JP2019038801A - Pharmaceutical - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new technique for suppressing a change in formulation in a pharmaceutical composition containing ambroxol or a salt thereof or a solvate thereof with ibprofen or a salt thereof or a solvate thereof. The following components (A), (B) and (C): (A) ibprofen or a salt thereof or a solvate thereof; (B) ambroxol or a salt thereof or a solvate thereof; C) A pharmaceutical product containing a pharmaceutical composition containing tranexamic acid or a salt thereof or a solvate thereof; in an airtight package. [Selection diagram] None

Description

  The present invention relates to pharmaceuticals and the like.

Ibuprofen is a kind of non-steroidal anti-inflammatory analgesic (NSAID), and is a drug used as a component of general cold medicine, antipyretic analgesic, etc. due to its excellent antipyretic analgesic action and the like (Non-patent Document 1). .
Ambroxol is an active metabolite of bromohexine known as an expectorant component, and is a drug known as a mucosal lubricating component and used as a component for general cold medicine because of its excellent expectorant action. Patent Document 2).

  And the pharmaceutical composition (general cold medicine etc.) which contains both components of ibuprofen and ambroxol is already known (for example, nonpatent literature 3). However, it has been reported that when both components of ibuprofen and ambroxol are allowed to coexist, the composition changes, and when blended in the same composition, the stability can be lost over time (Patent Document 1). Therefore, providing a technique for suppressing such a change in formulation is to provide a pharmaceutical such as a common cold medicine that contains both the components of ibuprofen and ambroxol having excellent pharmacological action and has good storage stability. This is expected to contribute to the promotion of self-medication in Japan and the reduction of national medical expenses.

JP 2017-43546 A

OTC Medicine Handbook 2013 Jiho Co., Ltd., March 25, 2013, pp. 212-213 OTC Medicine Handbook 2013 Jiho Co., Ltd., published on March 25, 2013, page 270 Attached document "Pablon Ace AX Tablet" Taisho Pharmaceutical Co., Ltd., July 2017

  Therefore, the present invention provides a new technique for suppressing a change in formulation in a pharmaceutical composition containing ibuprofen or a salt thereof or a solvate thereof and ambroxol or a salt thereof or a solvate thereof. Is an issue.

  Therefore, the present inventors have intensively studied to solve the above problems, and surprisingly contain ibuprofen or a salt thereof or a solvate thereof and ambroxol or a salt thereof or a solvate thereof. The pharmaceutical composition further contains tranexamic acid or a salt thereof, or a solvate thereof, and is contained in an airtight package such as a bottle package or PTP package. Completed the invention.

That is, the present invention includes the following components (A), (B) and (C):
(A) ibuprofen or a salt thereof or a solvate thereof;
(B) Ambroxol or a salt thereof or a solvate thereof;
(C) tranexamic acid or a salt thereof or a solvate thereof;
The pharmaceutical composition containing the is provided with a pharmaceutical product contained in an airtight package.

  ADVANTAGE OF THE INVENTION According to this invention, the mixing | blending change between ibuprofen or its salt, or those solvates, and ambroxol, its salt, or those solvates can be suppressed. Therefore, a medicament containing ibuprofen or a salt thereof or a solvate thereof and ambroxol or a salt thereof or a solvate thereof excellent in storage stability can be provided.

In this specification, “ibuprofen or a salt thereof or a solvate thereof” includes not only ibuprofen itself but also a pharmaceutically acceptable salt of ibuprofen (for example, an alkali metal salt such as sodium salt or potassium salt; calcium salt, magnesium A salt of a group 2 element such as a salt; an organic amine salt such as a phenethylamine salt; a salt with an amino acid such as lysine); a solvent of ibuprofen or a pharmaceutically acceptable salt thereof with water, alcohol, etc. Japanese products are also included, and these can be used alone or in combination.
As ibuprofen or a salt thereof or a solvate thereof, ibuprofen or an L-lysine salt thereof is preferable, and ibuprofen listed in the 17th revised Japanese Pharmacopoeia is particularly preferable.
Ibuprofen or a salt thereof or a solvate thereof is known and can be produced by a known method or the like, or a commercially available product may be used. Examples of commercially available products include ibuprofen manufactured by Yonezawa Hamari Chemical Co., Ltd.

  The content of ibuprofen or a salt thereof or a solvate thereof in the pharmaceutical composition is not particularly limited, and can be determined by appropriate examination according to the sex, age, symptoms, etc. of the user. For example, the amount of ibuprofen in free form equivalent can be 200 to 1000 mg, more preferably 300 to 800 mg, and particularly preferably 400 to 600 mg per day. In the present invention, ibuprofen or a salt thereof or a solvate thereof is preferably contained in an amount of 10 to 50% by mass in terms of free form of ibuprofen with respect to the total mass of the pharmaceutical composition, and is preferably contained in an amount of 15 to 45% by mass. It is more preferable to contain 20 to 40% by mass.

In the present specification, “ambroxol or a salt thereof or a solvate thereof” includes not only ambroxol itself but also a pharmaceutically acceptable salt of ambroxol (for example, hydrochloride, hydrobromide, Acid addition salts with inorganic acids such as hydroiodide, sulfate, nitrate, phosphate; benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate Acid addition salts with organic acids such as maleate, fumarate, tartrate, citrate and acetate), and ambroxol and its pharmaceutically acceptable salts with water and alcohol, etc. Solvates are also included, and one or more of these can be used in combination.
As ambroxol or a salt thereof or a solvate thereof, ambroxol hydrochloride is preferable.
Ambroxol or a salt thereof or a solvate thereof is known and can be produced by a known method or the like, or a commercially available product may be used. Examples of commercially available products include ambroxol hydrochloride manufactured by Shizuoka Caffeine Industries, Ltd.

  The content of ambroxol or a salt thereof or a solvate thereof in the pharmaceutical composition is not particularly limited, and can be determined by appropriate examination according to the sex, age, symptoms, etc. of the user. For example, 10-100 mg, more preferably 20-80 mg, particularly preferably 30-60 mg of ambroxol can be contained per day in terms of hydrochloride of ambroxol. In the present invention, it is preferable to contain 0.1 to 10% by mass of ambroxol or a salt thereof or a solvate thereof in terms of hydrochloride of ambroxol with respect to the total mass of the pharmaceutical composition. It is more preferable to contain 5-5 mass%, and it is especially preferable to contain 1-3 mass%.

