WO2013018766A1 - Stable pharmaceutical composition - Google Patents

Abstract

Provided is a stable pharmaceutical composition containing loxoprofen or a salt thereof, and butylscopolamine bromide. The loxoprofen or salt thereof and the butylscopolamine bromide that are contained in the pharmaceutical composition do not substantially contact one another.

Description

Stable pharmaceutical composition

The present invention relates to a stable pharmaceutical composition. More specifically, it relates to a stable pharmaceutical composition containing loxoprofen or a salt thereof and butyl scopolamine bromide.

Loxoprofen is a type of non-steroidal anti-inflammatory analgesic (NSAID), including rheumatoid arthritis, osteoarthritis, low back pain, shoulder periarthritis, cervical-shoulder arm syndrome, toothache, acute upper respiratory inflammation, post-surgical / post-traumatic It is known as effective for anti-inflammatory, analgesic and antipyretic after tooth extraction (Non-patent Document 1). Loxoprofen is a compound that has recently been converted to so-called switch OTC, and is expected as an active ingredient in OTC pharmaceuticals.

However, loxoprofen is also a kind of NSAID, and as a side effect, there is a possibility that disorders due to increased gastrointestinal motility may occur.
Therefore, it has been proposed to take butyl scopolamine bromide with analgesic / antispasmodic action together with loxoprofen from the viewpoint of taking side-effect reduction measures while obtaining sufficient antipyretic analgesic effect, and contains loxoprofen sodium and butyl scopolamine bromide As a preparation, a capsule containing these two components is known (Patent Document 1).

However, in Patent Document 1, there is no mention of how loxoprofen sodium and butyl scopolamine bromide are blended in the capsule, and there is no study on the stability of such a capsule. It has not been. Thus, at present, the interaction between loxoprofen or a salt thereof and butyl scopolamine bromide has not been studied so far.

Japanese Patent Laid-Open No. 2000-26313

First, the present inventor studied to make a pharmaceutical composition containing loxoprofen or a salt thereof and butyl scopolamine bromide into a solid formulation. It has been found that an interaction occurs between these compounds, and this interaction causes wetting and solidification of the mixture, making it difficult to maintain a stable state during storage.
Accordingly, an object of the present invention is to provide a stable pharmaceutical composition containing loxoprofen or a salt thereof and butyl scopolamine bromide.

Therefore, the present inventor has eagerly studied the storage stability of a pharmaceutical composition containing loxoprofen or a salt thereof and butyl scopolamine bromide in order to solve the above-mentioned problems. It was clarified that the interaction caused by this was the cause of the storage stability problem.
Then, this inventor discovered that the said interaction could be suppressed by making a pharmaceutical composition contain so that a loxoprofen or its salt, and butyl scopolamine bromide may not contact substantially.

That is, the present invention provides a pharmaceutical composition containing loxoprofen or a salt thereof and butyl scopolamine bromide so as not to substantially contact each other.
The present invention also provides a pharmaceutical composition comprising a granule containing loxoprofen or a salt thereof and butyl scopolamine bromide, wherein loxoprofen or a salt thereof and butyl scopolamine bromide are contained so as not to substantially contact each other. It is to provide.
Furthermore, the present invention provides a pharmaceutical composition comprising a granular material containing butyl scopolamine bromide and loxoprofen or a salt thereof, wherein loxoprofen or a salt thereof and butyl scopolamine bromide are contained so as not to substantially contact each other. It is to provide.
Furthermore, the present invention includes a granule containing loxoprofen or a salt thereof and a granule containing butyl scopolamine bromide, wherein loxoprofen or a salt thereof and butyl scopolamine bromide are contained so as not to substantially contact each other. A pharmaceutical composition is provided.

According to the present invention, it is possible to provide a pharmaceutical composition that not only reduces or suppresses damage caused by increased gastrointestinal motility, which is a side effect of loxoprofen, but also has excellent storage stability.

The pharmaceutical composition of the present invention contains loxoprofen or a salt thereof and butyl scopolamine bromide. First, these components will be described.

Loxoprofen or a salt thereof used in the pharmaceutical composition of the present invention includes loxoprofen itself, a pharmaceutically acceptable salt of loxoprofen, and further a solvation of loxoprofen or a pharmaceutically acceptable salt thereof with water, alcohol or the like. Things are also included. These are known compounds, and can be produced by known methods, or commercially available products can be used. In the present invention, loxoprofen or a salt thereof is preferably loxoprofen sodium hydrate (chemical name: Monosodium 2- [4-[(2-oxocyclopentyl) methyl] phenyl] propanoate dihydrate).

