JP2022084568A - Pharmaceutical composition - Google Patents

Abstract

To provide a technique that prevents incompatibility in a pharmaceutical composition containing loxoprofen or a salt thereof and cinnamon bark or its extract.SOLUTION: A pharmaceutical composition contains following components (A), (B) and (C): (A) loxoprofen or a salt thereof; (B) cinnamon bark or its extract; and (C) at least one selected from the group consisting of following components (C-1)-(C-3): (C-1) tranexamic acid or a salt thereof; (C-2) a xanthine derivative; and a basic compound (C-3) having an acid-neutralizing ability.SELECTED DRAWING: None

Description

The present invention relates to pharmaceutical compositions and the like.

Loxoprofen is a type of non-steroidal anti-inflammatory drug (NSAID), rheumatoid arthritis, osteoarthritis, lumbar pain, periarthritis shoulder, cervicobrachial syndrome, toothache, acute upper airway inflammation, post-surgery / post-traumatic It is known to be effective in anti-inflammatory, analgesic, and fever-relieving after tooth extraction (Non-Patent Document 1), and due to its excellent anti-fever analgesic effect, it is expected to be added to general anti-inflammatory drugs and anti-fever analgesics. In addition, cinnamon is known to have various pharmacological actions including antipyretic action (Non-Patent Document 2), and is used as a component of a common cold treatment drug, an antipyretic analgesic, and the like.
Therefore, a drug containing both loxoprofen and cinnamon is considered to be useful as a common cold medicine, an antipyretic analgesic, and the like.

Fifteenth revised Japanese Pharmacopoeia Manual Hirokawa Shoten Co., Ltd. C-4790-4795 17th Revised Japanese Pharmacopoeia Manual Hirokawa Shoten Co., Ltd. D-272-277

However, it is not known at all whether there is an interaction between loxoprofen or a salt thereof and cinnamon or an extract thereof that affects storage stability.
The present inventor investigated the storage stability between loxoprofen or a salt thereof and cinnamon or an extract thereof. When both components were mixed and stored, unexpectedly, a compounding change occurred between these components. , Found that solidification and significant discoloration of the mixture occur.

Therefore, an object of the present invention is to provide a technique for suppressing a compounding change in a pharmaceutical composition containing loxoprofen or a salt thereof and cinnamon or an extract thereof.

Therefore, the present inventor has made a diligent study to solve the above-mentioned problems, and surprisingly, a pharmaceutical composition containing loxoprofen or a salt thereof and cinnamon or an extract thereof has been further added to the following components 1 to 3. One or more selected:
1 Tranexamic acid or a salt thereof;
2 Xanthine derivatives typified by anhydrous caffeine;
3 Basic compounds with acid neutralizing ability represented by magnesium carbonate, magnesium oxide, and magnesium aluminometasilicate;
By means of containing loxoprofen or a salt thereof and a pharmaceutical composition containing Keihi or an extract thereof in an airtight package such as a bottle package or a blister pack, or a combination of these means. We have found that it is possible to suppress changes in the formulation as compared with the case where no measures are taken, and completed the present invention.

That is, in the present invention, the following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
(C) One or more selected from the group consisting of the following components (C-1) to (C-3);
(C-1) Tranexamic acid or a salt thereof;
(C-2) Xanthine derivative;
(C-3) Basic compound having acid neutralizing ability;
To provide a pharmaceutical composition containing.

Further, in the present invention, the following components (A) and (B):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
The pharmaceutical composition containing the above is to provide a pharmaceutical product contained in an airtight package.

Further, the present invention relates to the following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
(C) One or more selected from the group consisting of the following components (C-1) to (C-3);
(C-1) Tranexamic acid or a salt thereof;
(C-2) Xanthine derivative;
(C-3) Basic compound having acid neutralizing ability;
The pharmaceutical composition containing the above is to provide a pharmaceutical product contained in an airtight package.

According to the present invention, it is possible to suppress a change in the composition between loxoprofen or a salt thereof and cinnamon or an extract thereof. Therefore, it is possible to provide a drug having excellent storage stability containing loxoprofen or a salt thereof and cinnamon or an extract thereof.

<Ingredient (A)>
In the present invention, "loxoprofen or a salt thereof" includes not only loxoprofen itself, but also a pharmaceutically acceptable salt of loxoprofen, and a solvate of loxoprofen or a pharmaceutically acceptable salt thereof and water, alcohol, or the like. Is done. These are known compounds and can be produced by known methods, or commercially available compounds can be used. In the present invention, as loxoprofen or a salt thereof, loxoprofen sodium hydrate (chemical name: Monosodium 2- [4-[(2-oxocyclopentyl) methyl] phenyl] propanoate dihydrate) is preferable.

The content of loxoprofen or a salt thereof in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the gender, age, symptoms and the like of the user. For example, it can contain 10 to 300 mg of loxoprofen sodium anhydride per day, more preferably 30 to 240 mg, and particularly preferably 60 to 180 mg.
In the present invention, loxoprofen or a salt thereof is preferably contained in an amount of 0.1 to 91% by mass in terms of loxoprofen sodium anhydride, more preferably 1 to 35% by mass, based on the total mass of the pharmaceutical composition. It is more preferably contained in an amount of 2 to 30% by mass. Of these, it is more preferably contained in an amount of 3 to 25% by mass, further preferably contained in an amount of 4 to 20% by mass, and particularly preferably contained in an amount of 5 to 15% by mass.

<Ingredient (B)>
"Cinnamomum" (cinnamon bark) is a crude drug based on Cinnamomum cassia Blume (Lauraceae), but it is preferable to remove a part of the bark or the perimeter of Cinnamomum cassia Blume (Lauraceae). The morphology of cinnamon can be adjusted as needed, and it can be cut or crushed into small pieces or lumps, or crushed into powder. For example, "cinnamon powder" made from cinnamon powder is also used in the present invention. Can be done. Further, in consideration of convenience of handling at the time of manufacturing the pharmaceutical composition, cinnamon subjected to some kind of extraction treatment (hereinafter, referred to as "extract of cinnamon") may be used.
The above-mentioned "Cinnamon extract" includes those subjected to processing treatments such as heating, drying and pulverization in addition to the extraction treatment. Specifically, after making the keihi into an appropriate size as needed, a liquid leached by adding an appropriate extraction solvent, a liquid obtained by concentrating the leaching liquid (soft extract, tincture, etc.), and further dried. Things (dried extract, etc.) are also included in the "extract of Keihi" of the present invention.
In the present invention, the dried cinnamon extract is preferable as the cinnamon or its extract.

The method for producing the extract of cinnamon is not particularly limited. It can be produced with reference to a known method for producing a plant extract. Specifically, for example, cinnamon can be produced by cutting, heating, pulverizing or the like as necessary, and then adding an appropriate extraction solvent for extraction. The obtained extract may be further concentrated, dried or the like, if necessary.

Examples of the extraction solvent include lower monohydric alcohols such as methanol, ethanol, isopropanol and n-butanol (preferably linear or branched aliphatic alcohols having 1 to 6 carbon atoms); ethylene glycol and propylene glycol. , 1,3-butylene glycol, lower polyhydric alcohols such as glycerin; ethers such as diethyl ether; ketones such as acetone and ethyl methyl ketone; esters such as ethyl acetate; nitriles such as acetonitrile; pentane, hexane, Alkanes such as cyclopentane and cyclohexane; Harogenoalkanes such as dichloromethane and chloroform; Aromatic hydrocarbons such as benzene and toluene; Amidos such as dimethylformamide; Sulfoxides such as dimethylsulfoxide; Water (including hot water) and the like. Can be mentioned. These may be used individually or in combination of two or more. In the present invention, the extraction solvent is preferably water or a solvent containing at least a linear or branched aliphatic alcohol having 1 to 6 carbon atoms, and water, a linear or branched chain chain having 1 to 6 carbon atoms. It is more preferable that the solvent is selected from a mixed solution of an aliphatic alcohol and a linear or branched aliphatic alcohol having 1 to 6 carbon atoms, and it is selected from the group consisting of water, ethanol and a water / ethanol mixed solution. It is particularly preferable that the solvent is used.