  Further, the content mass ratio of ibuprofen or a salt thereof or a solvate thereof to ambroxol or a salt thereof or a solvate thereof in the pharmaceutical composition is not particularly limited, but ibuprofen or a salt thereof or a solvent thereof. It is preferable to contain 0.01 to 0.5 parts by mass of ambroxol or a salt thereof or a solvate thereof in terms of its hydrochloride with respect to 1 part by mass in terms of its free form. It is more preferable to contain -0.3 mass part, and it is especially preferable to contain 0.05-0.1 mass part.

In the present specification, "tranexamic acid or a salt thereof or a solvate thereof" includes tranexamic acid itself, and pharmaceutically acceptable salts of tranexamic acid (for example, hydrochloride, hydrobromide, hydrogen iodide). Acid addition salts with inorganic acids such as acid salts, sulfates, nitrates, phosphates; benzoates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, maleic acid Acid addition salts with organic acids such as salts, fumarate, tartrate, citrate and acetate; alkali metal salts such as sodium and potassium salts; metals of Group 2 elements such as calcium and magnesium salts Salts, organic amine salts such as phenethylamine salts; salts with amino acids such as lysine), and solvates of tranexamic acid or its pharmaceutically acceptable salts with water, alcohol, etc. It can be used in combination of two or more thereof.
As tranexamic acid or a salt thereof or a solvate thereof, tranexamic acid is preferable, and tranexamic acid listed in the 17th revised Japanese Pharmacopoeia is particularly preferable.
Tranexamic acid or a salt thereof or a solvate thereof is known and can be produced by a known method or the like, or a commercially available product may be used. Examples of commercially available products include tranexamic acid manufactured by Daiichi Sankyo Propharma Co., Ltd.

  The content of tranexamic acid or a salt thereof or a solvate thereof in the pharmaceutical composition is not particularly limited, and can be determined by appropriate examination depending on the degree of change in formulation. For example, it can contain 200 to 1200 mg, more preferably 300 to 1000 mg, and particularly preferably 400 to 800 mg of tranexamic acid per day in terms of free form of tranexamic acid. In the present invention, from the viewpoint of suppressing change in formulation, tranexamic acid or a salt thereof or a solvate thereof is contained in an amount of 5 to 60% by mass in terms of free form of tranexamic acid with respect to the total mass of the pharmaceutical composition. Is preferable, it is more preferable to contain 10-50 mass%, and it is especially preferable to contain 20-45 mass%.

In the pharmaceutical composition, the mass ratio of ibuprofen or a salt thereof or a solvate thereof and tranexamic acid or a salt thereof or a solvate thereof is not particularly limited, but from the viewpoint of suppressing a change in formulation, ibuprofen. Alternatively, it is preferable to contain 0.1 to 5 parts by mass of tranexamic acid or a salt thereof or a solvate thereof in terms of the free form with respect to 1 part by mass of the salt or solvate thereof in terms of the free form. It is more preferable to contain 0.3-4 mass parts, and it is especially preferable to contain 0.5-2 mass parts.
Furthermore, the content mass ratio of ambroxol or a salt thereof or a solvate thereof and tranexamic acid or a salt thereof or a solvate thereof in the pharmaceutical composition is not particularly limited, but from the viewpoint of suppressing change in formulation. 1 to 3 parts by mass of ambroxol or a salt thereof or a solvate thereof in terms of its hydrochloride, and 3 to 40 parts by mass of tranexamic acid or a salt or a solvate thereof in terms of its free form It is more preferable to contain 5-30 mass parts, and it is especially preferable to contain 7-20 mass parts.

  The medicinal composition is a medicinal component other than those described above, such as antipyretic analgesics, antihistamines, antitussives, noscapine, bronchodilators, expectorants, hypnotic sedatives, vitamins, xanthine derivatives, anti-inflammatory agents, gastric mucosa It may contain one or more selected from the group consisting of a protective agent, an antacid, an anticholinergic agent, a herbal medicine, a Kampo prescription, and the like.

Specific examples of antipyretic analgesics include aspirin, aspirin aluminum, acetaminophen, ethenzamide, sazapyrine, salicylamide, lactylphenetidine, sodium salicylate, and the like.
Specific examples of the antihistamine include azelastine hydrochloride, alimemazine tartrate, istipendil hydrochloride, iproheptin hydrochloride, ebastine, epinastine hydrochloride, emedastine fumarate, oxatomide, olopatadine hydrochloride, carbinoxamine diphenyldisulfone Acid salt, carbinoxamine maleate, clemastine fumarate, d-chlorpheniramine maleate, dl-chlorpheniramine maleate, ketotifen fumarate, difeterol hydrochloride, difeterol phosphate, diphenyl Pyraline hydrochloride, diphenylpyraline theocuroate, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, cyproheptazine hydrochloride hydrate, cetirizine hydrochloride, triprolid Hydrochloride, tripelenamine hydrochloride, tondilamine hydrochloride, fexofenadine, phenetadine hydrochloride, promethazine hydrochloride, promethazine methylene disalicylate, bepotastine besilate, homochlorcyclidine hydrochloride, mequitazine, methodirazine hydrochloride, meso Examples include buhydroline napadisilate and loratadine.

  Specific examples of the antitussive include codeine, codeine phosphate hydrate, dihydrocodeine, dihydrocodeine phosphate and other codeines, aloclamide hydrochloride, eprazinone hydrochloride, carbetapentane enoate, cloperastine hydrochloride, Cloperastine phendizoate, dibutate sodium, dimemorphan phosphate, tipepidine citrate, tipepidine hibenzate, dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthalate Phosphorus salt etc. are mentioned. Of these, codeines are preferred. According to this invention, even if it is a case where a pharmaceutical composition contains codeines, a mixing | blending change can be suppressed.

Specific examples of noscapine include noscapine hydrochloride and noscapine.
Specific examples of the bronchodilator include, for example, trimethquinol hydrochloride, phenylpropanolamine hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, 1-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, Examples include 1-methylephedrine saccharin salt, dl-methylephedrine saccharin salt, methoxyphenamine hydrochloride and the like.