The content of loxoprofen or a salt thereof in the pharmaceutical composition of the present invention may be determined by appropriately examining the dose per day according to the sex, age, symptoms, etc. of the user. For example, in terms of anhydrous loxoprofen sodium, the amount that can be taken 10 to 300 mg of loxoprofen or a salt thereof is preferable, more preferably 30 to 240 mg, more preferably 60 to 180 mg per day. The daily dose may be divided into 1 to 4 doses, and preferably 3 divided doses. As a single dose, 60 mg of loxoprofen sodium anhydride is preferable.

The content of loxoprofen or a salt thereof is preferably 0.4 to 90% by mass, and 1.2 to 75% by mass in terms of anhydrous loxoprofen sodium, based on the total mass of the pharmaceutical composition. Is more preferably 3 to 50% by mass, still more preferably 5 to 47% by mass.

The butyl scopolamine bromide used in the pharmaceutical composition of the present invention is a known compound, and can be produced by a known method or commercially available.

The content of butyl scopolamine bromide in the pharmaceutical composition of the present invention may be determined by appropriately examining the daily dose according to the sex, age, symptoms, etc. of the user. The amount of scopolamine bromide is preferably 3 to 1000 mg, more preferably 5 to 500 mg, and even more preferably 30 to 100 mg per day. The daily dose may be divided into 1 to 5 doses, and preferably 3 divided doses. The dose per dose is preferably 10 to 20 mg at a time, more preferably 10 mg and 20 mg as butyl scopolamine bromide.

The content ratio of loxoprofen or a salt thereof and butyl scopolamine bromide contained in the pharmaceutical composition of the present invention may be appropriately determined and determined according to the daily dose of each component described above. Alternatively, it is preferable to contain 0.01 to 100 parts by mass of butyl scopolamine bromide, more preferably 0.02 to 20 parts by mass with respect to 1 part by mass of the salt (in terms of loxoprofen sodium anhydrate). Those containing 05 to 10 parts by mass are more preferred, those containing 0.05 to 1 part by mass are more preferred, and those containing 0.1 to 0.5 parts by mass are particularly preferred.
Further, the content of butyl scopolamine bromide is preferably 1 to 10% by mass, more preferably 2 to 9% by mass, and more preferably 3 to 8% by mass with respect to the total mass of the pharmaceutical composition. Is more preferable.

In the present invention, it has been found for the first time that an interaction is caused by contact of loxoprofen or a salt thereof and butylscopolamine bromide in a pharmaceutical composition. Based on this finding, the interaction between the two components is improved by containing loxoprofen or a salt thereof and butyl scopolamine bromide so as not to substantially contact in the pharmaceutical composition.
That is, the pharmaceutical composition of the present invention contains loxoprofen or a salt thereof and butyl scopolamine bromide so that the loxoprofen or a salt thereof and butyl scopolamine bromide do not substantially contact each other in the pharmaceutical composition.

In the present invention, the phrase “containing so as not to substantially contact each other” means containing in a pharmaceutical composition such that loxoprofen or a salt thereof and butyl scopolamine bromide do not come into contact with each other to the extent that they do not exhibit an interaction. However, it is preferable to contain so that loxoprofen or a salt thereof and butyl scopolamine bromide do not come into contact with each other.

The pharmaceutical composition of the present invention can be formulated into various dosage forms by using known formulation additives according to known methods described in the 16th revised Japanese Pharmacopoeia General Rules for Preparations.
In addition, the dosage form according to the pharmaceutical composition of the present invention is not particularly limited, but a solid preparation containing loxoprofen or a salt thereof and butyl scopolamine bromide is preferable from the viewpoint of ease of administration, management of drug dosage, and the like. Specific examples of solid preparations include, for example, tablets (orally disintegrating tablets, chewable tablets, dispersible tablets, dissolving tablets; including oral tablets such as lozenges, sublingual tablets, buccal tablets, adhesive tablets, and gums) Examples include oral preparations such as capsules, pills, granules, fine granules, powders, dry syrups, oral jelly preparations, and the like which are orally administered are preferable. Moreover, the pharmaceutical composition of the present invention may be coated with a sugar coating, a film coating or the like by a known method.