The extraction operation is not particularly limited, and a known method used for the extraction operation from a plant can be adopted. Specifically, for example, immersion in an extraction fluid (cold pickling, hot pickling, percolation, etc.), super Extraction using a critical fluid or a subcritical fluid can be mentioned. In addition, in order to improve the extraction efficiency, stirring or homogenization in an extraction solvent may be performed.
The extraction temperature is not particularly limited and varies depending on the extraction solvent used, the extraction operation and the like, but it is preferably a temperature from about 5 ° C. to a temperature equal to or lower than the boiling point of the extraction solvent.
The extraction time is not particularly limited and varies depending on the extraction solvent used, the extraction operation and the like, but is preferably about 1 hour to 14 days.

Further, in the present invention, a Chinese cinnamon formulation containing these as an ingredient may be used as cinnamon or an extract thereof. Specific examples of such Chinese medicine prescriptions include kakkonto, keishito, saikokeishito, shoseiryuto, and maoto. And so on.

In the present invention, a commercially available product can be used as the cinnamon or its extract, and specific commercial products include, for example, cinnamon tincture, cinnamon tincture-N, cinnamon extract, cinnamon style extract, dried cinnamon extract, and Japanese Pharmacopoeia cinnamon oil. (The above are all manufactured by Nippon Powder Chemicals Co., Ltd.) and the like.

The content of Keihi or an extract thereof in the pharmaceutical composition of the present invention is not particularly limited, but is preferably 0.01 to 15% by mass, preferably 0.05 to 10% by mass, based on the total mass of the pharmaceutical composition. It is more preferable to contain 0.1 to 9.5% by mass, and particularly preferably 1 to 4% by mass.
When the content of Keihi or its extract is converted into the amount of crude drug, it is preferably 0.1 to 200% by mass in terms of the amount of crude drug with respect to the total mass of the pharmaceutical composition, which is 1 to 150. It is more preferably contained in an amount of 5 to 100% by mass, more preferably 10 to 50% by mass, and particularly preferably 10 to 50% by mass.

<Ingredient (C)>
(Component (C-1))
In the present invention, "tranexamic acid or a salt thereof" includes not only tranexamic acid itself, but also a pharmaceutically acceptable salt of tranexamic acid (for example, hydrochloride, hydrobromide, hydroiodide, sulfate, etc.). Acid addition salts with inorganic acids such as nitrates, phosphates; benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, maleate, fumarate, Acid addition salts with organic acids such as tartrates, citrates and acetates; alkali metal salts such as sodium salts and potassium salts; salts with Group 2 element metals such as calcium salts and magnesium salts; phenethylamine salts and the like Organic amine salt; salt with amino acid such as lysine, etc.), and also contains a solvent mixture of tranexamic acid and its pharmaceutically acceptable salt with water, alcohol, etc., and one or more of these. Can be used in combination.
Tranexamic acid or a salt thereof is known to cause a change in color tone and properties over time when stored in combination with loxoprofen or a salt thereof (Japanese Patent Laid-Open No. 2016-104812). However, as described in the examples below, both cinnamon or an extract thereof that causes solidification or significant discoloration when combined with loxoprofen or a salt thereof and tranexamic acid or a salt thereof as described above are used as loxoprofen or a salt thereof. Surprisingly, compounding changes are suppressed when combined with the salt.

As the tranexamic acid or a salt thereof, tranexamic acid is preferable, and tranexamic acid listed in the 17th revised Japanese Pharmacopoeia is particularly preferable.
Tranexamic acid or a salt 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 in the pharmaceutical composition of the present invention is not particularly limited, but is contained in an amount of 1 to 75% by mass in terms of free form of tranexamic acid with respect to the total mass of the pharmaceutical composition from the viewpoint of suppressing compounding changes. It is preferably contained in an amount of 5 to 70% by mass, more preferably 10 to 65% by mass, and particularly preferably 20 to 65% by mass.

Further, the content mass ratio of loxoprofen or a salt thereof and tranexamic acid or a salt thereof in the pharmaceutical composition of the present invention is not particularly limited, but from the viewpoint of suppressing compounding changes, loxoprofen or a salt thereof is 1 mass in terms of its free form. It is preferable to contain 0.1 to 20 parts by mass of tranexamic acid or a salt thereof in terms of free form, more preferably 0.5 to 15 parts by mass, and 1 to 10 parts by mass. Is more preferable, and it is particularly preferable that the content is 2 to 5 parts by mass.

(Component (C-2))
In the present invention, the "xanthine derivative" is preferably a compound represented by the following general formula (1).
The xanthine derivative is known to cause a state change over time when stored in combination with loxoprofen or a salt thereof (Japanese Patent Laid-Open No. 2015-227347). However, as described in Examples below, both cinnamon or its extract, which causes solidification or significant discoloration when combined with loxoprofen or a salt thereof, and a xanthine derivative as described above are combined with loxoprofen or a salt thereof. Surprisingly, when combined, changes in formulation are suppressed.

[In the formula (1), R ¹ and R ² each independently represent a hydrogen atom or a methyl group, and R ³ represents a hydrogen atom, a methyl group, a monohydroxypropyl group or a dihydroxypropyl group. ]

In formula (1), in R ³ , the monohydroxypropyl group is preferably a 2-hydroxypropyl group. The dihydroxypropyl group is preferably a 2,3-dihydroxypropyl group.

In the above general formula (1),
(1) When R ¹ is a methyl group, R ² is a methyl group, and R ³ is a methyl group, it means caffeine.
(2) When R ¹ is a methyl group, R ² is a methyl group, and R ³ is a hydrogen atom, it means theophylline.
(3) When R ¹ is a hydrogen atom, R ² is a methyl group, and R ³ is a methyl group, it means theobromine.
(4) When R ¹ is a methyl group, R ² is a hydrogen atom, and R ³ is a methyl group, it means paraxanthine.
(5) When R ¹ is a methyl group, R ² is a methyl group, and R ³ is a 2-hydroxypropyl group, it means proxophilin.
(6) When R ¹ is a methyl group, R ² is a methyl group, and R ³ is a 2,3-dihydroxypropyl group, it means diprophylline.

The compound of the general formula (1) is known, and in the present invention, a commercially available compound can be used in addition to the compound produced by a known method.
As the xanthin derivative, in addition to the compound represented by the above general formula (1), a pharmaceutically acceptable salt thereof (for example, a compound salt formed (for example, sodium benzoate caffeine (sodium benzoate and caffeine)) (Caffeine compound salt), aminophyllin (theophylline and ethylenediamine compound salt)), etc.), the compound represented by the general formula (1) or a solvent mixture of the salt and water, alcohol, etc. can also be used. Is also included in the "xanthine derivative", and the above-mentioned compounds (caffeine, theophylline, theobromine, paraxanthin, proxiphyllin and diprophylline) also include the compound, a salt thereof and a solvent mixture thereof. In the present invention, one or more of these xanthine derivatives can be used.

In the present invention, the xanthine derivative is preferably at least one selected from the group consisting of caffeine, theophylline, theobromine, paraxanthine, proxanthylline and diprophylline, and in particular, the pharmaceutical composition of the present invention is used as an antipyretic analgesic or a common cold treatment. Caffeine is preferable from the viewpoint of use as such. As the caffeine, caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine, and caffeine citrate are preferable specific examples, and among them, caffeine hydrate, anhydrous caffeine, and benzoic acid. Sodium caffeine is particularly preferred.

The content of the xanthine derivative in the pharmaceutical composition of the present invention is not particularly limited, but is contained in an amount of 0.1 to 80% by mass in terms of the free form of the xanthine derivative with respect to the total mass of the pharmaceutical composition from the viewpoint of suppressing the change in formulation. It is preferably contained in an amount of 0.5 to 75% by mass, more preferably 1 to 70% by mass, and particularly preferably 3 to 65% by mass.

Further, the content mass ratio of loxoprofen or a salt thereof and a xanthin derivative in the pharmaceutical composition of the present invention is not particularly limited, but from the viewpoint of suppressing a change in formulation, loxoprofen or a salt thereof is added to 1 part by mass in terms of its free form. , Xanthin derivative is preferably contained in an amount of 0.0001 to 15 parts by mass, more preferably 0.001 to 10 parts by mass, still more preferably 0.01 to 5 parts by mass, in terms of its free form. It is particularly preferable to contain 0.1 to 3 parts by mass.

