JP2022033294A - Pharmaceutical composition (6) containing loxoprofen - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition in which interaction between loxoprofen or a salt thereof and an interactive component is suppressed.

SOLUTION: A pharmaceutical composition being a solid preparation for analgestic-antipyretic contains the following components (A), (B) and (C): (A) loxoprofen or a salt thereof; (B) one or more kinds selected from a group consisting of bromovalerylurea and allylisopropylacetylurea and salts thereof; and (C) one or more kinds selected from a group consisting of magnesium aluminosilicate and magnesium aluminometasilicate.

SELECTED DRAWING: None

COPYRIGHT: (C)2022,JPO&INPIT

Description

The present invention relates to a pharmaceutical composition containing loxoprofen or a salt thereof.

Loxoprofen is a type of non-steroidal anti-inflammatory drug (NSAID), rheumatoid arthritis, osteoarthritis, lumbar pain, periarthritis of the shoulder, cervicobrachial syndrome, toothache, acute upper airway inflammation, post-surgery / post-trauma It is known to be effective in anti-inflammatory, analgesic, and antipyretic after tooth extraction (Non-Patent Document 1), and due to its excellent antipyretic and analgesic action, it is expected to be added to general anti-inflammatory drugs and antipyretic analgesics.

On the other hand, in general sensitizers and antipyretic analgesics, in addition to antipyretic analgesic component, antihistamine component, expectorant component, anti-inflammatory enzyme component, antitussive component, central nervous system excitatory component, hypnotic sedative component, anti-acetylcholine component, anti It contains a wide variety of combinations of ingredients such as plasmin ingredients and crude drug ingredients.

Specific examples of the antihistamine component include chlorpheniramine or a salt thereof; clemastine or a salt thereof; carbinoxamine or a salt thereof; diphenylpyraline or a salt thereof, and the like. It is used in various pharmaceutical products such as pharmaceuticals (Non-Patent Documents 2 to 5).
Of the above, chlorpheniramine has the following formula.

It is a compound represented by.
In addition, clemastine has the following formula.

It is a compound represented by.
In addition, carbinoxamine has the following formula.

It is a compound represented by.
Diphenylpyraline has the following formula.

It is a compound represented by. All of these compounds have a diarylmethyl structure as their common skeleton, and their chemical structures are very similar to each other.

Specific examples of the sputum component include bromhexine or a salt thereof; ambroxol or a salt thereof; a phenol derivative such as guaiacol sulfonic acid or a salt thereof, guayphenesin, cresol sulfonic acid or a salt thereof, or a salt thereof.
Of the above, bromhexine has the following formula.

It is a compound represented by, has a sputum removal effect based on a viscous adjusting effect that dilutes mucus by promoting the secretion of airway mucosa, is approved as a switch OTC drug, is used as a common cold medicine, and is used for medical purposes. , Used for sputum removal of acute / chronic bronchitis, dust pneumonia, etc. (Non-Patent Document 6).
In addition, ambroxol is the following formula

It is a compound represented by, and is known as an active metabolite of the above-mentioned bromhexine, which is a sputum component, and is also called a mucosal lubrication component. Approved as an over-the-counter drug, it is used for common cold treatment, and for medical use, it is used for sputum removal of acute / chronic bronchitis, pneumoconiosis, etc. (Non-Patent Document 7).

Further, a phenol derivative such as guaiacol sulfonic acid or a salt thereof, guaifenesin, cresol sulfonic acid or a salt thereof or a salt thereof is a component having an airway secretion promoting action or the like (Non-Patent Document 8).

Specific examples of the anti-inflammatory enzyme component include lysozyme or a salt thereof. These show mucopolysaccharide-degrading action and anti-inflammatory action, and are expected to decompose sputum and nasal mucus pus mucus and anti-inflammatory action by mucopolysaccharide-degrading action. It is a drug that is also used for the like (Non-Patent Document 9).

Specific examples of the antitussive component include codeines; ephedrines; dextromethorphan or salts thereof.
Of the above, codeines are known to be narcotic antitussive components having an antitussive effect by suppressing the function of the cough center. Based on this action, it is a drug used not only as a common cold treatment drug but also as an antitussive expectorant drug (Non-Patent Document 10).
In addition, ephedrines are known to bring about an antitussive action by a bronchodilator action based on a sympathetic nerve excitatory action. As an antitussive component, it is used not only as a common cold medicine and an antitussive expectorant, but also as an internal medicine for rhinitis for the purpose of alleviating nasal congestion due to vasoconstriction (Non-Patent Documents 11 and 12).
Further, dextromethorphan or a salt thereof is a central non-narcotic antitussive component, and is known to act directly on the cough center and exhibit an antitussive effect by suppressing the cough reflex. Based on this action, it is a drug used not only as a common cold medicine but also as an antitussive expectorant (Non-Patent Document 11).

Specific examples of the central nervous system stimulant component include xanthine derivatives such as caffeine. Caffeine exhibits central stimulant action, cardiotonic / diuretic action, gastric acid secretion enhancing action, smooth muscle relaxing action, etc., and is a drug used for antipyretic analgesics, antitussive expectorants, etc. in addition to general sensitizers (Non-Patent Document 13). ). In addition, other xanthine derivatives such as theophylline, paraxanthine, theobromine, aminophylline, diprophylline, and proxanthine, which have a structure similar to that of caffeine, also have a pharmacological action similar to that of caffeine. Theophylline is a drug that exhibits central stimulant action, cardiotonic / diuretic action, smooth muscle relaxing action, etc., and is used as an antitussive expectorant and antitussive. Aminophylline is a double salt of theophylline and ethylenediamine, and has the same action as theophylline, and diprophylline also has the same action as theophylline (Non-Patent Document 14). Proxanthylline also shows the same action as theophylline (Non-Patent Document 15), and paraxanthine and theobromine also show the same action.

Specific examples of the hypnotic and sedative component include isovaleryl-urea derivatives such as bromvaleryl urea and allylisopropylacetylurea.
Of the above, bromvalerylurea has the following formula.

It is a compound represented by.
In addition, allyl isopropyl acetyl urea has the following formula.

It is a compound represented by. All of these isovaleryl-urea derivatives have a sedative effect and are drugs to be blended in antipyretic analgesics and the like (Non-Patent Document 16).

Loxoprofen has been studied to be combined with various drugs because of its excellent pharmacological action, and various combinations with the above-mentioned components used in the common cold treatment drug and the like are also known.
For example, Patent Document 1 describes (1) one or more selected from (1) clemastines, pheniramines, carbinoxamine maleate, efedrins, codeins, phenylpropanolamine hydrochloride, therapeptase, lysoteam chloride and bromhexine hydrochloride. A drug and a pharmaceutical composition containing (2) loxoprofene as an active ingredient are described, and the document describes an enhanced analgesic effect when combined with carbinoxamine maleate, chlorpheniramine d-maleate or phenylpropanolamine hydrochloride. Actions; enhanced antihistamine action in combination with dihydrocodein phosphate, carbinoxamine maleate or bromhexine hydrochloride; enhanced antihistamine action in combination with carbinoxamine maleate or lysoteam chloride; clemastine fumarate or chlorpheniramine d-maleate The effect of enhancing the antihistamine effect by combining with lamin is disclosed.

Further, Patent Document 2 describes a composition for colds and rhinitis, which comprises at least one selected from the group consisting of (a) loxoprofens and (b) antiallergic agents and antihistamines. The effect of improving nasal congestion by combining with carbinoxamine maleate or chlorpheniramine maleate has been disclosed.
Further, Patent Document 3 describes a composition for colds, which comprises an expectorant and loxoprofen or a salt thereof, and enhances the effect on cough symptoms by combining with bromhexine hydrochloride or ambroxol. The action is disclosed.

Further, Patent Document 4 describes a pharmaceutical composition containing loxoprofen and one or more selected from ambroxol or bromhexine for suppressing goblet cell hyperplasia of sputum or airway, and hydrochloric acid. It is disclosed that the goblet cell hyperplasia inhibitory effect is exhibited in combination with ambroxol or bromhexine hydrochloride.
Further, Patent Document 5 describes a pharmaceutical composition for antitussive or expectorant containing one or more selected from loxoprofen and caffeine, ephedrine and codeine, and codeine phosphate or anhydrous. The expression of an inhibitory effect on goblet cell hyperplasia when combined with caffeine has been disclosed.

Japanese Unexamined Patent Publication No. 2000-143505 Japanese Unexamined Patent Publication No. 2001-199882 Japanese Unexamined Patent Publication No. 2001-172175 Japanese Unexamined Patent Publication No. 2008-13542 Japanese Unexamined Patent Publication No. 2007-314517

15th revised Japanese Pharmacopoeia Manual Hirokawa Shoten Co., Ltd. C-4790-4795 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 230 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 231 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 232 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 365 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 292 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 235 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 291-292 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 232 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 289 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 290 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 369 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 198-199 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. No. 292-294 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Page 688 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. pp. 199-200

However, it is not known at all whether or not an interaction that affects storage stability occurs between loxoprofen or a salt thereof and one or more of the components selected from 1 to 9 below.
Therefore, the present inventors first examined the storage stability of loxoprofen or a salt thereof and various components, and found that loxoprofen or a salt thereof and any of the following components 1 to 9:

1 The following general formula (1) including chlorpheniramine or a salt thereof, clemastine or a salt thereof, carbinoxamine or a salt thereof, diphenylpyraline or a salt thereof, and the like.

[In formula (1), X represents a single bond or an oxygen atom, Y represents a methine group or a nitrogen atom, R ¹ represents a hydrogen atom, a hydroxyl group or an alkyl group, and R ² has a substituent. It represents a cyclic amino group, or an aminoalkyl group which may have a substituent, and R ³ represents a hydrogen atom or a halogen atom. ]
Compound represented by (2) or a salt thereof (2) The following general formula (2) including bromhexine or a salt thereof, ambroxol or a salt thereof, and the like.

[In the formula (2), R ⁴ represents a hydrogen atom or a methyl group, and R ⁵ represents a hydrogen atom or a hydroxyl group. ]
Compound represented by 3 or a salt thereof 3 Guayacol sulfonic acid or a salt thereof, guaifenesin, cresol sulfonic acid or a salt thereof, etc. are included in the following general formula (3).

[In formula (3), R ⁶ represents an alkoxy group which may have an alkyl group or a substituent, and R ⁷ represents a hydrogen atom or a sulfo group. The phenolic hydroxyl group in the formula (3) may be etherified. ]
Compound represented by 4 or a salt thereof 4 Resoteam or a salt thereof 5 Codeines 6 Ephedrones 7 Dextromethorphan or a salt thereof 8 Xanthine derivative 9 Isovaleryl urea derivative (Note that the components selected from 1 to 9 above in the present specification). One or more species may be referred to as "interactive components".)

Unexpectedly, when the mixture is mixed and stored, an interaction occurs between these components, and this interaction causes a change of state such as wetting, solidification, and discoloration of the mixture over time, which causes a problem in stability. Found to occur.

Therefore, an object of the present invention is to provide a pharmaceutical composition in which the interaction between loxoprofen or a salt thereof and the above-mentioned interacting component is suppressed.

Therefore, the present inventors further investigated to solve this problem, and found that the interaction was suppressed by allowing a basic compound having an acid neutralizing ability to coexist with loxoprofen or a salt thereof and the above-mentioned interacting component. We found that we could do it, 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) One or more selected from the group consisting of the following components (B-1) to (B-9) (B-1) The following general formula (1)

[In formula (1), X represents a single bond or an oxygen atom, Y represents a methine group or a nitrogen atom, R ¹ represents a hydrogen atom, a hydroxyl group or an alkyl group, and R ² has a substituent. It represents a cyclic amino group, or an aminoalkyl group which may have a substituent, and R ³ represents a hydrogen atom or a halogen atom. ]
Compound represented by (B-2) or salt thereof (B-2) General formula (2) below

[In the formula (2), R ⁴ represents a hydrogen atom or a methyl group, and R ⁵ represents a hydrogen atom or a hydroxyl group. ]
Compound represented by (B-3) or salt thereof (B-3) General formula (3) below

[In formula (3), R ⁶ represents an alkoxy group which may have an alkyl group or a substituent, and R ⁷ represents a hydrogen atom or a sulfo group. The phenolic hydroxyl group in the formula (3) may be etherified. ]
Compound represented by (B-4) Resoteam or its salt (B-5) Codenes (B-6) Efedrins (B-7) Dextromethorphan or its salt (B-8) Xanthin derivative (B-8) B-9) Isovaleryl urea derivative (C) The present invention relates to a pharmaceutical composition containing a basic compound having an acid neutralizing ability.

According to the present invention, the interaction between loxoprofen or a salt thereof and an interacting component can be suppressed. Therefore, it is possible to provide a pharmaceutical composition containing loxoprofen or a salt thereof and an interacting component having excellent storage stability.
Further, it is possible to provide a pharmaceutical composition in which the interaction is suppressed, which contains loxoprofen or a salt thereof and an interacting component, easily and inexpensively without going through a complicated process.

<Pharmaceutical composition>
First, the pharmaceutical composition of the present invention will be described.
The component (A) of the present invention is loxoprofen or a salt thereof.
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, symptom, etc. 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 0.4 to 50% by mass, more preferably 1.2 to 30% by mass, in terms of loxoprofen sodium anhydride, based on the total mass of the pharmaceutical composition. It is preferably contained in an amount of 1.2 to 25% by mass, more preferably 1.2 to 25% by mass. Of these, 1.2 to 20% by mass is more preferable, 2.4 to 15% by mass is even more preferable, and 2.4 to 12% by mass is particularly preferable.

Next, the component (B) of the present invention will be described in detail.
In the present invention, the general formula (1)

[In formula (1), X represents a single bond or an oxygen atom, Y represents a methine group or a nitrogen atom, R ¹ represents a hydrogen atom, a hydroxyl group or an alkyl group, and R ² has a substituent. It represents a cyclic amino group, or an aminoalkyl group which may have a substituent, and R ³ represents a hydrogen atom or a halogen atom. ]
The compound represented by the above formula (1) or a salt thereof includes not only the compound represented by the above general formula (1) but also a pharmaceutically acceptable salt of the compound represented by the general formula (1). Specific examples of the compound represented by the general formula (1) or a salt thereof include, for example, a compound represented by the general formula (1), an inorganic acid salt or an organic acid salt of the compound represented by the general formula (1) ( For example, hydrochloride, maleate, fumarate, diphenyldisulfonate, theocrate, salicylate, tannate, besilate, phosphate, etc.) and the like can be mentioned. Further, in the chemical structure of the compound represented by the general formula (1), when asymmetric carbon is present, it has various optical isomers, but in the present invention, any optical isomer is included and is single. It may be an optical isomer of the above, or a mixture of various optical isomers. Further, the compound represented by the general formula (1) or a salt thereof may be in the state of a solvent, and the compound represented by the general formula (1) or a salt thereof and a solvent mixture of water, alcohol or the like may be used. Is also included in "a compound represented by the general formula (1) or a salt thereof".

In R ¹ , the alkyl group is preferably a linear or branched alkyl group having 1 to 3 carbon atoms. Specific examples thereof include a methyl group, an ethyl group, an n-propyl group and an isopropyl group, but a methyl group is preferable.
Further, as the above R ¹ , a hydrogen atom and an alkyl group are preferable, and a hydrogen atom and a methyl group are more preferable.

In R ² , the "cyclic amino group" in the cyclic amino group which may have a substituent is a 5- to 7-membered ring having at least one nitrogen atom, preferably one or two, as a ring-constituting atom. It means an alicyclic group.
Specific examples of such a cyclic amino group include a pyrrolidinyl group, a pyrazolidinyl group, a piperidinyl group, a piperazinyl group, a morpholinyl group, a homopiperidinyl group, a homopiperazinyl group and the like. Of these, a piperidinyl group, a piperazinyl group, and a homopiperazinyl group are preferable, and a piperidinyl group and a piperazinyl group are more preferable.

Further, examples of the "substituted group" in the cyclic amino group which may have a substituent include an alkylbenzoyl group, a 1,3-dihydro-2H-benzoimidazole-2-one-1-yl group and a carboxylalkoxy. Examples thereof include an alkyl group in which one or more groups selected from a group, a carboxyl group, a carboxylalkylphenyl group and a hydroxyl group may be substituted. Of these, an alkyl group, a carboxylalkoxyalkyl group, and a carboxylalkylphenyl (hydroxy) alkyl group are preferable.
Specific examples of the above "substituent" include, for example, a methyl group, a 3- (4-tert-butylbenzoyl) propyl group, and a 3- (1,3-dihydro-2H-benzoimidazole-2-one-1-yl). ) Propyl group, 2- (carboxymethoxy) ethyl group, 4- [4- (2-carboxypropane-2-yl) phenyl] -4-hydroxybutyl group, 3-carboxypropyl group and the like.

In R ² above, the "cyclic amino group which may have a substituent" includes 1-methylpiperidin-4-yl group, 4-methylhomopirazine-1-yl group, 1- [3- (4). -Tert-Butylbenzoyl) propyl] piperidine-4-yl group, 4- [3- (1,3-dihydro-2H-benzoimidazole-2-on-1-yl) propyl] piperazin-1-yl group, 4 -[2- (carboxymethoxy) ethyl] piperazin-1-yl group, 1- {4- [4- (2-carboxypropan-2-yl) phenyl] -4-hydroxybutyl} piperidine-4-yl group, A 1- (3-carboxypropyl) piperidine-4-yl group is preferred.

In R ² , the "aminoalkyl group" in the aminoalkyl group which may have a substituent is an amino group, a monoalkylamino group, a dialkylamino group or a cyclic amino group (the "cyclic amino group" is the above. It is synonymous with "cyclic amino group" in "cyclic amino group which may have a substituent") and means an alkyl group substituted. Of these, an alkyl group substituted with a dialkylamino group or a cyclic amino group is preferable. The cyclic amino group is preferably a pyrrolidinyl group.
Specific examples of such an aminoalkyl group include a 2- (dimethylamino) ethyl group, a 2- (pyrrolidin-2-yl) ethyl group, a 2-[(isopropyl) (methyl) amino] ethyl group and the like. Can be mentioned. Further, examples of the "substituent" in the aminoalkyl group which may have a substituent include a hydroxyl group, a phenyl group, an alkyl group and the like.

