Pharmaceutical composition containing loxoprofen

Abstract

The present invention addresses the problem of providing a bitterness-masked pharmaceutical composition that contains at least one selected from the group consisting of loxoprofen, salts thereof, and hydrates thereof. The present invention provides a pharmaceutical composition comprising: at least one selected from the group consisting of loxoprofen, salts thereof, and hydrates thereof; a sugar alcohol; and a compound including at least one metal selected from the group consisting of alkali metals and alkaline earth metals.

Description

Pharmaceutical compositions containing loxoprofen

[0001] The present invention relates to a pharmaceutical composition having a masked bitterness, which comprises at least one member selected from the group consisting of loxoprofen, a salt thereof, and a hydrate thereof.

[0002] Loxoprofen, a propionic acid-based nonsteroidal antipyretic, analgesic, and anti-inflammatory drug (hereinafter referred to as NSAIDs), exhibits the same inhibitory effect on prostaglandin biosynthesis as other NSAIDs, but is known to have strong antipyretic, analgesic, and anti-inflammatory effects.

[0003] Several methods for masking the bitterness of pharmaceuticals such as loxoprofen are known. Patent Document 1 describes masking the bitterness of pharmaceuticals such as ibuprofen, acetaminophen, and loxoprofen with stevia. Patent Document 2 describes masking the unpleasant taste of alkali metal salts of acidic drugs such as loxoprofen sodium with a methacrylic polymer compound.

[0004] Furthermore, as an oral composition containing rofecoxib and a sugar alcohol, Patent Document 3 describes an oral composition characterized by containing rofecoxib and one or more sugars selected from the group consisting of sucrose, maltitol, fructose, xylitol, trehalose, lactose and lactitol.

[0005] JP-A-9-52825 Patent No. 6812104 Patent No. 4585220

[0006] An object of the present invention is to provide a pharmaceutical composition containing at least one member selected from the group consisting of loxoprofen, a salt thereof, and a hydrate thereof, the bitterness of which is masked.

[0007] As a result of extensive research to solve the above problems, the inventors have discovered that the bitterness of at least one compound selected from the group consisting of rofecoxib, its salts, and their hydrates can be masked by combining at least one compound selected from the group consisting of rofecoxib, its salts, and their hydrates with a sugar alcohol and a compound containing at least one metal selected from the group consisting of alkali metals and alkaline earth metals, and have thus completed the present invention.

[0008] That is, aspects of the present invention are as follows. <1> A pharmaceutical composition comprising at least one selected from the group consisting of loxoprofen, a salt thereof, and a hydrate thereof, a sugar alcohol, and a compound containing at least one metal selected from the group consisting of alkali metals and alkaline earth metals. <2> The pharmaceutical composition according to <1>, further comprising a terpene. <3> The pharmaceutical composition according to <2>, wherein the terpene comprises menthol. <4> The pharmaceutical composition according to any one of <1> to <3>, further comprising a sweetener. <5> The pharmaceutical composition according to <4>, wherein the sweetener comprises stevia. <6> The pharmaceutical composition according to any one of <1> to <5>, wherein the sugar alcohol is at least one selected from the group consisting of lactitol, xylitol, sorbitol, erythritol, diglycerin, and polyglycerin. <7> The pharmaceutical composition according to any one of <1> to <6>, wherein the mass ratio of the content of the sugar alcohol to the content of at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof is 1:1 to 1:10. <8> The pharmaceutical composition according to any one of <1> to <7>, wherein the compound is a salt, oxide, or hydroxide of at least one metal selected from the group consisting of alkali metals and alkaline earth metals. <9> The pharmaceutical composition according to any one of <1> to <8>, wherein the compound comprises at least one selected from the group consisting of carbonates and bicarbonates of at least one metal selected from the group consisting of alkali metals and alkaline earth metals. <10> The pharmaceutical composition according to any one of <1> to <9>, wherein the compound comprises at least one selected from the group consisting of precipitated calcium carbonate, sodium bicarbonate, magnesium oxide, and magnesium hydroxide. <11> The pharmaceutical composition according to any one of <1> to <10>, wherein the mass ratio of the content of at least one selected from the group consisting of loxoprofen, a salt thereof, and a hydrate thereof to the content of the compound is 1:0.2 to 1:5. <12> The pharmaceutical composition according to any one of <1> to <11>, which is a solid composition or a liquid composition.<13> The pharmaceutical composition according to any one of <1> to <12>, which is in the form of tablets, fine granules, granules, capsules, orally disintegrating tablets, troches, drops, chewable tablets, or a liquid. <14> The pharmaceutical composition according to any one of <1> to <13>, which is an oral pharmaceutical composition. <15> The pharmaceutical composition according to any one of <1> to <14>, which is used as an antipyretic analgesic or a cold medicine. <16> A composition for adjusting bitterness, comprising: at least one selected from the group consisting of loxoprofen, a salt thereof, and a hydrate thereof; a sugar alcohol; and a compound containing at least one metal selected from the group consisting of alkali metals and alkaline earth metals.

[0009] According to the present invention, it is possible to provide a pharmaceutical composition in which the bitterness of at least one substance selected from the group consisting of loxoprofen, a salt thereof, and a hydrate thereof is masked.

[0010] Figure 1 shows the results of the change in food intake over time. Figure 2 shows the results of the change in water intake over time. Figure 3 shows the results of the change in water intake over time.

[0011] The pharmaceutical composition of the present invention is a pharmaceutical composition comprising at least one selected from the group consisting of loxoprofen, its salts and hydrates thereof, and a compound containing a sugar alcohol and at least one metal selected from the group consisting of alkali metals and alkaline earth metals.

[0012] <Loxoprofen, its salts, and hydrates thereof> The pharmaceutical composition of the present invention contains at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof. In the present invention, "at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof" is sometimes referred to as "loxoprofen or its salt," and refers to loxoprofen or a salt thereof (including a hydrate salt) (the salt is preferably a pharmacologically acceptable salt), preferably loxoprofen sodium, and more preferably loxoprofen sodium dihydrate. The at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof used in the present invention is listed as loxoprofen sodium hydrate in the 18th Edition of the Japanese Pharmacopoeia.