(Ingredient (C-3))
In the present invention, the "basic compound having an acid neutralizing ability" means a basic compound having an acid neutralizing ability. Here, the "acid neutralizing ability" can be determined by conducting a test in accordance with the anti-acid force test method described in the 17th revised Japanese Pharmacopoeia General Test Method. Among the components (C), a basic compound having an acid neutralizing ability (C-3) is preferable from the viewpoint of suppressing a change in the composition.

In the present invention, examples of the basic compound having an acid neutralizing ability include alkaline earth metals such as magnesium, aluminum and calcium and / or earth metal-based basic inorganic compounds and alkali metal-based basic compounds such as sodium and potassium. Basic inorganic compounds such as inorganic compounds and amine-based basic inorganic compounds; alkaline earth metals such as magnesium, aluminum and calcium and / or earth metal-based basic organic compounds and alkali metal-based basic organics such as sodium and potassium. Examples thereof include basic organic compounds such as compounds and amine-based basic organic compounds.

Among the above basic inorganic compounds, examples of the alkaline earth metal and / or the earth metal-based basic inorganic compound include magnesium silicate, magnesium aluminomerate, magnesium aluminum silicate, magnesium oxide, magnesium hydroxide, and water. Magnesium oxide / potassium aluminum sulfate co-precipitated product, magnesium carbonate, synthetic hydrotalcite, magnesium aluminometasilicate, dry aluminum hydroxide gel, synthetic aluminum silicate, synthetic aluminum silicate / hydroxypropyl starch / crystalline cellulose, water Magnesium oxide magnesium oxide, aluminum hydroxide gel, aluminum hydroxide / sodium hydrogen carbonate co-precipitated product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitated product, bentonite, calcium silicate , Magnesium such as calcium carbonate, precipitated calcium carbonate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, and inorganic salts of metals selected from aluminum and calcium.
Examples of the alkali metal-based basic inorganic compound include dry sodium carbonate, sodium hydroxide, sodium hydrogencarbonate, sodium carbonate hydrate, tetrasodium pyrophosphate, trisodium phosphate, and sodium hydrogenphosphate hydrate. Examples thereof include sodium and an inorganic salt of a metal selected from potassium such as anhydrous sodium pyrophosphate, anhydrous sodium monohydrogen phosphate, potassium hydroxide, potassium hydrogencarbonate, and potassium carbonate.

In the present invention, as the basic inorganic compound having an acid neutralizing ability, co-precipitation formation of magnesium silicate, magnesium aluminium silicate, magnesium aluminum silicate, magnesium oxide, magnesium hydroxide, magnesium hydroxide / potassium aluminum sulfate Goods, Magnesium Carbonate, Synthetic Hydrotalcite, Magnesium Aluminometasilicate, Dry Aluminum Hydroxide Gel, Synthetic Aluminum Phosphate, Synthetic Aluminum Silica / Hydroxypropylstarch / Crystalline Cellulose, Magnesium Hydroxide, Aluminum Hydroxide Gel, Water Aluminum oxide / sodium hydrogen carbonate co-precipitated product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitated product, bentonite, calcium silicate, calcium carbonate, precipitated calcium carbonate, phosphoric acid Calcium hydrogen, anhydrous calcium hydrogen phosphate, and sodium hydrogen carbonate are preferred.

In the above basic organic compounds, examples of the alkaline earth metal and / or the earth metal-based basic organic compound include aldioxa, dihydroxyaluminum / aminoacetate, scralfert hydrate, calcium pantothenate and the like. ..
Examples of the alkali metal-based basic organic compound include sodium citrate hydrate, disodium succinate hexahydrate, DL-sodium tartrate, L-sodium tartrate, sodium copper chlorophyllin, and sodium polyacrylate. '-Ribobamine disodium, copper chlorophyllin potassium and the like can be mentioned.
Examples of the amine-based basic organic compound include aminoacetic acid, L-arginine, and meglumine.

In the present invention, as the basic organic compound having an acid neutralizing ability, aldioxa, dihydroxyaluminum / aminoacetate, and scralfert hydrate are preferable.

In the present invention, as the basic compound, a crude drug containing a basic compound such as sardine bone, stone determination, and volley (oyster) may be used.

In the present invention, the basic compound having an acid neutralizing ability includes aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, and dihydroxyaluminum / aminoacetate from the viewpoint of suppressing compounding changes. , Aluminum hydroxide gel, Dry aluminum hydroxide gel, Aluminum hydroxide / magnesium carbonate mixed dry gel, Aluminum hydroxide / sodium hydrogen carbonate co-precipitate product, Aluminum hydroxide / calcium carbonate / magnesium carbonate co-precipitate product, One or more selected from the group consisting of a co-precipitation product of magnesium hydroxide / potassium aluminum sulfate, magnesium carbonate and magnesium aluminometasilicate is preferable, and a co-precipitation product of magnesium oxide, aluminum hydroxide / calcium carbonate / magnesium carbonate is preferable. , One or more selected from the group consisting of magnesium hydroxide / potassium aluminum sulfate co-precipitate, magnesium carbonate and magnesium aluminometasilicate, more preferably from the group consisting of magnesium oxide, magnesium carbonate and magnesium aluminometasilicate. One or more selected are particularly preferred.
The basic compound having an acid neutralizing ability may be used alone or in combination of two or more.

The content of the basic compound having an acid neutralizing ability in the pharmaceutical composition of the present invention is not particularly limited, but from the viewpoint of suppressing the compounding change, it is contained in an amount of 5 to 80% by mass with respect to the total mass of the pharmaceutical composition. It is preferably contained in an amount of 10 to 75% by mass, more preferably 15 to 70% by mass, and particularly preferably 20 to 65% by mass.

Further, the content mass ratio of loxoprofen or a salt thereof in the pharmaceutical composition of the present invention to a basic compound having an acid neutralizing ability is not particularly limited, but from the viewpoint of suppressing compounding changes, loxoprofen or a salt thereof is a free form thereof. In terms of 1 part by mass, it is preferable to contain 0.01 to 30 parts by mass of a basic compound having an acid neutralizing ability, more preferably 0.1 to 20 parts by mass, and 0.5 to 10 parts by mass. It is more preferably contained in parts by mass, and particularly preferably contained in an amount of 1 to 5 parts by mass.

The pharmaceutical composition has other components as medicinal properties such as antipyretic analgesic, antihistamine, antitussive, noscapine, bronchial dilator, expectorant, hypnotic sedative, vitamins, anti-inflammatory agent, gastric mucosa protective agent, etc. It may contain one or more selected from the group consisting of anticholinergic agents, crude drugs and the like.

Specific examples of the antipyretic analgesic include aspirin, aspirin aluminum, acetaminophen, ibuprofen, ethenzamide, sazapyrin, salicylamide, lactylphenetidine, and sodium salicylate.
Specific examples of the antihistamine include azelastin hydrochloride, alimemazine tartrate, isotipendyl hydrochloride, iproheptin hydrochloride, evastin, epinastine hydrochloride, emedastin fumarate, oxatomide, olopatazine hydrochloride, and carbinoxamine diphenyldisulfone. Hydrochloride, Carbinoxamine Maleate, Cremastine Fumarate, d-Chlorpheniramine Maleate, dl-Chlorpheniramine Maleate, Ketotifenfumarate, Diphenhydramine Hydrochloride, Diphenhydramine Phosphate, Diphenyl Pyraline hydrochloride, diphenylpyraline theocrate, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, cyproheptazine hydrochloride hydrate, cetilysin hydrochloride, triprolysine hydrochloride, tryperenamine hydrochloride, tonsilamine hydrochloride, fe Examples include xofenazine, phenetazine hydrochloride, promethazine hydrochloride, promethazine methylene disalicylate, bepotastine besilate, homochlorcyclidine hydrochloride, mequitazine, metodilazine hydrochloride, mebuhydrolinnapadisilate, loratazine, etc. Be done.