In R ² , the "aminoalkyl group which may have a substituent" includes 2- (dimethylamino) ethyl group, 2- (1-methylpyrrolidin-2-yl) ethyl group, and 2-[((1-methylpyrrolidin-2-yl) ethyl group". Methyl) (1-phenyl-1-hydroxypropane-2-yl) amino] ethyl groups are preferred.

In R ² , the alkyl group portion in the "alkyl group", "alkylbenzoyl group", "carboxyalkylphenyl group", "aminoalkyl group", "monoalkylamino group", and "dialkylamino group" is used. A linear or branched alkyl group having 1 to 6 carbon atoms is preferable, and specific examples thereof include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, and a hexyl group.
Further, in R ² , the alkoxy group portion of the "carboxyalkoxy group" is preferably a linear or branched alkoxy group having 1 to 6 carbon atoms, and specific examples thereof include a methoxy group, an ethoxy group and a propoxy group. , Butoxy group, pentyloxy group, hexyloxy group and the like.

^In R3 above, examples of the "halogen atom" include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom and the like, and in the present invention, the chlorine atom is preferable. Further, in the general formula (1), the substitution position on the phenyl group of R ³ is not particularly limited, but it is preferably substituted at the 4-position.

Further, the following combinations (i) to (iv) are preferable as the combination of X, Y, R ¹ , R ² and R ³ .
(I) X is a single bond, Y is a nitrogen atom, R ¹ is a hydrogen atom, R ² is an aminoalkyl group which may have a substituent, and R ³ is a halogen atom. Combination (ii) X is an oxygen atom, Y is a methine group, R ¹ is an alkyl group, R ² is an aminoalkyl group which may have a substituent, and R ³ is a halogen atom. A combination (iii) X is an oxygen atom, Y is a nitrogen atom, R ¹ is a hydrogen atom, R ² is an aminoalkyl group which may have a substituent, and R ³ is a halogen atom. Combination (iv) X is an oxygen atom, Y is a methine group, R ¹ is a hydrogen atom, R ² is a cyclic amino group which may have a substituent, and R ³ is hydrogen. A combination that is an atom

In the present invention, the compound represented by the general formula (1) or a salt thereof is a compound having a diarylmethyl structure as its common skeleton, specifically, for example, evastin or a salt thereof; oxatomide or a salt thereof; carbinoxamine. Carbinoxamine such as diphenyldisulfonate, carbinoxamine maleate or a salt thereof; clemastine such as clemastine fumarate or a salt thereof; chlorpheni such as d-chlorpheniramine maleate, dl-chlorpheniramine maleate Lamine or a salt thereof; diferrol or a salt thereof such as dipheterol hydrochloride and dipheterol phosphate; diphenylpyraline or a salt thereof such as diphenylpyraline hydrochloride and diphenylpyraline theocrate; diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine Diphenhydramine such as tannate or a salt thereof; Cetidine such as cetidine hydrochloride or a salt thereof; Fexophenazine or a salt thereof; Bepotastin such as bepotastin besilate or a salt thereof; Homochlor such as homochlorcyclidine hydrochloride Examples thereof include cyclidine or a salt thereof.
The compound represented by the general formula (1) and its salt, particularly the above-mentioned compound and its salt are known and can be produced by a known method, or commercially available ones can be used.

The content of the compound represented by the general formula (1) 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, symptom, etc. of the user. .. For example, it contains 0.01 to 400 mg of the compound represented by the general formula (1) or a salt thereof, more preferably 0.03 to 300 mg, and particularly preferably 0.1 to 200 mg per day. Can be blamed. The suitable content when a specific component is used as the compound represented by the general formula (1) or a salt thereof is exemplified below, but the present invention is not limited thereto.

In the pharmaceutical composition of the present invention, when ebastine or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof, the content thereof is preferably 0.1 to 50 mg per day. An amount that can be taken at 0.5 to 30 mg is more preferable, and an amount that can be taken at 1 to 20 mg is further preferable.
In the pharmaceutical composition of the present invention, when oxatomide or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof, the content thereof is preferably 0.3 to 200 mg per day. An amount that can be taken from 1 to 100 mg is more preferable, and an amount that can be taken from 6 to 60 mg is further preferable.
In the pharmaceutical composition of the present invention, when carbinoxamine or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof, the content thereof is preferably 0.1 to 60 mg per day. An amount that can be taken at 0.5 to 30 mg is more preferable, and an amount that can be taken at 1 to 16 mg is further preferable.

When clemastine or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof in the pharmaceutical composition of the present invention, the content thereof is 0.01 to 0.01 per day in terms of free form of clemastine. An amount that can be taken 5 mg is preferable, an amount that can be taken 0.05 to 3 mg is more preferable, and an amount that can be taken 0.1 to 2 mg is further preferable. In addition, 1.34 mg of clemastine fumarate corresponds to 1 mg as a free form of clemastine.
In the pharmaceutical composition of the present invention, when chlorpheniramine or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof, the content thereof is 0.1 to 20 mg per day. Preferably, an amount that can be taken at 0.6 to 12 mg is more preferable. When d-chlorpheniramine maleate is used as chlorpheniramine or a salt thereof, an amount of 0.1 to 15 mg per day is preferable, and an amount of 0.6 to 6 mg is more preferable. An amount that can be taken up to 5 mg is more preferable. When dl-chlorpheniramine maleate is used, an amount that can be taken at 0.5 to 20 mg, more preferably 1 to 12 mg, and even more preferably 2 to 10 mg per day.
In the pharmaceutical composition of the present invention, when diferrol or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof, the content thereof is preferably 1 to 300 mg per day, preferably 5 to 5 to. An amount that can be taken at 150 mg is more preferable, and an amount that can be taken at 10 to 100 mg is even more preferable.

When diphenylpyraline or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof in the pharmaceutical composition of the present invention, the content thereof is 0.1 to 13.5 mg per day. Is preferable, and an amount that can be taken from 1 to 4.5 mg is more preferable. When diphenylpyraline hydrochloride is used as diphenylpyraline or a salt thereof, an amount that can be taken in an amount of 0.1 to 12 mg per day is preferable, and an amount that can be taken in an amount of 1 to 4 mg is more preferable. When diphenylpyraline theocrate is used, an amount that can be taken in an amount of 0.1 to 13.5 mg per day is preferable, and an amount that can be taken in an amount of 1 to 4.5 mg is more preferable.
When diphenhydramine or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof in the pharmaceutical composition of the present invention, the content thereof is preferably 1 to 300 mg per day, preferably 5 to 5 to. An amount that can be taken at 200 mg is more preferable, and an amount that can be taken at 15 to 150 mg is even more preferable.
In the pharmaceutical composition of the present invention, when cetirizine or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof, the content thereof is preferably 0.1 to 50 mg per day. An amount that can be taken at 0.3 to 30 mg is more preferable, and an amount that can be taken at 1 to 20 mg is further preferable.

In the pharmaceutical composition of the present invention, when fexofenadine or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof, the content thereof is 0.3 to 200 mg per day. Preferably, an amount capable of taking 1 to 100 mg is more preferable, and an amount capable of taking 6 to 60 mg is further preferable.
In the pharmaceutical composition of the present invention, when bepotastine or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof, the content thereof is preferably 0.1 to 40 mg per day. An amount that can be taken at 0.5 to 30 mg is more preferable, and an amount that can be taken at 2 to 20 mg is even more preferable.
When homochlorcyclizine or a salt thereof is used as the compound represented by the general formula (1) or a salt thereof in the pharmaceutical composition of the present invention, the content thereof is an amount that can be taken in an amount of 0.3 to 180 mg per day. Is preferable, an amount that can be taken in an amount of 1 to 90 mg is more preferable, and an amount that can be taken in an amount of 3 to 60 mg is further preferable.

In the present invention, as the compound represented by the general formula (1) or a salt thereof, "chlorpheniramine or a salt thereof", "clemastine or a salt thereof", "carbinoxamine or a salt thereof" or "diphenylpyraline or a salt thereof". It is preferable to use.

In the present invention, "chlorpheniramine or a salt thereof" includes not only chlorpheniramine itself but also a pharmaceutically acceptable salt of chlorpheniramine.
Since chlorpheniramine has an asymmetric carbon, it has an optical isomer. However, in the present invention, any optical isomer may be contained, and a single optical isomer may be used, or a mixture of various optical isomers may be used. .. Of these, in the present invention, the d-form and the dl-form are preferable. Specific examples of the chlorpheniramine or a salt thereof include chlorpheniramine, chlorpheniramine maleate, d-chlorpheniramine maleate, dl-chlorpheniramine maleate and the like. In the present invention, d-chlorpheniramine maleate and dl-chlorpheniramine maleate are preferable, and d-chlorpheniramine maleate is particularly preferable. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

The content of chlorpheniramine 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 above-mentioned daily dose, but chlorpheniramine or a salt thereof may be used. It is preferably contained in an amount of 0.004 to 1.5% by mass, more preferably 0.02 to 0.8% by mass, and 0.04 to 0.7% by mass based on the total mass of the pharmaceutical composition. Is particularly preferable.

The content ratio of loxoprofen or a salt thereof and chlorpheniramine or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, and it should be appropriately examined and determined according to the daily dose of each of the above-mentioned components. However, loxoprofen or a salt thereof is preferably contained in an amount of 0.0001 to 1.5 parts by mass, preferably 0.0005 to 0.7, based on 1 part by mass of loxoprofen sodium anhydride. Those containing by mass are more preferable, and those containing 0.001 to 0.5 parts by mass are particularly preferable.

In the present invention, "clemastine or a salt thereof" includes not only clemastine itself but also a pharmaceutically acceptable salt of clemastine. Specific examples of cremastin or a salt thereof include cremastin, cremastin mineral salts (salts, nitrates, sulfates, etc.), cremastin organic acid salts (fumarate, methanesulfonates, etc.), and the like. In the present invention, clemastine fumarate is preferred. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

The content of clemastine 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 above-mentioned daily dose, but clemastine or a salt thereof may be used for the entire pharmaceutical composition. It is preferably contained in an amount of 0.008 to 0.4% by mass, more preferably 0.01 to 0.2% by mass, and 0.015 to 0.15% by mass in terms of free form of clemastine with respect to the mass. It is particularly preferable to contain it. In addition, 1.34 mg of clemastine fumarate corresponds to 1 mg as a free form of clemastine.

The content ratio of clemastine or its salt to lexoprofen 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 daily dose of each of the above-mentioned components. Alternatively, the salt thereof is preferably contained in an amount of 0.0006 to 0.5 parts by mass in terms of a free form of clemastine with respect to 1 part by mass in terms of loxoprofen sodium anhydride, and 0.0012 to 0.3 parts by mass. The one containing 0.002 to 0.1 parts by mass is more preferable, and the one containing 0.002 to 0.1 parts by mass is further preferable.

In the present invention, "carbinoxamine or a salt thereof" includes not only carbinoxamine itself but also a pharmaceutically acceptable salt of carbinoxamine. Specific examples of carbinoxamine or a salt thereof include carbinoxamine, carbinoxamine maleate, carbinoxamine diphenyldisulfonic acid salt and the like, and in the present invention, carbinoxamine maleate is more preferable. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

The content of carbinoxamine 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 above-mentioned daily dose, but carbinoxamine or a salt thereof is used in the entire pharmaceutical composition. It is preferably contained in an amount of 0.004 to 4% by mass, more preferably 0.02 to 2% by mass, and particularly preferably 0.04 to 1% by mass.

The content ratio of loxoprofen or a salt thereof and carbinoxamine or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the daily dose of each of the above-mentioned components. However, loxoprofen or a salt thereof is preferably contained in an amount of 0.0003 to 6 parts by mass, and more preferably 0.002 to 1 part by mass with respect to 1 part by mass in terms of loxoprofen sodium anhydride. , 0.005 to 0.3 parts by mass is more preferable.

In the present invention, "diphenylpyraline or a salt thereof" includes not only diphenylpyraline itself but also a pharmaceutically acceptable salt of diphenylpyraline. Specific examples of diphenylpyraline or a salt thereof include diphenylpyraline, diphenylpyraline hydrochloride, diphenylpyraline theocrate and the like, and in the present invention, diphenylpyraline hydrochloride and diphenylpyraline theocrate are preferable. Diphenylpyraline hydrochloride is particularly preferred. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

The content of diphenylpyraline 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 above-mentioned daily dose, but diphenylpyraline or a salt thereof may be used as a pharmaceutical composition. It is preferably contained in an amount of 0.004 to 1% by mass, more preferably 0.004 to 0.5% by mass, still more preferably 0.04 to 0.3% by mass, based on the total mass of the product. , 0.06 to 0.25% by mass is particularly preferable.

The content ratio of loxoprofen or a salt thereof and diphenylpyraline or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the daily dose of each of the above-mentioned components. However, it is preferable that loxoprofene or a salt thereof is contained in an amount of 0.0001 to 3 parts by mass, preferably 0.0005 to 2.5 parts by mass, based on 1 part by mass of loxoprofen sodium anhydride. Those containing 0.001 to 1 part by mass are more preferable, and those containing 0.001 to 0.5 part by mass are particularly preferable.

In the present invention, the general formula (2)

[In the formula (2), R ⁴ means a hydrogen atom or a methyl group, and R ⁵ represents a hydrogen atom or a hydroxyl group. ]
The compound represented by the above formula or a salt thereof includes not only the compound represented by the general formula (2) but also a pharmaceutically acceptable salt of the compound represented by the general formula (2). Specific examples of the compound represented by the general formula (2) or a salt thereof include inorganic acid salts such as a compound represented by the general formula (2) and a hydrochloride of the compound represented by the general formula (2). Organic acid salts are mentioned, and the hydrochloride of the compound represented by the general formula (2) is more preferable.

As the compound represented by the general formula (2) or a salt thereof,
(A) Bromhexine (a compound in which R ⁴ is a methyl group and R ⁵ is a hydrogen atom) or a salt thereof (b) Ambroxol (a compound in which R ⁴ is a hydrogen atom and R ⁵ is a hydroxyl group) or a salt thereof. Examples thereof include the salt (c) a compound in which R ⁴ is a methyl group and R ⁵ is a hydroxyl group or a salt thereof (d) a compound in which R ⁴ and R ⁵ are hydrogen atoms or a salt thereof, and examples thereof include (a) bromhexine or a salt thereof. Salts, (b) ambroxol or salts thereof are preferred, and bromhexine hydrochloride and ambroxol hydrochloride are particularly preferred.

Further, in the general formula (2), when R ⁵ is a hydroxyl group, the α carbon of the substituent becomes an asymmetric center, and an isomer selected from the S-form and the R-form exists. It may be any of them, or it may be a mixture thereof. These compounds may be used alone or in combination of two or more. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

The content of the compound represented by the general formula (2) 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, symptom, etc. of the user. .. For example, when the compound represented by the general formula (2) or a salt thereof is bromhexine or a salt thereof, 0.1 to 50 mg of bromhexine or a salt thereof is converted into bromhexine hydrochloride per day, more preferably 0. It can contain 5 to 25 mg, particularly preferably 1 to 15 mg in an amount that can be taken. When the compound represented by the general formula (2) or a salt thereof is ambroxol or a salt thereof, ambroxol or a salt thereof is converted into ambroxol hydrochloride in an amount of 0.1 to 150 mg per day. , More preferably 0.5 to 100 mg, particularly preferably 1 to 50 mg can be contained.

In the present invention, it is preferable that the compound represented by the general formula (2) or a salt thereof is contained in an amount of 0.001 to 20% by mass based on the total mass of the pharmaceutical composition. When the compound represented by the general formula (2) or a salt thereof is bromhexine or a salt thereof, it is preferably contained in an amount of 0.004 to 4% by mass in terms of bromhexine hydrochloride with respect to the total mass of the pharmaceutical composition. , 0.02 to 2% by mass is more preferable, and 0.04 to 1% by mass is particularly preferable. Further, when the compound represented by the general formula (2) or a salt thereof is ambroxol or a salt thereof, it contains 0.004 to 10% by mass in terms of ambroxol hydrochloride with respect to the total mass of the pharmaceutical composition. It is preferably contained in an amount of 0.02 to 7% by mass, more preferably 0.04 to 5% by mass, and particularly preferably contained in an amount of 0.04 to 5% by mass.

The content ratio of bromhexine or a salt thereof contained in the pharmaceutical composition of the present invention and the compound represented by the general formula (2) or a salt thereof is not particularly limited, and depends on the daily dose of each of the above-mentioned components. However, when the compound represented by the general formula (2) or a salt thereof is bromhexine or a salt thereof, loxoprofene or a salt thereof is added to 1 part by mass in terms of loxoprofen sodium anhydride. Bromhexine or a salt thereof is preferably contained in an amount of 0.0001 to 10 parts by mass in terms of bromhexine hydrochloride, more preferably 0.0005 to 2 parts by mass, and more preferably 0.001 to 1 part by mass. Especially preferable. When the compound represented by the general formula (2) or a salt thereof is ambroxol or a salt thereof, ambroxol or a salt thereof is added to 1 part by mass of ambroxol or a salt thereof in terms of loxoprofen sodium anhydride. It is preferably contained in an amount of 0.0001 to 10 parts by mass, more preferably 0.0005 to 5 parts by mass, and particularly preferably 0.001 to 3 parts by mass in terms of ambroxol hydrochloride.

In the present invention, the following general formula (3)

[In formula (3), R ⁶ represents an alkoxy group which may have an alkyl group or a substituent, and R ⁷ represents a hydrogen atom or a sulfo group. The phenolic hydroxyl group in the formula may be etherified. ]
The compound represented by the above formula or a salt thereof includes not only the compound represented by the general formula (3) but also a pharmaceutically acceptable salt of the compound represented by the general formula (3). Specific examples of the compound represented by the general formula (3) or a salt thereof include alkali metal salts such as a compound represented by the general formula (3) and a potassium salt of the compound represented by the general formula (3). The potassium salt of the compound represented by the general formula (3) is more preferable.