  Specific examples of expectorants include, for example, ammonia, fennel, ethylcysteine hydrochloride, ammonium chloride, carbocysteine, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, methylcysteine hydrochloride, 1-menthol, lysozyme hydrochloride Examples include salts.

Specific examples of the hypnotic sedative include allyl isopropyl acetyl urea and bromovalerylurea.
Specific examples of vitamins include vitamin B1, vitamin B2, vitamin B5, vitamin B6, vitamin B12, vitamin C, hesperidin and derivatives thereof, and salts thereof (specifically, for example, thiamine, thiamine chloride). Hydrochloride, thiamine nitrate, dicetiamine hydrochloride, sethiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octothiamine, chicotiamine, thiamine disulfide, bisivethiamine, bisbenchamine, prosultiamine, benfotiamine, riboflavin , Riboflavin phosphate, riboflavin butyrate, riboflavin sodium phosphate, panthenol, panthetin, sodium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate, cyanocobalamin, mecobara Emissions, ascorbic acid, sodium ascorbate, calcium ascorbate, hesperidin, etc.).

Specific examples of xanthine derivatives include caffeine (specifically, caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine, caffeine citrate, etc.), theophylline, theobromine, paraxanthine, Examples include proxyphylline and diprofylline.
Specific examples of the anti-inflammatory agent include glycyrrhizic acid and its derivatives and salts thereof (for example, dipotassium glycyrrhizinate and monoammonium glycyrrhizinate), seaprose, semi-alkaline proteinase, serrapeptase, procutase, pronase, bromelain Is mentioned.

Specific examples of the gastric mucosa protective agent include gefarnate, cetraxate hydrochloride, sofalcone, teprenone, methylmethionine sulfonium chloride, and the like.
Specific examples of the antacid include, for example, aminoacetic acid, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, magnesium aluminate hydroxide, hydroxide Aluminum gel, dry aluminum hydroxide gel, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / calcium carbonate / magnesium carbonate coprecipitation product, magnesium hydroxide , Coprecipitation product of magnesium hydroxide and potassium aluminum sulfate, magnesium carbonate, sodium hydrogen carbonate, precipitated calcium carbonate, magnesium aluminate metasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate Cuttlefish bone, stone Ke'Akira, Borei, and the like.

  Specific examples of the anticholinergic agent include oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, datsura extract, tipedium bromide, methyl atropine bromide, methyl anisotropine bromide, methyl scopolamine Bromide, methyl-1-hyostiamine bromide, methylbenactidium bromide, pirenzepine hydrochloride, butylscopolamine bromide, belladonna alkaloid, belladonna extract, belladonna total alkaloid, iodopropamide, diphenylpiperidinomethyldioxolane iodide, funnel extract, Examples include funnel root and funnel root total alkaloid citrate.

  Specific examples of herbal medicines include, for example, akamegashiwa (red buds), asenyaku (asenyaku), inyoukaku (horny sheep), fennel (yuka), engosaku (yenko), ogon (yellow japonicus), ousei (yellow spirit), Amber (yellow), Spruce (cherry bark), Auren (yellow ream), Onji (distant), Gajutsu (weather), valerian (deer herb), chamomile, caronin (Karojin), Kyokyo (kikyo), Kyonin ( Anzu), Kukoshi (coconut tree), Kukoyo (rice leaf), Keigai (rice cake), Keihi (cinnamon bark), Ketsumeishi (Keiko), Gentiana, Gennoshouko (current evidence), Kobushi (Katsukiko), Gooh (beef yellow), Garbage (Gomiko), Saishin (Spicy), Sansho (Yamakushi), Zion (Shizuku), Zikopi (Garder), Peonies (Glue), Musk (Mika), Shajin ( ), Shazenshi (car front child), Shazenso (car front grass), beast gall (including Yutan (bear gall)), gyoza (ginger), giryu (earth dragon), Xinyi (hot potato), sexan (stone wall), Senega, Senkyu (Ryukyu), Zenko (Mae-Hu), Senburi (Senri), Sojutsu (蒼朮), Sohakuhi (Kuwabara), Soyo (Soba), Taisan (Daegu), Chiksetsujinjin (Bamboo ginseng), Clove (Chick), Chinpi (Chinese Skin), Toki (Toki), Tokon (Nanten), Nantenjitsu (Minami Tenmi), Carrot (Ginseng), Baimo (Shuum), Bakumondou (Bakumon Winter), Hange (Half Summer) ), Bankouka (banka), hampi (anti-nasal), peony (white bean), peanut (white moth), bukuryo (茯苓), button pi (peony skin), maou (mao), rokjo (deer moth), and these Extract (extract, tincture, dry extract, etc.) and the like.

  Specific examples of Kampo prescriptions include, for example, Kakonto (Kakkonto), Keishito (Katsurayu), Kousosan (Kousosan), Psychokeito (Saiko Keito), Shosai Koto (Shosaikoto), Show Examples include Seiryuto (Seisei Ryuyu), Bakumondouto (Bakumon Fuyuto), Hangekoubokuto (Hankatsu Kobokuto), Maototo (Maoyuto), and the like.

  In the present specification, the dosage form of the “pharmaceutical composition” is not particularly limited, and may be any of solid, semi-solid, and liquid preparations, and can be selected according to the purpose of use. Examples of the dosage form of the pharmaceutical composition include the dosage forms described in the 17th revised Japanese Pharmacopoeia General Rules for Preparations. Specifically, for example, dosage forms for oral administration include tablets (including normal tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets, etc.), capsules, granules ( For example, including foamed granules, etc.), solid preparations such as powders and pills; semi-solid preparations such as oral jelly preparations; oral liquids (including elixirs, suspensions, emulsions, limonades, etc.), etc. Liquid preparations and the like. In addition, dosage forms for parenteral administration include injections, inhalants, eye drops, ear drops, nasal drops, suppositories, external solid preparations, external liquid preparations, sprays, ointments, creams, gels. And patches.

  The dosage form of the pharmaceutical composition is preferably a solid preparation from the viewpoint of ease of administration, etc., and tablets (for example, ordinary tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolution tablets) It is particularly preferably a solid preparation selected from tablets (including tablets and the like), capsules, granules (including foamed granules, etc.), powders and pills.