Specific examples of the antitussive agent include codeins such as codeine, codeine phosphate hydrate, dihydrocodein, and dihydrocodein phosphate, as well as alloclamid hydrochloride, epradinone hydrochloride, carbetapentanetancate, and cloperastine hydrochloride. Cloperastin fendizoate, dibunato sodium, dimemorphan phosphate, tipepidin citrate, tipepidin hibenzate, dextrometholphane, dextrometholphan hydrobromide hydrate, dextrometholphan phenol lid Phosphorus salt and the like can be mentioned.

Specific examples of noscapines include noscapine hydrochloride, noscapine and the like.
Specific examples of the bronchial dilator include trimetokinol hydrochloride, phenylpropanolamine hydrochloride, phenilephedrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, l-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, and the like. Examples thereof include l-methylephedrine saccharin salt, dl-methylephedrine saccharin salt, methoxyphenamine hydrochloride and the like.

Specific examples of the expectorant include ammonia / uikyosei, ethylcysteine hydrochloride, ammonium chloride, carbocisteine, guayphenesin, potassium guayacol sulfonate, potassium cresolsulfonate, methylcysteine hydrochloride, l-menthol, and lysoteam hydrochloride. Examples include salt.

Specific examples of the hypnotic sedative include allylisopropylacetylurea and bromvalerylurea.
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, disetiamine hydrochloride, setothiamine hydrochloride, flusultiamine, flusultiamine hydrochloride, octothiamine, sicothamine, thiamine disulfide, bisibuchiamine, bisbenchamine, prosultiamine, benfothamine, riboflavin , Riboflavin phosphate, Riboflavin butyrate, Sodium phosphate, pantenol, Pantetin, Sodium pantothenate, Pyridoxin hydrochloride, Pyridoxal phosphate, Cyanocobalamine, Mecobalamine, Ascorbic acid, Sodium ascorbate, Calcium ascorbate, Hesperidin, etc. ).

Specific examples of the anti-inflammatory agent include glycyrrhizic acid and its derivatives and salts thereof (for example, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.), seaprose, semi-alkali proteinase, serrapeptase, pronase, pronase, bromelain and the like. Can be 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 anticholinergic agent include oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, datsura extract, tipepidium bromide, methylatropine bromide, methylanisotropine bromide, and methylscopolamine. Bromide, Methyl-l-hyoscyamine bromide, Methylbenactidium bromide, Pyrenzepine hydrochloride, Butylscopolamine bromide, Belladonna alkaloid, Belladonna extract, Belladonna total alkaloid, Isopropamide iodide, Diphenylpiperidinomethyldioxorane iodide, Rohto extract, Examples thereof include funnel roots and total alkaloid citrates of funnel roots.

Specific examples of crude drugs include Akamega wrinkles (red buds), Asenyaku (Asenyaku), Inyoukaku (Tincture), Uiko (Ginger), Engosaku (Ginger), Ogon (Huangyu), Osei (Huangsei), and so on. Oubaku (yellow kashiwa), Ouhi (cherry bark), Ouren (yellow ream), Onji (distant soul), Gajutsu (selfish), Kanokosou (kagokusa), Kamitsure, Karonin (karoujin), Kikyo (kikyo), Kyonin (kikyo) Kyoujin), Kukoshi (Tincture), Kukoyo (Tincture leaf), Keigai (Atractylodes), Ketsumeishi (Ketsumeiko), Gentiana, Gennoshoko (Current evidence), Koubushi (Kabushi), Goou (Ushio), Gomishi (Gomiko), Saishin (Spicy), Sansho (Sansho), Zion (Shien), Jikoppi (Ground bone skin), Shakuyaku (Crude drug), Jakou (Crude drug), Shajin (Sasan), Shazenshi (Car front child), Shazensou (Car front grass) , Beast ginger (including Yutan (bear gall)), Ginger (Ginger), Jiryu (earth dragon), Shini (spicy), Sexan (stone), Senega, Senkyu (Kawakyu), Zenko (maehu), Senburi (Senburi), Soujutsu (Soujou), Souhakuhi (Kuwashirohide), Soyo (Suha), Taisan (Daisan), Chikusetsu carrot (Takebushi carrot), Chouji (Cho), Tincture (Chenpi), Touki (Toki) ), Tokon (spitting root), Nantenjitsu (Southern fruit), Carrot (carrot), Baimo (shell mother), Bakumondou (wheat gate winter), Hange (half-summer), Bankouka (bankohana), Hampi (anti-nose), Crude drugs such as Byakushi (white), Byakujutsu (white ginger), Bukuryo (茯 蓓), Buttonpi (peony skin), Maou (mao), Rokujo (deer mushroom) and their extracts (extracts, tinctures, dried extracts, etc.) Can be mentioned.

In the present specification, the dosage form of the "pharmaceutical composition" is not particularly limited, and may be a solid, semi-solid, or liquid preparation, and can be selected according to the purpose of use thereof and the like. Examples of the dosage form of the pharmaceutical composition include the dosage forms described in the 17th revised Japanese Pharmacopoeia General Regulations for Preparations. Specifically, for example, the dosage form for oral administration includes tablets (for example, ordinary tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, dispersion tablets, dissolving tablets, etc.), capsules, granules (including, etc.). For example, solid preparations such as effervescent granules), powders, rounds, etc .; semi-solid preparations such as oral jelly; oral liquids (including, for example, elixirs, suspensions, emulsions, limonades, etc.), etc. Examples thereof include liquid preparations of. Dosage forms for parenteral administration include injections, inhalants, eye drops, ear drops, nasal drops, suppositories, external solids, external solutions, sprays, ointments, creams, and gels. , Patches and the like.

As the dosage form of the pharmaceutical composition, a solid preparation is preferable from the viewpoint of ease of administration and administration, and tablets (for example, ordinary tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, dispersion tablets, dissolution tablets) are preferable. , Etc.), capsules, granules (including, for example, effervescent granules), powders and pills are particularly preferred.

The pharmaceutical composition can be produced, for example, by a known method described in the 17th revised Japanese Pharmacopoeia General Regulations for Formulation, etc., depending on the dosage form. In this case, a pharmaceutically acceptable carrier (formal additive) may be added to the pharmaceutical composition. Examples of such pharmaceutical additives include excipients, disintegrants, binders, lubricants, plasticizers, film-forming agents, powders, poorly water-soluble polymer substances, antioxidants, flavoring agents, sweeteners and the like. However, the present invention is not limited to these. The above-mentioned component (C) may be used as a pharmaceutical additive. 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), and the like. Can be mentioned.

Specific examples of the excipient include aluminum silicate, anhydrous sodium sulfate, anhydrous calcium hydrogen phosphate, sodium chloride, calcium silicate, light anhydrous silicate, heavy anhydrous silicate, calcium sulfate, and dicalcium phosphate. Inorganic excipients such as calcium hydrogen, 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, canten, xylitol, paraffin, crystalline cellulose, sucrose, malt sugar, lactose, lactose hydrate, sucrose, glucose, purulan, polyoxyethylene hydrogenated castor oil, martitol, Examples thereof include reduced starch candy, powdered reduced starch candy, erythritol, sorbitol, mannitol, lactitol, trehalose, reduced palatinose, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylaminoacetate, and organic excipients such as calcium citrate. 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, sodium croscarmellose, and crospovidone, carmellose, carmellose calcium, starch, sucrose fatty acid ester, gelatin, sodium hydrogencarbonate, and dextrin. Examples thereof include dehydroacetic acid and salts thereof, povidone, polyoxyethylene hydrogenated starch oil 60 and the like. These can be used alone or in combination of two or more.

Specific examples of the binder include hydrogenated beef fat, hydrogenated oil, hydrogenated vegetable oil, hardened soybean oil, carnauba wax, sardine honeydew, honeydew, mokurou and other fats and oils, as well as methyl cellulose, hydroxypropyl cellulose, hypromellose and carme. Sodium loin, starch (wheat starch, rice starch, corn starch, partially pregelatinized starch, etc.), dextrin, purulan, gum arabic, canten, gelatin, tragant, sodium alginate, povidone, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, polyvinyl acetal Examples thereof include diethylaminoacetate. These can be used alone or in combination of two or more.

