharmaceutical composition containing tranexamic acid or a salt thereof, in which the bitterness is masked. [Means for solving the problem]

[0007] As a result of extensive research, the present inventors discovered that the bitterness derived from tranexamic acid or a salt thereof can be masked by adding a nonionic surfactant to a formulation containing tranexamic acid or a salt thereof, and thus completed the present invention.

[0008] That is, the present invention relates to a composition comprising the following components (A) and (B): (A) Tranexamic acid or a salt thereof (B) Nonionic surfactant The present invention provides a pharmaceutical composition comprising: Effect of the Invention

[0009] According to the present invention, it is possible to provide a pharmaceutical composition in which the bitterness derived from tranexamic acid or a salt thereof is masked. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The pharmaceutical composition of the present invention contains tranexamic acid or a salt thereof as component (A). In the present invention, "tranexamic acid or a salt thereof" includes not only tranexamic acid itself, but also pharma- ceutically acceptable salts of tranexamic acid (e.g., acid addition salts with inorganic acids such as hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, and phosphate; acid addition salts with organic acids such as benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, maleate, fumarate, tartrate, citrate, and acetate; alkali metal salts such as sodium salt and potassium salt; salts with metals of Group 2 elements such as calcium salt and magnesium salt; organic amine salts such as phenethylamine salt; salts with amino acids such as lysine), and further solvates of tranexamic acid or a pharma- ceutically acceptable salt thereof with water, alcohol, or the like, and one or more of these can be used in combination.

[0011] In the present invention, as tranexamic acid or a salt thereof, tranexamic acid is preferred, and tranexamic acid listed in the 17th edition of the Japanese Pharmacopoeia is particularly preferred. Tranexamic acid or a salt thereof is known and can be produced by known methods, or a commercially available product may be used, such as tranexamic acid manufactured by Kyowa Pharma Chemical Co., Ltd. or tranexamic acid manufactured by Daiichi Sankyo Propharma Co., Ltd.

[0012] The content of tranexamic acid or a salt thereof in the pharmaceutical composition of the present invention may be appropriately set depending on the dosage form, dosage amount, etc., but from the viewpoints of improving taste, formulation stability, antipyretic and analgesic effects, etc., it is preferably contained in an amount of 0.01 to 10 mass%, more preferably 0.1 to 4.9 mass%, and even more preferably 1 to 2.9 mass%, based on the total mass of the pharmaceutical composition.

[0013] The pharmaceutical composition of the present invention contains a nonionic surfactant as component (B). By containing a nonionic surfactant, the bitterness derived from tranexamic acid or a salt thereof can be suppressed. In the present invention, specific examples of the "nonionic surfactant" include polyhydric alcohol fatty acid esters and polyhydric alcohol alkyl ethers such as propylene glycol mono fatty acid esters, ethylene glycol mono fatty acid esters, glycerin mono fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, sucrose fatty acid esters, methyl glucoside fatty acid esters, and alkyl polyglucosides, polyoxyethylene alkyl ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylene phytosterols, polyoxyethylene phytostanols, polyoxyethylene cholesterol, polyoxyethylene cholestanol, and polyoxyethylene polyoxypropylene alkyl ethers, polyoxyethylene mono fatty acid esters, polyethylene glycol fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitol fatty acid esters, polyoxyethylene methyl glucoside fatty acid esters, polyoxyethylene castor oil / hydrogenated castor oil, polyoxyethylene vegetable oil, polyoxyethylene alkyl ether fatty acid esters, and ether esters such as polyoxyethylene polyoxypropylene glycol. Among these, from the viewpoint of suppressing the bitterness of tranexamic acid or a salt thereof, ether esters are preferred, polyethylene glycol fatty acid esters and polyoxyethylene hydrogenated castor oil are more preferred, and polyoxyl stearate is even more preferred.

[0014] The average number of moles of ethylene oxide added in the polyoxyl stearate is not particularly limited, and may be from 2 to 75, and further from 40 to 55. One or more kinds of polyoxyl stearate may be used. Examples of polyoxyl stearate include polyoxyl 40 stearate (the numerical value is the average number of moles of ethylene oxide added; the same applies below), polyoxyl 45 stearate, polyoxyl 55 stearate, and the like. Among these, polyoxyl 40 stearate is preferred from the viewpoint of suppressing the bitterness of tranexamic acid or a salt thereof. In the present invention, as the polyoxyl stearate, commercially available products such as MYS-40MV manufactured by Nikko Chemicals Co., Ltd. can be used. Furthermore, the average number of moles of ethylene oxide added in the polyoxyethylene hydrogenated castor oil is not particularly limited, and may be from 1 to 100, and further from 40 to 60. One or more kinds of polyoxyethylene hydrogenated castor oils may be used. Examples of polyoxyethylene hydrogenated castor oils include polyoxyethylene hydrogenated castor oil 5 (the numerical value is the average number of moles of ethylene oxide added; the same applies below), polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, and polyoxyethylene hydrogenated castor oil 100. Among these, polyoxyethylene hydrogenated castor oil 60 is preferred from the viewpoint of suppressing the bitterness of tranexamic acid or a salt thereof. In the present invention, commercially available products such as NIKKOL HCO-40 and NIKKOL HCO-60 manufactured by Nikko Chemicals Co., Ltd., and Yaku-Zoki Uniox HC-40 and Yaku-Zoki Uniox HC-60 manufactured by NOF Corporation can be used as the polyoxyethylene hydrogenated castor oil.

[0015] From the viewpoint of suppressing the bitterness of tranexamic acid or a salt thereof, the content of component (B) in the pharmaceutical composition of the present invention is preferably 0.001 to 10 mass%, more preferably 0.01 to 5 mass%, even more preferably 0.04 to 3 mass%, and particularly preferably 0.1 to 1 mass%, relative to the total mass of the pharmaceutical composition.

[0016] In addition, the mass ratio of component (A) to component (B) in the pharmaceutical composition of the present invention is preferably 0.001 to 10 parts by mass, more preferably 0.01 to 1 part by mass, and particularly preferably 0.05 to 0.5 parts by mass of component (B) per part by mass of component (A), from the viewpoint of suppressing the bitterness of tranexamic acid or a salt thereof.