  Depending on the dosage form, the pharmaceutical composition can be produced by a known method described in, for example, the 17th revised Japanese Pharmacopoeia General Rules for Preparations. In this case, a pharmaceutically acceptable carrier (formulation additive) may be added to the pharmaceutical composition. Examples of such formulation additives include excipients, disintegrants, binders, lubricants, plasticizers, film forming agents, powders, poorly water-soluble polymeric substances, antioxidants, corrigents, sweeteners, etc. However, it is not limited to these. Specific examples of these pharmaceutical additives include those listed in the Pharmaceutical Additives Dictionary 2016 (published by Yakuji Nippo Co., Ltd.), Handbook of Pharmaceutical Excipients, Seventh Edition (published by Pharmaceutical Press), etc. Can be mentioned.

  Specific examples of the excipient include, for example, aluminum silicate, anhydrous sodium sulfate, anhydrous calcium hydrogen phosphate, sodium chloride, calcium silicate, light anhydrous silicic acid, heavy anhydrous silicic acid, calcium sulfate, monophosphate. Inorganic excipients such as calcium hydrogen phosphate, calcium hydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, sodium dihydrogen phosphate; candy flour, starch (wheat starch, rice starch, corn Starch, partially pregelatinized starch, etc.), fructose, caramel, agar, xylitol, paraffin, crystalline cellulose, sucrose, maltose, lactose, lactose hydrate, sucrose, glucose, pullulan, polyoxyethylene hydrogenated castor oil, maltitol, Reduced maltose water candy, powdered reduced maltose water candy, erythritol, Rubitoru, mannitol, lactitol, trehalose, reduced palatinose, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylamino acetate, organic excipients such as calcium citrate and the like. These can be used alone or in combination of two or more.

  Specific examples of the disintegrant include super disintegrants such as sodium carboxymethyl starch, croscarmellose sodium, crospovidone, carmellose, carmellose calcium, starch, sucrose fatty acid ester, gelatin, sodium bicarbonate, dextrin, Dehydroacetic acid and its salt, povidone, polyoxyethylene hydrogenated castor oil 60, etc. are mentioned. These can be used alone or in combination of two or more.

  Specific examples of the binder include oils and fats such as hydrogenated beef tallow oil, hydrogenated oil, hydrogenated vegetable oil, soybean hardened oil, carnauba wax, honey beeswax, beeswax, and owl, as well as methyl cellulose, hydroxypropyl cellulose, hypromellose, carme Sodium loose, starch (wheat starch, rice starch, corn starch, partially pregelatinized starch, etc.), dextrin, pullulan, gum arabic, agar, gelatin, tragacanth, sodium alginate, povidone, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, polyvinyl acetal Examples include diethylaminoacetate. These can be used alone or in combination of two or more.

  Specific examples of the lubricant include calcium stearate, magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, and the like. These can be used alone or in combination of two or more.

  Specific examples of the plasticizer include triethyl citrate, glycerin, sesame oil, sorbitol, castor oil, polysorbate 80 (polyoxyethylene (20) sorbitan oleate) and the like. These can be used alone or in combination of two or more.

  Specific examples of the film forming agent include alkyl celluloses such as methyl cellulose and ethyl cellulose; alginic acid such as sodium alginate or a salt thereof; carrageenan; carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, carboxymethyl cellulose potassium, carboxymethyl cellulose, carboxymethyl ethyl cellulose, and the like. Xanthan gum; hydroxyalkyl cellulose such as hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose); hydroxyalkylcellulose phthalate such as hydroxypropylmethylcellulose phthalate; pullulan; polyvinyl acetate Polyvinyl acetate phthalate, polyvinyl pyrrolidone, and the like. These can be used alone or in combination of two or more.

  Examples of the powder include organic powders or inorganic powders such as talc, titanium oxide, yellow ferric oxide, ferric oxide, and legal dyes. These can be used alone or in combination of two or more.

Specific examples of the poorly water-soluble polymer substance include carboxyvinyl polymer and aminoalkyl methacrylate copolymer. These can be used alone or in combination of two or more.
Specific examples of the antioxidant include ascorbic acid, sodium bisulfite, sodium sulfite, sodium edetate, erythorbic acid, tocopherol acetate, dibutylhydroxytoluene, natural vitamin E, tocopherol, butylhydroxyanisole and the like. These can be used alone or in combination of two or more.

  Specific examples of the corrigent include, for example, limonene, pinene, camphene, cymen, cineole, citronellol, geraniol, nerol, linalool, menthol, terpineol, rosinol, borneol, isoborneol, menthone, camphor, eugenol, synzeanol and the like. Terpenes: Spruce oil, orange oil, peppermint oil, camphor white oil, eucalyptus oil, turpentine oil, lemon oil, pepper oil, clove oil, cinnamon oil, lavender oil, fennel oil, chamomile oil, perilla oil, spearmint oil, etc. Essential oils containing terpenes such as ascorbic acid, tartaric acid, citric acid, malic acid and sour agents such as salts thereof. These can be used alone or in combination of two or more.

  Specific examples of the sweetening agent include aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin, sodium saccharin and the like, and one or more of these can be used in combination.

A pharmaceutical composition can be manufactured by a well-known method according to the dosage form.
For example, when the pharmaceutical composition is a solid preparation, it can be produced by appropriately combining unit operations such as pulverization, mixing, granulation, drying, sizing, classification, filling, tableting and coating.
More specifically, for example, when the dosage form of the pharmaceutical composition is a granular preparation such as granules, powders, pills, etc., ibuprofen or a salt thereof or a solvate thereof, ambroxol or a salt thereof or a solvent thereof In addition to Japanese products, tranexamic acid or salts thereof, or solvates thereof, if necessary, use additives such as excipients, binders, disintegrants, lubricants, etc. After mixing, granulate is obtained by granulation by a known granulation method such as extrusion granulation, rolling granulation, stirring granulation, fluidized bed granulation, spray granulation, melt granulation, crush granulation, etc. Further, it can be produced by classification, sizing, etc. as necessary. In addition, the obtained granulated material can also be coat | covered with a coating agent etc. by a well-known method.
In addition, when the dosage form of the pharmaceutical composition is a tablet, in addition to ibuprofen or a salt thereof or a solvate thereof, ambroxol or a salt thereof or a solvate thereof, tranexamic acid or a salt thereof or a solvate thereof If necessary, use appropriate formulation additives such as excipients, binders, disintegrants, lubricants, etc., and mix all or part of these components to obtain a mixture, which is directly compressed (tablet) ) (Direct powder compression method), and the above granulated product is classified and sized as necessary, and then compressed (tablet) (semi-dry granule compression method, dry granule compression method, wet granule compression method) For example). The obtained compressed product (tablet) can also be coated with a coating agent or the like by a known method.
Furthermore, when the dosage form of the pharmaceutical composition is a capsule, the above granulated product or compressed product may be filled into a capsule.