[0013] The amount of at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof contained in the pharmaceutical composition is not particularly limited, but is preferably 0.01 to 80% by mass, more preferably 0.1 to 80% by mass, alternatively 1 to 80% by mass, 2 to 50% by mass, 5 to 30% by mass, or 5 to 20% by mass, based on the total mass of the pharmaceutical composition.

[0014] The amount of loxoprofen, its salts, or hydrates thereof contained in one dosage unit (single dose) for adults is preferably 10 to 180 mg, more preferably 30 to 120 mg, and even more preferably 60 to 90 mg, calculated as the anhydrous amount, and the dosage is 1 to 3 times a day (up to 3 times a day).

[0015] <Sugar Alcohol> The pharmaceutical composition of the present invention contains a sugar alcohol. Examples of sugar alcohols include lactitol, xylitol, sorbitol, erythritol, mannitol, D-mannitol, maltitol, sorbitol, glycerin, diglycerin, polyglycerin, etc. The sugar alcohol is preferably at least one selected from the group consisting of lactitol, xylitol, sorbitol, and erythritol.

[0016] The mass ratio (weight ratio) of the content of at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof to the content of the sugar alcohol is preferably 1:1 to 1:10, more preferably 1:2 to 1:8, and even more preferably 1:3 to 1:6.

[0017] The amount of sugar alcohol contained in the pharmaceutical composition is not particularly limited, but is preferably 0.1 to 95% by mass, alternatively 0.5 to 70% by mass, alternatively 0.8 to 50% by mass, alternatively 1 to 30% by mass, or alternatively 1 to 20% by mass, based on the total mass of the pharmaceutical composition.

[0018] <Compound containing at least one metal selected from the group consisting of alkali metals and alkaline earth metals> The pharmaceutical composition of the present invention contains a compound containing at least one metal selected from the group consisting of alkali metals and alkaline earth metals (hereinafter also referred to as the present compound). Examples of alkali metals include, but are not limited to, sodium (Na) or potassium (K). Examples of alkaline earth metals include, but are not limited to, magnesium (Mg) or calcium (Ca). The present compound is preferably a salt, oxide, or hydroxide of at least one metal selected from the group consisting of alkali metals and alkaline earth metals. The present compound is preferably at least one selected from the group consisting of carbonates and bicarbonates of at least one metal selected from the group consisting of alkali metals and alkaline earth metals. Specific examples of the present compound include at least one selected from the group consisting of precipitated calcium carbonate, sodium bicarbonate, magnesium oxide, and magnesium hydroxide.

[0019] The mass ratio of the content of the at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof to the content of the compound is preferably 1:0.2 to 1:5, more preferably 1:0.3 to 1:4, and even more preferably 1:0.5 to 1:3.

[0020] The amount of the compound contained in the pharmaceutical composition is not particularly limited, but is preferably 0.1 to 80% by mass, alternatively 0.5 to 70% by mass, or alternatively 1 to 25% by mass, based on the total mass of the pharmaceutical composition.

[0021] <Terpenes> The pharmaceutical composition of the present invention may further contain terpenes, if desired. Terpenes are a general term (terpenoid) that includes terpene hydrocarbons as well as terpene alcohols, terpene aldehydes, terpene ketones, terpene oxides, terpene lactones, etc. The structure of the terpenes is not particularly limited, and examples include monoterpenes, sesquiterpenes, and derivatives thereof. The terpenes may be cyclic or chain-chain.

[0022] Examples of terpenes include menthol, isoborneol, irone, ocimene, carveol, carbotanacetone, carbomenthone, carvone, carene, calone, camphene, camphor, geraniol, sabinene, safranal, cyclocitral, citral, citronellal, citronellic acid, citronellol, cineole, cymene, silvestrene, thymol, isothujole, thujone, terpineol, terpinene, terpinolene, tricyclene, nerol, pinene, pinocampheol, pinol, piperitenone, phellandral, phellandrene, fenchene, fenchyl alcohol, perillyl alcohol, perillaldehyde, borneol, myrcene, menthone, ionol, ionone, linalool, limonene, etc. Terpenes may be used alone or in combination of two or more. Menthol is particularly preferred as a terpene.

[0023] When optical isomers of terpenes exist, all isomers are included unless otherwise specified. The isomers may be a single optical isomer or a mixture of various optical isomers in any ratio. For example, the term "menthol" includes both dl-menthol and d-menthol.

[0024] The amount of terpenes contained in the pharmaceutical composition is not particularly limited, but is preferably 0.01 to 15% by mass, alternatively 0.1 to 10% by mass, or alternatively 0.5 to 8% by mass, based on the total mass of the pharmaceutical composition.

[0025] <Sweetener> The pharmaceutical composition of the present invention may further contain a sweetener, if desired. The sweetener is not particularly limited and may be a natural sweetener or an artificial sweetener. Examples of natural sweeteners include stevia, licorice (glycyrrhizin), thaumatin, etc. Examples of artificial sweeteners include aspartame, neotame, sucralose, acesulfame potassium, saccharin, saccharin sodium, etc. These may be used alone or in combination of two or more. Stevia is preferred as the sweetener.

[0026] The amount of the sweetener contained in the pharmaceutical composition is not particularly limited, but is preferably 0.001 to 30% by mass, alternatively 0.001 to 10% by mass, alternatively 0.005 to 5% by mass, or alternatively 0.01 to 1% by mass, based on the total mass of the pharmaceutical composition.