In R ⁶ , the alkyl group is preferably a linear or branched alkyl group having 1 to 6 carbon atoms, and specific examples thereof include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, and a hexyl group. And so on. In the present invention, a methyl group is preferable.
The alkoxy group is preferably a linear or branched alkoxy group having 1 to 6 carbon atoms, and specific examples thereof include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a pentyloxy group, and a hexyloxy group. Can be mentioned. In the present invention, a methoxy group is preferable.
Examples of the group that can be substituted with the alkoxy group include a hydroxyl group; a halogen atom such as a bromine atom, a chlorine atom, a fluorine atom, and an iodine atom, and one or a plurality of these may be present.

In the above general formula (3), when the phenolic hydroxyl group is etherified, for example, a linear or branched monohydric alcohol having 1 to 3 carbon atoms in which the phenolic hydroxyl group is etherified is directly formed. Examples thereof include polyhydric alcohols having 1 to 3 carbon atoms in a chain or a branched chain in which a phenolic hydroxyl group is etherified. Examples of the monohydric alcohol include methanol, ethanol and propanol. Examples of the polyhydric alcohol include ethylene glycol, propylene glycol, and glycerin. In the present invention, a linear or branched polyhydric alcohol having 1 to 3 carbon atoms, particularly one in which a phenolic hydroxyl group is etherified with glycerin is preferable. When the phenolic hydroxyl group is etherified, the etherification reaction is not particularly limited.

Further, the following combinations (v) to (vii) are preferable as the combination of the phenolic hydroxyl groups, R ⁶ and R ⁷ in the formula (3).
(V) A combination in which the phenolic hydroxyl group is a non-etherified phenolic hydroxyl group, R ⁶ is an alkoxy group which may have a substituent, and R ⁷ is a sulfo group (vi) Phenol. A combination (vii) phenolic hydroxyl group in which the sex hydroxyl group is an etherified phenolic hydroxyl group, R ⁶ is an alkoxy group which may have a substituent, and R ⁷ is a hydrogen atom. A combination of non-etherified phenolic hydroxyl groups, where R ⁶ is an alkyl group and R ⁷ is a sulfo group.

As the compound represented by the general formula (3) of the present invention or a salt thereof, a 2-methoxyphenol derivative (guaiacol derivative) or a salt thereof, a 2-methylphenol derivative (cresol derivative) or a salt thereof is a suitable specific example. Can be mentioned.
Examples of the guaiacol derivative or a salt thereof include guaiacol glycerin ether (guaiacol glycerin ether; (2RS) -3- (2-methoxyphenoxy) propane-1,2-diol) or a salt thereof; guaiacol sulfonic acid, potassium guaiacol sulfonate and the like. Acids or salts thereof are preferred. Further, as the cresol derivative or a salt thereof, cresol sulfonic acid such as cresol sulfonic acid (2-methylphenol sulfonic acid) or potassium cresol sulfonic acid or a salt thereof is preferable.
Further, as the compound represented by the general formula (3) or a salt thereof, a guayacol derivative or a salt thereof is preferable, guayacol sulfonic acid or a salt thereof, guaifenesin is more preferable, and potassium guayacol sulfonate and guaifenesin are particularly preferable.
These are known compounds and can be produced by known methods, or commercially available compounds can be used.

The content of the compound represented by the general formula (3) 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, symptom, etc. of the user. .. For example, the compound represented by the general formula (3) or a salt thereof can be contained in an amount of 5 to 600 mg, more preferably 10 to 450 mg, and particularly preferably 25 to 300 mg per day. When a guaiacol derivative or a salt thereof is used as the compound represented by the general formula (3) or a salt thereof, 10 to 600 mg, more preferably 20 to 450 mg of the guaiacol derivative or a salt thereof per day is particularly preferable. It is preferable to contain an amount of 30 to 300 mg that can be taken. When a cresol derivative or a salt thereof is used as the compound represented by the general formula (3) or a salt thereof, the amount of the cresol derivative or a salt thereof is 5 to 550 mg, more preferably 10 to 400 mg, particularly suitable per day. Is preferably contained in an amount that can be taken in an amount of 25 to 270 mg.
In the present invention, it is preferable that the compound represented by the general formula (3) or a salt thereof is contained in an amount of 0.2 to 40% by mass based on the total mass of the pharmaceutical composition. When the compound represented by the general formula (3) or a salt thereof is a guayacol derivative or a salt thereof, it is preferably contained in an amount of 0.4 to 40% by mass, preferably 0.8 to 40% by mass, based on the total mass of the pharmaceutical composition. It is more preferably contained in an amount of 30% by mass, and particularly preferably contained in an amount of 1.2 to 25% by mass. Further, when the compound represented by the general formula (3) or a salt thereof is a cresol derivative or a salt thereof, it is preferably contained in an amount of 0.2 to 35% by mass, preferably 0.4 to 35% by mass, based on the total mass of the pharmaceutical composition. It is more preferably contained in an amount of 25% by mass, and particularly preferably contained in an amount of 1 to 20% by mass.

The content ratio of loxoprofen or a salt thereof contained in the pharmaceutical composition of the present invention and the compound represented by the general formula (3) or a salt thereof is not particularly limited, and depends on the daily dose of each of the above-mentioned components. The compound represented by the general formula (3) or a salt thereof is contained in an amount of 0.015 to 60 parts by mass based on 1 part by mass of loxoprofen or a salt thereof in terms of loxoprofen sodium anhydride. It is preferably contained in an amount of 0.04 to 15 parts by mass, and more preferably contained in an amount of 0.13 to 5 parts by mass.

In the present invention, "lysozyme or a salt thereof" includes not only lysozyme itself but also a pharmaceutically acceptable salt of lysozyme. Specific examples of the lysozyme or a salt thereof include lysozyme, lysozyme hydrochloride and the like, and lysozyme hydrochloride is preferable. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

The content of lysozyme 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, symptom, etc. of the user. For example, lysozyme or a salt thereof per day in terms of titer of lysozyme hydrochloride is 5 to 450 mg (titer), more preferably 10 to 360 mg (titer), and particularly preferably 15 to 270 mg (titer). ) It can contain an amount that can be taken. When lysozyme hydrochloride is used as lysozyme or a salt thereof, the amount of lysozyme hydrochloride is 5 to 450 mg (titer), more preferably 10 to 360 mg (titer), and particularly preferably 15 to 270 mg per day. (Titer) It is preferable to include an amount that can be taken.
In the present invention, it is preferable to contain lysozyme or a salt thereof in an amount of 0.2 to 30% by mass (titer) in terms of titer of lysoteam hydrochloride with respect to the total mass of the pharmaceutical composition, preferably 0.4 to 25% by mass. % (Titer) is more preferable, and 0.6 to 20% by mass (titer) is particularly preferable.

The content ratio of loxoprofen or a salt thereof and lysoteam or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the daily dose of each of the above-mentioned components. However, it is preferable that loxoprofene or a salt thereof is contained in an amount of 0.01 to 45 parts by mass (titer) in terms of titer of lysoteam hydrochloride with respect to 1 part by mass of loxoprofen sodium anhydride. Those containing 0.03 to 30 parts by mass (titer) are more preferable, those containing 0.04 to 12 parts by mass (titer) are further preferable, and those containing 0.08 to 5 parts by mass (titer). Is particularly preferable.

In the present invention, the "codeines" mean one or more selected from the group consisting of codeine, dihydrocodeine and salts thereof and solvates thereof. This group includes codeine and dihydrocodeine itself, as well as pharmaceutically acceptable salts of codeine and dihydrocodeine and their solvates. Specific examples of codeines include codeine, dihydrocodeine, codeine phosphate hydrate, dihydrocodeine phosphate and the like, and codeine phosphate water from the viewpoint of using the pharmaceutical composition of the present invention as a comprehensive sensitizer or the like. Japanese products and dihydrocodeine phosphate are more preferable, and dihydrocodeine phosphate is even more preferable. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

The content of codeine in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the gender, age, symptom, etc. of the user. For example, it can contain 2 to 60 mg of codeine, more preferably 4 to 48 mg, and particularly preferably 6 to 36 mg of codeine per day. When codeine phosphate hydrate is used as the codeines, the amount of codeine phosphate hydrate can be contained in an amount of 4 to 60 mg, more preferably 8 to 48 mg, and particularly preferably 12 to 36 mg per day. Is preferable. When dihydrocodeine phosphate is used, it is preferable to contain 2 to 30 mg of dihydrocodeine phosphate, more preferably 4 to 24 mg, and particularly preferably 6 to 24 mg per day.
In the present invention, it is preferable to contain codeines in an amount of 0.08 to 4% by mass based on the total mass of the pharmaceutical composition. When the codeines are codeine phosphate hydrate, the content is preferably 0.15 to 4% by mass, more preferably 0.3 to 3% by mass, and 0, based on the total mass of the pharmaceutical composition. It is particularly preferably contained in an amount of 5.5 to 2.5% by mass. Further, when the codeines are dihydrocodeine phosphate, it is preferably contained in an amount of 0.08 to 2% by mass, more preferably 0.16 to 1.5% by mass, based on the total mass of the pharmaceutical composition. It is particularly preferably contained in an amount of 0.24 to 1.5% by mass.

The content ratio of loxoprofen or a salt thereof and codeines contained in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the daily dose of each of the above-mentioned components. , Loxoprofen or a salt thereof is preferably contained in an amount of 0.005 to 4 parts by mass, more preferably 0.01 to 2 parts by mass, and 0, based on 1 part by mass of loxoprofen sodium anhydride. Those containing .02 to 1 part by mass are particularly preferable.

In the present invention, "ephedrines" means one or more selected from the group consisting of ephedrine, derivatives of ephedrine, and salts thereof. Here, examples of the derivative of ephedrine include norephedrine (phenylpropanolamine), methylephedrine and the like. Examples of the salt include salts of pharmaceutically acceptable inorganic acids and organic acids, and suitable specific examples thereof include hydrochlorides, sulfates, and saccharin salts. Further, since ephedrine has two asymmetric carbons, various optical isomers exist, but in the present invention, any optical isomer may be contained, and a single optical isomer may be used, and various optical isomers may be used. May be a mixture of. In the present invention, l-form and dl-form are preferable.

In the present invention, specific examples of ephedrines include, for example, l-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, l-methylephedrine saccharin salt, dl-methylephedrine saccharin salt, pseudoephedrine hydrochloride, pseudoephedrine sulfate and the like. These can be used alone or in combination of two or more. It should be noted that ephedrine and pseudoephedrine are in an enantiomeric relationship with each other. Of these, dl-methylephedrine hydrochloride is preferred in the present invention. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

Further, as the "ephedrines" in the present invention, Ephedra (Ephedra) containing these as a component can also be used.
Ephedra means the above-ground stem of Ephedra sinica Stapf, Ephedra intermedia Schrenk et CA Meyer or Ephedra equisetina Bunge (Ephedraceae), as published in the 15th Amendment of the Japanese Pharmacy. The morphology of Ephedra can be adjusted as needed and can be cut or crushed into small pieces, lumps or crushed into powder. For example, Ephedra powder is called "Ephedra powder".
In addition, Ephedra is made into an appropriate size based on the known method described in the 15th revised Japanese Pharmacopoeia General Regulations for Formulation, etc., and then exuded with an appropriate leachate or a concentrated leachate, that is, " It may be "extract" or "tincture". Leachants include lower monohydric alcohols such as methanol, ethanol and n-butanol; lower polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol and glycerin; ethers such as diethyl ether; acetone and ethyl. Ketones such as methyl ketone; esters such as ethyl acetate ester; halogenoalcans such as dichloromethane and chloroform; aromatic hydrocarbons such as benzene and toluene; and water and the like. These may be used alone or in combination of two or more. In addition, the extract can be dried.

In the present invention, when Ephedra is used as the ephedrines, Ephedra powder, Ephedra style extract, Ephedra soft extract, Ephedra dried extract, Ephedra extract and the like are preferable, and these can be used alone or in combination of two or more. Further, when Ephedra is used, it is also possible to use Ephedra (Kakkonto), Shoseiryuto (Shoseiryuto), Maoto (Maoto) and the like, which are Chinese herbal prescriptions containing Ephedra. These may be produced by a known method, or commercially available products may be used.

The content of ephedrine in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the gender, age, symptom, etc. of the user. For example, it can contain 5 to 500 mg of ephedrine, more preferably 10 to 360 mg, and particularly preferably 20 to 240 mg of ephedrine per day.
In addition, some or all of the ephedrines can be replaced with the above-mentioned Ephedra. When Ephedra is used as an ephedrine, for example, 0.1 to 25 g of Ephedra (equivalent amount of crude drug), more preferably 0.25 to 10 g (equivalent amount of crude drug), and particularly preferably 0 per day. .4 to 4 g (herbal medicine equivalent amount) can be contained in an amount that can be taken.
In the present invention, ephedrine is preferably contained in an amount of 0.1 to 40% by mass, more preferably 0.5 to 20% by mass, and 1 to 10% by mass based on the total mass of the pharmaceutical composition. Is more preferable, and it is particularly preferable that the content is 2 to 10% by mass. When Ephedra is used as the ephedrine, it is preferably contained in an amount of 1 to 98% by mass, more preferably 2 to 50% by mass, and 4 to 20% by mass based on the total mass of the pharmaceutical composition. It is particularly preferable to do so.

The content ratio of loxoprofen or a salt thereof and ephedrine contained in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the daily dose of each of the above-mentioned components. , Loxoprofen or a salt thereof is preferably contained in an amount of 0.001 to 50 parts by mass, more preferably 0.005 to 50 parts by mass, based on 1 part by mass of loxoprofen sodium anhydride. Those containing 0.015 to 50 parts by mass are more preferable. Of these, those containing 0.05 to 12 parts by mass are more preferable, and those containing 0.1 to 4 parts by mass are particularly preferable.

In the present invention, "dextromethorphan or a salt thereof" includes dextromethorphan itself, a pharmaceutically acceptable salt of dextromethorphan, and a pharmaceutically acceptable salt of dextromethorphan or dextromethorphan. Solvents with water, alcohol, etc. are also included. Specific examples of dextromethorphan or a salt thereof include dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthaline salt, and the like, and dextromethorphan hydrobromide hydrate. , Dextromethorphan phenolphthalin salt is preferred, and dextromethorphan hydrobromide hydrate is particularly preferred. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

The content of dextromethorphan 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, symptom, etc. of the user. For example, it can contain 0.1 to 270 mg of dextromethorphan or a salt thereof per day, more preferably 0.5 to 180 mg, and particularly preferably 1 to 90 mg. When dextromethorphan or a salt thereof is dextromethorphan hydrobromide hydrate, 6 to 60 mg of dextromethorphan hydrobromide hydrate, more preferably 15 to 60 mg, per day. Particularly preferably, it contains an amount that can be taken in an amount of 20 to 60 mg. When dextromethorphan or a salt thereof is dextromethorphan phenolphthalin salt, 9 to 90 mg of dextromethorphan phenolphthalin salt, more preferably 22 to 90 mg, and particularly preferably 30 to 30 mg per day. It is preferable to contain an amount that can be taken at 90 mg.
In the present invention, dextromethorphan or a salt thereof is preferably contained in an amount of 0.004 to 20% by mass, more preferably 0.02 to 15% by mass, and 0.04 based on the total mass of the pharmaceutical composition. It is particularly preferably contained in an amount of about 10% by mass.

The content ratio of loxoprofen or a salt thereof and dexstrometolfan or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, and is appropriately examined and determined according to the daily dose of each of the above-mentioned components. However, loxoprofen or a salt thereof is preferably contained in an amount of 0.0001 to 20 parts by mass, preferably 0.0005 to 10 parts by mass, based on 1 part by mass of loxoprofen sodium anhydride. Those containing a portion are more preferable, and those containing 0.001 to 5 parts by mass are particularly preferable.

In the present invention, the "xanthine derivative" is preferably a compound represented by the following general formula (4).

[In formula (4), R ⁸ and R ⁹ each independently represent a hydrogen atom or a methyl group, and R ¹⁰ represents a hydrogen atom, a methyl group, a monohydroxypropyl group or a dihydroxypropyl group. ]

In formula (4), in R ¹⁰ , the monohydroxypropyl group is preferably a 2-hydroxypropyl group. The dihydroxypropyl group is preferably a 2,3-dihydroxypropyl group.

In the above general formula (4),
(1) When R ⁸ is a methyl group, R ⁹ is a methyl group, and R ¹⁰ is a methyl group, it means caffeine.
(2) When R ⁸ is a methyl group, R ⁹ is a methyl group, and R ¹⁰ is a hydrogen atom, it means theophylline.
(3) When R ⁸ is a hydrogen atom, R ⁹ is a methyl group, and R ¹⁰ is a methyl group, it means theobromine.
(4) When R ⁸ is a methyl group, R ⁹ is a hydrogen atom, and R ¹⁰ is a methyl group, it means paraxanthine.
(5) When R ⁸ is a methyl group, R ⁹ is a methyl group, and R ¹⁰ is a 2-hydroxypropyl group, it means proxophilin.
(6) When R ⁸ is a methyl group, R ⁹ is a methyl group, and R ¹⁰ is a 2,3-dihydroxypropyl group, it means diprophylline.

The compound of the general formula (4), particularly the above-mentioned compound, 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 (4), a pharmaceutically acceptable salt thereof (for example, a compound salt formed (for example, sodium benzoate caffeine (sodium benzoate and caffeine)) (Caffeine compound salt), aminophylline (theophylline and ethylenediamine compound salt)), etc.), the compound represented by the general formula (4) or a solvent mixture of the salt and water, alcohol, etc. can also be used. Is also included in the "xanthin 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 may be appropriately examined and determined according to the gender, age, symptom and the like of the user. For example, the xanthine derivative can be contained in an amount that can be taken in an amount of 10 to 1000 mg, more preferably 20 to 800 mg, and particularly preferably 30 to 600 mg per day. In the present invention, the xanthine derivative is preferably contained in an amount of 0.4 to 65% by mass, more preferably 0.8 to 50% by mass, and 1.6 to 40% by mass, based on the total mass of the pharmaceutical composition. It is particularly preferable to contain it.