The embodiment of the pharmaceutical composition of the present invention will be described in more detail by taking a solid preparation as an example.
The solid preparation of the present invention includes (A) loxoprofen or a salt thereof, or a solid composition containing loxoprofen or a salt thereof, and (B) a solid composition containing butyl scopolamine bromide itself or butyl scopolamine bromide. The thing which is arrange | positioned so that a loxoprofen or its salt, and butyl scopolamine bromide may not mutually contact by the component which contains and comprises these solid compositions is mentioned. These solid compositions are in the form of powder, granules, tablets, and the like.

As specific forms of the solid preparation, the following (I)-(VIII) and the like can be exemplified, and these are described in known methods as described above, for example, the 16th revised Japanese Pharmacopoeia, General Rules for Preparations, etc. According to the known methods, it can be produced and formulated using appropriate formulation additives.

(I) One of loxoprofen or a salt thereof and butyl scopolamine bromide is granulated by an appropriate method to form a granular material, and the other loxoprofen or a salt thereof or butyl scopolamine bromide is blended without granulation. Preparations prepared by coating powders, granules, etc., as well as the granules, in a suitable manner.

(II) Loxoprofen or a salt thereof and butyl scopolamine bromide are separately granulated by an appropriate method to form a granular material, and a powder or granule prepared by blending these, and the granular material by an appropriate method. Coated formulation. In addition, the xanthine derivative etc. which are mentioned later may be contained in either one of the granular materials or in both granular materials, or may be formulated separately from these granular materials.
(III) Capsule filled with powder or granule prepared in (I) or (II) above.
(IV) A tablet obtained by tableting the granular material produced in the above (I) or (II) by an appropriate method. Tableting can be achieved not only by the compression method but also by molding into a certain shape by an appropriate method.

(V) A multilayer tablet prepared so that loxoprofen or a salt thereof and butyl scopolamine bromide do not substantially contact each other, and a preparation in which the multilayer tablet is further coated by an appropriate method. The multi-layer tablet is preferably one in which loxoprofen or a salt thereof and butyl scopolamine bromide are located in different layers, and the multi-layer tablet having three or more layers includes a layer containing loxoprofen or a salt thereof and a layer containing butyl scopolamine bromide. Those positioned so as not to contact each other are more preferable. In addition, the granular material manufactured by said (I) and (II) can be used as a loxoprofen or its salt, and a butyl scopolamine bromide. In such multilayer tablets, the xanthine derivative and the like described later may be located in either the layer containing loxoprofen or a salt thereof, the layer containing butyl scopolamine bromide, or in both layers. Moreover, you may locate in the intermediate | middle layer of either layer.
(VI) One of Loxoprofen or a salt thereof and butylscopolamine bromide was placed in a core tablet (also referred to as a core tablet or a central tablet) so that loxoprofen or a salt thereof and butylscopolamine bromide were not substantially in contact with each other. Nucleated tablets, and preparations obtained by coating the nucleated tablets with an appropriate method. In addition, the granular material manufactured by said (I) and (II) can be used as a loxoprofen or its salt, and a butyl scopolamine bromide.

(VII) In place of the granular material of (I) or (II) above, either or both of loxoprofen or a salt thereof and butyl scopolamine bromide is added to a cyclodextrin such as α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin. A preparation using an inclusion compound included in dextrins.
(VIII) A preparation comprising either one of loxoprofen or a salt thereof and butyl scopolamine bromide in a preparation prepared by an ordinary method, and having a sugar coating layer or a film coating layer, and the other sugar coating layer or coating layer is provided on the other side. And a preparation prepared such that loxoprofen or a salt thereof and butyl scopolamine bromide do not substantially contact each other (when the dosage form is a tablet, it is called a sugar-coated tablet or a film-coated tablet).

Granules in the above (I) and (II) are known granulations such as extrusion granulation, rolling granulation, stirring granulation, fluidized bed granulation, spray drying granulation, crushed granulation, melt granulation, etc. Depending on the method, it may be prepared using appropriate formulation additives. In the present invention, any of the granular material containing loxoprofen or a salt thereof and the granular material containing butyl scopolamine bromide may be produced by the same granulation method or by different granulation methods. It may be.