In the present invention, the pharmaceutical composition is further accommodated in an airtight package (hereinafter, in this specification, a product obtained by accommodating a pharmaceutical composition in an airtight package is referred to as “medicine”). In the present invention, in addition to the airtight package, the pharmaceutical may further include a package that does not correspond to the following “airtight package”, and the pharmaceutical composition is contained directly or indirectly in the airtight package. It only has to be done.
In this specification, `` airtight package '' means a package that can suppress the intrusion of solid or liquid foreign substances in the state of normal handling, transportation or storage, etc., and is defined in the 17th revised Japanese Pharmacopoeia General Rules. It is a concept including “airtight container” and “sealed container”. As the airtight package, any of a regular shape and an irregular shape can be used. Specifically, for example, bottle packaging, SP (Stripe Package) packaging, PTP (Press Through Package) packaging, pillow packaging, stick packaging, etc. Is mentioned. The hermetic package may be a combination of a plurality of these. Specifically, for example, an embodiment in which the pharmaceutical composition is first packaged in PTP packaging and further packaged in pillow packaging, etc. .
The airtight package is preferably at least one selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging, and stick packaging from the viewpoint of suppressing change in formulation, and at least including PTP packaging ( A combination of PTP packaging and further packaging such as bottle packaging, SP packaging, pillow packaging, stick packaging, etc., if necessary) is particularly preferred.

  The packaging material (material) of the hermetic package is not particularly limited. For example, glass, plastic (polyester such as polyethylene terephthalate and polyethylene naphthalate); polyethylene (low density (LDPE), medium density (MDPE), high density (HDPE) Materials such as polypropylene, polyolefins such as polypropylene, polycarbonates, polystyrene, etc.), metals (aluminum, etc.) and the like used in the fields of pharmaceuticals and foods, etc., alone or in combination of two or more. it can.

For example, the packaging material used for bottle packaging is not particularly limited, and examples thereof include glass, plastic, metal, and the like, and one or more of these can be combined as appropriate. As a material for bottle packaging, glass, polyethylene, and polypropylene are preferable, glass, low density polyethylene (LDPE), and high density polyethylene (HDPE) are more preferable, and glass and high density polyethylene (HDPE) are particularly preferable.
When packaging a bottle, for example, an appropriate amount of the pharmaceutical composition may be stored in the bottle and then sealed with an appropriate stopper or lid. In addition, what is necessary is just to select the thing of the magnitude | size according to the quantity etc. of the pharmaceutical composition to store suitably, and, as a capacity | capacitance of a bottle, it is about 10-500 mL, for example, 14-400 mL is preferable, 24-350 mL Is more preferable.

  Moreover, the packaging material used for SP packaging, PTP packaging, pillow packaging, stick packaging, and the like is not particularly limited. For example, biaxially oriented polypropylene (OPP), biaxially oriented polyester (PET), glycol-modified PET ( PET-G), biaxially stretched nylon (ONy, PA), cellophane, paper, low density polyethylene (LDPE), linear low density polyethylene (L-LDPE), ethylene-vinyl acetate copolymer (EVA), none Stretched polypropylene (CPP, IPP), ionomer resin (IO), ethylene-methacrylic acid copolymer (EMAA), polyacrylonitrile (PAN), biaxially stretched polyvinylidene chloride (PVDC), ethylene-vinyl alcohol copolymer resin (EVOH) ), Polyvinyl chloride (PVC), cyclic polyolefin (COC), Resin such as stretched nylon (CNy), polycarbonate (PC), polystyrene (PS), hard vinyl chloride (VSC), metal foil such as aluminum foil (AL), and the like, one or more of these Can be combined as appropriate.

  When carrying out SP packaging, PTP packaging, pillow packaging, stick packaging, etc., it may be produced by a known method using a sheet using one or more of the packaging materials as described above. In this case, the packaging material Can have a multilayer structure appropriately combined. Examples of a method for forming a multilayer structure using two or more kinds of packaging materials as a sheet include a method of laminating the packaging materials to produce a laminated sheet. The laminated sheet can be produced by a known method such as extrusion lamination, dry lamination, coextrusion lamination, thermal lamination, wet lamination, non-solvent lamination, heat lamination and the like. Moreover, a well-known commercial item can also be used for the sheet | seat for SP packaging, PTP packaging, pillow packaging, and stick packaging.

  In the said sheet | seat, as a single layer sheet using 1 type of packaging materials, a PVC sheet, a CPP sheet, etc. are mentioned, Moreover, as a laminated sheet using 2 or more types of packaging materials, the sheet | seat structure is, for example, Laminated PVC and PVDC (PVC / PVDC; hereinafter abbreviated), 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 sheet shown on the left uses two or more types as CPP), etc., but are limited to these. Is not to be done.

As a form of PTP packaging, a pharmaceutical composition is stored one by one or one dosage unit in a pocket formed in a resin sheet or the like by a known method, and then a sheet made of metal foil such as aluminum foil is used as a constituent material. For example, the lid may be used as a lid material. In addition, it is good also as what is called double-sided aluminum PTP packaging using the sheet | seat which uses aluminum foil as a constituent material as a sheet | seat which forms a pocket. In the present invention, it is preferable that the PTP packaging is further packaged by pillow packaging (for example, aluminum pillow packaging or the like) from the viewpoint of suppressing change in formulation.
Examples of forms of SP packaging, pillow packaging, and stick packaging include packaging a pharmaceutical composition one by one or one dosage unit using a resin sheet or a sheet containing aluminum foil as a constituent material by a known method. . In the present invention, it is preferable to use a sheet containing aluminum foil as a constituent material from the viewpoint of suppressing change in formulation.