The blending ratio of loxoprofen or a salt thereof and a xanthin derivative contained in the pharmaceutical composition of the present invention may be appropriately examined and determined according to the daily dose of each of the above-mentioned components, but loxoprofen may be determined. Alternatively, the salt thereof is preferably contained in an amount of 0.03 to 100 parts by mass, more preferably 0.08 to 27 parts by mass, based on 1 part by mass of loxoprofen sodium anhydride. Those containing 2 to 10 parts by mass are more preferable.

In the present invention, the "isovaleryl urea derivative" means one or more selected from the group consisting of bromvalerylurea, allylisopropylacetylurea and salts thereof. Of these, bromvalerylurea is preferable.
Since the isovaleryl urea derivative has an asymmetric carbon, various optical isomers exist. However, in the present invention, any optical isomer may be contained, and a single optical isomer may be used, and various optical isomers may be used. May be a mixture of.

The content of the isovaleryl-urea derivative in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the gender, age, symptom, etc. of the user. For example, when the isovaleryl-urea derivative is bromvaleryl-urea or a salt thereof, the amount of bromvaleryl-urea contained in a free form is 10 to 1000 mg, more preferably 30 to 800 mg, and particularly preferably 60 to 600 mg per day. Can be blamed. When the isovaleryl-urea derivative is allyl isopropyl acetyl urea or a salt thereof, 1 to 500 mg of allyl isopropyl acetyl urea is taken per day, more preferably 10 to 300 mg, and particularly preferably 20 to 180 mg. It can contain as much as possible.

In the present invention, the isovaleryl-urea derivative is preferably contained in an amount of 0.1 to 95% by mass based on the total mass of the pharmaceutical composition. In particular, when the isovaleryl urea derivative is bromvalerylurea or a salt thereof, it is preferable to contain 1 to 95% by mass of bromvalerylurea in terms of free form with respect to the total mass of the pharmaceutical composition, preferably 4 to 90% by mass. It is more preferably contained in an amount of 8 to 80% by mass, and particularly preferably contained in an amount of 8 to 80% by mass. When the isovaleryl urea derivative is allyl isopropyl acetyl urea or a salt thereof, it is preferable to contain allyl isopropyl acetyl urea in an amount of 0.1 to 70% by mass in terms of free form with respect to the total mass of the pharmaceutical composition, from 1 to 40. It is more preferably contained in an amount of 2 to 24% by mass, and particularly preferably contained in an amount of 2 to 24% by mass.

The content ratio of loxoprofen or a salt thereof and an isovalerylurea derivative contained in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the daily dose of each of the above-mentioned components. When the isovaleryl urea derivative is bromvalerylurea or a salt thereof, it contains 0.03 to 100 parts by mass of bromvalerylurea or a salt thereof in terms of 1 part by mass in terms of loxoprofen sodium anhydride and 0.03 to 100 parts by mass in terms of bromvalerylurea or a salt thereof. Those containing 0.05 to 50 parts by mass are more preferable, those containing 0.1 to 30 parts by mass are further preferable, and those containing 0.3 to 10 parts by mass are particularly preferable. When the isovaleryl urea derivative is allyl isopropyl acetyl urea or a salt thereof, loxoprofen or a salt thereof is used in an amount of 1 part by mass in terms of loxoprofen sodium anhydride, and allyl isopropyl acetyl urea or a salt thereof is used in a free form of 0.003 to The one containing 50 parts by mass is preferable, the one containing 0.04 to 10 parts by mass is more preferable, and the one containing 0.1 to 3 parts by mass is particularly preferable.

Next, the component (C) of the present invention will be described in detail.
The component (C) is a basic compound having an acid neutralizing ability. Here, 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 antiacidity test method described in the 15th revised Japanese Pharmacy Law General Test Method.

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 organic compounds such as sodium and potassium. Examples thereof include basic organic compounds such as compounds and amine-based basic organic compounds.

In 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, aluminum silicate, magnesium oxide, magnesium hydroxide, magnesium hydroxide and potassium aluminum sulfate. Material, magnesium carbonate, synthetic hydrotalcite, magnesium aluminometasilicate, dry aluminum hydroxide gel, synthetic aluminum silicate, synthetic aluminum silicate, hydroxypropyl starch, crystalline cellulose, magnesium hydroxide, aluminum hydroxide gel, water 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, 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. ´-ribonucleotide 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 sucralfate 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, suitable specific examples of the basic compound having an acid neutralizing ability include magnesium aluminomerate, magnesium silicate, aluminum magnesium silicate, magnesium oxide, magnesium hydroxide, precipitated calcium carbonate, and phosphorus anhydrous. One or more selected from the group consisting of calcium hydrogenate and magnesium aluminometasilicate can be mentioned, and particularly preferably, magnesium aluminomerate silicate, magnesium silicate, magnesium oxide, magnesium hydroxide, in terms of suppressing interaction. One or more selected from the group consisting of precipitated calcium carbonate, anhydrous calcium hydrogen phosphate and magnesium aluminometasilicate can be mentioned.
The basic compound may be used alone or in combination of two or more. These are known compounds and can be produced by known methods, or commercially available compounds can be used.

Further, as the basic compound having an acid neutralizing ability, a compound that can be used as an antacid can be mentioned as a preferable specific example. Specific examples of the basic compound having an acid neutralizing ability that can be used as an acid control agent include aminoacetic acid, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, and magnesium oxide. , Dihydroxyaluminum aminoacetate, aluminum hydroxide magnesium hydroxide, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide / magnesium carbonate mixed dry gel, co-precipitated product of aluminum hydroxide / sodium hydrogencarbonate, aluminum hydroxide / carbonic acid Co-precipitated product of calcium / magnesium carbonate, magnesium hydroxide, co-precipitated product of magnesium hydroxide / aluminum potassium sulfate, magnesium carbonate, sodium hydrogen carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, Examples include calcium hydroxide, sardine bone, stone determination, and volley. Antacids are roughly classified into absorbable antacids and local antacids according to their properties, but in the present invention, local antacids are preferable from the viewpoint of preventing alkalosis.

The content of the basic compound having an acid neutralizing ability in the pharmaceutical composition of the present invention is not particularly limited, and may be appropriately examined and determined according to the effect of suppressing the interaction between loxoprofen and the interacting component. .. For example, an amount of 1 to 20000 mg per day is preferable, an amount of 10 to 10000 mg is more preferable, and an amount of 20 to 5000 mg is particularly preferable. In the present invention, the basic compound having an acid neutralizing ability is preferably contained in an amount of 0.04 to 99.9% by mass, preferably 0.4 to 99.9% by mass, based on the total mass of the pharmaceutical composition. Is more preferable, and 0.8 to 99.9% by mass is particularly preferable.

When aldioxa is used as the basic compound having an acid neutralizing ability, an amount of 10 to 800 mg per day is preferable, and an amount of 30 to 400 mg is more preferable.
When using squid bone, an amount of 10 to 6000 mg per day is preferable, and an amount of 30 to 3000 mg is more preferable.
When a dry aluminum hydroxide gel is used, an amount of 10 to 6000 mg per day is preferable, and an amount of 30 to 3000 mg is more preferable.
When magnesium silicate aluminate is used, an amount of 10 to 8000 mg per day is preferable, and an amount of 30 to 4000 mg is more preferable.
When calcium silicate is used, an amount of 1 to 600 mg per day is preferable, and an amount of 30 to 300 mg is more preferable.
When magnesium silicate is used, an amount of 10 to 12000 mg per day is preferable, and an amount of 30 to 6000 mg is more preferable.
When magnesium aluminum silicate is used, an amount of 1 to 500 mg per day is preferable, and an amount of 20 to 225 mg is more preferable.
When synthetic aluminum silicate is used, an amount of 10 to 20000 mg per day is preferable, and an amount of 30 to 10000 mg is more preferable.
When synthetic aluminum silicate, hydroxypropyl starch, and crystalline cellulose are used, an amount of 10 to 3500 mg per day is preferable, and an amount of 30 to 1800 mg is more preferable.

When synthetic hydrotalcite is used, an amount of 10 to 8000 mg per day is preferable, and an amount of 30 to 4000 mg is more preferable.
When magnesium oxide is used, an amount of 10 to 2000 mg per day is preferable, and an amount of 30 to 1000 mg is more preferable.
When dihydroxyaluminum aminoacetate is used, an amount of 10 to 6000 mg per day is preferable, and an amount of 30 to 3000 mg is more preferable.
When magnesium hydroxide alumina is used, an amount of 10 to 8000 mg per day is preferable, and an amount of 30 to 4000 mg is more preferable.
When the aluminum hydroxide gel is used, it is preferable to take 10 to 6000 mg per day in terms of dry aluminum hydroxide gel, and more preferably 30 to 3000 mg.
When the aluminum hydroxide / sodium hydrogen carbonate coprecipitation product is used, an amount of 10 to 4000 mg per day is preferable, and an amount of 30 to 2000 mg is more preferable.
When using the aluminum hydroxide / magnesium carbonate mixed dry gel, the amount of 10 to 6000 mg per day is preferable, and the amount of 30 to 3000 mg is more preferable.
When an aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitated product is used, an amount of 10 to 8000 mg per day is preferable, and an amount of 30 to 4000 mg is more preferable.
When magnesium hydroxide is used, an amount of 10 to 5000 mg per day is preferable, and an amount of 30 to 2400 mg is more preferable.
When the coprecipitation product of magnesium hydroxide and potassium aluminum sulfate is used, the amount of 10 to 4000 mg per day is preferable, and the amount of 30 to 2000 mg is more preferable.

When sucralfate hydrate is used, an amount of 10 to 6500 mg per day is preferable, and an amount of 30 to 3250 mg is more preferable.
When stone determination is used, an amount of 10 to 6000 mg per day is preferable, and an amount of 30 to 3000 mg is more preferable.
When sodium hydrogen carbonate is used, an amount of 10 to 10000 mg per day is preferable, and an amount of 30 to 5000 mg is more preferable.
When calcium carbonate is used, an amount of 10 to 1500 mg per day is preferable, and an amount of 30 to 700 mg is more preferable.
When magnesium carbonate is used, an amount of 10 to 4000 mg per day is preferable, and an amount of 30 to 2000 mg is more preferable.
When the precipitated calcium carbonate is used, an amount of 10 to 6000 mg per day is preferable, and an amount of 30 to 3000 mg is more preferable.
When bentonite is used, an amount of 1 to 200 mg per day is preferable, and an amount of 10 to 100 mg is more preferable.
When using volley (oyster), the amount of 10 to 6000 mg per day is preferable, and the amount of 30 to 3000 mg is more preferable.

When anhydrous calcium hydrogen phosphate is used, an amount of 10 to 5000 mg per day is preferable, and an amount of 30 to 2400 mg is more preferable.
When magnesium aluminometasilicate is used, an amount of 10 to 8000 mg per day is preferable, and an amount of 30 to 4000 mg is more preferable.
When calcium hydrogen phosphate is used, an amount of 10 to 9000 mg per day is preferable, and an amount of 30 to 4500 mg is more preferable.

The content ratio of loxoprofen or a salt thereof contained in the pharmaceutical composition of the present invention and a basic compound having an acid neutralizing ability is not particularly limited, and is appropriately examined according to the effect of suppressing the interaction between loxoprofen and the interacting component. However, it is preferable that the loxoprofene or a salt thereof contains 0.003 to 2000 parts by mass of a basic compound having an acid neutralizing ability with respect to 1 part by mass in terms of loxoprofen sodium anhydride. The one containing 0.01 to 100 parts by mass is more preferable, and the one containing 0.02 to 30 parts by mass is particularly preferable.

The pharmaceutical composition of the present invention includes the following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof;
(B) One or more selected from the group consisting of the following components (B-1-1) to (B-9-1);
(B-1-1) chlorpheniramine or a salt thereof, (B-1-2) clemastine or a salt thereof, (B-1--3) carbinoxamine or a salt thereof, (B-1--4) diphenylpyraline or a salt thereof. , (B-2-1) bromhexin or a salt thereof, (B-2-2) ambroxol or a salt thereof, (B-3-1) a guayacol derivative or a salt thereof, (B-3-2) a cresol derivative or a salt thereof. One or more selected from the group consisting of the salt, (B-4) lysoteam or a salt thereof, (B-5-1) codeine, dihydrocodein and salts thereof and a mixture thereof, (B-6-1). One or more selected from the group consisting of efedrin, noruefedrin and methylefedrin and salts thereof, (B-7) dextrometholphan or a salt thereof, (B-8-1) caffeine, (B-9-1). One or more (C) basic compounds having an acid neutralizing ability selected from the group consisting of bromvaleryllurea and allylisopropylacetylurea;
A pharmaceutical composition containing

The following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof;
(B) One or more selected from the group consisting of the following components (B-1-1) to (B-9-1-1);
(B-1-1) chlorpheniramine or its salt, (B-1-2) clemastine or its salt, (B-1--3) carbinoxamine or its salt, (B-1--4) diphenylpyraline or its salt , (B-2-1) bromhexin or a salt thereof, (B-2-2) ambroxol or a salt thereof, (B-3-1-1) guaifenecin or a salt thereof, (B-3-1-2). Guayacol sulfonic acid or a salt thereof, (B-3-2-1) cresol sulfonic acid or a salt thereof, (B-4) lysoteam or a salt thereof, (B-5-1-1) dihydrocodein or a salt thereof, (B-). 6-1-1) Methylefedrin or its salt, (B-7) Dextrometorphan or its salt, (B-8-1) Caffeine, (B-9-1-1) Bromvalerylurea (C) acid Basic compound with harmony;
A pharmaceutical composition containing the above is particularly preferable.

The pharmaceutical composition of the present invention can be produced, for example, by a known method described in the 15th revised Japanese Pharmacopoeia General Regulations for Formulations and the like. The dosage form is not particularly limited, and may be solid, semi-solid, or liquid, and may be a shape normally used in pharmaceutical products depending on the purpose of use and the like. can. Specifically, the dosage form includes, for example, tablets (including chewable tablets, effervescent tablets, orally disintegrating tablets, etc.), troches, drops, hard capsules, soft capsules, granules, fine granules, etc. Solid formulations such as powders, rounds, dry syrups, suppositories, poultices, plasters; licking agents, chewing gum agents, jelly agents, jelly-like drops, whipping agents, ointments, creams, foams, inhalers. Semi-solid preparations such as agents and nazar gels; 15th revised Japanese Pharmacy such as liquid preparations such as syrups, drinks, capsules, liquor, liquids, eye drops, aerosols, sprays and sprays. Dosage forms described in the general rules for pharmaceutical products can be mentioned. Among these, a solid preparation is preferable, a solid preparation selected from the group consisting of tablets, capsules, pills, granules, powders and fine granules is more preferable, tablets or capsules are further preferable, and tablets are particularly preferable. In this regard, the solid preparation is generally advantageous not only in terms of convenience of administration and control of drug dosage, but also as specifically described in Test Example 14 below, the pharmaceutical composition of the present invention. It was clarified that when the product is a solid product, its expansion over time is suppressed. Therefore, according to the present invention, it is possible to provide a solid preparation having excellent stability, which is less likely to cause cracking or chipping of the coating, sugar coating or capsule when coated or sugar-coated, or when the capsule is filled. ..

When the pharmaceutical composition of the present invention is a solid preparation, loxoprofen or a salt thereof and an interacting component in the solid preparation are contained in the solid preparation so as not to substantially contact each other, and the product is manufactured and prepared. The product is more preferable. The pharmaceutical product prepared by containing it so as not to substantially contact each other can be easily understood by a general pharmaceutical technical researcher, and based on a known method, an appropriate pharmaceutical additive is used. Can be manufactured and formulated. Specifically, the following (a)-(f) can be exemplified as the form of the solid preparation, and these can be produced and formulated by a known method.

(A) Powders, granules, etc. made by granulating one of loxoprofen or a salt thereof and an interacting component by an appropriate method to form granules, and incorporating the other into the granules without granulation. In addition, a preparation obtained by coating the granules by a more appropriate method. The basic compound having an acid neutralizing ability used in the present invention may be contained in the granules or may be contained separately from the granules.
(B) Loxoprofen or a salt thereof, and an interacting component are separately granulated by an appropriate method into granules, and powders and granules made by containing these, and the granules are further appropriate. The product coated by the method. The basic compound having an acid neutralizing ability used in the present invention may be contained in one of the granules, in both granules, or these granules. It may be contained separately.
(C) Capsules filled with powders, granules, etc. made in (a) or (b) above.
(D) A tablet obtained by tableting the granules or the like produced in (a) or (b) above.
(E) Loxoprofen or a salt thereof, a multi-layer tablet prepared so that the interacting components do not come into contact with each other, and a preparation obtained by coating the multi-layer tablet by a more appropriate method. The multi-layer tablet preferably has loxoprofen or a salt thereof and an interacting component located in different layers from each other, and as a multi-layer tablet having three or more layers, a layer containing loxoprofen or a salt thereof and an interacting component are used. It is more preferable that the containing layers are positioned so as not to touch each other. As the loxoprofen or a salt thereof and the interacting component, the granules produced in (a) and (b) above can be used. In a multi-layer tablet, the basic compound having acid neutralizing ability may be located in either the layer containing loxoprofen or a salt thereof or the layer containing an interacting component, or may be separately located in both layers. May be. Further, it may be located in the middle layer of any of the layers.
(F) A nucleated tablet in which either loxoprofen or a salt thereof, or an interacting component is placed in a core tablet, and a preparation obtained by coating the core tablet by a more appropriate method. As the loxoprofen or a salt thereof and the interacting component, the granules produced in (a) and (b) above can be used. In the nucleated tablet, the basic compound having an acid neutralizing ability may be located in the nuclear tablet, may be located in the outer shell, or may be separately located in both the nuclear tablet and the outer shell. May be good.
The above-mentioned solid preparation may be coated with a sugar coating, a film coating, or the like by a known method.

Examples of the route for taking the pharmaceutical composition of the present invention include oral and parenteral such as transrectal and vaginal, and in the present invention, an orally administered preparation is preferable. In addition, the pharmaceutical composition of the present invention can be taken before meals, between meals, after meals, before bedtime, etc., in 1 to 4 divided doses per day.