[0027] <Other Components in the Pharmaceutical Composition> The pharmaceutical composition of the present invention may contain an antacid from the viewpoint of suppressing gastric mucosal damage. Examples of antacids include alkaline earth metal and / or earth metal basic inorganic compounds such as magnesium oxide, magnesium silicate, magnesium aluminosilicate, magnesium aluminum silicate, magnesium hydroxide, a co-precipitation product of magnesium hydroxide and aluminum potassium sulfate, magnesium carbonate, synthetic hydrotalcite, magnesium aluminometasilicate, dried aluminum hydroxide gel, synthetic aluminum silicate, magnesium alumina hydroxide, aluminum hydroxide gel, a co-precipitation product of aluminum hydroxide and sodium bicarbonate, a mixed dried gel of aluminum hydroxide and magnesium carbonate, and a co-precipitation product of aluminum hydroxide, magnesium carbonate, and calcium carbonate. Examples of alkali metal basic inorganic compounds include inorganic salts of metals selected from magnesium, aluminum, and calcium, such as bentonite, calcium silicate, calcium carbonate, precipitated calcium carbonate, calcium hydrogen phosphate, and anhydrous calcium hydrogen phosphate; examples of alkali metal basic inorganic compounds include inorganic salts of metals selected from sodium and potassium, such as dry sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium carbonate hydrate, sodium hydrogen phosphate hydrate, anhydrous sodium monohydrogen phosphate, potassium hydroxide, potassium bicarbonate, and potassium carbonate; and other compounds include borax and glycine, and one or more components selected from these may be blended. Among these, one or more components selected from the group consisting of magnesium oxide, magnesium aluminometasilicate, aluminum hydroxide gel, and glycine are preferred.

[0028] The pharmaceutical composition of the present invention may contain caffeines, such as caffeine hydrate, anhydrous caffeine, sodium caffeine benzoate, and caffeine citrate.

[0029] The pharmaceutical composition of the present invention may contain a sedative, such as allylisopropylacetylurea or bromovalerylurea.

[0030] The pharmaceutical composition of the present invention may further contain other active ingredients, such as antitussives / expectorants, antihistamines, anti-inflammatory agents, anticholinergic agents, other vitamins, and xanthine derivatives, as needed, within the scope of the present invention. If there are any contraindications for these ingredients, the composition may be formulated by dividing the ingredients into granules or the like.

[0031] Examples of antitussives / expectorants include codeine, codeine phosphate hydrate, dihydrocodeine, dihydrocodeine phosphate, dibunate sodium, dimemorfan phosphate, tipepidine citrate, tipepidine hibenzate, dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthalin salt, alloclamide hydrochloride, cloperastine hydrochloride, cloperastine fendizoate, pentoxyverine citrate, and nosca pine, noscapine hydrochloride, trimetoquinol hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, l-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, L-carbocysteine, ambroxol hydrochloride, bromhexine hydrochloride, L-ethylcysteine ​​hydrochloride, and the like.

[0032] Examples of antihistamines include azelastine hydrochloride, alimemazine tartrate, ebastine, epinastine hydrochloride, emedastine fumarate, oxatomide, olopatadine hydrochloride, carbinoxamine, clemastine fumarate, diphenyl disulfonate, carbinoxamine maleate, d-chlorpheniramine maleate, dl-chlorpheniramine maleate, ketotifen fumarate, diphenylpyraline hydrochloride, diphenylpyraline teoclate, difenyl pyraline hydrochloride, diphenyl pyraline teoclate ... Examples of such antihistamines include phenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, triprolidine hydrochloride, tripelennamine hydrochloride, thonzylamine hydrochloride, fexofenadine, fenethazine hydrochloride, promethazine hydrochloride, promethazine, mequitazine, methdilazine hydrochloride, loratadine, isopentyl hydrochloride, diphenthenol hydrochloride, methdilazine hydrochloride, mebhydrozine napadisilate, promethazine methylenedisalicylate, and diphenthenol phosphate.

[0033] Anti-inflammatory agents include glycyrrhizinic acid and its derivatives and salts thereof (for example, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.), tranexamic acid, etc.

[0034] Anticholinergic agents include scopolamine hydrobromide, Datura extract, methylscopolamine bromide, methyl-l-hyoscyamine bromide, pirenzepine hydrochloride, butylscopolamine bromide, belladonna alkaloids, belladonna extract, belladonna total alkaloids, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, Scopolia root extract, Scopolia root total alkaloid citrate, and the like.

[0035] Examples of vitamins include vitamin A, vitamin C, vitamin B1, vitamin B2, vitamin B5, vitamin B6, vitamin B12, vitamin P, vitamin E, hesperidin, nicotinic acid, nicotinamide, panthenol, calcium pantothenate, sodium pantothenate, biotin, a mixture of equal parts of potassium and magnesium aspartate, inositol hexanicotinate, ursodeoxycholic acid, L-cysteine, L-cysteine ​​hydrochloride, orotin, gamma oryzanol, calcium glycerophosphate, calcium gluconate, gluconolactone, glucuronic acid amide, sodium chondroitin sulfate, carrot, coix seed, and iodine. Examples of xanthine derivatives other than the above-mentioned caffeine (other xanthine derivatives) include theophylline and theobromine.

[0036] Examples of vitamins include vitamin B1 and derivatives thereof, such as thiamine, thiamine chloride hydrochloride, thiamine nitrate, dicethiamine hydrochloride, setotiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octotiamine, shikotiamine, thiamine disulfide, bis-ibutiamine, bis-bentiamine, prosultiamine, and benfotiamine, and salts thereof; vitamin B2 and derivatives thereof, such as riboflavin, riboflavin phosphate, riboflavin butyrate, and riboflavin sodium phosphate, and salts thereof; pantothenic acid, panthenol, pantethine, pantothenic acid, panthenol ... One or more ingredients selected from the group consisting of vitamin B5 and its derivatives and salts such as calcium pantothenate and sodium pantothenate; vitamin B6 and its derivatives and salts such as pyridoxine hydrochloride and pyridoxal phosphate; vitamin B12 and its derivatives and salts such as cyanocobalamin and mecobalamin; vitamin C and its derivatives and salts such as ascorbic acid, sodium ascorbate and calcium ascorbate; and hesperidin and its derivatives and salts.

[0037] These additives are not limited to those listed above, and one of these may be used alone or two or more of them may be used in combination.

[0038] <Formulation and Form of Pharmaceutical Composition> The pharmaceutical composition of the present invention can be formulated according to a conventional method. When formulating, the pharmaceutical composition can be formulated using known methods and additives as appropriate. Additives may be added as appropriate within a range that does not impair the effects of the present invention.