[0017] The pharmaceutical composition of the present invention may further contain a sweetener as component (C). Examples of sweeteners include sugars such as sucrose, glucose, fructose, invert sugar, lactose, trehalose, and honey, starch hydrolysates such as candy powder, sugar alcohols such as sorbitol, maltitol, erythritol, and xylitol, and high-intensity sweeteners such as sucralose, saccharin and its salts, aspartame, acesulfame potassium, and stevia extract. Among these, sugar alcohols and high-intensity sweeteners are preferred, with erythritol, sucralose, sodium saccharin, and acesulfame potassium being more preferred, and sucralose and acesulfame potassium being particularly preferred.

[0018] The content of component (C) in the pharmaceutical composition of the present invention is preferably 0.001 to 20 mass%, more preferably 0.01 to 10 mass%, even more preferably 0.1 to 5 mass%, and particularly preferably 1 to 3 mass%, based on the total mass of the pharmaceutical composition, from the viewpoints of sweetness, production stability, and the like.

[0019] The mass ratio of component (A) to component (C) in the pharmaceutical composition of the present invention is preferably 0.01 to 10 parts by mass, more preferably 0.05 to 5 parts by mass, and particularly preferably 0.1 to 1 part by mass of component (C) per part by mass of component (A) from the viewpoints of sweetness, formulation stability, and the like. In addition, the mass ratio of component (B) to component (C) in the pharmaceutical composition of the present invention is preferably 0.01 to 50 parts by mass, more preferably 0.1 to 20 parts by mass, even more preferably 0.5 to 10 parts by mass, and particularly preferably 2 to 7 parts by mass of component (C) per part by mass of component (B) from the viewpoints of sweetness, formulation stability, and the like.

[0020] The pharmaceutical composition of the present invention may further contain a flavor as component (D). Examples of the flavoring include citrus flavorings such as orange flavoring, lemon flavoring, and grapefruit flavoring, vanilla flavoring, mint flavoring, apple flavoring, ginger flavoring, honey flavoring, grape flavoring, menthol, peppermint oil, and caramel. Among these, citrus flavors are preferred, orange flavor, lemon flavor, and grapefruit flavor are more preferred, and orange flavor and grapefruit flavor are particularly preferred.

[0021] From the viewpoints of flavor, production stability, and the like, the content of component (D) in the pharmaceutical composition of the present invention is preferably 0.000001 to 0.01 mass%, more preferably 0.000005 to 0.001 mass%, and even more preferably 0.00001 to 0.0001 mass%, relative to the total mass of the pharmaceutical composition.

[0022] The mass ratio of component (A) to component (D) in the pharmaceutical composition of the present invention is preferably 0.0000001 to 0.001 part by mass, more preferably 0.000001 to 0.0005 parts by mass, and particularly preferably 0.00001 to 0.0001 part by mass of component (D) per part by mass of component (A) from the viewpoints of flavor, formulation stability, and the like. In addition, the mass ratio of component (B) to component (D) in the pharmaceutical composition of the present invention is preferably 0.000001 to 0.01 part by mass, more preferably 0.00001 to 0.001 part by mass, and particularly preferably 0.00005 to 0.0005 part by mass of component (D) per part by mass of component (B) from the viewpoints of flavor, formulation stability, and the like.

[0023] The pharmaceutical composition may contain, as a medicinal ingredient, one or more ingredients other than those mentioned above, for example, one or more selected from the group consisting of antipyretics, antihistamines, antitussives, bronchodilators, expectorants, hypnotics and sedatives, vitamins, anti-inflammatory agents, gastric mucosa protective agents, anticholinergic agents, and herbal medicines, etc. The content of such pharmaceutical ingredients can be appropriately set within a range that does not impair the object of the present invention.

[0024] Examples of antipyretic analgesics include aspirin, aluminum aspirin, acetaminophen, ibuprofen, ethenzamide, sazapirin, salicylamide, sodium salicylate, lactylphenetidine, and loxoprofen sodium.

[0025] Examples of antihistamines include azelastine hydrochloride, alimemazine tartrate, isothipendyl hydrochloride, iproheptine hydrochloride, ebastine, epinastine hydrochloride, emedastine fumarate, oxatomide, olopatadine hydrochloride, carbinoxamine diphenyl disulfonate, carbinoxamine maleate, clemastine fumarate, d-chlorpheniramine maleate, dl-chlorpheniramine maleate, ketotifen fumarate, difeterol hydrochloride, difeterol phosphate, and diphenylpyraline hydrochloride. , diphenylpyraline teoclate, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, cyproheptadine hydrochloride hydrate, cetirizine hydrochloride, triprolidine hydrochloride, tripelennamine hydrochloride, thonzylamine hydrochloride, fexofenadine, fenethazine hydrochloride, promethazine hydrochloride, promethazine methylene disalicylate, bepotastine besilate, homochlorcyclizine hydrochloride, mequitazine, methdilazine hydrochloride, mebhydroline napadisilate, loratadine and the like.

[0026] Examples of antitussives include codeines such as codeine, codeine phosphate hydrate, dihydrocodeine, and dihydrocodeine phosphate, as well as alloclamide hydrochloride, eprazinone hydrochloride, carbetapentane citrate, cloperastine hydrochloride, cloperastine fendizoate, dibunate sodium, dimemorphan phosphate, dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthalin salt, noscapine hydrochloride, and noscapine.

[0027] Examples of bronchodilators include caffeine, theophylline, theopromine, trimetoquinol hydrochloride, paraxanthine, phenylpropanolamine hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, proxyphylline, diprophylline, l-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, l-methylephedrine saccharin salt, dl-methylephedrine saccharin salt, methoxyphenamine hydrochloride, etc.

[0028] Examples of expectorants include ambroxol, ammonia-fennel extract, ethylcysteine ​​hydrochloride, ammonium chloride, carbocysteine, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, methylcysteine ​​hydrochloride, l-menthol, and lysozyme hydrochloride.

[0029] Examples of hypnotic sedatives include allylisopropylacetylurea and bromvalerylurea. Examples of vitamins include vitamin B1, vitamin B2, vitamin B5, vitamin B6, vitamin B12, vitamin C, hesperidin and its derivatives and salts thereof (specifically, for example, thiamine, thiamine chloride hydrochloride, thiamine nitrate, dicethiamine hydrochloride, setotiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octotiamine, shikotiamine, thiamine disulfide, bis-ibuthiamine, bis-bentiamine, prosultiamine, benfotiamine, riboflavin, riboflavin phosphate, riboflavin butyrate, riboflavin sodium phosphate, panthenol, pantethine, sodium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate, cyanocobalamin, mecobalamin, ascorbic acid, sodium ascorbate, calcium ascorbate, hesperidin, etc.).