  In the present specification, the occupation ratio (volume ratio) inside the package of the pharmaceutical composition in the pharmaceutical product is usually 25 to 90%, preferably 28 to 75% when the package is a bottle package, 30 to 50% is more preferable. When the package is SP packaging, PTP packaging, pillow packaging, or stick packaging, it is usually 30 to 98%, preferably 40 to 95%, more preferably 45 to 93%, and particularly preferably 50 to 90%. . In this case, the occupation rate means the occupation rate of the pharmaceutical composition with respect to the entire volume inside the package, and the filling or inner plug for preventing damage of the pharmaceutical composition stored inside the package. Etc. are not considered in calculating the space occupancy.

  As the airtight package, a commercially available package may be used as it is, or a commercially available packaging material may be processed and used. Examples of commercially available bottle packaging bodies include glass bottles (manufactured by Saiya Glass Industry Co., Ltd.), tablet bottles (manufactured by Tokyo Glass Co., Ltd.), Z-series (manufactured by Hanshin Chemical Industry Co., Ltd.), and the like. It is done. Moreover, as a package of a commercially available pillow package, Lami Zip (registered trademark) (manufactured by Nippon Shokubai Co., Ltd.) and the like can be mentioned. Furthermore, as packaging materials for SP packaging, PTP packaging, pillow packaging and stick packaging, Sumilite VSS, Sumilite VSL, Sumilite NS, Sumilite FCL (above, manufactured by Sumitomo Bakelite Co., Ltd.), TAS series (Taisei Chemical Co., Ltd.) Manufactured), PTP vinyl foil, PTP super foil (Mitsubishi Resin Co., Ltd.), Nippaku aluminum foil (manufactured by Nippon Foil Co., Ltd.), aluminum foil silver plain (manufactured by Daiwa Chemical Industry Co., Ltd.), etc. It is done.

  The method for accommodating the pharmaceutical composition in the hermetic package is not particularly limited, and can be achieved by placing the pharmaceutical composition in the package by an appropriate means such as charging the pharmaceutical composition into the package. In this case, a means for putting a desiccant (for example, a columnar (tablet type) or a sheet) into the package together with the pharmaceutical composition may be used.

  In the present invention, the pharmaceutical composition or the pharmaceutical product contains ibuprofen which is a kind of NSAID or a salt thereof or a solvate thereof, and ambroxol having an expectorant action or a salt thereof or a solvate thereof. For example, headache, toothache, pain after extraction, sore throat, ear pain, joint pain, neuralgia, low back pain, muscle pain, stiff shoulder pain, bruise pain, fracture pain, sprain pain, menstrual pain (menstrual pain), trauma pain Efficacy or effects such as analgesia, antipyretic fever, fever, cold symptoms (sore pain, chills, fever, headache, sputum, joint pain, muscle pain), etc. It is useful as a medicine) and antipyretic analgesics.

  The route of taking the pharmaceutical composition is not particularly limited and can be determined and appropriately determined according to the disease to be applied, the type of preparation, the sex, age, symptoms, etc. of the user, but from the viewpoint of ease of taking Oral administration is preferred. In addition, the pharmaceutical composition can be taken 1 to 4 times per day before meals, between meals, after meals, before going to bed.

In addition, although this specification is not limited to these at all, the invention of the following aspects is disclosed, for example.
[1A] The following components (A), (B) and (C):
(A) ibuprofen or a salt thereof or a solvate thereof;
(B) Ambroxol or a salt thereof or a solvate thereof;
(C) tranexamic acid or a salt thereof or a solvate thereof;
A pharmaceutical product comprising a pharmaceutical composition containing the product contained in an airtight package.
[2A] The pharmaceutical product according to [1A], wherein the pharmaceutical composition is a solid preparation.
[3A] The pharmaceutical product according to [1A] or [2A], wherein the dosage form of the pharmaceutical composition is a tablet, capsule, granule, powder or pill.
[4A] The pharmaceutical product according to any one of [1A] to [3A], wherein the airtight package is at least one selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging, and stick packaging.
[5A] The pharmaceutical product according to any one of [1A] to [4A], wherein the hermetic package includes at least a PTP package.

[1B] The following components (A), (B) and (C) for accommodation in an airtight package:
(A) ibuprofen or a salt thereof or a solvate thereof;
(B) Ambroxol or a salt thereof or a solvate thereof;
(C) tranexamic acid or a salt thereof or a solvate thereof;
A pharmaceutical composition comprising:
[2B] The pharmaceutical composition according to [1B], which is a solid preparation.
[3B] The pharmaceutical composition according to [1B] or [2B], wherein the dosage form is a tablet, capsule, granule, powder or pill.
[4B] The pharmaceutical composition according to any one of [1B] to [3B], wherein the airtight package is at least one selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging, and stick packaging.
[5B] The pharmaceutical composition according to any one of [1B] to [4B], wherein the airtight package includes at least a PTP package.

[1C] The following components (A) and (B):
(A) ibuprofen or a salt thereof or a solvate thereof;
(B) Ambroxol or a salt thereof or a solvate thereof;
In addition to the following component (C):
(C) tranexamic acid or a salt thereof or a solvate thereof;
And a method for stabilizing the pharmaceutical composition (for example, a method for stabilizing the components (A) and / or (B). The method includes the step of stabilizing the pharmaceutical composition, including the step of containing the pharmaceutical composition in an airtight package. The “method” is preferably “a method for suppressing change in formulation”, and particularly preferably “a method for suppressing change in formulation between components (A) and (B)”.
In this method, the order of the step of containing the component (A), the component (B) and the component (C) in the pharmaceutical composition, and the step of storing the pharmaceutical composition in an airtight package is not particularly limited. For example, the components (A), (B), and (C) may be contained in the pharmaceutical composition in any order and then contained in an airtight package, and the components (A), (B) , (C) may be contained in the pharmaceutical composition, and then contained in an airtight package, and then the remaining components may be further contained in the pharmaceutical composition.
[2C] The method according to [1C], wherein the pharmaceutical composition is a solid preparation.
[3C] The method according to [1C] or [2C], wherein the dosage form of the pharmaceutical composition is a tablet, capsule, granule, powder or pill.
[4C] The method according to any one of [1C] to [3C], wherein the airtight package is at least one selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging, and stick packaging.
[5C] The method according to any one of [1C] to [4C], wherein the airtight package includes at least a PTP package.

  EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited at all by these.

[Test Example 1] Stability test 1
Samples 1 to 4 shown below were prepared and stored for 1 week under conditions of 40 ° C. and 75% relative humidity (RH). The state of the mixture in the sample immediately after the start of storage, 1 day, 2 days and 1 week And the presence or absence of a change in the composition was confirmed.
The results are shown in Table 1.

[Sample 1]
24.0 parts by weight of ibuprofen (Yonezawa Hamari Pharmaceutical Co., Ltd .: ibuprofen) and 1.8 parts by weight of ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: ambroxol hydrochloride) were mixed. Thereafter, 5.0 parts by mass of purified water was added and kneaded to obtain a mixture.
[Sample 2]
24.0 parts by weight of ibuprofen (Yonezawa Hamari Pharmaceutical Co., Ltd .: ibuprofen) and 1.8 parts by weight of ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: ambroxol hydrochloride) were mixed. Thereafter, 5.0 parts by mass of purified water was added and kneaded to obtain a mixture. 3.0 g of the obtained mixture was put into a glass bottle (manufactured by Saiya Glass Industry Co., Ltd .: A-102K) and covered, and this was used as Sample 2. The occupation ratio (volume ratio) of the mixture inside the glass bottle was 41.7%.

[Sample 3]
24.0 parts by mass of ibuprofen (manufactured by Yonezawa Hamari Pharmaceutical Co., Ltd .: ibuprofen), 1.8 parts by mass of ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: ambroxol hydrochloride) and tranexam After mixing 30.0 parts by mass of acid (Daiichi Sankyo Propharma Co., Ltd .: trade name: Japanese Pharmacopoeia Tranexamic acid), 11.2 parts by mass of purified water was added and kneaded to obtain a mixture. Sample 3 was designated.
[Sample 4]
24.0 parts by mass of ibuprofen (manufactured by Yonezawa Hamari Pharmaceutical Co., Ltd .: ibuprofen), 1.8 parts by mass of ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: ambroxol hydrochloride) and tranexam After mixing 30.0 parts by mass of acid (Daiichi Sankyo Propharma Co., Ltd., trade name: Japanese Pharmacopoeia Tranexamic acid), 11.2 parts by mass of purified water was added and kneaded to obtain a mixture. 3.0 g of the obtained mixture was put into a glass bottle (manufactured by Saiya Glass Industry Co., Ltd .: A-102K) and covered, and this was used as Sample 4. The occupation ratio (volume ratio) of the mixture inside the glass bottle was 41.7%.

From the test results shown in Table 1, in Sample 1 in which ibuprofen and ambroxol hydrochloride were mixed, it was found that the mixture changed after 2 days from the start of storage and the mixture solidified.
Similarly to sample 1, sample 2 in which ibuprofen and ambroxol hydrochloride were mixed and contained in an airtight package, and sample 3 in which tranexamic acid was further mixed in addition to ibuprofen and ambroxol hydrochloride were used. It was found that the mixture changed after 2 days from the start of storage and the mixture solidified.
On the other hand, in sample 4 in which tranexamic acid was further mixed in addition to ibuprofen and ambroxol hydrochloride, and this was contained in an airtight package, the white powder state was maintained even after one week of storage, just after the start of storage. It turned out to be dripping.

  Based on the above test results, the compounding change between ibuprofen or a salt thereof or a solvate thereof and ambroxol or a salt thereof or a solvate thereof was determined by incorporating tranexamic acid or a salt thereof or a solvate thereof. It has been clarified that an excellent suppression effect is exhibited by combining both means, while it cannot be suppressed at all by only one of the means for carrying out and the means accommodated in the airtight package.

[Test Example 2] Stability test 2
Sample 5 shown below was prepared and stored for 1 week under conditions of 40 ° C. and 75% relative humidity (RH). The condition of the mixture in the sample was evaluated immediately after the start of storage and after 1 week, and whether there was any change in the composition It was confirmed.
The results are shown in Table 2.

[Sample 5]
24.0 parts by mass of ibuprofen (manufactured by Yonezawa Hamari Pharmaceutical Co., Ltd .: ibuprofen), 1.8 parts by mass of ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: ambroxol hydrochloride) and tranexam After mixing 30.0 parts by mass of acid (Daiichi Sankyo Propharma Co., Ltd., trade name: Japanese Pharmacopoeia Tranexamic acid), 11.2 parts by mass of purified water was added and kneaded to obtain a mixture. Of the obtained mixture, 0.3 g of a resin sheet (manufactured by Sumitomo Bakelite Co., Ltd .: trade name Sumilite VSS-1202-R) in which a pocket (a cylindrical recess having a diameter of 12 mm and a height of 6 mm) was formed in advance. It was put in the pocket portion, and then covered with PTP aluminum foil (manufactured by Daiwa Chemical Industry Co., Ltd .: trade name: aluminum foil silver plain) and PTP packaged. In addition, the occupation rate (volume ratio) in the pocket part of the PTP sheet of the mixture was 73.7%.

  From the test results shown in Table 2, even when PTP packaging was used as an airtight package instead of the bottle packaging used in Sample 4 of Test Example 1, as with Sample 4, ibuprofen or a salt thereof or a solvate thereof was used. It was confirmed that an excellent inhibitory effect was exerted on the change in formulation with ambroxol or a salt thereof or a solvate thereof.

[Test Example 3] Stability test 3
Exactly the same test as in Test Example 2 was performed, except that the storage conditions were changed to a humidity not adjusted at a temperature of 40 ° C.
The results are shown in Table 3.

  From the test results shown in Table 3, even when the storage conditions were changed, it was also excellent with respect to the mixing change between ibuprofen or a salt thereof or a solvate thereof and ambroxol or a salt thereof or a solvate thereof. It was confirmed that the inhibitory action was exhibited.