[0039] Examples of additives include pharmaceutically acceptable carriers such as excipients, binders, disintegrants, disintegration aids, lubricants, fluidizing agents, glossing agents, foaming agents, moisture-proofing agents, surfactants, stabilizers, emulsifiers, antioxidants, fillers, preservatives, flavoring agents, refreshing agents, flavors, fragrances, colorants, base materials, coating agents, sugar-coating agents, plasticizers, dispersants, and antifoaming agents. Conventionally known formulation additives that can be used in pharmaceutical compositions can be used for the above-mentioned purposes.

[0040] Examples of excipients include candy powder, gum arabic, powdered gum arabic, cocoa butter, caramel, sodium carboxymethyl starch, hydrated silicon dioxide, anhydrous amorphous silicon oxide, xylitol, magnesium aluminosilicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, anhydrous calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate granules, calcium monohydrogen phosphate, calcium hydrogen phosphate hydrate, calcium hydrogen phosphate granules, sodium hydrogen phosphate hydrate, calcium dihydrogen phosphate hydrate, sodium dihydrogen phosphate hydrate, potassium dihydrogen phosphate, crystalline cellulose, crystalline cellulose-carmellose sodium, crystalline cellulose (fine particles), crystalline cellulose (granules), powdered cellulose, synthetic aluminum silicate, synthetic aluminum silicate-hydroxypropyl starch-crystalline cellulose, wheat starch, rice flour, rice starch, heavy anhydrous silicic acid, refined sucrose, refined sucrose spherical granules, gelatin, D-sorbitol, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose , dextrin, corn starch, corn starch granules, trehalose, silicon dioxide, lactose hydrate, lactose granules, sucrose, potato starch, hydroxypropyl starch, partially pregelatinized starch, powdered sugar, powdered candy, powdered reduced maltose syrup, powdered cellulose, pectin, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 60, maltitol, D-mannitol, calcium sulfate, erythritol, glucose, fructose, etc.

[0041] The binder may be one or more components selected from gum arabic, powdered gum arabic, dried plum powder, gelatin, shellac, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose, pullulan, povidone, polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified), methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, butyl methacrylate-methyl methacrylate copolymer, methyl cellulose, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, and the like.

[0042] Examples of disintegrants include sodium carboxymethyl starch, carmellose, carmellose calcium, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, hydroxypropyl starch, partially pregelatinized starch, and the like.

[0043] Examples of disintegration aids include carboxymethyl starch sodium, carmellose, carmellose calcium, croscarmellose sodium, light anhydrous silicic acid, crystalline cellulose, sodium bicarbonate, precipitated calcium carbonate, lactose hydrate, hydroxypropyl starch, polysorbate 40, polysorbate 60, polysorbate 80, macrogol 1500, macrogol 4000, and the like.

[0044] Examples of lubricants include magnesium stearate, calcium stearate, talc, sucrose fatty acid esters, glycerin fatty acid esters, polyethylene glycol, hydrogenated oil, and sodium stearyl fumarate.

[0045] The fluidizing agent may be one or more components selected from the group consisting of hydrous silicon dioxide, light anhydrous silicic acid, synthetic aluminum silicate, heavy anhydrous silicic acid, magnesium alumina hydroxide, stearic acid, calcium stearate, magnesium stearate, tricalcium phosphate, talc, calcium hydrogen phosphate granules, and the like.

[0046] The glossing agent may be, for example, one or more components selected from carnauba wax, white beeswax, purified shellac, Macrogol 400, Macrogol 1500, Macrogol 4000, Macrogol 6000, Macrogol 6000NF, beeswax, etc.

[0047] As the foaming agent, for example, one or more components selected from dry sodium carbonate, tartaric acid, potassium hydrogen tartrate, sodium hydrogen carbonate, anhydrous citric acid, etc. may be blended.

[0048] The moisture-proofing agent may be one or more components selected from the group consisting of ethyl cellulose, olive oil, dried aluminum hydroxide gel, glycerin, magnesium silicate, light anhydrous silicic acid, hardened oil, synthetic aluminum silicate, sucrose fatty acid ester, stearic acid, magnesium stearate, purified shellac, purified sucrose, talc, neutral anhydrous sodium sulfate, precipitated calcium carbonate, a mixture of fumaric acid, stearic acid, polyvinyl acetal diethylaminoacetate, and hydroxypropyl methylcellulose 2910, and polyvinyl acetal diethylaminoacetate.

[0049] The surfactant may be one or more components selected from, for example, sucrose fatty acid esters, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan beeswax, polyoxyethylene nonylphenyl ether, polyoxyethylene (20) polyoxypropylene (20) glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (10) polyoxypropylene (4) cetyl ether, polysorbate 20, polysorbate 60, polysorbate 80, macrogol 400, sorbitan monooleate, glycerin monostearate, sorbitan monostearate, sorbitan monolaurate, sodium lauryl sulfate, and the like.

[0050] Examples of stabilizers include adipic acid, L-aspartic acid, sodium L-aspartate, DL-alanine, L-alanine, L-arginine, L-arginine hydrochloride, sodium alginate, propylene glycol alginate, benzoic acid, sodium benzoate, ethylenediamine, calcium disodium edetate, sodium edetate, tetrasodium edetate, tetrasodium edetate tetrahydrate, zinc chloride, ammonium chloride, calcium chloride hydrate, cetylpyridinium chloride, ferric chloride, sodium chloride, magnesium chloride, and calcium chloride. Stain, L-histidine hydrochloride, cocoa butter, carboxyvinyl polymer, carmellose calcium, carmellose sodium, hydrated silicon dioxide, dried sodium carbonate, glycine, glycerin, glycerin fatty acid ester, calcium gluconate hydrate, sodium gluconate, magnesium gluconate, potassium L-glutamate, sodium L-glutamate, L-lysine glutamate, light anhydrous silicic acid, crystalline sodium dihydrogen phosphate, sodium chondroitin sulfate, zinc oxide, L-cystine, L-cysteine, tartaric acid, sucrose fatty acid ester Stearic acid, refined gelatin, refined soy lecithin, gelatin, gelatin hydrolysate, sorbitan fatty acid ester, taurine, talc, calcium carbonate, potassium bicarbonate, sodium bicarbonate, sodium carbonate hydrate, magnesium carbonate, natural vitamin E, tocopherol, tocopherol acetate, lactose, concentrated glycerin, povidone, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene hydrogenated castor oil, poly Polyoxyethylene (42) polyoxypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxyethylene coconut oil fat glyceryl (7E.O.), polysorbate 20, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), macrogol 300, macrogol 400, macrogol 4000, anhydrous citric acid,One or more ingredients selected from anhydrous sodium citrate, anhydrous sodium monohydrogen phosphate, anhydrous sodium dihydrogen phosphate, methylcellulose, l-menthol, glycerin monostearate, medicinal charcoal, magnesium sulfate hydrate, DL-malic acid, sodium hydrogen phosphate hydrate, potassium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, L-leucine, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, etc. may be blended.