[0030] Anti-inflammatory agents include, for example, glycyrrhizinic acid and its derivatives and salts thereof (e.g., dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.), seaprose, semi-alkaline proteinase, serrapeptase, proctase, pronase, bromelain, etc.

[0031] Examples of gastric mucosa protecting agents include gefarnate, cetraxate hydrochloride, sofalcone, teprenone, methylmethionine sulfonium chloride, and the like.

[0032] Examples of anticholinergic agents include oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, Datura extract, tipepidium bromide, methylatropine bromide, methylanisotropine bromide, methylscopolamine bromide, methyl-l-hyoscyamine bromide, methylbenactidium bromide, pirenzepine hydrochloride, butylscopolamine bromide, belladonna alkaloids, belladonna extract, belladonna total alkaloids, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, Scolytsum extract, Scolytsum root, and Scolytsum root total alkaloid citrate.

[0033] Examples of herbal medicines include Mallotus japonicus (Mallotus julibrissin), Asarum japonica (Asarum hyacinthus), Eucalyptus globulus (Eucalyptus globulus), Fennel (Fennel), Corydalis rhamnoides (Corydalis chinensis), Scutellaria baicalensis (Scutellaria baicalensis), Phellodendron bark (Prunus persica), Coptis japonica (Coptis chinensis), Onji (Citrus orbiculatus), Zedoary (Gajus rhizome), Valerian (Valeriana japonica), Chamomile (Camellia recutita), Platycodon grandiflorum (Platycodon grandiflorum), Apricot kernel (Apricot kernel), Lycium chinense (Lycium bark), Lycium chinense leaf (Lycium bark), and Cinnamon bark. , Cassia Root, Gentiana Root, Gentian Root, Magnolia Root, Bezoar, Schisandra Root, Saishin, Sansho, Asclepias Root, Chinese Peony, Musk, Shajin, and Prunus Root , Shazensou (Carnivorous grass), Animal gall (including Yutan (bear gall)), Shokyo (Ginger), Jiryu (Earth dragon), Shini (Magnolia), Sekisan (Garlic), Senega, Cnikyu (Chinese cucumber), Zenko (Forsythia globulus), Senburi (Senburi), Soujutsu (Chinese atractylodes), Sohakuhi (Mulberry bark), Soyou (Persea gracilis), Taisan (Garlic), Chikusetsuninjin (Bamboo joint ginseng), Chou (Clove), Chinpi (Citrus unshiu peel), Touki (Angelica acutiloba), Examples of herbal medicines include angelica tree, ipecac (ipecac root), nandina fruit, carrot, Fritillaria root, Ophiopogon, Pinellia gracilis, safflower, hampi, white atractylodes, white atractylodes, poria rhizomatous root, peony bark, ephedra, and velvet antler, as well as extracts thereof (extracts, tinctures, dried extracts, etc.).

[0034] In the present invention, the pharmaceutical composition may be in any form of solid, semi-solid, or liquid, and may be in a form generally used in pharmaceuticals, quasi-drugs, etc., depending on the intended use. For example, the pharmaceutical composition may be in the form of solid preparations such as tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets, oral tablets (including lozenges, sublingual tablets, buccal tablets, adhesive tablets, and gums)), capsules, granules (including effervescent granules), powders, and pills; liquid preparations such as oral liquids (including elixirs, suspensions, emulsions, and lemonades), syrups, and oral liquids; and semi-solid preparations such as oral jellies and oral semi-solids, as described in the General Provisions of Preparations of the 17th Revised Japanese Pharmacopoeia, etc. In the present invention, from the viewpoints of ease of administration, production efficiency, and the like, liquid and semi-solid compositions are preferred, and a dosage form selected from the group consisting of oral liquids, syrups, oral liquids, and oral jellies is more preferred, with oral liquids being particularly preferred.

[0035] In the present invention, from the viewpoint of ease of administration, etc., it is preferable that the pharmaceutical composition contains water. The water content in the pharmaceutical composition of the present invention is not particularly limited, but is preferably 10 to 99% by mass, more preferably 50 to 97% by mass, and even more preferably 80 to 95% by mass, based on the total mass of the pharmaceutical composition.

[0036] The pharmaceutical composition of the present invention may contain additives used in the fields of pharmaceuticals and quasi-drugs, etc., depending on the dosage form, administration method, etc. Examples of such additives include excipients, binders, disintegrants, lubricants, pH adjusters, antioxidants, surfactants or emulsifiers other than component (B), colorants, flavorings, preservatives, gelling agents, coating agents, etc.

[0037] Examples of excipients include calcium silicate, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid, and the like. Examples of binders include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, and the like. Examples of disintegrants include carmellose, carmellose calcium, croscarmellose sodium, crospovidone, low-substituted hydroxypropylcellulose, and the like. Examples of lubricants include carnauba wax, magnesium stearate, and talc. Examples of pH adjusters include organic acids and salts thereof, such as citric acid and malic acid; inorganic acids and salts thereof, such as hydrochloric acid; and inorganic bases, such as sodium hydroxide. Examples of the antioxidant include ascorbic acid and its salts, erythorbic acid and its salts, edetic acid and its salts, sodium hydrogen sulfite, and propyl gallate. Examples of the surfactant or emulsifier other than component (B) include cationic surfactants, anionic surfactants, and amphoteric surfactants. Examples of colorants include Yellow No. 5, tar dyes, iron sesquioxide, caramel, and the like. Examples of flavoring agents include citric acid and its salts, L-glutamic acid and its salts, povidone, l-menthol, malic acid and its salts, and the like. Preservatives include, for example, benzoic acid and its salts, parabens, and the like. Examples of gelling agents include gelatin, pectin, gellan gum, carrageenan, locust bean gum, xanthan gum, guar gum, tara gum, tragacanth gum, curdlan, sodium alginate, dextrin, and agar. Examples of coating agents include film-forming polymers such as carboxymethylethylcellulose, cellulose acetate phthalate, methacrylic acid copolymer S, methacrylic acid copolymer L, methacrylic acid copolymer LD, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, etc. When forming a film, it is also possible to blend plasticizers such as triethyl citrate, triacetin, polyethylene glycol, etc.; powders such as talc, titanium oxide, yellow ferric oxide, ferric oxide, legal dyes, light anhydrous silicic acid, and hydrous silicon dioxide.