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

Specific examples of the film-forming agent include alkyl cellulose such as methyl cellulose and ethyl cellulose; alginic acid such as sodium alginate or a salt thereof; carrageenan; sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, potassium carboxymethyl cellulose, carboxymethyl cellulose, carboxymethyl ethyl cellulose and the like. Carboxymethyl Cellulose; Xanthan Gum; Hydroxyalkyl Cellulose such as Hydroxymethyl Cellulose, Hydroxyethyl Cellulose, Hydroxypropyl Cellulose, Hypromellose (Hypromellose); ; Polyvinylpyrrolidone and the like can be mentioned. These can be used alone or in combination of two or more.

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

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

Specific examples of the flavoring agent include limonene, pinen, camphen, cymen, cineole, citronellol, geraniol, nerol, linalol, menthol, terpineol, rosinol, borneol, isobornole, menthon, camphor, eugenol, syntheilanol and the like. Telpen; Tohi oil, orange oil, peppermint oil, citrus oil, eucalyptus oil, terepine oil, lemon oil, ginger oil, butterfly oil, keihi oil, lavender oil, uikyo oil, chamomile oil, perilla oil, spare mint oil, etc. The terpene-containing essential oils; ascorbic acid, tartrate acid, citric acid, malic acid, acidulants such as salts thereof and the like can be mentioned. These can be used alone or in combination of two or more.

Specific examples of the sweetener 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.

The pharmaceutical composition can be produced by a known method depending on the dosage form thereof.
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, granulation, classification, filling, tableting, and coating.
More specifically, for example, when the dosage form of the pharmaceutical composition is a granular preparation such as a granule, a powder, or a round, it is necessary in addition to the components (A) to (B) or the components (A) to (C). After mixing all or part of these components using pharmaceutical additives such as excipients, binders, disintegrants, and lubricants, extrusion granulation, rolling granulation, stirring granulation, and flow It can be manufactured by granulating by a known granulation method such as layer granulation, spray granulation, melt granulation, crushing granulation, etc. to obtain a granulated product, and further classifying, sizing, etc. as necessary. can. The obtained granulated product can also be coated with a coating agent or the like by a known method.
When the dosage form of the pharmaceutical composition is a tablet, in addition to the components (A) to (B) or the components (A) to (C), if necessary, an excipient, a binder, a disintegrant, a lubricant, etc. The above-mentioned granules are required to obtain a mixture by mixing all or part of these components using appropriate pharmaceutical additives of the above and directly compress (tablet) the mixture (direct powder compression method). It can be manufactured by compression (tablet tableting) after classification, granulation, etc. according to the above (semi-dry granule compression method, dry granule compression method, wet granule compression method, etc.). The obtained compressed product (tablet) can also be coated with a coating agent or the like by a known method.
Further, when the dosage form of the pharmaceutical composition is a capsule, the above-mentioned granulated product, compressed product, or the like may be filled in the capsule.

In the present invention, the pharmaceutical composition may be further contained in an airtight package from the viewpoint of suppressing the change in formulation (hereinafter, in the present specification, the pharmaceutical composition is contained in the airtight package). Is referred to as a "pharmaceutical product"). In the present invention, the pharmaceutical product may be provided with a package other than the following "airtight package" in addition to the airtight package, and the pharmaceutical composition is directly or indirectly contained in the airtight package. You just have to.
As used herein, the term "airtight package" means a package that can suppress the intrusion of solid or liquid foreign matter under normal handling, transportation, 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, either a fixed form or an amorphous package can be used. Specifically, for example, bottle packaging, SP (Strip Package) packaging, PTP (Press Through Package) packaging, pillow packaging, stick packaging and the like can be used. Can be mentioned. The airtight package may be a combination of a plurality of these, and as such a combination, specifically, for example, the pharmaceutical composition is first packaged in PTP packaging, which is further packaged in pillow packaging. Examples include packaging.
The airtight package is preferably one or more selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging, and stick packaging from the viewpoint of suppressing changes in formulation, and includes at least PTP packaging ( A combination of PTP packaging and, if necessary, other packaging such as bottle packaging, SP packaging, pillow packaging, stick packaging, etc.) is particularly preferable.

The packaging material (material) of the airtight package is not particularly limited, and for example, glass, plastic (polyethylene terephthalate, polyethylene naphthalate and other polyesters; polyethylene (low density (LDPE), medium density (MDPE), high density (HDPE)). , Polyethylene and other polyolefins; Polyethylene; Polyethylene, etc.), metals (aluminum, etc.) and other materials used in the fields of pharmaceuticals, foods, etc., may be used alone or in combination of two or more. can.

For example, the packaging material used for bottle packaging is not particularly limited, and examples thereof include glass, plastic, and metal, and one or more of these can be appropriately combined. As the material for the 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 in a bottle, for example, the pharmaceutical composition may be stored in an appropriate quantity in the bottle, and then sealed with an appropriate stopper or lid. The size of the bottle may be appropriately selected according to the quantity of the pharmaceutical composition to be stored, and the capacity of the bottle is, for example, about 10 to 500 mL, preferably 14 to 400 mL, and 24 to 350 mL. Is more preferable.

The packaging materials used for SP packaging, PTP packaging, pillow packaging, stick packaging and the like are not particularly limited, and for example, biaxially stretched polypropylene (OPP), biaxially stretched polyester (PET), glycol-modified 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), unstretched nylon (CNy), polycarbonate (PC), polystyrene (PS), hard vinyl chloride (VSC) and other resins, and aluminum foil (AL). Metal foil and the like can be mentioned, and one or more of these can be appropriately combined.

In SP packaging, PTP packaging, pillow packaging, stick packaging, etc., it may be manufactured by a known method using a sheet using one or more of the above-mentioned packaging materials, and in this case, the packaging material. Can also have a multi-layer structure that is appropriately combined. As a method of forming a multi-layer structure using two or more kinds of packaging materials as a sheet, a method of laminating the packaging materials to produce a laminated sheet can be mentioned. The laminated sheet can be produced by a known method such as extruded laminating, dry laminating, co-extruded laminating, thermal laminating, wet laminating, non-solvent laminating, heat laminating and the like. Further, as the sheets for SP packaging, PTP packaging, pillow packaging and stick packaging, known commercially available products can also be used.

In the above sheet, examples of the single-layer sheet using one type of packaging material include PVC sheets and CPP sheets, and examples of the laminated sheet using two or more types of packaging materials include, for example, the sheet configuration. A laminate of PVC and PVCC (PVC / PVDC; hereinafter abbreviated in the same manner), PVC / PVDC / PE / PVC, PVC / PVCC / PE / PVDC / PVC, CPP / COC / CPP, PVC / PCTFE, CPP. / PCTFE, PVC / AL / PA, PVC / AL, CPP / AL, CPP / CPP / CPP (the sheet on the left uses two or more types of CPP), but is limited to these. It is not something that will be done.

As a form of PTP packaging, one or one administration unit of a pharmaceutical composition is stored in pockets formed in a desired number on a resin sheet or the like by a known method, and then a sheet made of a metal foil such as aluminum foil is used as a constituent material. It is possible to use it as a lid material to cover it. The sheet forming the pocket may be a so-called double-sided aluminum PTP package using a sheet made of aluminum foil as a constituent material. In the present invention, it is preferable to further wrap the PTP wrapping with pillow wrapping (for example, aluminum pillow wrapping) from the viewpoint of suppressing the change in composition.
Examples of the forms of SP packaging, pillow packaging, and stick packaging include packaging the pharmaceutical composition one by one or one administration unit at a time using a resin sheet, a sheet containing aluminum foil as a constituent material, or the like by a known method. .. In the present invention, it is preferable to use a sheet made of aluminum foil as a constituent material from the viewpoint of suppressing a change in composition.

In the present specification, the occupancy ratio (floor area ratio) of the pharmaceutical composition in the pharmaceutical product is usually 25 to 90%, preferably 28 to 75% when the package is bottle-wrapped. 30-50% 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 occupancy rate means the occupancy rate of the pharmaceutical composition with respect to the total volume inside the package, and the filling or the inner plug for preventing the pharmaceutical composition stored inside the package from being damaged. Etc. are not taken into consideration when calculating the space occupancy rate.