[0051] Examples of emulsifiers include glycerin fatty acid esters, propylene glycol fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyethylene glycol fatty acid esters, and hydrogenated soybean phospholipids.

[0052] Examples of antioxidants include ascorbic acid, L-ascorbic acid stearate, citric acid hydrate, soybean lecithin, natural vitamin E, natural vitamin E, tocopherol, tocopherol acetate, ascorbic acid palmitate, and sodium pyrosulfite.

[0053] Examples of fillers include RSS No. 1 raw rubber, starch acrylate 1000, hydrous silicon dioxide, titanium oxide, silicon dioxide, and calcium hydrogen phosphate.

[0054] Examples of preservatives include benzoic acid, sodium benzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, methyl parahydroxybenzoate, dehydroacetic acid, sodium dehydroacetate, sorbic acid, and phenoxyethanol.

[0055] The flavoring agent may be one or more ingredients selected from sodium chloride, orange, orange oil, cacao powder, fructose, caramel, xylitol, calcium citrate, citric acid hydrate, sodium citrate hydrate, L-glutamic acid, sodium L-glutamate, grapefruit extract, brown sugar, saccharin, saccharin sodium hydrate, tartaric acid, D-tartaric acid, potassium hydrogen tartrate, DL-sodium tartrate, sucralose, stevia extract, purified stevia extract, Swertia japonica, D-sorbitol, tannic acid, trehalose hydrate, fructooligosaccharide, powdered sugar, peppermint powder, D-mannitol, dl-menthol, l-menthol, menthol powder, green tea powder, DL-malic acid, sodium DL-malate, lemon oil, rose oil, and the like.

[0056] Examples of the cooling agent include fennel oil, d-camphor, dl-camphor, cinnamon oil, peppermint water, peppermint oil, and l-menthol.

[0057] As the flavoring, for example, one or more components selected from orange flavor, guarana extract, sweet orange, strawberry, brown sugar flavor, strawberry flavor, cherry flavor, banana powder flavor, peach essence, fruit essence, peppermint, melon powder flavor, 1-menthol, peppermint oil, etc. can be blended.

[0058] Examples of fragrances include fennel powder, fennel oil, ethyl vanillin, d-camphor, dl-camphor, spearmint oil, turpentine, pineapple powder flavor 51357, pineapple powder flavor 59492, peppermint water, peppermint oil, vanilla powder flavor 54286, vanillin, bergamot oil, d-borneol, dl-borneol, dl-menthol, l-menthol, eucalyptus oil, rose water, and rose oil.

[0059] Examples of colorants that can be blended include one or more components selected from yellow iron oxide, yellow ferric oxide, orange essence, brown iron oxide, carbon black, caramel, β-carotene, gold leaf, black iron oxide, titanium oxide, ferric oxide, dizazo yellow, Food Blue No. 1, Food Yellow No. 4, Food Yellow No. 5, Food Blue No. 2 Aluminum Lake, Food Yellow No. 4 Aluminum Lake, Food Red No. 2, Food Red No. 3, Food Red No. 102, ferric oxide / glycerin suspension, copper chlorophyllin sodium, copper chlorophyll, phenol red, malachite green, methylene blue, medicinal charcoal, riboflavin, riboflavin butyrate, riboflavin sodium phosphate, green tea powder, and rose oil.

[0060] The bases include gum arabic powder, pregelatinized starch, ethyl cellulose, cacao butter, carnauba wax, carboxyvinyl polymer, carmellose, carmellose sodium, reduced maltose syrup, hydrated silicon dioxide, dried aluminum hydroxide gel, agar, agar powder, xanthan gum, glycine, glycerin, glycerin fatty acid ester, light anhydrous silicic acid, crystalline cellulose, hardened oil, synthetic aluminum silicate, synthetic magnesium sodium silicate, titanium oxide, tartaric acid, sucrose fatty acid ester, silicone oil, stearic acid, magnesium stearate, gelatin, D-sorbitol, talc, calcium carbonate, corn starch, lactic acid, ethyl lactate, calcium lactate hydrate, lactic acid-glycolic acid copolymer, concentrated glycerin, potato starch, and hydroxypropyl cellulose. The composition may contain one or more ingredients selected from the group consisting of cellulose, hypromellose, pullulan, pectin, povidone, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), microcrystalline wax, macrogol 200, macrogol 300, macrogol 400, macrogol 1000, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 6000NF, macrogol 20000, D-mannitol, glycerin monostearate, sorbitan monostearate, batyl monostearate, propylene glycol monostearate, polyethylene glycol monostearate, sodium lauryl sulfate, and polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer.