[0038] The method of administration of the pharmaceutical composition of the present invention is not particularly limited and can be appropriately selected depending on the purpose of use of the composition, etc., but oral administration is preferred. The method of use and dosage of the pharmaceutical composition are not particularly limited and may be appropriately selected and determined depending on the purpose of use of the composition, the administration method, the dosage form of the composition, etc. The dosage is, for example, an amount that allows 100 to 1000 mg of component (A) to be taken per day, preferably an amount that allows 200 to 750 mg to be taken, and more preferably an amount that allows 250 to 500 mg to be taken.

[0039] The pharmaceutical composition of the present invention can be provided by filling it into a container. For example, it can be filled into a container made of synthetic resin (polyethylene terephthalate, nylon, etc.), aluminum foil, glass, etc. It may be packaged in small portions for each oral dose. Among these, it is preferable to fill it into a glass bottle, etc. The inside of the container may be filled with nitrogen gas from the viewpoint of maintaining the quality.

[0040] Furthermore, in the present invention, the pharmaceutical composition may be contained in an airtight package (hereinafter, in this specification, a pharmaceutical composition contained in an airtight package will be referred to as a "packaged pharmaceutical composition"). In this case, the packaged pharmaceutical composition may further comprise, in addition to the airtight package, a package that does not fall under the category of "airtight package" described below (hereinafter, also referred to as "other packages"), and the pharmaceutical composition may be directly or indirectly contained in the airtight package. An example of an embodiment in which the pharmaceutical composition is indirectly contained in an airtight package is an embodiment in which the pharmaceutical composition is contained in the above-mentioned "other packages" and this is then contained in the airtight package.

[0041] In this specification, the term "airtight packaging" refers to packaging that can prevent the intrusion of solid or liquid foreign matter under normal handling, transportation, storage, etc., and is a concept that includes "airtight container" and "sealed container" defined in the General Rules of the Japanese Pharmacopoeia, 17th Edition. As the airtight packaging, either a fixed shape or an irregular shape can be used, and specific examples include bottle packaging, SP (Strip Package) packaging, PTP (Press Through Package) packaging, pillow packaging, stick packaging, etc. As the airtight packaging, a combination of these may be used, and examples include a form in which a pharmaceutical composition is first packaged in a PTP package and then further packaged in a pillow package.

[0042] The packaging material (raw material) of the airtight package is not particularly limited, and may be, for example, glass, plastic (polyesters such as polyethylene terephthalate, polyethylene naphthalate, etc.; polyethylene (including low density (LDPE), medium density (MDPE), high density (HDPE)), polyolefins such as polypropylene, etc.; polycarbonate; polystyrene, etc.), metals (aluminum, etc.), etc., which are used in the fields of pharmaceuticals, etc., may be used alone or in combination of two or more kinds as appropriate.

[0043] For example, the packaging material used for bottle packaging is not particularly limited, and includes the above-mentioned glass, plastic, metal, etc., and one or more of these can be appropriately combined. As the material for bottle packaging, glass, polyethylene, and polypropylene are preferred, glass, low density polyethylene (LDPE), high density polyethylene (HDPE), and polypropylene are more preferred, glass, high density polyethylene (HDPE), and polypropylene are even more preferred, and glass is particularly preferred. In packaging in a bottle, for example, an appropriate amount of the pharmaceutical composition is placed in the bottle, and then the bottle is sealed with an appropriate stopper or lid. The size of the bottle may be appropriately selected according to the amount of the composition to be placed, and the capacity of the bottle is, for example, about 10 to 500 mL, preferably 14 to 400 mL, and more preferably 24 to 350 mL.

[0044] In addition, packaging materials used for SP packaging, PTP packaging, pillow packaging, stick packaging, and the like are not particularly limited, and examples thereof include biaxially oriented polypropylene (OPP), biaxially oriented polyester (PET), glycol-modified PET (PET-G), biaxially oriented nylon (ONy, PA), cellophane, paper, low-density polyethylene (LDPE), linear low-density polyethylene (L-LDPE), ethylene-vinyl acetate copolymer (EVA), non-oriented polypropylene (CPP, IPP), ionomer resin (IO ), ethylene-methacrylic acid copolymer (EMAA), polyacrylonitrile (PAN), biaxially oriented polyvinylidene chloride (PVDC), ethylene-vinyl alcohol copolymer resin (EVOH), polyvinyl chloride (PVC), cyclic polyolefin (COC), unoriented nylon (CNy), polycarbonate (PC), polystyrene (PS), rigid polyvinyl chloride (VSC), and other resins; and metal foils such as aluminum foil (AL), and one or more of these can be appropriately combined.

[0045] When SP packaging, PTP packaging, pillow packaging, stick packaging, etc. are made, a sheet using one or more of the above-mentioned packaging materials may be produced by a known method, and in this case, the packaging materials may be appropriately combined to form a multi-layer structure. As a method for forming a multi-layer structure using two or more packaging materials as a sheet, a method of laminating the packaging materials to produce a laminated sheet may be mentioned. The laminated sheet can be produced by a known method such as extrusion lamination, dry lamination, co-extrusion lamination, thermal lamination, wet lamination, non-solvent lamination, heat lamination, etc. In addition, the sheets for SP packaging, PTP packaging, pillow packaging, and stick packaging may be commercially available products known in the art.

[0046] Among the above-mentioned sheets, examples of single-layer sheets using one type of packaging material include PVC sheets and CPP sheets, while examples of laminated sheets using two or more types of packaging materials include sheet configurations such as a laminate of PVC and PVDC (PVC / PVDC; hereinafter the same abbreviation), PVC / PVDC / PE / PVC, PVC / PVDC / PE / PVDC / PVC, CPP / COC / CPP, PVC / PCTFE, CPP / PCTFE, PVC / AL / PA, PVC / AL, CPP / AL, CPP / CPP / CPP (the above-mentioned sheets use two or more types of CPP), but are not limited to these.