As the airtight package, a commercially available package may be used as it is, or a commercially available package material may be processed and used. Examples of commercially available bottle packaging include glass bottles (manufactured by Isoya Glass Industry Co., Ltd.), tablet bottles (manufactured by Tokyo Glass Co., Ltd.), Z-series (manufactured by Hanshin Kasei Kogyo Co., Ltd.), and the like. Be done. Examples of commercially available pillow packaging include Lamizip (registered trademark) (manufactured by Japan Co., Ltd.) and the like. Furthermore, as packaging materials for SP packaging, PTP packaging, pillow packaging and stick packaging, Sumilite VSS, Sumilite VSL, Sumilite NS, Sumilite FCL (all manufactured by Sumitomo Bakelite Co., Ltd.), TAS series (Taisei Kako Co., Ltd.) , PTP vinyl foil, PTP super foil (above, manufactured by 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. Be done.

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

In the present invention, the pharmaceutical composition or pharmaceutical product contains loxoprofene, which is a kind of NSAID, or a salt thereof, and Keihi or an extract thereof having various pharmacological actions such as antipyretic action. Therefore, for example, headache, toothache, and tooth extraction. Later pain, sore throat, ear pain, joint pain, nerve pain, lower back pain, muscle pain, stiff shoulder pain, bruising pain, fracture pain, numbness pain, menstrual pain (physiological pain), traumatic pain relief, bad cold, fever It has the effect or effect of relieving fever, various symptoms of cold (throat pain, cold, fever, headache, tan, joint pain, muscle pain), etc. It is useful as.

The route of administration of the pharmaceutical composition is not particularly limited and can be appropriately examined and determined according to the disease to be applied, the type of the drug, the gender, age, symptoms, etc. of the user, but from the viewpoint of ease of administration. , Oral administration is preferred. In addition, the pharmaceutical composition can be taken before meals, between meals, after meals, before bedtime, etc., in 1 to 4 divided doses per day.

The present specification is not limited to these, but discloses, for example, the invention of the following aspects.
[1A] The following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
(C) One or more selected from the group consisting of the following components (C-1) to (C-3);
(C-1) Tranexamic acid or a salt thereof;
(C-2) Xanthine derivative;
(C-3) Basic compound having acid neutralizing ability;
A pharmaceutical composition containing.
[2A] The pharmaceutical composition according to [1A], wherein the component (B) is an extract of cinnamon.
[3A] The pharmaceutical composition according to [2A], wherein the extract of Keihi uses water or a solvent containing at least a linear or branched fatty alcohol having 1 to 6 carbon atoms as an extraction solvent.
[4A] The pharmaceutical composition according to any one of [1A] to [3A], wherein the component (B) is a cinnamon extract extracted with a solvent selected from the group consisting of water, ethanol and a water / ethanol mixed solution.
[5A] The component (C-2) is at least one selected from the group consisting of caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate, [1A] to [4A]. The pharmaceutical composition according to any of the above.
[6A] The component (C-3) is aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum / aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, water. Mixed dry gel of aluminum oxide / magnesium carbonate, co-precipitated product of aluminum hydroxide / sodium hydrogen carbonate, co-precipitated product of aluminum hydroxide / calcium carbonate / magnesium carbonate, co-precipitated product of magnesium hydroxide / potassium aluminum sulfate, The pharmaceutical composition according to any one of [1A] to [5A], which is one or more selected from the group consisting of magnesium carbonate and magnesium aluminometasilicate.
[7A] The pharmaceutical composition according to any one of [1A] to [6A], which is a solid preparation.
[8A] The pharmaceutical composition according to any one of [1A] to [7A], wherein the dosage form is a tablet, a capsule, a granule, a powder or a pill.

Further, the present specification is not limited to these, but also discloses, for example, the invention of the following aspects.
[1B] The following components (A) and (B):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
A pharmaceutical product containing a pharmaceutical composition containing the above, which is contained in an airtight package.
[2B] The pharmaceutical product according to [1B], wherein the component (B) is an extract of cinnamon.
[3B] The pharmaceutical product according to [2B], wherein the extract of Keihi uses water or a solvent containing at least a linear or branched aliphatic alcohol having 1 to 6 carbon atoms as an extraction solvent.
[4B] The pharmaceutical product according to any one of [1B] to [3B], wherein the component (B) is a Keihi extract extracted with a solvent selected from the group consisting of water, ethanol and a water / ethanol mixed solution.
[5B] The drug according to any one of [1B] to [4B], wherein the pharmaceutical composition is a solid preparation.
[6B] The pharmaceutical product according to any one of [1B] to [5B], wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.
[7B] The pharmaceutical product according to any one of [1B] to [6B], wherein the airtight package is one or more selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging and stick packaging.

Further, the present specification is not limited to these, but also discloses, for example, the invention of the following aspects.
[1C] The following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
(C) One or more selected from the group consisting of the following components (C-1) to (C-3);
(C-1) Tranexamic acid or a salt thereof;
(C-2) Xanthine derivative;
(C-3) Basic compound having acid neutralizing ability;
A pharmaceutical product containing a pharmaceutical composition containing the above, which is contained in an airtight package.
[2C] The pharmaceutical product according to [1C], wherein the component (B) is an extract of cinnamon.
[3C] The pharmaceutical product according to [2C], wherein the extract of Keihi uses water or a solvent containing at least a linear or branched aliphatic alcohol having 1 to 6 carbon atoms as an extraction solvent.
[4C] The pharmaceutical product according to any one of [1C] to [3C], wherein the component (B) is a cinnamon extract extracted with a solvent selected from the group consisting of water, ethanol and a water / ethanol mixed solution.
[5C] The component (C-2) is at least one selected from the group consisting of caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate, [1C] to [4C]. Any of the listed drugs.
[6C] The component (C-3) is aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum / aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, water. Mixed dry gel of aluminum oxide / magnesium carbonate, co-precipitated product of aluminum hydroxide / sodium hydrogen carbonate, co-precipitated product of aluminum hydroxide / calcium carbonate / magnesium carbonate, co-precipitated product of magnesium hydroxide / potassium aluminum sulfate, The drug according to any one of [1C] to [5C], which is one or more selected from the group consisting of magnesium carbonate and magnesium aluminometasilicate.
[7C] The drug according to any one of [1C] to [6C], wherein the pharmaceutical composition is a solid preparation.
[8C] The pharmaceutical product according to any one of [1C] to [7C], wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.
[9C] The drug according to any one of [1C] to [8C], wherein the airtight package comprises at least a PTP package.

Further, the present specification is not limited to these, but also discloses, for example, the invention of the following aspects.
[1D] The following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
(C) One or more selected from the group consisting of the following components (C-1) to (C-3);
(C-1) Tranexamic acid or a salt thereof;
(C-2) Xanthine derivative;
(C-3) Basic compound having acid neutralizing ability;
A method for suppressing a change in formulation, which comprises a step of incorporating the above into the same pharmaceutical composition.
[2D] The method according to [1D], wherein the component (B) is an extract of cinnamon.
[3D] The method according to [2D], wherein the extract of Keihi uses water or a solvent containing at least a linear or branched aliphatic alcohol having 1 to 6 carbon atoms as an extraction solvent.
[4D] The method according to any one of [1D] to [3D], wherein the component (B) is a Keihi extract extracted with a solvent selected from the group consisting of water, ethanol and a water / ethanol mixed solution.
[5D] The component (C-2) is at least one selected from the group consisting of caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate, [1D] to [4D]. Any of the methods described.
[6D] The component (C-3) is aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum / aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, water. Mixed dry gel of aluminum oxide / magnesium carbonate, co-precipitated product of aluminum hydroxide / sodium hydrogen carbonate, co-precipitated product of aluminum hydroxide / calcium carbonate / magnesium carbonate, co-precipitated product of magnesium hydroxide / potassium aluminum sulfate, The method according to any one of [1D] to [5D], which is one or more selected from the group consisting of magnesium carbonate and magnesium aluminometasilicate.
[7D] The method according to any one of [1D] to [6D], wherein the pharmaceutical composition is a solid preparation.
[8D] The method according to any one of [1D] to [7D], wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.