In the pharmaceutical composition of the present invention, as pharmaceutical ingredients, drugs other than loxoprofen or a salt thereof, an interactive ingredient, and a basic compound having an acid neutralizing ability, for example, antipyretic analgesics, antihistamines, antitussives, noscapines, etc. It may contain one or more selected from the group consisting of bronchial dilators, analgesics, vitamins, anti-inflammatory agents, gastric mucosa protective agents, anticholinergic agents, crude drugs, Chinese herbal formulas and the like. These components are preferably blended in the solid formulation.

Examples of the antipyretic analgesic include aspirin, aspirin aluminum, acetaminophen, isopropylantipyrine, ibuprofen, ethenzamide, sazapyrin, salicylamide, sodium salicylate, thiaramid hydrochloride, lactylphenetidine and the like.

Examples of the antihistamine include azelastin hydrochloride, alimemazine tartrate, isotipendyl hydrochloride, iproheptin hydrochloride, epinastine hydrochloride, emedastin fumarate, ketotifen fumarate, triproridin hydrochloride, tryperenamine hydrochloride, tonsilamine hydrochloride. , Fenetazine hydrochloride, promethazine hydrochloride, promethazine methylene disalicylate, mekitadine, metodirazine hydrochloride, mebuhydrolinnapadisicrate and the like.

Antitussives include, for example, alloclamid hydrochloride, epradinone hydrochloride, carbetapentanetancate, cloperastine hydrochloride, cloperastinfendizoate, dibunato sodium, dimemorphan phosphate, tipepidine citrate, etc. Examples thereof include tipepidin hibenzate.

Examples of noscapines include noscapine hydrochloride, noscapine and the like.
Examples of the bronchodilator include trimetokinol hydrochloride, phenylephrine hydrochloride, methoxyphenamine hydrochloride and the like.

Examples of the sputum-removing agent include ammonia / uikyosei, ethylcysteine hydrochloride, ammonium chloride, carbocisteine, methylcysteine hydrochloride, l-menthol and the like.

Examples of vitamins include vitamin B ₁ , vitamin B ₂ , vitamin B ₅ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, hesperidin and derivatives thereof, and salts thereof (for example, thiamine, thiamine chloride hydrochloride, thiamine nitrification). Thing, disetiamine hydrochloride, setothiamine hydrochloride, flusultiamine, flusultiamine hydrochloride, octothiamine, sicothiamine, thiamine disulfide, bisibuchiamine, bisbenchamine, prosultiamine, benfothamine, riboflavin, riboflavin phosphate ester , Riboflavin butyrate, sodium riboflavin phosphate, pyridoxin hydrochloride, pyridoxal phosphate, cyanicobalamine, mecobalamine, ascorbic acid, sodium ascorbate, calcium ascorbate, hesperidin, etc.).

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, tranexamic acid, pronase, pronase, bromelain and the like. ..

Examples of the gastric mucosa protective agent include gefarnate, cetraxate hydrochloride, sofalcone, teprenone, methylmethionine sulfonium chloride and the like.

Anticholinergic agents include oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, datonna extract, tipepidium bromide, methylatropine bromide, methylanisotropine bromide, methylscopolamine bromide, methyl-l-. Hyoscyamine bromide, methylbenactidium bromide, pyrenzepine hydrochloride, butylscopolamine bromide, belladonna alkaloid, belladonna extract, belladonna total alkaloid, isopropamide iodide, diphenylpiperidinomethyldioxolan iodide, funnel extract, funnel root, funnel root total Examples include alkaloid citrate.

Herbal medicines include red bud wrinkles (red buds), asenyaku (Atractylodes lanceolata), inyokaku (innocent sheep), uikyo (scented scent), engosaku (rolling cloves), augon (yellow sardines), atractylodes lanceolata (yellow spirits), atractylodes lanceolata (yellow sardines), and atractylodes lanceolata. (Sakurahide), Ouren (Huangren), Onji (Clove), Gajutsu (I am), Kanokosou (Kakosou), Kamitsure, Karonin (Karoujin), Kikyo (Kikyou), Kyonin (Kyoujin), Kukoshi (Kukoshi) Child), Kukouyo (Atractylodes lanceolata), Keigai (Atractylodes lanceolata), Keihi (Keihi), Ketsumeishi (Ketsumeiko), Gentiana, Gennoshoko (current evidence), Koubushi (Kabushi), Goou (Ushio), Gomishi (Gomiko), Saishin ( Spicy), Sansho (Sansho), Zion (Shien), Jikoppi (ground bone skin), Shakuyaku (herbal medicine), Jakou (herbal medicine), Shajin (Sasan), Shazenshi (car front child), Shazensou (car front grass), Beast gall (including Yutan (bear gall)), Shokyo (ginger), Jiryu (earth dragon), Shini (spicy), Sexan (stone 蒜), Senega, Senkyu (Kawakyu), Zenko (maehu), Senburi (Chishin), Soujutsu (Atractylodes lanceolata), Souhakuhi (Kuwashirohide), Soyo (Suha), Taisan (Daisan), Chikusetsu carrot (Takebushi carrot), Clove (Clove), Chinpi (Chen skin), 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), Byakushi Crude drugs such as (white), byakujutsu (white 朮), bukuryo (茯 蓓), buttonpi (peony skin), rokjo (deer mushroom) and their extracts (extracts, tinctures, dried extracts, etc.) and the like can be mentioned.

Chinese medicine prescriptions include Keishito (Keishito), Kososan (Kososan), Saikokeishito (Saikokeishito), Shosaikoto (Shosaikoto), Bakumondoto (Bakumondoto), Hangekobokuto. (Hangekobokuto) and the like.

The pharmaceutical composition of the present invention is preferably one other than the following (a) to (l).
(A) Loxoprofen sodium dihydrate 45 mg (converted as anhydrous), ethenzamid 125 mg, anhydrous caffeine 80 mg, β-cyclodextrin 254 mg, aspartame 30 mg, citric acid 965 mg, sodium hydrogen carbonate 813 mg, lactose 38 mg and stearer per tablet. A 2400 mg effervescent tablet containing 50 mg of magnesium acid.
(B) Loxoprofen sodium dihydrate 60 mg (converted as anhydrate), carbinoxamine maleate 4 mg, dl-methylephedrine hydrochloride 20 mg, therapeptase 10 mg, β-cyclodextrin 254 mg, aspartame 30 mg, citric acid 965 mg, hydrogen carbonate per tablet. A 2400 mg effervescent tablet containing 813 mg of sodium, 194 mg of lactose and 50 mg of magnesium stearate.

(C) In 6 tablets (1400 mg in total), pseudoephedrine hydrochloride 180 mg, loxoprofen sodium 180 mg, magnesium oxide 400 mg, magnesium aluminometasilicate 140 mg, crystalline cellulose 120 mg, corn starch 140 mg, hydroxypropyl cellulose 60 mg, croscarmellose sodium 15 mg, stearate. A tablet containing 25 mg of magnesium, 6 mg of triacetin and an appropriate amount of lactose.
(D) Psoid effedrin hydrochloride 180 mg, loxoprofen sodium 90 mg, ibuprofen 225 mg, magnesium oxide 350 mg, magnesium aluminometasilicate 140 mg, crystalline cellulose 120 mg, corn starch 140 mg, hydroxypropyl cellulose 60 mg, croscarmellose sodium 15 mg in 6 tablets (1400 mg in total). , Magnesium stearate 25 mg, triacetin 6 mg and an appropriate amount of lactose.

(E) Pseudoephedrine hydrochloride 180 mg, loxoprofen sodium 180 mg, magnesium oxide 400 mg, magnesium aluminometasilicate 140 mg, purified sucrose 1400 mg, stevia extract product 15 mg, corn starch 1200 mg, polysorbate 80 80 mg, stearate in 3 packets (4500 mg in total). A fine granule containing 25 mg of magnesium and an appropriate amount of lactose.
(F) Psoid effedrin hydrochloride 180 mg, loxoprofen sodium 90 mg, ibuprofen 225 mg, magnesium oxide 400 mg, magnesium aluminometarate 140 mg, purified sucrose 1400 mg, stevia extract product 15 mg, corn starch 1100 mg, polysorbate 80 80 mg in 3 packets (4500 mg in total). , Magnesium stearate 25 mg and an appropriate amount of lactose.

(G) A hard capsule containing 180 mg of pseudoephedrine hydrochloride, 180 mg of sodium loxoprofen, 400 mg of magnesium oxide, 600 mg of corn starch, 80 50 mg of polysorbate, 25 mg of magnesium stearate, an appropriate amount of lactose and 480 mg of capsules in 6 capsules (2,500 mg in total).
(H) A hard capsule containing 180 mg of pseudoephedrine hydrochloride, 90 mg of sodium loxoprofen, 225 mg of ibuprofen, 400 mg of magnesium oxide, 500 mg of corn starch, 50 mg of polysorbate, 25 mg of magnesium stearate, an appropriate amount of lactose and 480 mg of capsules in 6 capsules (2,500 mg in total). ..

(I) A tablet containing 60 mg of sodium loxoprofen dihydrate, 240 mg of magnesium oxide, 30 mg of caffeine or theophylline, 50 mg of hydroxypropyl cellulose and an appropriate amount of magnesium stearate in 1 or 2 tablets.
(J) A fine granule containing 60 mg of sodium dihydrate, 240 mg of magnesium oxide, 30 mg of caffeine or theophylline, 100 mg of hydroxypropyl cellulose, 10 mg of magnesium stearate, and an appropriate amount of low-substituted hydroxypropyl cellulose in one packet.

(K) Capsules containing 60 mg of sodium loxoprofen dihydrate, 240 mg of magnesium oxide, 30 mg of caffeine or theophylline, 50 mg of hydroxypropyl cellulose, 10 mg of magnesium stearate, 15 mg of polysorbate and an appropriate amount of corn starch in 1 to 2 capsules. ..
(L) In 60 mL, loxoprofen sodium dihydrate 60 mg, magnesium oxide 240 mg, caffeine or theophylline 30 mg, hydroxypropyl cellulose 50 mg, sodium benzoate 140 mg, citric acid 80 mg, concentrated glycerin 530 mg, polyvinyl alcohol 100 mg, ethanol (95). %) A syrup containing 220 mg and the balance of purified water.

The pharmaceutical composition of the present invention may be further stored in the presence of a desiccant from the viewpoint of suppressing interaction. Hereinafter, a product containing the pharmaceutical composition and desiccant of the present invention in a container may be referred to as the "pharmaceutical preparation" of the present invention.

<Pharmaceutical product>
Next, the above-mentioned pharmaceutical preparation will be described.
In the pharmaceutical preparation of the present invention, the desiccant is not particularly limited. Naturally, the shape is not limited, and examples thereof include plate-shaped and bag-shaped sheet molds, cylinder-shaped (tablet-shaped) molded ones, and those obtained by applying paper wrapping or film coating to the cylindrical ones. But it may be.

Specific examples of the desiccant include silica gel, silica alumina gel (alofene), natural zeolite, synthetic zeolite (molecular sieve), calcium chloride, quicklime (calcium oxide), bentonite clay (montmorillonite), magnesium chloride, and magnesium oxide. Etc., and may be a mixture of these and activated carbon. Of these, one or more selected from the group consisting of silica gel, silica alumina gel (alophane), synthetic zeolite (molecular sieve), and calcium chloride is more preferable.

Commercially available products can be used as the desiccant, and examples of the commercially available products include Cibrette, MS-Tablet, MS-Serum W, Tokai Gel, Desikite 25, Alpsheet, Yamahito Pharmaceutical Co., Ltd. manufactured by Tokai Chemical Industry Co., Ltd. Dryan (registered trademark) packaged product, Dryan (registered trademark) tablet, Dryan (registered trademark) sheet, Secard, Arosheet, Zeosheet manufactured by Shinagawa Kasei Co., Ltd., OZO manufactured by OZO Kagaku Giken Co., Ltd., stock Examples include ID sheet manufactured by the company ID, ID packing desiccant, and the like.

In the pharmaceutical preparation of the present invention, the content of the desiccant may be appropriately examined and determined, but is preferably 0.05 to 35 parts by mass, preferably 0.15 to 17 parts by mass with respect to 1 part by mass of loxoprofen or a salt thereof. The unit is more preferable.
Further, with respect to 1 part by mass of the pharmaceutical composition of the present invention, 0.001 to 1 part by mass is preferable, and 0.004 to 0.4 part by mass is more preferable.

The container used for the pharmaceutical preparation of the present invention is not particularly limited as long as it can be used as a container for foods, supplements, pharmaceuticals, health foods, etc. Possible ones are preferred. Examples of the standard container include bottles, cans, boxes and the like. Examples of the amorphous container include bags (pillow packaging, stick packaging, PTP packaging, SP packaging, etc.). Of these containers, specifically, bottles and bags are preferable.

The member for forming the container is not particularly limited, and examples thereof include members such as paper, glass, resin or resin film, or metal or metal film, and a composite structure or a multilayer structure in which these members are appropriately combined can be mentioned. It may be the one with. Further, it is preferable that the moisture permeable member such as paper is subjected to the moisture permeable prevention treatment.
The container may be transparent, translucent, or opaque.

The method for storing the pharmaceutical composition and the desiccant of the present invention in a container is not particularly limited, and both can be achieved by arranging them by an appropriate means such as putting them in a container.

For storage in the container, for example, when the container is a bottle, a desiccant (preferably a columnar (tablet type)) is placed in the bottle or stored in the back side (inner cap) of the bottle lid, and the present invention is used. This can be achieved by storing the pharmaceutical composition of the above in a bottle or the like. When stored in a bottle, the dosage form of the pharmaceutical composition of the present invention is preferably a solid preparation.

When the container is a bag, it can be achieved by storing a desiccant (preferably a plate-shaped or bag-shaped sheet type) and the pharmaceutical composition of the present invention in the bag. When stored in a bag, the dosage form of the pharmaceutical composition of the present invention is preferably a solid preparation.

Further, the pharmaceutical composition of the present invention may be once packaged in SP packaging, PTP packaging or a bag, and then the packaged pharmaceutical composition and a desiccant may be enclosed in a bag. More specifically, a form in which a pharmaceutical composition packaged in SP or PTP and a plate-shaped or bag-shaped sheet-type desiccant are combined and packaged in a pillow may be mentioned. Further, the pillow package may be stored in a box or the like. When the pharmaceutical composition is once packaged in SP packaging, PTP packaging or a bag, the dosage form of the pharmaceutical composition of the present invention is preferably a solid preparation.

Since the pharmaceutical composition of the present invention contains loxoprofen, which is a kind of NSAID, or a salt thereof, headache, toothache, pain after tooth extraction, sore throat, ear pain, joint pain, nerve pain, lower back pain, muscle pain, and stiff shoulder pain.・ Bruising pain ・ Fracture pain ・ Nenza pain ・ Menstrual pain (physiological pain) ・ Analgesia of traumatic pain, cold / fever relief, cold symptoms (throat pain, bad cold, fever, headache, joint pain, muscles It has an efficacy or effect on (pain) and is useful as a general anti-inflammatory drug (cold drug) and an anti-fever analgesic.

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.
[Test Example 1] Examination of interaction between loxoprofen sodium hydrate and chlorpheniramine maleate After preparing the following mixtures 1-A to 1-E, they are placed in a glass bottle (3K standard bottle) and 1 at 60 ° C. It was stored for a week, and the state of the mixture immediately after the start of storage, 1 day, 2 days, and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 1.

[Mixture 1-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 491.6 mg and d-chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: chlorpheniramine D-maleate) 8 .4 mg was mixed to give Mix 1-A.
[Mixture 1-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Loxoprofen sodium hydrate from Japan Pharmacy) 491.6 mg, d-chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: chlorpheniramine D-maleate) 8 .4 mg and 500 mg of magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowasuimag) were mixed to obtain Mixture 1-B.

[Mixture 1-C]
Mixture 1-C was obtained by the same method as in Mixture 1-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name magnesium silicate) was used instead of magnesium hydroxide.
[Mixture 1-D]
Mixture 1-D was obtained by the same method as Mixture 1-B except that 500 mg of anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) was used instead of magnesium hydroxide. rice field.
[Mixture 1-E]
Mixture 1-E was obtained in the same manner as in Mixture 1-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.

From the test results shown in Table 1, it was found that in the mixture 1-A in which only loxoprofen sodium hydrate and d-chlorpheniramine maleate were mixed, an interaction occurred and the mixture solidified.
On the other hand, in the mixtures 1-B, 1-C, 1-D and 1-E obtained by adding a basic compound having an acid neutralizing ability to loxoprofen sodium hydrate and d-chlorpheniramine maleate and mixing them. It was found that even after storage for one week, the state of the white powder was maintained as in the case immediately after the start of storage.
From the above test results, the basic compound having acid neutralizing ability used in 1-B to 1-E is represented by the general formula (1) including loxoprofen or a salt thereof and chlorpheniramine or a salt thereof. It has been clarified that it has an action of suppressing the interaction with the compound or a salt thereof.

[Test Example 2] Examination of interaction between loxoprofen sodium hydrate and clemastine fumarate After preparing the following mixtures 2-A to 2-F, they are placed in a glass bottle (3K standard bottle) at 60 ° C. for 1 week. It was stored, and the state of the mixture immediately after the start of storage, 1 day, 2 days, and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 2.

[Mixture 2-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 496.7 mg and clemastine fumarate (manufactured by Dite: trade name: clemastine fumarate) 3.3 mg are mixed, and the mixture 2 -A was obtained.
[Mixture 2-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name: Loxoprofen sodium hydrate) 496.7 mg, cremastine fumarate (manufactured by Dite: trade name: cremastine fumarate) 3.3 mg and magnesium hydroxide (Kyowa) Chemical industry: trade name Kyowasui mug) 500 mg was mixed to obtain a mixture 2-B.
[Mixture 2-C]
Mixture 2-C was obtained by the same method as in Mixture 2-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name: Magnesium Aluminate silicate) was used instead of magnesium hydroxide.