[0047] The form of PTP packaging may be such that the composition is stored in a desired number of pockets formed in a resin sheet or the like by a known method, one by one, or in one dosage unit, and then covered with a sheet made of a metal foil such as aluminum foil as a lid material. The sheet used to form the pocket may also be a so-called double-sided aluminum PTP package, in which a sheet made of aluminum foil is used as a constituent material. When using PTP packaging, it is preferable to further package the PTP package in a pillow package (for example, an aluminum pillow package, etc.). Examples of the form of SP packaging, pillow packaging, and stick packaging include packaging the composition one piece or one dosage unit by a known method using a resin sheet, a sheet made of aluminum foil, etc. In the case of SP packaging, pillow packaging, and stick packaging, it is preferable to use a sheet made of aluminum foil.

[0048] In this specification, the occupancy rate (volume rate) of the pharmaceutical composition in the packaged pharmaceutical composition is usually 25 to 90%, preferably 28 to 75%, and more preferably 30 to 50% when the package is a bottle package. When the package is a SP package, PTP package, pillow package, or stick package, the occupancy rate is usually 30 to 98%, preferably 40 to 95%, more preferably 45 to 93%, and particularly preferably 50 to 90%. In this case, the occupancy rate means the occupancy rate of the composition relative to the total volume inside the package, and fillers, inner stoppers, and the like for preventing damage to the composition stored inside the package are not taken into consideration when calculating the space occupancy rate.

[0049] As the airtight packaging body, a commercially available packaging body may be used as it is, or a commercially available packaging material may be processed and used. Examples of commercially available bottle packaging packaging bodies include glass bottles (manufactured by Isoya Glass Industry Co., Ltd.), tablet bottles (manufactured by Tokyo Glass Co., Ltd.), and Z-series (manufactured by Hanshin Chemical Industry Co., Ltd.). Examples of commercially available pillow packaging packaging bodies include Lamizip (registered trademark) (manufactured by Nippon Seisakusho Co., Ltd.). Furthermore, examples of packaging materials for SP packaging, PTP packaging, pillow packaging, and stick packaging include SUMILITE VSS, SUMILITE VSL, SUMILITE NS, and SUMILITE FCL (all manufactured by Sumitomo Bakelite Co., Ltd.), TAS series (manufactured by Taisei Kako Co., Ltd.), PTP vinyl foil, and PTP super foil (all manufactured by Mitsubishi Plastics Co., Ltd.), Nippaku aluminum foil (manufactured by Nippon Foil Co., Ltd.), and plain silver aluminum foil (manufactured by Daiwa Chemical Industry Co., Ltd.).

[0050] The method of housing the pharmaceutical composition in the airtight package is not particularly limited, and can be achieved by placing the composition in the package by an appropriate means such as pouring the composition into the package. In this case, a means of pouring a desiccant (e.g., cylindrical (tablet) or sheet-shaped) into the package together with the composition may be used.

[0051] The pharmaceutical composition and packaged pharmaceutical composition of the present invention can be used as a drug, a quasi-drug, etc., and the purpose of its use is not particularly limited. However, since it contains (A) tranexamic acid or a salt thereof and (B) a nonionic surfactant, it can be suitably used as a medicine for the treatment of headache, toothache, pain after tooth extraction, sore throat, earache, joint pain, neuralgia, lower back pain, menstrual pain (period pain), pain after trauma, and for reducing fever after chills or fever, etc.

[0052] In the present invention, the method for producing the pharmaceutical composition is not particularly limited, and the pharmaceutical composition can be produced by a known method described in, for example, the General Provisions for Preparations in the 17th Edition of the Japanese Pharmacopoeia, depending on the type and amount of the ingredients to be blended, the properties of the composition, the dosage form, the purpose, etc. For example, the pharmaceutical composition can be produced through a process of mixing and heating the ingredients (A) to (D) and water, other pharmaceutical ingredients, and additives added as necessary, followed by cooling and filtering. In addition, as described above, when filling a container, the pharmaceutical composition can be produced through a further filling process.

[0053] In addition, the present specification discloses the following aspects of the invention, for example, but is not limited to these. The following components (A) and (B): (A) Tranexamic acid or a salt thereof (B) Nonionic surfactant A method for suppressing the bitterness of component (A) in a pharmaceutical composition, comprising the step of incorporating the above in the same pharmaceutical composition. In the invention of such an embodiment, the order of the step of incorporating component (A) and the step of incorporating component (B) is not particularly limited, as long as a composition containing component (A) and component (B) is produced directly or indirectly.

[0054] The following components (A), (B) and (C): (A) Tranexamic acid or a salt thereof (B) Nonionic surfactant (C) Sweeteners A pharmaceutical composition comprising:

[0055] The following components (A), (B) and (C): (A) Tranexamic acid or a salt thereof (B) Nonionic surfactant (C) Sweeteners A method for suppressing the bitterness of component (A) in a pharmaceutical composition, comprising the step of incorporating the above in the same pharmaceutical composition. In the invention of such an embodiment, the order of the step of incorporating component (A), the step of incorporating component (B), and the step of incorporating component (C) is not particularly limited, as long as a composition containing component (A), component (B), and component (C) is produced directly or indirectly.

[0056] The following components (A), (B) and (D): (A) Tranexamic acid or a salt thereof (B) Nonionic surfactant (D)Fragrance A pharmaceutical composition comprising:

[0057] The following components (A), (B) and (D): (A) Tranexamic acid or a salt thereof (B) Nonionic surfactant (D)Fragrance A method for suppressing the bitterness of component (A) in a pharmaceutical composition, comprising the step of incorporating the above in the same pharmaceutical composition. In the invention of such an embodiment, the order of the step of incorporating component (A), the step of incorporating component (B), and the step of incorporating component (D) is not particularly limited, as long as a composition containing component (A), component (B), and component (D) is produced directly or indirectly.

[0058] The following components (A), (B), (C) and (D): (A) Tranexamic acid or a salt thereof (B) Nonionic surfactant (C) Sweeteners (D)Fragrance A pharmaceutical composition comprising:

[0059] The following components (A), (B), (C) and (D): (A) Tranexamic acid or a salt thereof (B) Nonionic surfactant (C) Sweeteners (D)Fragrance A method for suppressing the bitterness of component (A) in a pharmaceutical composition, comprising the step of incorporating the above in the same pharmaceutical composition. In the invention of such an embodiment, the order of the step of incorporating component (A), the step of incorporating component (B), the step of incorporating component (C), and the step of incorporating component (D) is not particularly limited, as long as a composition containing component (A), component (B), component (C), and component (D) is produced directly or indirectly. In this embodiment of the invention, the meanings of various terms, the amounts of each component, etc. are all the same as those explained for the pharmaceutical composition described above. EXAMPLES

[0060] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0061] [Test Example 1] Evaluation of the effect of suppressing the bitterness of oral liquid preparations containing tranexamic acid In order to evaluate the effect of suppressing the bitterness of tranexamic acid, the following oral liquid preparations Samples 1 to 4 were produced and subjected to a sensory evaluation by the method described below.