Further, the present specification is not limited to these, but also discloses, for example, the invention of the following aspects.
[1E] The following components (A) and (B):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
A method for suppressing a change in formulation, which comprises a step of incorporating the pharmaceutical composition into the same pharmaceutical composition and a step of accommodating the pharmaceutical composition in an airtight package.
[2E] The method according to [1E], wherein the component (B) is an extract of cinnamon.
[3E] The method according to [2E], wherein the extract of Keihi uses water or a solvent containing at least a linear or branched fatty alcohol having 1 to 6 carbon atoms as an extraction solvent.
[4E] The method according to any one of [1E] to [3E], wherein the component (B) is a cinnamon extract extracted with a solvent selected from the group consisting of water, ethanol and a water / ethanol mixed solution.
[5E] The method according to any one of [1E] to [4E], wherein the pharmaceutical composition is a solid preparation.
[6E] The method according to any one of [1E] to [5E], wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.
[7E] The method according to any one of [1E] to [6E], wherein the airtight package is one or more selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging and stick packaging.

Further, the present specification is not limited to these, but also discloses, for example, the invention of the following aspects.
[1F] The following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
(C) One or more selected from the group consisting of the following components (C-1) to (C-3);
(C-1) Tranexamic acid or a salt thereof;
(C-2) Xanthine derivative;
(C-3) Basic compound having acid neutralizing ability;
A method for suppressing a change in formulation, which comprises a step of incorporating the pharmaceutical composition into the same pharmaceutical composition and a step of accommodating the pharmaceutical composition in an airtight package.
[2F] The method according to [1F], wherein the component (B) is an extract of cinnamon.
[3F] The method according to [2F], wherein the extract of Keihi uses water or a solvent containing at least a linear or branched fatty alcohol having 1 to 6 carbon atoms as an extraction solvent.
[4F] The method according to any one of [1F] to [3F], wherein the component (B) is a cinnamon extract extracted with a solvent selected from the group consisting of water, ethanol and a water / ethanol mixed solution.
[5F] The component (C-2) is at least one selected from the group consisting of caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate, [1F] to [4F]. Any of the methods described.
[6F] The component (C-3) is aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum / aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, water. Mixed dry gel of aluminum oxide / magnesium carbonate, co-precipitated product of aluminum hydroxide / sodium hydrogen carbonate, co-precipitated product of aluminum hydroxide / calcium carbonate / magnesium carbonate, co-precipitated product of magnesium hydroxide / potassium aluminum sulfate, The method according to any one of [1F] to [5F], which is one or more selected from the group consisting of magnesium carbonate and magnesium aluminometasilicate.
[7F] The method according to any one of [1F] to [6F], wherein the pharmaceutical composition is a solid preparation.
[8F] The method according to any one of [1F] to [7F], wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.
[9F] The method according to any one of [1F] to [8F], wherein the airtight package comprises at least PTP packaging.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

[Test Example 1] Stability test 1
After preparing the samples 1 to 4 shown below, they are stored in a dark place for 1 day under the conditions of 40 ° C. and 75% relative humidity (RH), and the state of the mixture in the sample immediately after the start of storage and after 1 day is visually evaluated. Then, it was confirmed whether or not there was a change in the composition.
The results are shown in Table 1.

[Sample 1]
10 parts by mass of Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate) and 1 part by mass of Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) (22 in terms of crude drug equivalent) (Parts by mass) was mixed to obtain a mixture, which was used as sample 1.
[Sample 2]
10 parts by mass of loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: loxoprofen sodium hydrate) and 1 part by mass of Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) (22 in terms of crude drug equivalent) By mass) were mixed to obtain a mixture. 3 g of the obtained mixture was placed in a glass bottle (manufactured by Isoya Glass Industry Co., Ltd .: A-102K) and covered with a lid, which was used as sample 2. The occupancy ratio (floor area ratio) of the mixture inside the glass bottle was 25%.

[Sample 3]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: Loxoprofen sodium hydrate) 10 parts by mass, Keihi dry extract (manufactured by Alps Pharmaceutical Industry Co., Ltd .: Keihi dry extract) 1 part by mass (22 in terms of crude drug equivalent) 20 parts by mass) and tranexamic acid (manufactured by Kyowa Pharma Chemical Co., Ltd .: trade name: Japanese Pharmacopoeia tranexamic acid) were mixed to obtain a mixture, which was used as sample 3.
[Sample 4]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: Loxoprofen sodium hydrate) 10 parts by mass, Keihi dry extract (manufactured by Alps Pharmaceutical Industry Co., Ltd .: Keihi dry extract) 1 part by mass (22 in terms of crude drug equivalent) 20 parts by mass) and 20 parts by mass of tranexamic acid (manufactured by Kyowa Pharma Chemical Co., Ltd .: trade name: tranexamic acid according to the Japanese Pharmacy) were mixed to obtain a mixture. 3 g of the obtained mixture was placed in a glass bottle (manufactured by Isoya Glass Industry Co., Ltd .: A-102K) and covered with a lid, which was used as sample 4. The occupancy ratio (floor area ratio) of the mixture inside the glass bottle was 25%.

From the test results shown in Table 1, it was found that when loxoprofen sodium hydrate and dried cinnamon extract were mixed (Sample 1), the formulation changed one day after the start of storage, and the mixture discolored and solidified. ..
On the other hand, sample 2 in which loxoprofen sodium hydrate and dry Keihi extract were mixed and contained in an airtight package (bottle package), sample 3 in which loxoprofen sodium hydrate and dry Keihi extract were further mixed with tranexamic acid. It was found that the degree of discoloration was reduced and solidification was suppressed. Further, in Sample 4, which was further mixed with loxoprofen sodium hydrate and dried Keihi extract and further mixed with tranexamic acid and contained in an airtight package (bottle package), the sample 4 was white after storage for 1 day as well as immediately after the start of storage. It was found that the state of the powder was maintained.

From the above test results, the compounding change that occurs in the pharmaceutical composition containing loxoprofen or a salt thereof and Keihi or an extract thereof is a means for further incorporating tranexamic acid or a salt thereof in the pharmaceutical composition, and the pharmaceutical composition is airtightly packaged. It has been clarified that it is suppressed by means of accommodating in the body, or by means of further containing tranexamic acid or a salt thereof in the pharmaceutical composition and accommodating it in an airtight package. Further, it has been clarified that the means for further containing tranexamic acid or a salt thereof in the pharmaceutical composition and accommodating it in the airtight package is remarkably excellent in the degree of suppression of the formulation change.

[Test Example 2] Stability test Part 2
After preparing the samples 5 to 8 shown below, store them in a dark place for 1 day under the conditions of 40 ° C and 75% relative humidity (RH), and visually evaluate the state of the mixture in the sample immediately after the start of storage and after 1 day. Then, it was confirmed whether or not there was a change in the composition.
The results are shown in Table 2.

[Sample 5]
10 parts by mass of Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate) and 1 part by mass of Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) (22 in terms of crude drug equivalent) (Parts by mass) was mixed to obtain a mixture, which was used as sample 5.
[Sample 6]
10 parts by mass of loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: loxoprofen sodium hydrate) and 1 part by mass of Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) (22 in terms of crude drug equivalent) By mass) were mixed to obtain a mixture. 3 g of the obtained mixture was placed in a glass bottle (manufactured by Isoya Glass Industry Co., Ltd .: A-102K) and covered with a lid, which was used as sample 6. The occupancy ratio (floor area ratio) of the mixture inside the glass bottle was 25%.

[Sample 7]
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate) 10 parts by mass, Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) 1 part by mass (22 as crude drug equivalent) 20 parts by mass) and anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: anhydrous caffeine) were mixed to obtain a mixture, which was used as sample 7.
[Sample 8]
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate) 10 parts by mass, Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) 1 part by mass (22 as crude drug equivalent) 20 parts by mass) and anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: anhydrous caffeine) were mixed to obtain a mixture. 3 g of the obtained mixture was placed in a glass bottle (manufactured by Isoya Glass Industry Co., Ltd .: A-102K) and covered with a lid, which was used as sample 8. The occupancy ratio (floor area ratio) of the mixture inside the glass bottle was 30%.