[0061] Examples of coating agents include ethyl acrylate-methyl methacrylate copolymer dispersion, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, gum arabic, gum arabic powder, ethyl cellulose, ethyl cellulose aqueous dispersion, carnauba wax, carboxyvinyl polymer, gold leaf, silver leaf, triethyl citrate, glycerin, glycerin fatty acid ester, hardened oil, titanium oxide, sucrose fatty acid ester, stearyl alcohol, stearic acid, magnesium stearate, purified gelatin, purified shellac, gelatin, D-sorbitol, talc, calcium carbonate, magnesium carbonate, medium gold leaf, precipitated calcium carbonate, concentrated glycerin, white shellac, hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose 2910-titanium oxide-macrogol 400 mixture, hypromellose, fumaric acid-stearic acid-polyvinyl acetal diethylamino Examples of the acrylic acid copolymer include methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, methyl acrylate-methacrylic acid-methyl methacrylate copolymer, methylcellulose, 2-methyl-5-vinylpyridine methylacrylate-methacrylic acid copolymer, aluminum monostearate, glycerin monostearate, sorbitan monostearate, sorbitan monolaurate, calcium sulfate, and polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer.

[0062] Examples of sugar-coating agents that can be blended include one or more components selected from gum arabic, powdered gum arabic, ethyl cellulose, carnauba wax, carmellose sodium, 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, pullulan, povidone, polyvinyl alcohol (partially saponified), macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, calcium hydrogen phosphate hydrate, calcium dihydrogen phosphate hydrate, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, and the like.

[0063] Examples of the plasticizer that can be blended include one or more components selected from triethyl citrate, glycerin, glycerin fatty acid esters, D-sorbitol, medium-chain fatty acid triglycerides, triacetin, concentrated glycerin, castor oil, polyoxyethylene hydrogenated castor oil 60, propylene glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polysorbate 80, macrogol 400, macrogol 600, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000 NF, glycerin monostearate, isopropyl linoleate, and liquid paraffin.

[0064] Dispersants include aminoalkyl methacrylate polymer RS, gum arabic, powdered gum arabic, carboxyvinyl polymer, sodium carboxymethyl starch, powdered agar, citric acid hydrate, sodium citrate hydrate, glycerin, glycerin fatty acid ester, magnesium silicate, light aluminum oxide, light anhydrous silicic acid, crystalline cellulose, titanium oxide, sucrose fatty acid ester, stearic acid, magnesium stearate, D-sorbitol, soybean lecithin, and low-substituted hydroxypropyl cellulose. , dextrin, corn starch, lactose hydrate, concentrated glycerin, potato starch, hydroxyethyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose, povidone, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polysorbate 20, polysorbate 60, polysorbate 80, microcrystalline wax, macrogol 300, macrogol 4000, macrogol 6000, macrogol 6000NF, anhydrous sodium citrate, methylcellulose, glycerin monooleate, sorbitan monooleate, aluminum monostearate, glycerin monostearate, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, sodium lauryl sulfate, and the like can be blended.

[0065] The antifoaming agent may be one or more components selected from ethanol, glycerin fatty acid ester, dimethylpolysiloxane (for internal use), dimethylpolysiloxane / silicon dioxide mixture, sucrose fatty acid ester, silicone antifoaming agent, silicone oil, sorbitan fatty acid ester, polysorbate 80, etc.

[0066] These additives are not limited to those listed above, and one of these may be used alone or two or more of them may be used in combination.

[0067] The form of the pharmaceutical composition of the present invention is not particularly limited, but is preferably a solid composition or a liquid composition.

[0068] The pharmaceutical composition of the present invention can be in a dosage form described in the General Provisions for Preparations of the 18th Edition of the Japanese Pharmacopoeia, etc., such as a formulation for oral administration (including tablets, fine granules, granules, capsules, orally disintegrating tablets, drops, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets, etc.), a formulation for oral application (including oral tablets, troches, sublingual tablets, buccal tablets, adhesive tablets, gums, etc.), or a liquid. The pharmaceutical composition is preferably a tablet, fine granules, granules, capsules, orally disintegrating tablets, troches, drops, chewable tablets, or a liquid. The pharmaceutical composition is preferably a solid formulation. The pharmaceutical composition of the present invention is preferably an oral pharmaceutical composition.

[0069] The solid preparation is preferably a tablet, powder, fine granule, granule, capsule, or pill as described in the Japanese Pharmacopoeia, 18th Edition, more preferably a granule or tablet, and most preferably a tablet. Furthermore, when a granule is subjected to a particle size test according to the Japanese Pharmacopoeia, 18th Edition, a granule that passes entirely through a No. 18 (850 μm) sieve and retains 10% or less of the total amount on a No. 30 (500 μm) sieve is sometimes referred to as a fine granule.

[0070] Granules or tablets may be prepared by coating the preparation with a water-soluble polymer, etc. Examples include film-coated granules and film-coated tablets. Solid preparations may also be sugar-coated.

[0071] When the solid preparation is a tablet, it can be a single-layer tablet or a multi-layer tablet made by compressing two or more layers of powders or granules of different compositions. When the tablet is a multi-layer tablet, the at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof and the specified herbal medicine may be in the same layer or in different layers.

[0072] The pharmaceutical composition of the present invention may be temporarily packaged in SP packaging, PTP packaging, stick packaging, bottle packaging, etc., and then stored airtight. These may also be pillow-packaged, and stored in a box, etc. In other words, a pharmaceutical according to one embodiment of the present invention may comprise a pharmaceutical composition and a packaging material for packaging the pharmaceutical composition. Materials used for SP packaging, PTP packaging, stick packaging, and pillow packaging are not particularly limited, and include, for example, single-layer resin films such as polyvinyl chloride film, polyvinylidene chloride film, polypropylene film, polyethylene terephthalate film, and polyethylene film, multi-layer films combining these resin films, and resin films with aluminum foil attached thereto.

[0073] The packaging material for the pharmaceutical composition of the present invention is preferably, for example, packaging made of a material that is less susceptible to moisture (packaging made of at least one of a moisture-proof material and a gas barrier material). For example, a packaging made of a material that is less susceptible to moisture (moisture-proof material) may be PTP (polypropylene) + polyethylene aluminum pillow packaging (a combination of PTP and polyethylene aluminum pillow packaging). Furthermore, taking into consideration the suppression of an increase in the moisture content of the pharmaceutical composition, the storage stability of the pharmaceutical composition, and the stability of the pharmaceutical composition after opening, PTP packaging (Al-Al packaging) using aluminum on both sides may be used as a packaging made of a material that is less susceptible to moisture (moisture-proof material). If moisture absorption is a concern, a desiccant or the like may be simultaneously stored within the bottle packaging or pillow packaging. Known gas barrier materials may be used and are not particularly limited. For example, a laminate film having a functional barrier layer may be used, which may also serve as the moisture-proof material or may be used in combination with the moisture-proof material. Furthermore, the packaging material for the pharmaceutical composition of the present invention is not particularly limited, and environmentally friendly materials such as recycled plastics, biomass plastics, and biodegradable plastics may be used for part or all of the packaging material, as needed, and environmentally friendly containers and packaging may also be used.