The granule containing loxoprofen or a salt thereof can be produced by granulating by an appropriate method based on a known method. However, 10% of Roseol (registered trademark) fine particles manufactured by Sakai Chemical Co., Ltd. Doso Pharmaceutical Co., Ltd. Loxoprofen Sodium Fine Granules 10% "CH", Medisa Shinyaku Co., Ltd. Kentan (registered trademark) 10% fine granules, Biomedix Co., Ltd. Ponaperto (registered trademark) 10% fine granules, 10% Lingelies (Registered Trademark) manufactured by Yoshindo Co., Ltd., 10% Loxonin (Registered Trademark) manufactured by Daiichi Sankyo Co., Ltd., Lolfenamin (Registered Trademark) manufactured by Nichi-Iko Co., Ltd. Commercially available products such as 10% can be used.

The interaction between loxoprofen or a salt thereof and butyl scopolamine bromide is not only included in the pharmaceutical composition so as not to substantially contact, but in addition to these, a xanthine derivative, tranexamic acid or a salt thereof, a silicate compound, a carbonic acid One or more selected from the group consisting of compounds, phosphate compounds, hydroxides, metal oxides, cellulose derivatives or salts thereof and oils and fats (in the present specification, these are collectively referred to as xanthine derivatives, etc.) Can also be suppressed. For this reason, the pharmaceutical composition containing these xanthine derivatives etc. is also mentioned as an aspect of this invention.
In this case, the following (i) to (viii) are exemplified as specific forms when the pharmaceutical composition containing a xanthine derivative or the like, especially the dosage form of the pharmaceutical composition is a solid preparation: These are based on the methods (I) to (VIII) described above. About specific formulation etc., it can manufacture and formulate suitably using a formulation additive by the well-known method as described in the 16th revision Japanese Pharmacopoeia general formulation etc. similarly to the above-mentioned.

(I) Loxoprofen or a salt thereof, butyl scopolamine bromide, xanthine derivative, etc., and either loxoprofen or a salt thereof and butyl scopolamine bromide are granulated by an appropriate method to form a granular material, and the other loxoprofen or Powders and granules prepared by blending the salt or butyl scopolamine bromide without granulation, and preparations in which the granules are further coated by an appropriate method. In such a preparation, the xanthine derivative or the like may be contained in the granular material, or may be contained separately from the granular material.
(Ii) Powder obtained by granulating loxoprofen or a salt thereof and butyl scopolamine bromide separately by an appropriate method using loxoprofen or a salt thereof, butyl scopolamine bromide and xanthine derivatives, etc., respectively, by a suitable method And granules, as well as preparations in which the granular material is further coated by an appropriate method. In such a preparation, the xanthine derivative or the like may be contained in one of the granular materials, or may be contained in both of the granular materials, or may be formulated separately from these granular materials. May be.
(Iii) A capsule filled with the powder or granule prepared in (i) or (ii) above.
(Iv) A tablet obtained by tableting the granular material produced in (i) or (ii) above by an appropriate method. Tableting can be achieved not only by the compression method but also by molding into a certain shape by an appropriate method.
(V) A multi-layer tablet produced using loxoprofen or a salt thereof, butyl scopolamine bromide and xanthine derivatives, etc. so that loxoprofen or a salt thereof and butyl scopolamine bromide are not substantially in contact with each other, and the multi-layer tablet by an appropriate method. Coated formulation. The multi-layer tablet is preferably one in which loxoprofen or a salt thereof and butyl scopolamine bromide are located in different layers, and the multi-layer tablet having three or more layers includes a layer containing loxoprofen or a salt thereof and a layer containing butyl scopolamine bromide. Those positioned so as not to contact each other are more preferable. In addition, the granular material manufactured by said (i) and (ii) can be used as a loxoprofen or its salt, and a butyl scopolamine bromide. In the multilayer tablet, the xanthine derivative or the like may be located in either the layer containing loxoprofen or a salt thereof, the layer containing butyl scopolamine bromide, or may be located in both layers. Moreover, you may locate in the intermediate | middle layer of either layer.
(Vi) Loxoprofen or a salt thereof, butyl scopolamine bromide and xanthine derivatives, etc., and either loxoprofen or a salt thereof and butyl scopolamine bromide are arranged in a core tablet (also referred to as a core tablet or a central tablet), and loxoprofen or a salt thereof And a nucleated tablet produced so that butylscopolamine bromide does not substantially contact each other, and a preparation in which the nucleated tablet is further coated by an appropriate method. In addition, the granular material manufactured by said (i) and (ii) can be used as a loxoprofen or its salt, and a butyl scopolamine bromide. In the dry-coated tablet, the xanthine derivative or the like may be positioned in the core tablet, may be positioned in the outer shell, or may be separately positioned in either the core tablet or the outer shell.
(Vii) Loxoprofen or a salt thereof, butyl scopolamine bromide and xanthine derivative, etc. are used, and instead of the granular material of (i) or (ii) above, either or both of loxoprofen or a salt thereof and butyl scopolamine bromide is α- A preparation using an inclusion compound which is included by cyclodextrins such as cyclodextrin, β-cyclodextrin and γ-cyclodextrin. The xanthine derivative or the like may be located in the vicinity of either one of the clathrate compounds, or may be located in the vicinity of both clathrate compounds.
(Viii) Loxoprofen or a salt thereof, butyl scopolamine bromide, xanthine derivative, etc., containing either one of loxoprofen or a salt thereof and butyl scopolamine bromide in a usual method, and a sugar coating layer or a film coating layer A preparation prepared so as to contain the other in the sugar-coating layer or the coating layer, so that loxoprofen or a salt thereof and butylscopolamine bromide are not substantially in contact with each other (if the dosage form is a tablet, Referred to as film-coated tablets). The xanthine derivative or the like may be located in a preparation prepared by a usual method, may be located in a sugar coating layer or a film coating layer, and separately located in either a sugar coating layer or a film coating layer. Further, it may be located in any of the sugar coating layer and the film coating layer in the preparation.