From the test results shown in Table 2, it was found that when loxoprofen sodium hydrate and dried cinnamon extract were mixed (Sample 5), the formulation changed one day after the start of storage, and the mixture discolored and solidified. ..
On the other hand, sample 6 in which loxoprofen sodium hydrate and dry Keihi extract were mixed and contained in an airtight package (bottle package), sample 6 in which loxoprofen sodium hydrate and dry Keihi extract were mixed, and anhydrous caffeine was further mixed. In No. 7, it was found that the degree of discoloration was reduced and solidification was suppressed. Further, in sample 8 in which anhydrous caffeine was further mixed with loxoprofen sodium hydrate and dry Keihi extract and contained in an airtight package (bottle package), the sample 8 was stored for one day in the same manner as immediately after the start of storage. It was found that the state of the white powder was maintained.

From the above test results, the compounding change that occurs in the pharmaceutical composition containing loxoprofen or a salt thereof and Keihi or an extract thereof is a means for further incorporating the xanthin derivative into the pharmaceutical composition, and the pharmaceutical composition is contained in an airtight package. It has been clarified that it is suppressed by the means for the above-mentioned method or the means for further containing the xanthine derivative in the pharmaceutical composition and containing it in the airtight package. Further, it was clarified that the means for further containing the xanthine derivative in the pharmaceutical composition and accommodating it in the airtight package is remarkably excellent in the degree of suppressing the change in the formulation.

[Test Example 3] Stability test No. 3
After preparing the samples 9 to 16 shown below, store them in a dark place for 1 day under the conditions of 40 ° C and 75% relative humidity (RH), and visually evaluate the state of the mixture in the sample immediately after the start of storage and after 1 day. Then, it was confirmed whether or not there was a change in the composition.
The results are shown in Table 3.

[Sample 9]
10 parts by mass of Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate) and 1 part by mass of Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) (22 in terms of crude drug equivalent) (Parts by mass) was mixed to obtain a mixture, which was used as sample 9.
[Sample 10]
10 parts by mass of loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: loxoprofen sodium hydrate) and 1 part by mass of Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) (22 in terms of crude drug equivalent) By mass) were mixed to obtain a mixture. 3 g of the obtained mixture was placed in a glass bottle (manufactured by Isoya Glass Industry Co., Ltd .: A-102K) and covered with a lid, which was used as sample 10. The occupancy ratio (floor area ratio) of the mixture inside the glass bottle was 30%.

[Sample 11]
10 parts by mass of Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate), 1 part by mass of Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) (22 in terms of crude drug equivalent) 20 parts by mass) and 20 parts by mass of magnesium carbonate (manufactured by Kyowa Chemical Industry Co., Ltd .: magnesium carbonate) were mixed to obtain a mixture, which was used as sample 11.
[Sample 12]
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate) 10 parts by mass, Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) 1 part by mass (22 as crude drug equivalent) 20 parts by mass) and magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: magnesium oxide) were mixed to obtain a mixture, which was used as sample 12.
[Sample 13]
10 parts by mass of Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate), 1 part by mass of Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) (22 in terms of crude drug equivalent) 20 parts by mass) and 20 parts by mass of magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd .: Neucillin) were mixed to obtain a mixture, which was used as sample 13.

[Sample 14]
10 parts by mass of Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate), 1 part by mass of Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) 20 parts by mass) and 20 parts by mass of magnesium carbonate (manufactured by Kyowa Chemical Industry Co., Ltd .: magnesium carbonate) were mixed to obtain a mixture. 3 g of the obtained mixture was placed in a glass bottle (manufactured by Isoya Glass Industry Co., Ltd .: A-102K) and covered with a lid, which was used as sample 14. The occupancy ratio (floor area ratio) of the mixture inside the glass bottle was 30%.
[Sample 15]
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate) 10 parts by mass, Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) 1 part by mass (22 as crude drug equivalent) 20 parts by mass) and magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: magnesium oxide) were mixed to obtain a mixture. 3 g of the obtained mixture was placed in a glass bottle (manufactured by Isoya Glass Industry Co., Ltd .: A-102K) and covered with a lid, which was used as sample 15. The occupancy ratio (floor area ratio) of the mixture inside the glass bottle was 30%.
[Sample 16]
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: Loxoprofen sodium hydrate) 10 parts by mass, Keihi dry extract (manufactured by Alps Yakuhin Kogyo Co., Ltd .: Keihi dry extract) 1 part by mass (22 as a raw drug equivalent amount) 20 parts by mass) and 20 parts by mass of magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd .: Neucillin) were mixed to obtain a mixture. 3 g of the obtained mixture was placed in a glass bottle (manufactured by Isoya Glass Industry Co., Ltd .: A-102K) and covered with a lid, which was used as sample 16. The occupancy ratio (floor area ratio) of the mixture inside the glass bottle was 30%.

From the test results shown in Table 3, it was found that when loxoprofen sodium hydrate and dried cinnamon extract were mixed (Sample 9), the formulation changed one day after the start of storage, and the mixture discolored and solidified. ..
On the other hand, in the sample 10 in which loxoprofen sodium hydrate and dried cinnamon extract were mixed and contained in an airtight package (bottle package), it was found that the degree of discoloration was reduced and solidification was suppressed. In addition to loxoprofen sodium hydrate and dried Keihi extract, various basic compounds having acid neutralizing ability (Sample 11: magnesium carbonate, sample 12: magnesium oxide, sample 13: magnesium aluminometasilicate) are mixed. In addition to the sample, loxoprofen sodium hydrate, and dried Keihi extract, a basic compound having acid neutralizing ability (Sample 14: magnesium carbonate, sample 15: magnesium oxide, sample 16: magnesium aluminometasilicate) is mixed. It was found that in various samples containing this in an airtight package (bin package), the state of white powder was maintained even after storage for one day as in the case immediately after the start of storage.

From the above test results, the compounding change that occurs in the pharmaceutical composition containing loxoprofen or a salt thereof and Keihi or an extract thereof is a means for further incorporating a basic compound having an acid neutralizing ability into the pharmaceutical composition, a pharmaceutical composition. It has been clarified that the substance is suppressed by a means for accommodating the substance in an airtight package or a means for incorporating a basic compound having an acid neutralizing ability into the pharmaceutical composition and accommodating the substance in the airtight package. Further, it has been clarified that the means for further incorporating a basic compound having an acid neutralizing ability in the pharmaceutical composition and the means for accommodating the basic compound in the airtight package are remarkably excellent in the degree of suppression of the formulation change.

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

Claims (8)

The following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof;
(B) Cinnamon or its extract;
(C) One or more selected from the group consisting of the following components (C-1) to (C-3);
(C-1) Tranexamic acid or a salt thereof;
(C-2) Xanthine derivative;
(C-3) Basic compound having acid neutralizing ability;
A pharmaceutical composition containing. The pharmaceutical composition according to claim 1, wherein the component (B) is an extract of Keihi extracted with a solvent containing water or a linear or branched aliphatic alcohol having 1 to 6 carbon atoms. The pharmaceutical composition according to claim 1 or 2, wherein the component (C-2) is at least one selected from the group consisting of caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate. thing. Ingredient (C-3) is aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum / aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide. Magnesium carbonate mixed dry gel, co-precipitated product of aluminum hydroxide / sodium hydrogen carbonate, co-precipitated product of aluminum hydroxide / calcium carbonate / magnesium carbonate, co-precipitated product of magnesium hydroxide / potassium aluminum sulfate, magnesium carbonate and The pharmaceutical composition according to any one of claims 1 to 3, which is at least one selected from the group consisting of magnesium aluminometasilicate. The pharmaceutical composition according to any one of claims 1 to 4, which is a solid preparation. The pharmaceutical composition according to any one of claims 1 to 5, wherein the dosage form is a tablet, a capsule, a granule, a powder or a pill. A drug in which the pharmaceutical composition according to any one of claims 1 to 6 is contained in an airtight package. The pharmaceutical product according to claim 7, 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.