[0074] <Uses> The pharmaceutical composition of the present invention can be suitably used for the purpose of suppressing fever, pain, and inflammation. The pharmaceutical composition of the present invention is preferably for anti-inflammatory purposes.

[0075] The pharmaceutical composition of the present invention may be used as a "composition for adjusting bitterness." For example, the composition of the present invention may be used as a "composition for adjusting bitterness, comprising at least one selected from the group consisting of loxoprofen, a salt thereof, and a hydrate thereof, a sugar alcohol, and a compound containing at least one metal selected from the group consisting of alkali metals and alkaline earth metals."

[0076] According to the composition for adjusting bitterness of the present invention, the bitterness of a pharmaceutical composition can be adjusted appropriately by adding a sugar alcohol and a compound containing at least one metal selected from the group consisting of alkali metals and alkaline earth metals, which have a bitter taste, to at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof, which have a bitter taste. That is, according to the present invention, an unexpected effect (a heterogeneous effect of being able to adjust bitterness with bitterness) was confirmed, in which the bitterness of a composition containing at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof can be adjusted by adding a compound containing at least one metal selected from the group consisting of alkali metals and alkaline earth metals, which have a bitter taste.

[0077] The active ingredients, loxoprofen, its salts, and hydrates thereof, and diclofenac, naproxen, their salts, and hydrates thereof, each have antipyretic, analgesic, and anti-inflammatory effects. Therefore, the pharmaceutical composition of the present invention is suitable for use as an antipyretic analgesic, particularly for relieving pain from headache, menstrual pain, toothache, pain after tooth extraction, sore throat, lower back pain, joint pain, muscle pain, stiff shoulders, earache, bruises, fractures, sprains, and trauma, and for reducing fever during chills and fever. It is also suitable for use as a cold medicine for relieving cold symptoms (runny nose, stuffy nose, cough, phlegm, sore throat, fever, chills, headache, sneezing, joint pain, and muscle pain).

[0078] The present invention will be explained in more detail below by way of examples, but the present invention is not limited to these examples in any way.

[0079] <Test Materials> (1) Test Substances The following test substances were used: Loxoprofen sodium hydrate (LOX) (anhydrous equivalent factor: 1.134), magnesium hydroxide, precipitated calcium carbonate, sodium bicarbonate, xylitol, l-menthol, and stevia.

[0080] (2) Reagents Water for injection: Otsuka Pharmaceutical Factory, Inc. Isoflurane: Mylan EPD LLC

[0081] (3) Animals Used: Four-week-old male Slc:ddY (SPF) mice were obtained from Japan SLC Co., Ltd. Animals were individually identified by ear punching on the day of arrival. The animals were acclimatized from arrival to the day of group allocation, with the arrival date being considered day 0 and the quarantine period lasting until the 7th. General observations were conducted daily. Body weights were measured on arrival day 1 (the day after arrival), day 3, and day 7 using a top-pan electronic balance (GX-6000, A&D Co., Ltd.) and an animal scale (DH-R1500N, Shinko Denshi Co., Ltd.).

[0082] (4) Breeding Method: Animals were individually housed in polysulfone cages (173W x 242D x 126H mm) placed on a stainless steel movable rack (1790W x 470D x 1650H mm) in a breeding room with a temperature of 22±3°C (actual measurement: 21.7-23.9°C), humidity of 50±20% (actual measurement: 38.0-61.7%), ventilation rate of 13-17 times / hour (all-fresh system filtered through a HEPA filter), and lighting time of 8:00-20:00 (12 hours light, 12 hours dark). Animals were fed ad libitum with solid feed Lab MR Stock (Nosan Corporation) placed on the cage lid. Drinking water was provided ad libitum via a polysulfone waterer (stainless steel tip) with tap water (during the quarantine acclimation period) or each administered substance (during the test period). Cages and bedding (Paperclean) were replaced at least once a week, water dispensers twice a week, and other equipment twice a month, all of which were replaced with autoclaved, high-pressure steam sterilized equipment.

[0083] <Test Method> (1) Grouping The weights of 5-week-old mice were measured after the quarantine and acclimation period. Using the weight values ​​obtained as an index, mice were divided into groups according to the following group composition table by stratified sequential randomization.

[0084]

[0085] (2) Preparation of Substances to be Administered (2-1) Vehicle Water for injection was used as the vehicle.

[0086] (2-2) Preparation of Test Substance Group B 5670.4 mg of LOX was weighed out, dissolved in the medium, and the total volume was adjusted to 500 mL to prepare the substance to be administered.

[0087] Preparation method for Group C 5670.8 mg of LOX and 5000.4 mg of magnesium hydroxide were weighed out, and the medium was added to dissolve them. The total volume was then adjusted to 500 mL to prepare the substance to be administered.

[0088] Preparation method for Group D 5670.1 mg of LOX and 5000.6 mg of precipitated calcium carbonate were weighed out, and the medium was added to dissolve them, and the total volume was adjusted to 500 mL to prepare the substance to be administered.

[0089] Preparation method for Group H 5670.1 mg of LOX, 5000.8 mg of sodium bicarbonate, and 25000.6 mg of xylitol were weighed out, dissolved in the medium, and the total volume was adjusted to 500 mL to prepare the substance to be administered.

[0090] Preparation method for Group I 5670.6 mg of LOX, 5000.1 mg of sodium bicarbonate, 25000.9 mg of xylitol, and 506.1 mg of 1-menthol were weighed, dissolved in the medium, and the total volume was adjusted to 500 mL to prepare the administered substance.