Next, the above-mentioned xanthine derivatives and the like, that is, “consisting of“ xanthine derivative, tranexamic acid or its salt, silicic acid compound, carbonic acid compound, phosphoric acid compound, hydroxide, metal oxide, cellulose derivative or its salt and fats and oils ” One type or two or more types selected from the group will be described.

As the xanthine derivative used in the pharmaceutical composition of the present invention, a compound represented by the following general formula (I) is preferable.

[Wherein, R ₁ and R ₂ each independently represent a hydrogen atom or a methyl group. R ₃ represents a hydrogen atom, a methyl group, a monohydroxypropyl group or a dihydroxypropyl group. ]

In R ₃ described above, the monohydroxypropyl group is preferably a 2-hydroxypropyl group. The dihydroxypropyl group is preferably a 2,3-dihydroxypropyl group.

In the general formula (I),
(1) R ₁ is a methyl group, R ₂ is a methyl group, and R ₃ is a methyl group means caffeine.
(2) R ₁ is a methyl group, R ₂ is a methyl group, and R ₃ is a hydrogen atom means theophylline.
(3) R ₁ is a hydrogen atom, R ₂ is a methyl group, and R ₃ is a methyl group means theobromine.
(4) R ₁ is a methyl group, R ₂ is a hydrogen atom, and R ₃ is a methyl group means paraxanthine.
(5) A compound in which R ₁ is a methyl group, R ₂ is a methyl group, and R ₃ is a 2-hydroxypropyl group means proxyphylline.
(6) R ₁ is a methyl group, R ₂ is a methyl group, and R ₃ is a 2,3-dihydroxypropyl group means a diprofylline.

The compounds of the general formula (I), especially the above-mentioned compounds are known, and in the present invention, commercially available products can be used in addition to those produced by known methods.
In addition, as the caffeine and theophylline, those in which a double salt is formed (sodium benzoate caffeine (double salt of sodium benzoate and caffeine), aminophylline (double salt of theophylline and ethylenediamine)) or the like may be used. it can.
As the xanthine derivative used in the pharmaceutical composition of the present invention, caffeine is preferable from the viewpoint of using the pharmaceutical composition of the present invention as an antipyretic analgesic or a general cold medicine. Specific examples of the caffeine include caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate. Among these, caffeine hydrate, anhydrous caffeine, and sodium benzoate caffeine are more preferable.

In addition, when a xanthine derivative is used, the content of the xanthine derivative is appropriately determined based on the interaction inhibitory effect of loxoprofen or a salt thereof and butyl scopolamine bromide and the daily dose according to the sex, age, symptom, etc. of the user. The amount that can be taken 10 to 1000 mg per day is preferred, the amount that can be taken 20 to 800 mg is more preferred, and the amount that can be taken 40 to 600 mg is even more preferred.
The content of the xanthine derivative is preferably 2 to 90% by mass, more preferably 10 to 85% by mass, further preferably 20 to 80% by mass, and further preferably 20 to 50% by mass with respect to the total mass of the pharmaceutical composition. 20 to 40% by mass is preferable.
Further, the content ratio of loxoprofen or a salt thereof and a xanthine derivative may be determined by appropriate examination according to the daily dose of each component described above, but 1 part by mass of loxoprofen or a salt thereof (loxoprofen sodium) The amount of xanthine derivative is preferably 0.03 to 100 parts by mass, more preferably 0.08 to 27 parts by mass, and 0.2 to 10 parts by mass of xanthine derivatives. More preferred are those containing 0.2 to 5 parts by mass.