[Mixture 2-D]
Mixture 2-D was obtained by the same method as in Mixture 2-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.
[Mixture 2-E]
Mixture 2-E was obtained by the same method as in Mixture 2-B except that 500 mg of magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) was used instead of magnesium hydroxide.
[Mixture 2-F]
Mixture 2-F was obtained by the same method as in Mixture 2-B except that 500 mg of precipitated calcium carbonate (manufactured by Sankyo Seiko Co., Ltd .: Precipitated Calcium Carbonate) was used instead of magnesium hydroxide.

From the test results shown in Table 2, it was found that in the mixture 2-A in which only loxoprofen sodium hydrate and clemastine fumarate were mixed, an interaction occurred and the mixture was wetted.
On the other hand, in the mixtures 2-B, 2-C, 2-D, 2-E and 2-F in which a basic compound having an acid neutralizing ability is further added to loxoprofen sodium and clemastine fumarate, the mixture is 1 It was found that the state of the white powder was maintained even after the weekly storage as in the case immediately after the start of storage.
From the above test results, the basic compound having acid neutralizing ability used in 2-B to 2-F is a compound represented by the general formula (1) including loxoprofen or a salt thereof and clemastine or a salt thereof. Or, it has been clarified that it has an action of suppressing the interaction with the salt thereof.

[Test Example 3] Examination of interaction between loxoprofen sodium hydrate and carbinoxamine maleate After preparing the following mixtures 3-A to 3-E, they are placed in a glass bottle (3K standard bottle) at 60 ° C. It was stored for 1 week, and the state of the mixture immediately after the start of storage, 1 day, 2 days and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 3.

[Mixture 3-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 482.3 mg and carbinoxamine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: carbinoxamine maleate) 17.7 mg were mixed. Mixture 3-A was obtained.
[Mixture 3-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 482.3 mg, carbinoxamine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: carbinoxamine maleate) 17.7 mg and magnesium hydroxide (Made by Kyowa Kagaku Kogyo: trade name Kyowasuimag) 500 mg was mixed to obtain a mixture 3-B.

[Mixture 3-C]
Mixture 3-C was obtained by the same method as in Mixture 3-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name: magnesium silicate aluminate) was used instead of magnesium hydroxide.
[Mixture 3-D]
Mixture 3-D was obtained by the same method as in Mixture 3-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.
[Mixture 3-E]
Mixture 3-E was obtained by the same method as in Mixture 3-B except that 500 mg of magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) was used instead of magnesium hydroxide.

From the test results shown in Table 3, it was found that in the mixture 3-A in which only loxoprofen sodium hydrate and carbinoxamine maleate were mixed, an interaction occurred, the mixture solidified, and then the color changed.
On the other hand, in the mixtures 3-B, 3-C, 3-D and 3-E, which are a mixture of loxoprofen sodium hydrate and carbinoxamine maleate with a basic compound having an acid neutralizing ability. It was found that the state of the white powder was maintained even after storage for one week as in the case immediately after the start of storage.
From the above test results, the basic compound having acid neutralizing ability used in 3-B to 3-E is a compound represented by the general formula (1) including loxoprofen or a salt thereof and carbinoxamine or a salt thereof. Or, it has been clarified that it has an action of suppressing the interaction with the salt thereof.

[Test Example 4] Examination of Interaction between Loxoprofen Sodium Hydrate and Diphenylpyraline Hydrochloride After preparing each of the following mixtures 4-A to 4-E, they are placed in a glass bottle (3K standard bottle) at 60 ° C. for 1 week. It was stored, and the state of the mixture immediately after the start of storage, 1 day, 3 days, and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 4.

[Mixture 4-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 490.4 mg and diphenylpyraline hydrochloride (manufactured by Kongo Chemical Co., Ltd .: trade name: diphenylpyraline hydrochloride) 9.6 mg are mixed, and the mixture 4 -A was obtained.
[Mixture 4-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Loxoprofen sodium hydrate from Japan Pharmacy) 490.4 mg, diphenylpyraline hydrochloride (manufactured by Kongo Chemical Co., Ltd .: trade name: diphenylpyraline hydrochloride) 9.6 mg and magnesium hydroxide (Kyowa) Chemical Industry: Trade name: Kyowasuimag) 500 mg was mixed to obtain Mixture 4-B.

[Mixture 4-C]
Mixture 4-C was obtained by the same method as in Mixture 4-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name: Magnesium Aluminate silicate) was used instead of magnesium hydroxide.
[Mixture 4-D]
Mixture 4-D was obtained by the same method as in Mixture 4-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.
[Mixture 4-E]
Mixture 4-E was obtained by the same method as in Mixture 4-B except that 500 mg of precipitated calcium carbonate (manufactured by Sankyo Seiko Co., Ltd .: precipitated calcium carbonate CA) was used instead of magnesium hydroxide.

From the test results shown in Table 4, it was found that in the mixture 4-A in which only loxoprofen sodium hydrate and diphenylpyraline hydrochloride were mixed, an interaction occurred, the mixture was moistened, and then discolored.
On the other hand, in the mixtures 4-B, 4-C, 4-D and 4-E, which are a mixture of loxoprofen sodium hydrate and diphenylpyraline hydrochloride with a basic compound having an acid neutralizing ability, one week. It was found that the state of the white powder was maintained even after storage as in the case immediately after the start of storage.
From the above test results, the basic compound having acid neutralizing ability used in 4-B to 4-E is represented by the general formula (1) including loxoprofen or a salt thereof and diphenylpyraline or a salt thereof. It has been clarified that it has an action of suppressing the interaction with the compound or a salt thereof.

[Test Example 5] Examination of interaction between loxoprofen sodium hydrate and bromhexine hydrochloride After preparing each of the following mixtures 5-A to 5-D, place them in a glass bottle (3K standard bottle) and store at 60 ° C. for 1 week. Then, the state of the mixture immediately after the start of storage, 1 day, 2 days and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 5.

[Mixture 5-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 472.3 mg and bromhexine hydrochloride (manufactured by Sanyo Chemicals: trade name: bromhexine hydrochloride) 27.7 mg are mixed, and the mixture 5 -A was obtained.
[Mixture 5-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Nippon Pharmaceutical Bureau Loxoprofen sodium hydrate) 472.3 mg, bromhexine hydrochloride (manufactured by Sanyo Chemicals: trade name: bromhexine hydrochloride) 27.7 mg and magnesium hydroxide (Kyowa) (Chemical industry: trade name: Kyowasui mug) 500 mg was mixed to obtain a mixture 5-B.

[Mixture 5-C]
Mixture 5-C was obtained by the same method as in Mixture 5-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name: Magnesium Aluminate silicate) was used instead of magnesium hydroxide.
[Mixture 5-D]
Mixture 5-D was obtained by the same method as in Mixture 5-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.

From the test results shown in Table 5, it was found that in the mixture 5-A in which only loxoprofen sodium hydrate and bromhexine hydrochloride were mixed, an interaction occurred, the mixture solidified, and then discolored.
On the other hand, in the mixtures 5-B, 5-C and 5-D, which are a mixture of loxoprofen sodium hydrate and bromhexine hydrochloride with a basic compound having an acid neutralizing ability, storage is started even after storage for 1 week. It was found that the state of the white powder was maintained as immediately after.
From the above test results, the basic compound having acid neutralizing ability used in 5-B to 5-D is a compound represented by the general formula (2) including loxoprofen or a salt thereof and bromhexine or a salt thereof. Or, it has been clarified that it has an action of suppressing the interaction with the salt thereof.

[Test Example 6] Examination of Interaction between Loxoprofen Sodium Hydrate and Ambroxol Hydrochloride After preparing each of the following mixtures 6-A to 6-C, they are placed in a glass bottle (3K standard bottle) and 1 at 60 ° C. It was stored for a week, and the state of the mixture immediately after the start of storage, 1 day, 3 days, and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 6.

[Mixture 6-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 409.8 mg and ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: ambroxol hydrochloride) 90.2 mg The mixture was mixed to obtain a mixture 6-A.
[Mixture 6-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name: Loxoprofen sodium hydrate) 409.8 mg, ambroxol hydrochloride (manufactured by Shizuoka Caffeine Kogyo: trade name: ambroxol hydrochloride) 90.2 mg and 500 mg of magnesium aluminometate (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name magnesium aluminate silicate) was mixed to obtain a mixture 6-B.
[Mixture 6-C]
Mixture 6-C was obtained by the same method as in Mixture 6-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium silicate aluminate.

From the test results shown in Table 6, it was found that in the mixture 6-A in which only loxoprofen sodium hydrate and ambroxol hydrochloride were mixed, an interaction occurred, the mixture was strongly wetted, and then discolored.
On the other hand, in the mixtures 6-B and 6-C obtained by adding a basic compound having an acid neutralizing ability to loxoprofen sodium hydrate and ambroxol hydrochloride and mixing them, even after storage for 1 week and immediately after the start of storage. Similarly, it was found that the state of the white powder was maintained.
From the above test results, the basic compound having acid neutralizing ability used in 6-B and 6-C is represented by the general formula (2) including loxoprofen or a salt thereof and ambroxol or a salt thereof. It has been clarified that it has an action of suppressing the interaction with the compound or a salt thereof.

[Test Example 7] Examination of Interaction between Loxoprofen Sodium Hydrate and Potassium Guayacol Sulfonate After preparing each of the following mixtures 7-A to 7-E, place them in a glass bottle (3K standard bottle) at 60 ° C. for 1 week. It was stored, and the state of the mixture immediately after the start of storage, 1 day, 3 days, and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 7.

[Mixture 7-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 224.9 mg and potassium guayacol sulfonate (manufactured by Yonezawa Hamari Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 275.1 mg are mixed. And the mixture 7-A was obtained.
[Mixture 7-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Loxoprofen sodium hydrate from Japan Pharmacy) 224.9 mg, potassium guayacol sulfonate (manufactured by Yonezawahama Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 275.1 mg and water 500 mg of magnesium oxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: Kyowasuimag) was mixed to obtain a mixture 7-B.

[Mixture 7-C]
Mixture 7-C was obtained by the same method as in Mixture 7-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name magnesium silicate) was used instead of magnesium hydroxide.
[Mixture 7-D]
Mixture 7-D was obtained by the same method as in Mixture 7-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.
[Mixture 7-E]
Mixture 7-E was obtained by the same method as in Mixture 7-B except that 500 mg of precipitated calcium carbonate (manufactured by Sankyo Seiko Co., Ltd .: precipitated calcium carbonate CA) was used instead of magnesium hydroxide.

From the test results shown in Table 7, it was found that in the mixture 7-A in which only loxoprofen sodium hydrate and potassium guayacol sulfonate were mixed, an interaction occurred and the mixture was wetted.
On the other hand, in the mixtures 7-B, 7-C, 7-D and 7-E in which a basic compound having an acid neutralizing ability was further added to loxoprofen sodium hydrate and potassium guayacol sulfonate for 1 week. It was found that the state of the white powder was maintained even after storage as in the case immediately after the start of storage.
From the above test results, the basic compound having an acid neutralizing ability used in 7-B to 7-E is represented by the general formula (3) including loxoprofen or a salt thereof and guayacol sulfonic acid or a salt thereof. It has been clarified that it has an action of suppressing the interaction with the compound or a salt thereof.

[Test Example 8] Examination of interaction between loxoprofen sodium hydrate and lysozyme hydrochloride After preparing each of the following mixtures 8-A to 8-F, put them in a glass bottle (3K standard bottle) and store at 60 ° C. for 1 week. Then, the state of the mixture immediately after the start of storage, 1 day, 3 days and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 8.

[Mixture 8-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 347.1 mg and lysozyme hydrochloride (manufactured by Eisai: trade name: lysozyme chloride) 152.9 mg are mixed, and the mixture 8-A is mixed. Obtained.
[Mixture 8-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Loxoprofen sodium hydrate from Japan Pharmacy) 347.1 mg, lysoteam hydrochloride (manufactured by Eisai: trade name: lysoteam chloride) 152.9 mg and magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd.) : Trade name: Kyowasui mug) 500 mg was mixed to obtain a mixture 8-B.
[Mixture 8-C]
Mixture 8-C was obtained by the same method as in Mixture 8-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name: Magnesium Aluminate silicate) was used instead of magnesium hydroxide.

[Mixture 8-D]
Mixture 8-D was obtained by the same method as in Mixture 8-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.
[Mixture 8-E]
Mixture 8-E was obtained by the same method as in Mixture 8-B except that 500 mg of precipitated calcium carbonate (manufactured by Sankyo Seiko Co., Ltd .: precipitated calcium carbonate CA) was used instead of magnesium hydroxide.
[Mixture 8-F]
Mixture 8-F was obtained by the same method as in Mixture 8-B except that 500 mg of magnesium silicate (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name magnesium silicate (light)) was used instead of magnesium hydroxide.

From the test results shown in Table 8, it was found that in the mixture 8-A in which only loxoprofen sodium hydrate and lysozyme hydrochloride were mixed, an interaction occurred, the mixture was moistened, and then solidified.
On the other hand, in the mixtures 8-B, 8-C, 8-D, 8-E and 8-F obtained by adding a basic compound having an acid neutralizing ability to loxoprofen sodium hydrate and lysoteam hydrochloride and mixing them. It was found that the state of the white powder was maintained even after storage for 1 week as in the case immediately after the start of storage.
From the above test results, it is clear that the basic compound having acid neutralizing ability used in 8-B to 8-F has an action of suppressing the interaction between loxoprofen or a salt thereof and lysozyme or a salt thereof. became.

[Test Example 9] Examination of interaction between loxoprofen sodium hydrate and dihydrocodeine phosphate After preparing the following mixtures 9-A to 9-C, they are placed in a glass bottle (3K standard bottle) at 60 ° C. for 1 week. It was stored, and the state of the mixture immediately after the start of storage, 1 day, 2 days, and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 9.

[Mixture 9-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 447.4 mg and dihydrocodeine phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 52.6 mg are mixed. And the mixture 9-A was obtained.
[Mixture 9-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Loxoprofen sodium hydrate) 447.4 mg, dihydrocodein phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodein phosphate "Shionogi") 52.6 mg and Kay 500 mg of magnesium aluminate (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: magnesium silicate aluminate) was mixed to obtain a mixture 9-B.
[Mixture 9-C]
Mixture 9-C was obtained by the same method as in Mixture 9-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium silicate aluminate.

From the test results shown in Table 9, it was found that in the mixture 9-A in which only loxoprofen sodium hydrate and dihydrocodeine phosphate were mixed, an interaction occurred, the mixture solidified, and then discolored.
On the other hand, in the mixtures 9-B and 9-C obtained by adding a basic compound having an acid neutralizing ability to loxoprofen sodium hydrate and dihydrocodein phosphate, the same as immediately after the start of storage after 1 week of storage. It was found that the state of the white powder was maintained.
From the above test results, it was clarified that the basic compound having an acid neutralizing ability used in 9-B and 9-C has an action of suppressing the interaction between loxoprofen or a salt thereof and codeines. ..

[Test Example 10] Examination of interaction between loxoprofen sodium hydrate and dl-methylephedrine hydrochloride After preparing the following samples 10-A to 10-G, put them in a glass bottle (3K standard bottle) at 50 ° C. The mixture was stored for 6 days, and the state of the mixture immediately after the start of storage, 1 day, 2 days, and 6 days was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 10.

[Mixture 10-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 225 mg and dl-methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 25 mg The mixture was mixed to obtain a mixture 10-A.
[Mixture 10-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 225 mg, dl-methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 25 mg and Magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowasuimag) was mixed with 500 mg to obtain a mixture 10-B.
[Mixture 10-C]
Mixture 10-C was obtained by the same method as in Mixture 10-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name magnesium silicate) was used instead of magnesium hydroxide.

[Mixture 10-D]
Mixture 10-D was obtained by the same method as in Mixture 10-B except that 500 mg of anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) was used instead of magnesium hydroxide. rice field.
[Mixture 10-E]
Mixture 10-E was obtained by the same method as in Mixture 10-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.
[Mixture 10-F]
Mixture 10-F was obtained by the same method as in Mixture 10-B except that 500 mg of precipitated calcium carbonate (manufactured by Sankyo Seiko Co., Ltd .: precipitated calcium carbonate CA) was used instead of magnesium hydroxide.
[Mixture 10-G]
Mixture 10-G was obtained by the same method as in Mixture 10-B except that 500 mg of magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) was used instead of magnesium hydroxide.

From the test results shown in Table 10, it was found that in the mixture 10-A in which only loxoprofen sodium hydrate and dl-methylephedrine hydrochloride were mixed, an interaction occurred and the mixture solidified.
On the other hand, a mixture 10-B, 10-C, 10-D, 10-E, 10- It was found that in F and 10-G, the state of the white powder was maintained even after storage for 6 days as in the case immediately after the start of storage.
From the above test results, it was clarified that the basic compound having an acid neutralizing ability used in 10-B to 10-G has an action of suppressing the interaction between loxoprofen or a salt thereof and ephedrines. rice field.

[Test Example 11] Examination of interaction between loxoprofen sodium hydrate and dextromethorphan hydrobromic acid hydrate After preparing the following mixtures 11-A to 11-E, put them in a glass bottle (3K standard bottle). The mixture was stored at 60 ° C. for 1 week, and the state of the mixture immediately after the start of storage, 1 day, 3 days and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 11.

[Mixture 11-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 404.9 mg and dextromethorphan hydrobromic acid hydrate (manufactured by Daiichi Fine Chemicals: trade name: dextromethorphan HBR) 95 .1 mg was mixed to give Mix 11-A.
[Mixture 11-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Loxoprofen sodium hydrate) 404.9 mg, dextromethorphan hydrobromide hydrate (manufactured by Daiichi Fine Chemicals: trade name: dextromethorphan HBR) 95 .1 mg and 500 mg of magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowasuimag) were mixed to obtain a mixture 11-B.
[Mixture 11-C]
Mixture 11-C was obtained by the same method as in Mixture 11-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name magnesium silicate) was used instead of magnesium hydroxide.