[0091] Preparation method for Group J: 5670.1 mg of LOX, 5000.4 mg of sodium bicarbonate, 20000.9 mg of xylitol, 505.7 mg of 1-menthol, and 500.4 mg of stevia were weighed, dissolved in the medium, and the total volume was adjusted to 500 mL to prepare the administered substance.

[0092] (3) Method of administration of the substance: From the day of grouping, the prepared solution for administration was placed in a water dispenser and given to the rats ad libitum as drinking water for a period of 3 days.

[0093] (4) Measurement of food intake and water intake The food intake and water intake were measured using an electronic balance once a day. All measurements were recorded to one decimal place.

[0094] The day the administration of the test substance began was designated as day 0, and the amount of food (in, including the cage lid) and the mass of water (in) were measured. At the next measurement, the amount of remaining food (out, including the cage lid) and the mass of water (out) were measured and calculated using the following formula.

[0095] Day 0 food mass (in) - Day 1 food mass (out) = Day 1 food intake (g) Day 0 water mass (in) - Day 1 water mass (out) = Day 1 water intake (g)

[0096] <Results> (1) Changes in food intake The results of changes in food intake are shown in Figure 1 and Table 2.

[0097] (3) Changes in water intake The results of changes in water intake are shown in Figures 2, 3, Tables 3 and 4.

[0098]

[0099]

[0100]

[0101] In the food intake over time shown in Figure 1 and Table 2, food intake increased in Groups H, I, and J compared to Group B. In the water intake over time shown in Figure 3 and Table 4, water intake increased in Groups H, I, and J compared to Group B. According to the results of the Examples, it is believed that the bitterness of the composition was masked by adding a compound containing a sugar alcohol and at least one metal selected from the group consisting of alkali metals and alkaline earth metals that conventionally have a bitter taste to at least one compound selected from the group consisting of loxoprofen, its salts, and hydrates thereof, thereby increasing the food and water intake of the mice.

[0102] According to the composition for adjusting bitterness of the present invention, the bitterness of the pharmaceutical composition can be adjusted appropriately by adding a sugar alcohol and a compound containing at least one metal selected from the group consisting of bitter alkali metals and alkaline earth metals to at least one member selected from the group consisting of bitter-tasting loxoprofen, its salts, and their hydrates.

[0103] That is, according to the present invention, an unexpected effect was confirmed that the bitterness of a composition containing at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof can be adjusted by adding a compound containing at least one metal selected from the group consisting of bitter alkali metals and alkaline earth metals. It can also be considered that a unique effect was confirmed in that adjusting the bitterness of a pharmaceutical composition with a bitter compound can improve the ease of taking a pharmaceutical composition containing loxoprofen.

[0104] Although the preferred embodiments and examples of the present invention have been described above, the present invention is not limited to these. Additions, omissions, substitutions, and other modifications to the configuration are possible without departing from the spirit of the present invention.

[0105] The pharmaceutical composition of the present invention is suitably used as an antipyretic analgesic, particularly for relieving pain such as headache, menstrual pain (period pain), toothache, pain after tooth extraction, sore throat, lower back pain, joint pain, muscle pain, stiff shoulder pain, earache, pain from bruises, bone fractures, sprains, and pain from trauma, and for reducing fever during chills and fever, and is also suitably used as a cold medicine for relieving various cold symptoms (runny nose, stuffy nose, cough, phlegm, sore throat, fever, chills, headache, sneezing, joint pain, and muscle pain).

Claims

1. A pharmaceutical composition comprising at least one member selected from the group consisting of loxoprofen, its salts, and hydrates thereof, and a compound containing a sugar alcohol and at least one metal selected from the group consisting of alkali metals and alkaline earth metals.

2. The pharmaceutical composition of claim 1, further comprising terpenes.

3. The pharmaceutical composition of claim 2, wherein the terpenes include menthol.

4. The pharmaceutical composition of claim 1, further comprising a sweetener.

5. The pharmaceutical composition of claim 4, wherein the sweetener comprises stevia.

6. The pharmaceutical composition according to any one of claims 1 to 5, wherein the sugar alcohol is at least one selected from the group consisting of lactitol, xylitol, sorbitol, erythritol, diglycerin, and polyglycerin.

7. A pharmaceutical composition according to any one of claims 1 to 5, wherein the mass ratio of the content of at least one selected from the group consisting of loxoprofen, its salts, and hydrates thereof to the content of the sugar alcohol is 1:1 to 1:

10.

8. The pharmaceutical composition according to any one of claims 1 to 5, wherein the compound is a salt, oxide or hydroxide of at least one metal selected from the group consisting of alkali metals and alkaline earth metals.

9. The pharmaceutical composition according to any one of claims 1 to 5, wherein the compound comprises at least one selected from the group consisting of carbonates and bicarbonates of at least one metal selected from the group consisting of alkali metals and alkaline earth metals.

10. The pharmaceutical composition according to any one of claims 1 to 5, wherein the compound comprises at least one selected from the group consisting of precipitated calcium carbonate, sodium bicarbonate, magnesium oxide and magnesium hydroxide.

11. The pharmaceutical composition according to any one of claims 1 to 5, wherein the mass ratio of the content of at least one compound selected from the group consisting of loxoprofen, its salts, and hydrates thereof to the content of the compound is 1:0.2 to 1:

5.

12. The pharmaceutical composition according to any one of claims 1 to 5, which is a solid or liquid composition.

13. The pharmaceutical composition according to any one of claims 1 to 5, which is in the form of a tablet, fine granules, granules, capsules, orally disintegrating tablets, troches, drops, chewable tablets or liquid.

14. The pharmaceutical composition according to any one of claims 1 to 5, which is an oral pharmaceutical composition.

15. The pharmaceutical composition according to any one of claims 1 to 5, which is used as an antipyretic analgesic or cold remedy.

16. A composition for adjusting bitterness, comprising: at least one member selected from the group consisting of loxoprofen, a salt thereof, and a hydrate thereof; a sugar alcohol; and a compound containing at least one metal selected from the group consisting of alkali metals and alkaline earth metals.

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