Tranexamic acid or a salt thereof used in the pharmaceutical composition of the present invention includes tranexamic acid itself, a pharmaceutically acceptable salt of tranexamic acid, and further, tranexamic acid or a pharmaceutically acceptable salt thereof, water, alcohol, etc. And solvates thereof. These are known compounds, and can be produced by known methods, or commercially available products can be used. In the present invention, as tranexamic acid or a salt thereof, tranexamic acid is preferable from the viewpoint of using the pharmaceutical composition of the present invention as an antipyretic analgesic, a general cold medicine, or the like, and Japanese Pharmacopoeia tranexamic acid is preferable.

In addition, when tranexamic acid or a salt thereof is used, the content of tranexamic acid or a salt thereof is one day according to the inhibitory effect on the interaction between loxoprofen or a salt thereof and butyl scopolamine bromide, the sex, age, and symptoms of the user. The dose may be determined by appropriate examination according to the dose per dose, but it is preferably an amount that can be taken from 50 to 2000 mg in terms of free form of tranexamic acid, more preferably an amount that can be taken from 70 to 750 mg, and an amount that can be taken from 400 to 750 mg. Is more preferable.
The content of tranexamic acid or a salt thereof is preferably 10 to 95% by mass, more preferably 30 to 85% by mass, further preferably 40 to 80% by mass, and more preferably 40 to 70% by mass with respect to the total mass of the pharmaceutical composition. % Is particularly preferred.
Further, the content ratio of loxoprofen or a salt thereof and tranexamic acid or a salt thereof may be appropriately determined and determined according to the daily dose of each component described above, but 1 part by mass of loxoprofen or a salt thereof. (In terms of loxoprofen sodium anhydride), tranexamic acid or a salt thereof is preferably contained in an amount of 0.1 to 200 parts by mass in terms of a free form of tranexamic acid, more preferably 0.2 to 25 parts by mass. The content is preferably 2 to 12.5 parts by mass, more preferably 2 to 5 parts by mass.

Examples of the silicate compound used in the pharmaceutical composition of the present invention include silicate compounds and salts of silicate compounds. As a salt of such a silicic acid compound, an inorganic salt is preferable.
Examples of the inorganic salt include metal salts, and examples of the metal constituting such metal ions include alkaline earth metals such as magnesium and calcium; alkali metals such as sodium; and group 13 metals such as aluminum. Can be mentioned.
Specific examples of the silicate compound as described above include synthetic aluminum silicate, hydrous magnesium silicate, hydrous magnesium silicate (natural), synthetic sodium magnesium silicate, hydrous silicon dioxide, magnesium aluminate silicate, calcium silicate. , Magnesium silicate, magnesium aluminum silicate, light anhydrous silicic acid, diatomaceous earth, silicon dioxide, bentonite, magnesium aluminate metasilicate and the like. These may be used alone or in combination of two or more. In addition, these are well-known things and can manufacture by a well-known method, and can use a commercially available thing.
Among the silicic acid compounds as described above, hydrous silicic acid compounds such as hydrous silicon dioxide, hydrous magnesium silicate, hydrous magnesium silicate (natural) or salts thereof; light anhydrous silicic acid such as light anhydrous silicic acid or salts thereof; Silicic acid such as silicon dioxide, calcium silicate, magnesium aluminate silicate and magnesium aluminate metasilicate or a salt thereof is preferred. Among these, a salt of a hydrous silicate compound, light anhydrous silicic acid, and a silicate are more preferable.