[Mixture 11-D]
Mixture 11-D was obtained by the same method as in Mixture 11-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.
[Mixture 11-E]
Mixture 11-E was obtained by the same method as in Mixture 11-B except that 500 mg of precipitated calcium carbonate (manufactured by Sankyo Seiko Co., Ltd .: precipitated calcium carbonate CA) was used instead of magnesium hydroxide.

From the test results shown in Table 11, it was found that in the mixture 11-A in which only loxoprofen sodium hydrate and dextromethorphan hydrobromic acid hydrate were mixed, an interaction occurred and the mixture was wetted.
On the other hand, mixtures 11-B, 11-C, 11-D and 11-, which are a mixture of loxoprofen sodium hydrate and dextromethorphan hydrobromic acid hydrate with a basic compound having an acid neutralizing ability. In E, it was found that the state of the white powder was maintained even after storage for one week as in the case immediately after the start of storage.
From the above test results, it can be seen that the basic compound having an acid neutralizing ability used in 11-B to 11-E has an action of suppressing the interaction between loxoprofen or a salt thereof and dextromethorphan or a salt thereof. It became clear.

[Test Example 12] Examination of interaction between sodium loxoprofen hydrate and caffeine benzoate After preparing the following mixtures 12-A to 12-F, they are placed in a glass bottle (3K standard bottle) at 60 ° C. for 1 week. It was stored, and the state of the mixture immediately after the start of storage, 1 day, 3 days, and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 12.

[Mixture 12-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 202.6 mg and sodium benzoate caffeine (manufactured by Shizuoka Caffeine: trade name: sodium benzoate caffeine) 297.4 mg are mixed. And the mixture 12-A was obtained.
[Mixture 12-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 202.6 mg, sodium benzoate caffeine (manufactured by Shizuoka caffeine: trade name: sodium benzoate caffeine) 297.4 mg and water Magnesium oxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowasuimag) was mixed with 500 mg to obtain a mixture 12-B.
[Mixture 12-C]
Mixture 12-C was obtained by the same method as in Mixture 12-B except that 500 mg of magnesium silicate (Made by Tomita Pharmaceutical Co., Ltd .: trade name magnesium silicate) was used instead of magnesium hydroxide.

[Mixture 12-D]
Mixture 12-D was obtained by the same method as in Mixture 12-B except that 500 mg of magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: heavy magnesium oxide) was used instead of magnesium hydroxide.
[Mixture 12-E]
Mixture 12-E was obtained by the same method as in Mixture 12-B except that 500 mg of magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) was used instead of magnesium hydroxide.
[Mixture 12-F]
Mixture 12-F was obtained by the same method as in Mixture 12-B except that 500 mg of precipitated calcium carbonate (manufactured by Sankyo Seiko Co., Ltd .: precipitated calcium carbonate CA) was used instead of magnesium hydroxide.

From the test results shown in Table 12, it was found that in the mixture 12-A in which only loxoprofen sodium hydrate and sodium benzoate caffeine were mixed, an interaction occurred and the mixture solidified.
On the other hand, in the mixtures 12-B, 12-C, 12-D, 12-E and 12-F in which a basic compound having an acid neutralizing ability was further added to loxoprofen sodium and sodium benzoate caffeine, the mixture was mixed. It was found that the state of the white powder was maintained even after storage for one week as in the case immediately after the start of storage.
From the above test results, it was clarified that the basic compound having an acid neutralizing ability used in 12-B to 12-F has an action of suppressing the interaction between loxoprofen or a salt thereof and a xanthine derivative. ..

[Test Example 13] Examination of interaction between loxoprofen sodium hydrate and bromvalerylurea After preparing the following mixtures 13-A to 13-D, they were placed in a glass bottle (3K standard bottle) and stored at 60 ° C. for 1 week. Immediately after the start of storage, the state of the mixture after 1 day, 3 days and 1 week was evaluated, and the presence or absence of interaction was confirmed. The results are shown in Table 13.

[Mixture 13-A]
Mix 127 mg of loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: Japanese Pharmacopoeia Loxoprofen sodium hydrate) and 373 mg of bromvalerylurea (manufactured by Yashiro Pharmaceutical Co., Ltd .: Japanese Pharmacopoeia bromovalerylurea P) to prepare the mixture 13-A. Obtained.
[Mixture 13-B]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 127 mg, bromvalerylurea (manufactured by Yashiro Pharmaceutical Co., Ltd .: trade name Japanese Pharmacopoeia bromovalerylurea P) 373 mg and magnesium silicate (Tomita Pharmaceutical Co., Ltd.) Manufactured by: Trade name: Magnesium aluminate silicate) 500 mg was mixed to obtain a mixture 13-B.
[Mixture 13-C]
Mixture 13-C was obtained by the same method as in Mixture 13-B except that 500 mg of magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) was used instead of magnesium aluminate silicate.
[Mixture 13-D]
Mixture 13-D was obtained by the same method as in Mixture 13-B except that 500 mg of magnesium silicate (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name magnesium silicate (light)) was used instead of magnesium silicate aluminate.

From the test results shown in Table 13, it was found that in the mixture 13-A in which only loxoprofen sodium hydrate and bromvalerylurea were mixed, an interaction occurred and the mixture solidified.
On the other hand, in the mixtures 13-B, 13-C and 13-D obtained by adding a basic compound having an acid neutralizing ability to loxoprofen sodium hydrate and bromvalerylurea, even after storage for 1 week, immediately after the start of storage. It was found that the state of the white powder was maintained as in the case of.
From the above test results, it was clarified that the basic compound having an acid neutralizing ability used in 13-B to 13-D has an action of suppressing the interaction between loxoprofen or a salt thereof and an isovaleryl urea derivative. rice field.

[Test Example 14] Examination of swelling of tablets containing loxoprofen sodium hydrate and an interacting component The interaction (solidification, solidification,) between loxoprofen or a salt thereof and the interacting component confirmed in Test Examples 1 to 13. In order to confirm the effect of (change in state such as wetting) on the solid preparation, tablets containing loxoprofen sodium hydrate and interacting ingredients were produced, and the presence or absence of swelling over time was confirmed.
Specifically, after preparing the tablets 14-A to 14-C shown below, they are stored at 60 ° C. for 1 month, the thickness of the tablets immediately after preparation and after 1 month storage is measured, and further expanded according to the following formula. The rate (%) was calculated. The results (average value of expansion rate of 3 tablets per various tablets) are shown in Table 14.

Expansion rate (%) = {(Thickness of tablet after storage for 1 month)-(Thickness of tablet immediately after preparation)} / (Thickness of tablet immediately after preparation) x 100

[Tablet 14-A]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Nippon Pharmacopoeia Loxoprofen sodium hydrate) 340.5 g, d-chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: chlorpheniramine D-maleate) 5 .8 g, dl-methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name in the Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 100.0 g, guaifenecin (manufactured by Alps Pharmaceutical Industry: trade name in the Japanese Pharmacopoeia) 416.7 g, anhydrous Caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name anhydrous caffeine) 66.7 g, hydroxypropyl cellulose (manufactured by Nippon Soda: trade name HPC-L) 121.5 g, carmellose calcium (manufactured by Gotoku Yakuhin: trade name ECG505) 405 g, lactose hydrate (DMV: trade name: lactose 200M) 494.3 g, and crystalline cellulose (Asahi Kasei Chemicals: trade name: Theoras PH-101) 1917.0 g, high-speed stirring granulator (Paurek: VG-25) After putting into a mold) and mixing, 230 g of purified water was added and kneaded to obtain a granulated product. This granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type), dried, and then sized using a granulator (Okada Seiko: ND-10 type). 3867.5 g of this sizing product and 182.5 g of magnesium stearate (manufactured by Taihei Kagaku Kogyo: trade name: magnesium stearate (vegetable)) are put into a mixer (manufactured by Kotobuki: PM50 type) and mixed, and then have a diameter of 8 Tableting was performed using a tableting machine (manufactured by Hata Iron Works: HT-AP18SS type) equipped with a .5 mm pestle, and a tablet having a mass of 270 mg was obtained.

[Tablet 14-B]
Tablets 14-B were obtained by the same method as in Tablets 14-A except that anhydrous calcium hydrogen phosphate, which is a basic compound having an acid neutralizing ability, was used instead of crystalline cellulose.
Specifically, loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Nippon Pharmacopoeia Loxoprofen sodium hydrate) 340.5 g, d-chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: D-maleic acid) Chlorpheniramine) 5.8 g, dl-methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name: Nippon Pharmacopoeia dl-methylephedrine hydrochloride powder) 100.0 g, guaifenecin (manufactured by Alps Pharmaceutical Co., Ltd .: trade name: Guaiphenesin) 416.7 g, anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name anhydrous caffeine) 66.7 g, hydroxypropyl cellulose (manufactured by Nippon Soda: trade name HPC-L) 121.5 g, carmellose calcium (manufactured by Gotoku Yakuhin) : Trade name ECG505) 405 g, lactose hydrate (DMV: trade name lactose 200M) 494.3 g, and anhydrous calcium hydrogen phosphate (Kyowa Kagaku Kogyo: trade name anhydrous calcium hydrogen phosphate GS-H) 1917.0 g Was put into a high-speed stirring granulator (manufactured by Paulek: VG-25 type) and mixed, and then 300 g of purified water was added and kneaded to obtain a granulated product. This granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type), dried, and then sized using a granulator (Okada Seiko: ND-10 type). 3867.5 g of this sizing product and 182.5 g of magnesium stearate (manufactured by Taihei Kagaku Kogyo: trade name: magnesium stearate (vegetable)) are put into a mixer (manufactured by Kotobuki: PM50 type) and mixed, and then have a diameter of 8 Tableting was performed using a tableting machine (manufactured by Hata Iron Works: HT-AP18SS type) equipped with a .5 mm pestle, and a tablet having a mass of 270 mg was obtained.

[Tablet 14-C]
Tablet 14-C was obtained by the same method as in Tablet 14-A except that a combination of anhydrous calcium hydrogen phosphate and magnesium aluminometasilicate, which are basic compounds having acid neutralizing ability, was used instead of crystalline cellulose. rice field.
Specifically, loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Nippon Pharmacy, Loxoprofen sodium hydrate) 340.5 g, d-chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: D-maleic acid) Chlorpheniramine) 5.8 g, dl-methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacy dl-methylephedrine hydrochloride powder) 100.0 g, guaifenecin (manufactured by Alps Pharmaceutical Co., Ltd .: trade name: Guaiphenesin) 416.7 g, anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name anhydrous caffeine) 66.7 g, hydroxypropyl cellulose (manufactured by Nippon Soda: trade name HPC-L) 121.5 g, carmellose calcium (manufactured by Gotoku Yakuhin) : Trade name ECG505) 405 g, lactose hydrate (DMV: trade name lactose 200M) 494.3 g, anhydrous calcium hydrogen phosphate (Kyowa Kagaku Kogyo: trade name anhydrous calcium hydrogen phosphate GS-H) 1433.7 g, And magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 483.3 g is put into a high-speed stirring granulator (manufactured by Paulek: VG-25 type) and mixed, and then 1500 g of purified water is added and kneaded. Then, a granulated product was obtained. This granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type), dried, and then sized using a granulator (Okada Seiko: ND-10 type). 3867.5 g of this sizing product and 182.5 g of magnesium stearate (manufactured by Taihei Kagaku Kogyo: trade name: magnesium stearate (vegetable)) are put into a mixer (manufactured by Kotobuki: PM50 type) and mixed, and then have a diameter of 8 Tableting was performed using a tableting machine (manufactured by Hata Iron Works: HT-AP18SS type) equipped with a .5 mm pestle, and a tablet having a mass of 270 mg was obtained.

From the test results shown in Table 14, in the case of tablets 14-A containing a component interacting with loxoprofen sodium hydrate and not containing a basic compound having an acid neutralizing ability, the tablets became longer with the passage of time. It became clear that it swelled. On the other hand, it was revealed that the swelling of the tablets was suppressed in the tablets 14-B and 14-C containing loxoprofen sodium hydrate, an interacting component and a basic compound having an acid neutralizing ability.
From the above test results, the solid preparation containing loxoprofen or a salt thereof, an interacting component, and a basic compound having an acid neutralizing ability is excellent in stability with suppressed expansion over time. Became clear.

[Example 1]
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Loxoprofen sodium hydrate from Japan Pharmacy) 408.6 g, d-chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: chlorpheniramine D-maleate) 7 g , Magnesium hydroxide (manufactured by Kyowa Chemical Industry: trade name Kyowasui mug) 400 g, hydroxypropyl cellulose (manufactured by Nippon Soda: trade name HPC-L) 145.8 g, carmellose calcium (manufactured by Gotoku Pharmaceutical: trade name ECG505) 486 g, and 3364 g of crystalline cellulose (manufactured by Asahi Kasei Chemicals: trade name: Theoras PH-101) was put into a high-speed stirring granulator (manufactured by Paulek: VG-25 type) and mixed, and then purified water 1972.6 g was added and kneaded. Obtained granules. This granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type), dried, and then sized using a granulator (Okada Seiko: ND-10 type). 4811.4 g of this sizing product and 48.6 g of magnesium stearate (manufactured by Taihei Kagaku Kogyo: trade name: magnesium stearate (vegetable)) are put into a mixer (manufactured by Kotobuki: PM50 type) and mixed, and then have a diameter of 8 Tableting was performed using a tableting machine (manufactured by Hata Iron Works: HT-AP18SS type) equipped with a .5 mm die, and 18,000 tablets having a mass of 270 mg were obtained.

[Example 2]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
d-Chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: D-chlorpheniramine maleate) 3.5 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1682 mg
Magnesium stearate 24.3 mg

[Example 3]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
d-Chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: D-chlorpheniramine maleate) 3.5 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1682 mg
Magnesium stearate 24.3 mg

[Example 4]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
d-Chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: D-chlorpheniramine maleate) 3.5 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1682 mg
Magnesium stearate 24.3 mg

[Example 5]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Clemastine fumarate (manufactured by Dite: trade name clemastine fumarate) 1.34 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1684.16 mg
Magnesium stearate 24.3 mg

[Example 6]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Carbinoxamine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: carbinoxamine maleate) 7.5 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1678 mg
Magnesium stearate 24.3 mg

[Example 7]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Carbinoxamine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: carbinoxamine maleate) 7.5 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1678 mg
Magnesium stearate 24.3 mg

[Example 8]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 4.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Carbinoxamine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: carbinoxamine maleate) 7.5 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1678 mg
Magnesium stearate 24.3 mg

[Example 9]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Diphenylpyraline hydrochloride (manufactured by Kongo Chemical Co., Ltd .: trade name: diphenylpyraline hydrochloride) 4 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1681.5 mg
Magnesium stearate 24.3 mg

[Example 10]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Diphenylpyraline hydrochloride (manufactured by Kongo Chemical Co., Ltd .: trade name: diphenylpyraline hydrochloride) 4 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1681.5 mg
Magnesium stearate 24.3 mg

[Example 11]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromhexine hydrochloride (manufactured by Sanyo Chemical Co., Ltd .: trade name: bromhexine hydrochloride) 12 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1673.5 mg
Magnesium stearate 24.3 mg

[Example 12]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromhexine hydrochloride (manufactured by Sanyo Chemical Co., Ltd .: trade name: bromhexine hydrochloride) 12 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1673.5 mg
Magnesium stearate 24.3 mg

[Example 13]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromhexine hydrochloride (manufactured by Sanyo Chemical Co., Ltd .: trade name: bromhexine hydrochloride) 12 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1673.5 mg
Magnesium stearate 24.3 mg

[Example 14]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name ambroxol hydrochloride) 45 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1640.5 mg
Magnesium stearate 24.3 mg

[Example 15]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name ambroxol hydrochloride) 45 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1640.5 mg
Magnesium stearate 24.3 mg

[Example 16]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name ambroxol hydrochloride) 45 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1640.5 mg
Magnesium stearate 24.3 mg

[Example 17]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Guaifenesin (manufactured by Alps Pharmaceuticals: trade name guaifenesin) 250 mg
Magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowa Suimag) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 18]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Guaifenesin (manufactured by Alps Pharmaceuticals: trade name guaifenesin) 250 mg
Magnesium aluminate silicate (manufactured by Tomita Pharmaceutical Co., Ltd .: Brand name Magnesium aluminate silicate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 19]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Guaifenesin (manufactured by Alps Pharmaceuticals: trade name guaifenesin) 250 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 20]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Guaifenesin (manufactured by Alps Pharmaceuticals: trade name guaifenesin) 250 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 21]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 204.3 mg
Guaifenesin (manufactured by Alps Pharmaceuticals: trade name guaifenesin) 250 mg
Magnesium aluminate metasilicate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 22]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Guaifenesin (manufactured by Alps Pharmaceuticals: trade name guaifenesin) 250 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 23]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Potassium guayacol sulfonate (manufactured by Yonezawahama Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 250 mg
Magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowa Suimag) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 24]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Potassium guayacol sulfonate (manufactured by Yonezawahama Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 250 mg
Magnesium aluminate silicate (manufactured by Tomita Pharmaceutical Co., Ltd .: Brand name Magnesium aluminate silicate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 25]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Potassium guayacol sulfonate (manufactured by Yonezawahama Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 250 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 26]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Potassium guayacol sulfonate (manufactured by Yonezawahama Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 250 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 27]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Potassium guayacol sulfonate (manufactured by Yonezawahama Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 250 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 28]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Potassium guayacol sulfonate (manufactured by Yonezawahama Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 250 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1435.5 mg
Magnesium stearate 24.3 mg

[Example 29]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowa Suimag) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1661.5 mg
Magnesium stearate 24.3 mg

[Example 30]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1661.5 mg
Magnesium stearate 24.3 mg

[Example 31]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1661.5 mg
Magnesium stearate 24.3 mg

[Example 32]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1661.5 mg
Magnesium stearate 24.3 mg

[Example 33]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 4.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1661.5 mg
Magnesium stearate 24.3 mg

[Example 34]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
dl-Methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 60 mg
Magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowa Suimag) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1625.5 mg
Magnesium stearate 24.3 mg

[Example 35]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
dl-Methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 60 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1625.5 mg
Magnesium stearate 24.3 mg