[0062] [Sample 1] 250 mg of tranexamic acid (trade name: Tranexamic Acid, manufactured by Kyowa Pharma Chemical Co., Ltd.) was dissolved and suspended in purified water to obtain Sample 1 with a total volume of 10 ml.

[0063] [Sample 2] Sample 2 was obtained in the same manner as Sample 1, except that 4 mg of polyoxyl 40 stearate (manufactured by Nikko Chemicals Co., Ltd., product name MYS-40MV) was added.

[0064] [Sample 3] Sample 3 was obtained in the same manner as Sample 1, except that 40 mg of polyoxyl 40 stearate (manufactured by Nikko Chemicals Co., Ltd., product name MYS-40MV) was added.

[0065] [Evaluation of Bitterness] The bitterness of 10 ml of each of the oral liquid preparations of Samples 1 to 3 was evaluated by three panelists with sufficient time between each evaluation. After each evaluation, it was confirmed that the evaluations by all three panelists were consistent. The bitterness was evaluated as follows: ◎ = "almost no bitterness felt", ○ = "slightly bitter", △ = "bitter", × = "too bitter to take". The results are shown in Table 1.

[0066] [Table 1]

[0067] As shown in Table 1, when Sample 1 was taken, a bitter taste derived from the tranexamic acid was observed, which was so strong that it could not be taken. In contrast, in Samples 2 and 3, in which polyoxyl 40 stearate was added to Sample 1, the bitterness was suppressed when taken. Moreover, from the evaluation results of Samples 2 and 3, it was confirmed that increasing the blending amount of polyoxyl 40 stearate enhanced the effect of suppressing bitterness.

[0068] [Test Example 2] Evaluation of the bitterness suppressing effect of oral liquid preparations containing tranexamic acid In order to evaluate the effect of suppressing the bitterness of tranexamic acid, oral liquid preparations of Samples 4 to 6 were prepared and subjected to sensory evaluation by the method described below.

[0069] [Sample 4] 250 mg of tranexamic acid (manufactured by Kyowa Pharma Chemical Co., Ltd., product name: Tranexamic Acid), 40 mg of polyoxyl 40 stearate (manufactured by Nikko Chemicals Co., Ltd., product name: MYS-40MV), 30 mg of acesulfame potassium (manufactured by Mitsubishi Corporation Life Sciences Corporation, product name: Sunet Pharma Grade D), 30 mg of sucralose (manufactured by San-Ei Gen F.F.I., product name: Sucralose P), and 56 mg of sodium citrate (manufactured by Satsuma Kako Co., Ltd., product name: Sodium Citrate Hydrate) were dissolved and suspended in purified water to obtain Sample 4 with a total volume of 10 ml.

[0070] [Sample 5] Sample 5 was obtained in the same manner as Sample 4, except that 50 mg of anhydrous caffeine (trade name: Anhydrous Caffeine, manufactured by Mitsubishi Chemical Corporation) was added.

[0071] [Sample 6] Sample 6 was obtained in the same manner as Sample 4, except that 40 mg of polyoxyethylene hydrogenated castor oil 60 (trade name HCO-60, manufactured by Nikko Chemicals Co., Ltd.) was used instead of polyoxyl 40 stearate.

[0072] [Bitterness and sweetness evaluation] The bitterness and sweetness of the oral liquid preparations of Samples 4 to 6 were evaluated by three panelists at sufficient intervals after taking 10 ml of each. After the evaluation, each panelist confirmed that the evaluations by all three panelists were consistent. The bitterness was evaluated as follows: ◎ = "almost no bitterness", ○ = "slightly bitter", △ = "slightly bitter", and × = "so bitter that the tablet cannot be taken". The sweetness was evaluated as ◎ = "definitely sweet", ○ = "slightly sweet", △ = "almost no sweetness", and × = "no sweetness at all". The results are shown in Table 2.

[0073] [Table 2]

[0074] As shown in Table 2, in Samples 4 and 6, the bitterness derived from tranexamic acid was suppressed, and the sweetness derived from sweeteners such as acesulfame potassium and sucralose was observed. In addition, in sample 5, which was prepared by adding anhydrous caffeine to sample 4, the bitterness derived from tranexamic acid and anhydrous caffeine was suppressed, and the sweetness derived from sweeteners such as acesulfame potassium and sucralose was observed.

[0075] [Test Example 3] Evaluation of the effect of suppressing the bitterness of oral liquid preparations containing tranexamic acid In order to evaluate the effect of suppressing the bitterness of tranexamic acid, liquid preparations of Samples 7 to 9 were prepared and subjected to sensory evaluation by the method described below.

[0076] [Sample 7] 250 mg of tranexamic acid (manufactured by Kyowa Pharma Chemical Co., Ltd., product name: Tranexamic Acid), 40 mg of polyoxyl 40 stearate (manufactured by Nikko Chemicals Co., Ltd., product name: MYS-40MV), 30 mg of acesulfame potassium (manufactured by Mitsubishi Corporation Life Sciences Ltd., product name: Sunet Pharma Grade D), 30 mg of sucralose (manufactured by San-Ei Gen F.F.I., product name: Sucralose P), 0.005 mg of orange flavoring, and 56 mg of sodium citrate (manufactured by Satsuma Kako Co., Ltd., product name: Sodium Citrate Hydrate) were dissolved and suspended in purified water to obtain Sample 7 with a total volume of 10 ml.

[0077] [Sample 8] Sample 8 was obtained in the same manner as Sample 7, except that 50 mg of anhydrous caffeine (trade name: Anhydrous Caffeine, manufactured by Mitsubishi Chemical Corporation) was added.

[0078] [Sample 9] Sample 9 was obtained in the same manner as Sample 8, except that 0.006 mg of grapefruit flavor was used instead of the orange flavor.