In addition, when a silicate compound is used, the content of the silicate compound is determined based on the inhibitory effect of the interaction between loxoprofen or a salt thereof and butyl scopolamine bromide, and the daily dose according to the sex, age, and symptoms of the user. Depending on the situation, it may be determined by appropriate examination. For example, the amount of the silicic acid compound that can be taken from 1 to 1500 mg per day is preferred, the amount that can be taken from 5 to 1000 mg is more preferred, and the amount that can be taken from 10 to 500 mg is even more preferred.
The content of the silicate compound is preferably 0.05 to 80% by mass, more preferably 0.1 to 60% by mass, and still more preferably 0.2 to 55% by mass with respect to the total mass of the pharmaceutical composition. 0.2 to 35% by mass is more preferable, and 0.2 to 5% by mass is particularly preferable.
Further, the content ratio of loxoprofen or a salt thereof and a silicate compound may be determined by appropriate examination according to the daily dose of each component described above, but 1 part by mass of loxoprofen or a salt thereof (loxoprofen) Those containing 0.003 to 150 parts by mass of a silicic acid compound, more preferably 0.02 to 35 parts by mass, and 0.04 to 10 parts by mass in terms of sodium anhydride) Are more preferable, and those containing 0.04 to 1 part by mass are more preferable.

The carbonate compound used in the pharmaceutical composition of the present invention includes potassium carbonate, magnesium carbonate, aluminum hydroxide / magnesium carbonate mixed dried gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, calcium carbonate, precipitated carbonate Calcium, sodium hydrogen carbonate, sodium hydrogen carbonate hydrate, potassium hydrogen carbonate, aluminum hydroxide / sodium hydrogen carbonate coprecipitation products, etc., including carbonate compounds, using bandit bones, stone decision, oysters, etc. Also good. These are known compounds and the like, and can be produced by known methods or commercially available products.
Among these, salts composed of metal ions such as alkali metals (sodium, potassium, etc.) and alkaline earth metals (magnesium, calcium, etc.) and carbonate ions or hydrogen carbonate ions, and hydrates of such salts A coprecipitation product is preferable, and a salt composed of alkaline earth metal ions and carbonate ions or a coprecipitation product thereof is more preferable.

In addition, when using a carbonic acid compound, the content of the carbonic acid compound is not particularly limited, and the effect of suppressing the interaction between loxoprofen or a salt thereof and butylscopolamine bromide and the sex, age, and symptoms of the user per day It may be determined by appropriate examination according to the dose. The amount that can be taken 1 to 1500 mg of carbonic acid compound per day is preferable, the amount that can be taken 5 to 1000 mg is more preferable, and the amount that can be taken 10 to 500 mg is more preferable.
The content of the carbonic acid compound is preferably 0.05 to 80% by mass, more preferably 0.1 to 60% by mass, and still more preferably 0.2 to 55% by mass with respect to the total mass of the pharmaceutical composition.
Further, the content ratio of loxoprofen or a salt thereof and a carbonic acid compound may be appropriately determined and determined according to the daily dose of each component described above, but 1 part by mass of loxoprofen or a salt thereof (loxoprofen sodium) The amount of carbonic acid compound is preferably 0.003 to 150 parts by weight, more preferably 0.02 to 35 parts by weight, and more preferably 0.05 to 10 parts by weight. preferable.

Examples of the phosphoric acid compound used in the pharmaceutical composition of the present invention include metal ions such as alkali metals (sodium, potassium, etc.) and alkaline earth metals (magnesium, calcium, etc.), phosphate ions, phosphoric acid (one). Examples thereof include salts composed of hydrogen ions, dihydrogen phosphate ions, glycerophosphate ions or pyrophosphate ions, and hydrates of such salts. Specific examples of such phosphoric acid compounds include calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, tetrasodium pyrophosphate, trisodium phosphate, sodium hydrogen phosphate hydrate, anhydrous sodium pyrophosphate, anhydrous phosphoric acid Examples thereof include sodium hydrogen and calcium glycerophosphate, and bandit bones and oysters containing a phosphate compound may be used. These are known compounds and the like, and can be produced by known methods or commercially available products.
Among the phosphate compounds as described above, a salt composed of alkaline earth metal ions and hydrogen phosphate ions is preferable.

In addition, when using a phosphoric acid compound, the content of the phosphoric acid compound is determined by the daily dose according to the inhibitory effect on the interaction between loxoprofen or a salt thereof and butyl scopolamine bromide, the sex, age, and symptoms of the user. Depending on the situation, it may be determined by appropriate examination. The amount that can be taken 1 to 1500 mg of carbonic acid compound per day is preferable, the amount that can be taken 5 to 1000 mg is more preferable, and the amount that can be taken 10 to 500 mg is more preferable.
The content of the phosphoric acid compound is preferably 0.05 to 80% by mass, more preferably 0.1 to 60% by mass, further preferably 0.2 to 55% by mass, based on the total mass of the pharmaceutical composition. 1 to 20% by mass is particularly preferred.
Further, the content ratio of loxoprofen or a salt thereof and a phosphoric acid compound may be appropriately determined and determined according to the daily dose of each component described above, but 1 part by mass of loxoprofen or a salt thereof (loxoprofen) Those containing 0.003 to 150 parts by mass of a phosphoric acid compound, more preferably 0.02 to 35 parts by mass, and 0.05 to 10 parts by mass with respect to sodium anhydride Are more preferable, and those containing 0.1 to 1 part by mass are particularly preferable.