[Example 36]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
dl-Methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 60 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1625.5 mg
Magnesium stearate 24.3 mg

[Example 37]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
dl-Methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 60 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1625.5 mg
Magnesium stearate 24.3 mg

[Example 38]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 4.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
dl-Methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 60 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1625.5 mg
Magnesium stearate 24.3 mg

[Example 39]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 150 mg
Magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowa Suimag) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1535.5 mg
Magnesium stearate 24.3 mg

[Example 40]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 150 mg
Magnesium aluminate silicate (manufactured by Tomita Pharmaceutical Co., Ltd .: Brand name Magnesium aluminate silicate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1535.5 mg
Magnesium stearate 24.3 mg

[Example 41]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 150 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1535.5 mg
Magnesium stearate 24.3 mg

[Example 42]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 150 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1535.5 mg
Magnesium stearate 24.3 mg

[Example 43]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 150 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1535.5 mg
Magnesium stearate 24.3 mg

[Example 44]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 150 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1535.5 mg
Magnesium stearate 24.3 mg

[Example 45]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 150 mg
Dry aluminum hydroxide gel (manufactured by Kyowa Kagaku Kogyo: trade name: dry aluminum hydroxide gel) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1535.5 mg
Magnesium stearate 24.3 mg

[Example 46]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 150 mg
Synthetic hydrotalcite (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: synthetic hydrotalcite) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1535.5 mg
Magnesium stearate 24.3 mg

[Example 47]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromvalerylurea (manufactured by Yashiro Pharmaceutical Co., Ltd .: Brand name: Japanese Pharmacopoeia Bromovalerylurea P) 600 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1085.5 mg
Magnesium stearate 24.3 mg

[Example 48]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromvalerylurea (manufactured by Yashiro Pharmaceutical Co., Ltd .: Brand name: Japanese Pharmacopoeia Bromovalerylurea P) 600 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1085.5 mg
Magnesium stearate 24.3 mg

[Example 49]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromvalerylurea (manufactured by Yashiro Pharmaceutical Co., Ltd .: Brand name: Japanese Pharmacopoeia Bromovalerylurea P) 600 mg
Dry aluminum hydroxide gel (manufactured by Kyowa Kagaku Kogyo: trade name: dry aluminum hydroxide gel) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1085.5 mg
Magnesium stearate 24.3 mg

[Example 50]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromvalerylurea (manufactured by Yashiro Pharmaceutical Co., Ltd .: Brand name: Japanese Pharmacopoeia Bromovalerylurea P) 600 mg
Synthetic hydrotalcite (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: synthetic hydrotalcite) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1085.5 mg
Magnesium stearate 24.3 mg

[Example 51]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Allyl isopropyl acetyl urea (manufactured by Kongo Chemical Co., Ltd .: trade name Alipronal "Congo") 180 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1505.5 mg
Magnesium stearate 24.3 mg

[Example 52]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Allyl isopropyl acetyl urea (manufactured by Kongo Chemical Co., Ltd .: trade name Alipronal "Congo") 180 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1505.5 mg
Magnesium stearate 24.3 mg

[Example 53]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Allyl isopropyl acetyl urea (manufactured by Kongo Chemical Co., Ltd .: trade name Alipronal "Congo") 180 mg
Dry aluminum hydroxide gel (manufactured by Kyowa Kagaku Kogyo: trade name: dry aluminum hydroxide gel) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1505.5 mg
Magnesium stearate 24.3 mg

[Example 54]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Allyl isopropyl acetyl urea (manufactured by Kongo Chemical Co., Ltd .: trade name Alipronal "Congo") 180 mg
Synthetic hydrotalcite (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: synthetic hydrotalcite) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1505.5 mg
Magnesium stearate 24.3 mg

[Example 55]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Clemastine fumarate (manufactured by Dite: trade name clemastine fumarate) 1.34 mg
Lysozyme hydrochloride (manufactured by Eisai: trade name: lysozyme chloride) 90 mg
Belladonna Total Alkaloid 0.3mg
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Noscapine 48 mg
dl-Methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 60 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 75 mg
Benfotiamine (vitamin B1 derivative) 24 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline Cellulose 1362.86 mg
Magnesium stearate 24.3 mg

[Example 56]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name ambroxol hydrochloride) 45 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
dl-Methylephedrine hydrochloride (manufactured by Alps Pharmaceutical Co., Ltd .: trade name Japanese Pharmacopoeia dl-methylephedrine hydrochloride powder) 60 mg
dl-Chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: chlorpheniramine maleate) 7.5 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 75 mg
Thiamine nitrification (vitamin B1 nitrate) 24 mg
Riboflavin (vitamin B2) 12 mg
Ascorbic acid (vitamin C) 500mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 938 mg
Magnesium stearate 24.3 mg

[Example 57]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Ethenzamide 252 mg
Bromvalerylurea (manufactured by Yashiro Pharmaceutical Co., Ltd .: Brand name: Japanese Pharmacopoeia Bromovalerylurea P) 600 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 150 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 883.5 mg
Magnesium stearate 24.3 mg

[Example 58]
A tablet containing the following components in 9 tablets (daily dose) was produced by the same method as in Example 1.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Allyl isopropyl acetyl urea (manufactured by Kongo Chemical Co., Ltd .: trade name Alipronal "Congo") 180 mg
Anhydrous caffeine (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name: anhydrous caffeine) 240 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 300 mg
Hydroxypropyl cellulose 72.9 mg
Carmellose Calcium 243mg
Crystalline cellulose 1165.5 mg
Magnesium stearate 24.3 mg

[Example 59]
30 tablets obtained in Example 1 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 60]
30 tablets obtained in Example 2 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 61]
Thirty tablets obtained in Example 3 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 62]
30 tablets obtained in Example 4 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 63]
30 tablets obtained in Example 5 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 64]
30 tablets obtained in Example 6 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 65]
30 tablets obtained in Example 7 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 66]
30 tablets obtained in Example 8 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 67]
30 tablets obtained in Example 9 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 68]
30 tablets obtained in Example 10 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 69]
Thirty tablets obtained in Example 11 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 70]
30 tablets obtained in Example 12 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 71]
Thirty tablets obtained in Example 13 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 72]
30 tablets obtained in Example 14 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 73]
30 tablets obtained in Example 15 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 74]
30 tablets obtained in Example 16 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 75]
Thirty tablets obtained in Example 17 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 76]
30 tablets obtained in Example 18 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 77]
Thirty tablets obtained in Example 19 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 78]
30 tablets obtained in Example 20 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 79]
30 tablets obtained in Example 21 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 80]
30 tablets obtained in Example 22 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 81]
30 tablets obtained in Example 23 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 82]
30 tablets obtained in Example 24 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 83]
30 tablets obtained in Example 25 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 84]
30 tablets obtained in Example 26 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 85]
30 tablets obtained in Example 27 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 86]
30 tablets obtained in Example 28 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 87]
Thirty tablets obtained in Example 29 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 88]
30 tablets obtained in Example 30 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 89]
Thirty tablets obtained in Example 31 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 90]
30 tablets obtained in Example 32 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 91]
30 tablets obtained in Example 33 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 92]
30 tablets obtained in Example 34 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 93]
30 tablets obtained in Example 35 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 94]
Thirty tablets obtained in Example 36 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 95]
30 tablets obtained in Example 37 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 96]
30 tablets obtained in Example 38 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 97]
Thirty tablets obtained in Example 39 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 98]
30 tablets obtained in Example 40 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 99]
Thirty tablets obtained in Example 41 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 100]
Thirty tablets obtained in Example 42 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 101]
Thirty tablets obtained in Example 43 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 102]
Thirty tablets obtained in Example 44 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 103]
30 tablets obtained in Example 45 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 104]
Thirty tablets obtained in Example 46 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 105]
Thirty tablets obtained in Example 47 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 106]
30 tablets obtained in Example 48 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 107]
Thirty tablets obtained in Example 49 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 108]
30 tablets obtained in Example 50 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 109]
30 tablets obtained in Example 51 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 110]
30 tablets obtained in Example 52 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 111]
Thirty tablets obtained in Example 53 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 112]
Thirty tablets obtained in Example 54 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 113]
Thirty tablets obtained in Example 55 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 114]
30 tablets obtained in Example 56 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 116]
Thirty tablets obtained in Example 57 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 116]
30 tablets obtained in Example 58 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Kasei Kogyo: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 117] Preparation in which loxoprofen sodium hydrate and dihydrocodein phosphate do not substantially come into contact with each other 68.1 g of loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate), 29 .2 g of Macrogor 6000 (manufactured by Nippon Yushi: brand name Macrogor 6000P) and 24.3 g of corn starch (manufactured by Nissho Chemical Co., Ltd .: brand name corn starch ST-C) are stirred in a glass beaker on a hot water bath at 65 ° C. Then, after cooling, it was sieved with No. 18 sieve to obtain granulated product. The obtained granules include 8 g of dihydrocodein phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodein phosphate "Shionogi"), 81 g of carmellose calcium (manufactured by Gotoku Pharmaceutical Co., Ltd .: trade name: ECG505), and 524.6 g of lactose hydrate (manufactured by Gotoku Pharmaceutical Co., Ltd.). DMV: trade name: lactose 200M), magnesium hydroxide 66.7g (Kyowa Kagaku Kogyo: trade name: Kyowa Suimag) and magnesium stearate: 8.1g (Taipei Kagaku Kogyo: trade name: magnesium stearate (vegetable)) After mixing, tableting was performed using a tableting machine (manufactured by Hata Iron Works: HT-AP18SS type) equipped with a die having a diameter of 8.5 mm, and a tablet having a mass of 270 mg was obtained.

[Example 118] A tablet having the following components and amounts in 9 tablets of a preparation in which loxoprofen sodium hydrate and dihydrocodeine phosphate do not substantially come into contact with each other was produced by the same method as in Example 117.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1573.9 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Magnesium stearate 24.3 mg

[Example 119] A tablet having the following components and amounts in 9 tablets of a preparation in which loxoprofen sodium hydrate and dihydrocodeine phosphate do not substantially come into contact with each other was produced by the same method as in Example 117.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Hydrogenated oil (manufactured by Kawaken Fine Chemicals: trade name K-3 wax-200) 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1573.9 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Magnesium stearate 24.3 mg

[Example 120] A tablet having the following components and amounts in 9 tablets of a preparation in which loxoprofen sodium hydrate and dihydrocodeine phosphate do not substantially come into contact with each other was produced by the same method as in Example 117.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1573.9 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Magnesium stearate 24.3 mg

[Example 121] A tablet having the following components and amounts in 9 tablets of a preparation in which loxoprofen sodium hydrate and dihydrocodeine phosphate do not substantially come into contact with each other was produced by the same method as in Example 117.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1573.9 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Magnesium stearate 24.3 mg

[Example 122] A tablet having the following components and amounts in 9 tablets of a preparation in which loxoprofen sodium hydrate and dihydrocodeine phosphate do not substantially come into contact with each other was produced by the same method as in Example 117.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Dihydrocodeine Phosphate (manufactured by Shionogi Pharmaceutical Co., Ltd .: trade name: dihydrocodeine phosphate "Shionogi") 24 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1573.9 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Magnesium stearate 24.3 mg

[Example 123] A preparation having substantially no contact between loxoprofen sodium hydrate and d-chlorpheniramine maleate. Tablets having the following components and amounts in 9 tablets are produced by the same method as in Example 117. did.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
d-Chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: D-chlorpheniramine maleate) 3.5 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1594.4 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Magnesium stearate 24.3 mg

[Example 124] A preparation having substantially no contact between loxoprofen sodium hydrate and d-chlorpheniramine maleate. Tablets having the following components and amounts in 9 tablets are produced by the same method as in Example 117. did.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
d-Chlorpheniramine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: D-chlorpheniramine maleate) 3.5 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1594.4 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Magnesium stearate 24.3 mg

[Example 125] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and clemastine fumarate do not substantially come into contact with each other is produced by the same method as in Example 117. did.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Clemastine fumarate (manufactured by Dite: trade name clemastine fumarate) 1.34 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1596.6 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Magnesium stearate 24.3 mg

[Example 126] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and carbinoxamine maleate are not substantially in contact with each other, in the same manner as in Example 117. Manufactured by.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Carbinoxamine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: carbinoxamine maleate) 7.5 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1590.4 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Magnesium stearate 24.3 mg

[Example 127] A preparation in which loxoprofen sodium hydrate and carbinoxamine maleate are not substantially in contact with each other. A tablet containing the following components in 9 tablets (daily dose) is prepared in the same manner as in Example 117. Manufactured by.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Carbinoxamine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: carbinoxamine maleate) 7.5 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1590.4 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Magnesium stearate 24.3 mg

[Example 128] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and carbinoxamine maleate are not substantially in contact with each other, in the same manner as in Example 117. Manufactured by.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Carbinoxamine maleate (manufactured by Kongo Chemical Co., Ltd .: trade name: carbinoxamine maleate) 7.5 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1590.4 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Magnesium stearate 24.3 mg

[Example 129] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and diphenylpyraline hydrochloride do not substantially come into contact with each other is produced by the same method as in Example 117. did.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Diphenylpyraline hydrochloride (manufactured by Kongo Chemical Co., Ltd .: trade name: diphenylpyraline hydrochloride) 4 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1593.9 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Magnesium stearate 24.3 mg

[Example 130] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and diphenylpyraline hydrochloride do not substantially come into contact with each other is produced by the same method as in Example 117. did.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Diphenylpyraline hydrochloride (manufactured by Kongo Chemical Co., Ltd .: trade name: diphenylpyraline hydrochloride) 4 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1593.9 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Magnesium stearate 24.3 mg

[Example 131] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and bromhexine hydrochloride do not substantially come into contact with each other was produced by the same method as in Example 117. ..
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromhexine hydrochloride (manufactured by Sanyo Chemical Co., Ltd .: trade name: bromhexine hydrochloride) 12 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1585.9 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Magnesium stearate 24.3 mg

[Example 132] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and bromhexine hydrochloride do not substantially come into contact with each other was produced by the same method as in Example 117. ..
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromhexine hydrochloride (manufactured by Sanyo Chemical Co., Ltd .: trade name: bromhexine hydrochloride) 12 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1585.9 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Magnesium stearate 24.3 mg

[Example 133] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and bromhexine hydrochloride do not substantially come into contact with each other was produced by the same method as in Example 117. ..
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromhexine hydrochloride (manufactured by Sanyo Chemical Co., Ltd .: trade name: bromhexine hydrochloride) 12 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1585.9 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Magnesium stearate 24.3 mg

[Example 134] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and ambroxol hydrochloride do not substantially come into contact with each other by the same method as in Example 117. Manufactured.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name ambroxol hydrochloride) 45 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1552.9 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate) 200 mg
Magnesium stearate 24.3 mg

[Example 135] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and ambroxol hydrochloride do not substantially come into contact with each other by the same method as in Example 117. Manufactured.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name ambroxol hydrochloride) 45 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1552.9 mg
Magnesium aluminate aluminate (manufactured by Fuji Chemical Industry Co., Ltd .: trade name Neucillin UFL2) 200 mg
Magnesium stearate 24.3 mg

[Example 136] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and ambroxol hydrochloride do not substantially come into contact with each other by the same method as in Example 117. Manufactured.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Ambroxol hydrochloride (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name ambroxol hydrochloride) 45 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1552.9 mg
Precipitated calcium carbonate (manufactured by Sankyo Seiko: trade name: precipitated calcium carbonate) 200 mg
Magnesium stearate 24.3 mg

[Example 137] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and potassium guayacol sulfonate do not substantially come into contact with each other is produced by the same method as in Example 117. did.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Potassium guayacol sulfonate (manufactured by Yonezawahama Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 250 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1347.9 mg
Magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name Kyowa Suimag) 200 mg
Magnesium stearate 24.3 mg

[Example 138] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and potassium guayacol sulfonate do not substantially come into contact with each other is produced by the same method as in Example 117. did.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Potassium guayacol sulfonate (manufactured by Yonezawahama Pharmaceutical Co., Ltd .: trade name: potassium guayacol sulfonate) 250 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1347.9 mg
Magnesium aluminate silicate (manufactured by Tomita Pharmaceutical Co., Ltd .: Brand name Magnesium aluminate silicate) 200 mg
Magnesium stearate 24.3 mg

[Example 139] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and sodium benzoate caffeine do not substantially come into contact with each other by the same method as in Example 117. Manufactured.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Sodium benzoate caffeine (manufactured by Shizuoka caffeine: trade name: sodium benzoate caffeine) 300 mg
Macrogol 6000 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 1297.9 mg
Anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Industry Co., Ltd .: trade name: anhydrous calcium hydrogen phosphate GS-H) 200 mg
Magnesium stearate 24.3 mg

[Example 140] A tablet containing the following components in 9 tablets (daily dose) of a preparation in which loxoprofen sodium hydrate and bromvalerylurea do not substantially come into contact with each other was produced by the same method as in Example 117.
Loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo: trade name Japanese Pharmacopoeia loxoprofen sodium hydrate) 204.3 mg
Bromvalerylurea (manufactured by Yashiro Pharmaceutical Co., Ltd .: Brand name: Japanese Pharmacopoeia Bromovalerylurea P) 600 mg
Hydrogenated oil 87.6 mg
Corn starch 72.9 mg
Carmellose Calcium 243mg
Lactose hydrate 997.9 mg
Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd .: trade name: heavy magnesium oxide) 200 mg
Magnesium stearate 24.3 mg

According to the present invention, the interaction between loxoprofen or a salt thereof and an interacting component can be suppressed. Therefore, it is possible to provide a pharmaceutical composition containing loxoprofen or a salt thereof and an interacting component having excellent storage stability.

Claims (1)

The following components (A), (B) and (C):
(A) Loxoprofen or a salt thereof (B) One or more selected from the group consisting of bromvalerylurea and allylisopropylacetylurea and salts thereof (C) Selected from the group consisting of magnesium silicate aluminate and magnesium aluminometasilicate A pharmaceutical composition which is a solid preparation for antipyretic and analgesic, which contains one or more of the above.