[Production Example 1]
According to a conventional method, tablets containing the following components per 6 tablets (2.4 g) were produced. The obtained tablets were PTP-packaged by a conventional method to obtain the pharmaceutical product of Production Example 1.
Ibuprofen 600mg
Tranexamic acid 750mg
Ambroxol hydrochloride 45mg
Cremastine fumarate 1.34mg
Anhydrous caffeine 75mg
dl-Methylephedrine hydrochloride 60mg
Dihydrocodeine phosphate 24mg
Thiamine nitrate 25mg
Riboflavin 12mg
Crystalline cellulose appropriate amount trehalose 300mg
Macrogol 12mg
Croscarmellose sodium 80mg
Polyvinyl alcohol (partially saponified product) 10mg
Light anhydrous silicic acid 4mg
Hardened oil 10mg
Magnesium stearate 48mg
Hypromellose 65mg
Titanium oxide 6.5mg
Carnauba wax

[Production Example 2]
A granule containing the following components (3 packages: 3.6 g) was produced by a conventional method. The obtained granule was packaged in an aluminum pillow by a conventional method so as to be 1.2 g per package, whereby a pharmaceutical product of Production Example 2 was obtained.
Ibuprofen 450mg
Tranexamic acid 750mg
Ambroxol hydrochloride 45mg
Cremastine fumarate 1.34mg
Anhydrous caffeine 40mg
dl-Methylephedrine hydrochloride 60mg
Dihydrocodeine phosphate 24mg
Thiamine nitrate 25mg
Riboflavin 12mg
Crystalline cellulose appropriate amount Erythritol 850mg
Trehalose 590mg
Pullulan 184mg
Ammonio alkyl methacrylate copolymer 10mg
Croscarmellose sodium 80mg
Aspartame 82mg

[Production Example 3]
By a conventional method, tablets containing the following components per 9 tablets (4.5 g) were produced. The obtained tablet was PTP-packed by a conventional method, and this was further packaged with an aluminum pillow to obtain a pharmaceutical product of Production Example 3.
Ibuprofen 600mg
Tranexamic acid 750mg
Ambroxol hydrochloride 45mg
Dihydrocodeine phosphate 24mg
dl-Methylephedrine hydrochloride 60mg
Isopropamide iodide 6mg
Chlorpheniramine maleate 7.5mg
Anhydrous caffeine 75mg
Magnesium oxide 300mg
Ascorbic acid 300mg
Thiamine nitrate 24mg
Riboflavin 12mg
Crystalline cellulose Appropriate amount of light anhydrous silicic acid 12mg
Lactose 6mg
Low substituted hydroxypropylcellulose 678mg
D-mannitol 650mg
Corn starch 60mg
Magnesium stearate 24mg
Talc 6mg
Hypromellose 70mg
Macrogol 11mg
Titanium oxide 8mg

[Production Example 4]
By a conventional method, a granule containing the following components (3 capsules: 4.5 g) was produced. The obtained granule was packaged in an aluminum pillow by a conventional method so as to be 1.5 g per package, and a pharmaceutical product of Production Example 4 was obtained.
Ibuprofen 450mg
Tranexamic acid 420mg
Ambroxol hydrochloride 45mg
Dihydrocodeine phosphate 24mg
dl-Methylephedrine hydrochloride 60mg
Isopropamide iodide 6mg
Chlorpheniramine maleate 7.5mg
Anhydrous caffeine 75mg
Ascorbic acid 300mg
Thiamine nitrate 24mg
Riboflavin 12mg
Crystalline cellulose appropriate amount Carmellose calcium 1106mg
Light anhydrous silicic acid 4mg
Low substituted hydroxypropylcellulose 1380mg
Talc 4mg
Tartaric acid 105mg
Saccharin sodium 100mg
l-Menthol 4mg

[Production Example 5]
A tablet containing the following ingredients per 2 tablets (1.5 g) was produced by a conventional method. The obtained tablet was PTP-packed by a conventional method, and this was further placed in a paper box to obtain a pharmaceutical product of Production Example 5.
Ibuprofen 200mg
Tranexamic acid 250mg
Ambroxol hydrochloride 15mg
L-carbocysteine 250mg
Dihydrocodeine phosphate 8mg
dl-Methylephedrine hydrochloride 20mg
Chlorpheniramine maleate 2.5mg
Anhydrous caffeine 25mg
Magnesium oxide 100mg
Ascorbic acid 100mg
Thiamine nitrate 8mg
Riboflavin 4mg
Crystalline cellulose Appropriate amount of light anhydrous silicic acid 20mg
Lactose 150mg
Hypromellose 45mg
Low substituted hydroxypropylcellulose 45mg
Talc 70mg
Sodium starch glycolate 50mg

[Production Example 6]
According to a conventional method, tablets containing the following components per 9 tablets (2.52 g) were produced. The obtained tablets were PTP-packaged by a conventional method to obtain the pharmaceutical product of Production Example 6.
Ibuprofen 600mg
Tranexamic acid 750mg
Ambroxol hydrochloride 45mg
Dihydrocodeine phosphate 24mg
dl-Methylephedrine hydrochloride 60mg
Chlorpheniramine maleate 3.5mg
Anhydrous caffeine 75mg
Lactose appropriate amount hypromellose 60mg
Anhydrous citric acid 40mg
Calcium silicate 30mg
84mg hydroxypropylcellulose
Carmellose calcium 100mg
Light anhydrous silicic acid 70mg
Magnesium stearate 70mg
Triacetin 7mg
Talc 13mg
Titanium oxide 10mg
Carnauba wax

  According to the present invention, since it is possible to provide a pharmaceutical composition containing both ibuprofen and ambroxol components having excellent pharmacological action and excellent in storage stability, it can be used, for example, in the pharmaceutical industry.

Claims (4)

The following components (A), (B) and (C):
(A) ibuprofen or a salt thereof or a solvate thereof;
(B) Ambroxol or a salt thereof or a solvate thereof;
(C) tranexamic acid or a salt thereof or a solvate thereof;
A pharmaceutical product comprising a pharmaceutical composition containing the product contained in an airtight package.   The pharmaceutical product according to claim 1, wherein the pharmaceutical composition is a solid preparation.   The pharmaceutical product according to claim 1 or 2, wherein the dosage form of the pharmaceutical composition is a tablet, capsule, granule, powder or pill.   The pharmaceutical product according to any one of claims 1 to 3, wherein the hermetic package is at least one selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging, and stick packaging.