[0079] [Evaluation of bitterness, sweetness, and flavor] The bitterness, sweetness, and flavor of each of the oral liquid preparations, Samples 7 to 9, were evaluated by three panelists at sufficient intervals. After each evaluation, each panelist confirmed that the evaluations by all three panelists were consistent. Bitterness was evaluated as follows: ◎ = "almost no bitterness", ○ = "slightly bitter", △ = "slightly bitter", and × = "so bitter that it cannot be taken". Sweetness was evaluated as ◎ = "clearly sweet", ○ = "slightly sweet", △ = "almost no sweetness", and × = "no sweetness at all". Flavor was evaluated as ◎ = "clearly flavor derived from the flavor", ○ = "slightly flavor derived from the flavor", △ = "almost no flavor derived from the flavor", and × = "no flavor derived from the flavor at all". The results are shown in Table 3.

[0080] [Table 3]

[0081] As shown in Table 3, in sample 7, the bitterness derived from the tranexamic acid was suppressed, and the sweetness derived from the sweetener and the flavor derived from the flavoring were observed. In addition, in sample 8, which was prepared by adding anhydrous caffeine to sample 7, the bitterness derived from tranexamic acid and anhydrous caffeine was suppressed, and the sweetness derived from sweeteners such as acesulfame potassium and sucralose, and the flavor derived from the fragrance were observed. Furthermore, in sample 9, which used grapefruit flavoring instead of the orange flavoring in sample 8, the bitterness derived from tranexamic acid and anhydrous caffeine was suppressed, as in sample 8, and the sweetness derived from sweeteners such as acesulfame potassium and sucralose, and the flavor derived from the flavoring were observed. When Samples 7 and 8 were stored at 40°C for 3 months, no changes in appearance such as precipitation or sedimentation were observed.

[0082] From the above test results, it was revealed that the bitterness derived from tranexamic acid can be suppressed by causing tranexamic acid to coexist with a nonionic surfactant. It was also revealed that the coexistence of tranexamic acid, a nonionic surfactant, a sweetener, and a flavoring makes it possible to suppress the bitterness derived from tranexamic acid without impairing the sweetness and flavor.

[0083] [Production Example 1] (Liquid for internal use) A liquid composition containing the following ingredients and amounts per 10 mL was prepared by a conventional method and placed in a glass container to obtain the oral liquid preparation of Preparation Example 1. Loxoprofen sodium hydrate 68.1mg Riboflavin sodium phosphate 4mg Caffeine anhydrous 50mg Tranexamic acid 250mg Polyoxyl 40 stearate 40mg DL-Malic acid, sodium citrate hydrate, sodium benzoate, butyl paraoxybenzoate, acesulfame potassium, sucralose, erythritol, orange flavor

[0084] [Production Example 2] (Oral liquid) A liquid composition containing the following ingredients and amounts per 10 mL was prepared by a conventional method and placed in a glass container to obtain the oral liquid preparation of Preparation Example 2. Loxoprofen sodium hydrate 68.1mg Riboflavin sodium phosphate 4mg Ascorbic Acid 165mg Caffeine anhydrous 50mg Tranexamic acid 250mg Polyoxyethylene hydrogenated castor oil 60 30mg DL-Malic acid, sodium citrate hydrate, sodium benzoate, butyl paraoxybenzoate, acesulfame potassium, sucralose, erythritol, orange flavor

[0085] [Production Example 3] (Liquid for internal use) A liquid composition containing the following ingredients and amounts per 10 mL was prepared by a conventional method and placed in a glass container to obtain the oral liquid preparation of Preparation Example 3. Loxoprofen sodium hydrate 68.1mg Riboflavin sodium phosphate 4mg Caffeine anhydrous 50mg Tranexamic acid 250mg Polyoxyl 40 stearate 357.6mg DL-Malic acid, sodium citrate hydrate, sodium benzoate, butyl paraoxybenzoate, sodium saccharin, lemon flavor

[0086] [Production Example 4] (Liquid for internal use) A liquid composition containing the following ingredients and amounts per 10 mL was prepared by a conventional method and placed in a glass container to obtain the oral liquid preparation of Preparation Example 4. Loxoprofen sodium hydrate 68.1mg Riboflavin sodium phosphate 4mg Caffeine anhydrous 50mg Tranexamic acid 250mg Polysorbate 80 100mg DL-Malic acid, sodium citrate hydrate, sodium benzoate, butyl paraoxybenzoate, polysorbate 80, acesulfame potassium, sucralose, erythritol, grapefruit flavoring

[0087] [Production Example 5] (Liquid for internal use) A liquid composition containing the following ingredients and amounts per 10 mL was prepared by a conventional method and placed in a glass container to obtain the oral liquid preparation of Preparation Example 5. Loxoprofen sodium hydrate 68.1mg Riboflavin sodium phosphate 4mg Caffeine anhydrous 50mg Tranexamic acid 250mg Ascorbic Acid 165mg Polyoxyl 40 stearate 20mg Sodium benzoate, butyl parahydroxybenzoate, acesulfame potassium, sucralose, sodium hydroxide, sodium bisulfite, propyl gallate, caramel, grapefruit flavor

[0088] [Production Example 6] (Liquid for internal use) A liquid composition containing the following ingredients and amounts per 10 mL was prepared by a conventional method and placed in a glass container to obtain the oral liquid preparation of Preparation Example 6. Loxoprofen sodium hydrate 68.1mg Riboflavin sodium phosphate 4mg Caffeine anhydrous 50mg Tranexamic acid 250mg Polyoxyl 40 stearate 20mg Sodium benzoate, butyl parahydroxybenzoate, acesulfame potassium, sucralose, citric acid hydrate, grapefruit flavor

[0089] [Production Example 7] (Oral liquid) A liquid composition containing the following ingredients and amounts per 10 mL was prepared by a conventional method and placed in a glass container to obtain the oral liquid preparation of Preparation Example 7. Ibuprofen 200mg Riboflavin sodium phosphate 4mg Ascorbic Acid 165mg Caffeine anhydrous 50mg Tranexamic acid 250mg Polyoxyethylene hydrogenated castor oil 60 30mg DL-Malic acid, sodium citrate hydrate, sodium benzoate, butyl paraoxybenzoate, acesulfame potassium, sucralose, erythritol, orange flavor

[0090] [Production Example 8] (Liquid for internal use) A liquid composition containing the following ingredients and amounts per 10 mL was prepared by a conventional method and placed in a glass container to obtain the oral liquid preparation of Preparation Example 8. Ibuprofen 200mg Riboflavin sodium phosphate 4mg Caffeine anhydrous 50mg Tranexamic acid 250mg Polyoxyl 40 stearate 357.6mg DL-Malic acid, sodium citrate hydrate, sodium benzoate, butyl paraoxybenzoate, sodium saccharin, lemon flavor

[0091] [Production Example 9] (Tablets) Tablets of 2700 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner, packaged in PTPs, and then packaged in pillowcases. Loxoprofen sodium hydrate 204.3mg Tranexamic acid 750mg d-Chlorpheniramine maleate 3.5mg Dihydrocodeine phosphate 24mg Ambroxol hydrochloride 45mg dl-Methylephedrine hydrochloride 60mg Caffeine anhydrous 75mg Benfotiamine 25mg Silica anhydride, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax

[0092] [Production Example 10] (Tablets) Tablets of 2700 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner, packaged in PTPs, and then packaged in pillowcases. Loxoprofen sodium hydrate 204.3mg Tranexamic acid 750mg Dipotassium glycyrrhizinate 62mg d-Chlorpheniramine maleate 3.5mg Dihydrocodeine phosphate 24mg Ambroxol hydrochloride 45mg dl-Methylephedrine hydrochloride 60mg Caffeine anhydrous 75mg Riboflavin 12mg Silica anhydride, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax

[0093] [Production Example 11] (Tablets) Tablets of 2700 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner, packaged in PTPs, and then packaged in pillowcases. Loxoprofen sodium hydrate 204.3mg Tranexamic acid 750mg d-Chlorpheniramine maleate 3.5mg Dihydrocodeine phosphate 24mg Guaifenesin 250mg dl-Methylephedrine hydrochloride 60mg Caffeine anhydrous 75mg Benfotiamine 25mg Silica anhydride, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax

[0094] [Production Example 12] (Tablets) Tablets of 2700 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner and placed in a low-density polyethylene bottle. Ibuprofen 600mg Tranexamic acid 750mg d-Chlorpheniramine maleate 3.5mg Belladonna total alkaloids 0.3mg Dihydrocodeine phosphate 24mg Noscapine 48mg Pseudoephedrine hydrochloride 135mg Caffeine anhydrous 75mg Hesperidin 45mg Cinnamon dried extract 30mg (equivalent to 660mg of raw herbal medicine) Silica anhydride, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax

[0095] [Production Example 13] (Tablets) Tablets of 2700 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner, packaged in PTPs, and then packaged in pillowcases. Ibuprofen 600mg Tranexamic acid 750mg Dipotassium glycyrrhizinate 62mg d-Chlorpheniramine maleate 3.5mg Dihydrocodeine phosphate 24mg dl-Methylephedrine hydrochloride 60mg Caffeine anhydrous 75mg Riboflavin 12mg Cinnamon dried extract 30mg (equivalent to 660mg of raw herbal medicine) Silica anhydride, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax

[0096] [Production Example 14] (Tablets) Tablets of 2700 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner and placed in a low-density polyethylene bottle. Ibuprofen 600mg Tranexamic acid 750mg Dipotassium glycyrrhizinate 62mg d-Chlorpheniramine maleate 3.5mg Dihydrocodeine phosphate 24mg dl-Methylephedrine hydrochloride 60mg Caffeine anhydrous 75mg Riboflavin 12mg Hesperidin 45mg Polyoxyl 40 stearate 30mg Silica anhydrous, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, acesulfame potassium, sucralose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax, grapefruit flavoring

[0097] [Production Example 15] (Tablets) Tablets of 2700 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner, packaged in PTPs, and then packaged in pillowcases. Ibuprofen 600mg Tranexamic acid 750mg Dipotassium glycyrrhizinate 62mg d-Chlorpheniramine maleate 3.5mg Dihydrocodeine phosphate 24mg dl-Methylephedrine hydrochloride 60mg Caffeine anhydrous 75mg Riboflavin 12mg Hesperidin 45mg Silica anhydride, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax

[0098] [Production Example 16] (Tablets) Tablets of 2700 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner and placed in a low-density polyethylene bottle. Ibuprofen 600mg Tranexamic acid 750mg Dipotassium glycyrrhizinate 62mg d-Chlorpheniramine maleate 3.5mg Dihydrocodeine phosphate 24mg dl-Methylephedrine hydrochloride 60mg Caffeine anhydrous 75mg Riboflavin 12mg Cinnamon dried extract 30mg (equivalent to 660mg of raw herbal medicine) Polyoxyethylene hydrogenated castor oil 60 25mg Silica anhydrous, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, acesulfame potassium, sucralose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax, orange flavor

[0099] [Production Example 17] (Tablets) Tablets of 3600 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner, packaged in PTPs, and then packaged in pillowcases. Ibuprofen 600mg Tranexamic acid 750mg Dipotassium glycyrrhizinate 62mg d-Chlorpheniramine maleate 3.5mg Belladonna total alkaloids 0.3mg Dihydrocodeine phosphate 24mg Noscapine 48mg L-Carbocisteine ​​750mg dl-Methylephedrine hydrochloride 60mg Caffeine anhydrous 75mg Cinnamon dried extract 30mg (equivalent to 660mg of raw herbal medicine) Silica anhydride, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax

[0100] [Production Example 18] (Tablets) Tablets of 2700 mg each containing the following ingredients in a daily dose (out of 9 tablets) were manufactured in a conventional manner and placed in a low-density polyethylene bottle. Ibuprofen 600mg Tranexamic acid 750mg Dipotassium glycyrrhizinate 62mg d-Chlorpheniramine maleate 3.5mg Belladonna total alkaloids 0.3mg Dihydrocodeine phosphate 24mg Ambroxol hydrochloride 45mg dl-Methylephedrine hydrochloride 60mg Caffeine anhydrous 75mg Riboflavin 12mg Silica anhydride, hypromellose, citric acid, lactose, calcium silicate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, triacetin, talc, titanium dioxide, yellow No. 5, carnauba wax

Claims

1. The following components (A) and (B): (A) Tranexamic acid or a salt thereof (B) Nonionic surfactant A pharmaceutical composition comprising:

2. Furthermore, the following component (C): (C) Sweeteners The pharmaceutical composition according to claim 1, characterized in that it contains:

3. Furthermore, the following component (D): (D) Fragrance The pharmaceutical composition according to claim 1 or 2, characterized in that it contains:

Images