Examples of the hydroxide used in the pharmaceutical composition of the present invention include dihydroxyaluminum aminoacetate (aluminum glycinate), magnesium magnesium hydroxide, aluminum hydroxide, aluminum hydroxide gel, sodium hydroxide, magnesium hydroxide, dried Aluminum hydroxide, dry aluminum hydroxide gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, magnesium hydroxide / Examples include a coprecipitation product of potassium aluminum sulfate. These are known compounds, and can be produced by known methods, or commercially available products can be used.
Among these, a salt composed of a metal ion and a hydroxide ion, a coprecipitation product of such a salt, and a (dry) gel are preferable. Examples of the metal include alkali metals (sodium, potassium, etc.); alkaline earth metals (magnesium, calcium, etc.); Group 13 metals (aluminum, etc.), and alkaline earth metals are preferred.

When using hydroxide, the content of hydroxide depends on the daily dose according to the inhibitory effect of the interaction between loxoprofen or its salt and butyl scopolamine bromide and the sex, age, symptoms, etc. of the user. Therefore, it may be determined after appropriate consideration. The amount that can be taken 1 to 1500 mg of hydroxide per day is preferable, the amount that can be taken 5 to 1000 mg is more preferable, and the amount that can be taken 10 to 500 mg is more preferable.
The content of the hydroxide is preferably 0.05 to 80% by mass, more preferably 0.1 to 60% by mass, and further preferably 0.2 to 55% by mass with respect to the total mass of the pharmaceutical composition.
In addition, the content ratio of loxoprofen or a salt thereof and a hydroxide may be determined by appropriate examination according to the daily dose of each component described above, but 1 part by mass of loxoprofen or a salt thereof (loxoprofen) Those containing 0.003 to 150 parts by weight of hydroxide, more preferably 0.02 to 35 parts by weight, more preferably 0.05 to 10 parts by weight based on sodium anhydride Is more preferable.

The metal in the metal oxide used in the pharmaceutical composition of the present invention is preferably an alkaline earth metal (magnesium, calcium, etc.), a transition metal (titanium, iron, etc.), a group 13 metal (aluminum, etc.), and the like.
Examples of the metal oxide composed of the above metals include aluminum oxide, magnesium oxide, titanium oxide, yellow iron sesquioxide, brown iron oxide, black iron oxide, iron sesquioxide, and synthetic hydrotalcite. These are known compounds and can be produced by a known method or commercially available.

When using a metal oxide, the content of the metal oxide depends on the daily dose according to the inhibitory effect of the interaction between loxoprofen or its salt and butyl scopolamine bromide and the sex, age, and symptoms of the user. Therefore, it may be determined after appropriate consideration. The amount that can be taken 0.01 to 800 mg of metal oxide per day is preferred, the amount that can be taken 0.1 to 600 mg is more preferred, and the amount that can be taken 1 to 400 mg is more preferred.
The content of the metal oxide is preferably 0.0002 to 80% by mass, more preferably 0.002 to 60% by mass, and further preferably 0.02 to 55% by mass with respect to the total mass of the pharmaceutical composition.
In addition, the content ratio of loxoprofen or a salt thereof and a metal oxide may be determined by appropriate examination according to the daily dose of each component described above, but 1 part by mass of loxoprofen or a salt thereof (loxoprofen) The amount of the metal oxide is preferably 0.00003 to 80 parts by mass, more preferably 0.0004 to 20 parts by mass, and 0.005 to 7 parts by mass in terms of sodium anhydride Is more preferable.

Cellulose derivatives or salts thereof used in the pharmaceutical composition of the present invention include cellulose itself, etherified hydroxy groups in cellulose, etherified cellulose esters, cross-linked polymers thereof and salts thereof, etc. Is mentioned. Examples of such salts include metal salts such as alkali metal salts (sodium salts, potassium salts, etc.) and alkaline earth metal salts (calcium salts, etc.).
Specifically, cellulose such as crystalline cellulose and powdered cellulose; carboxyalkyl cellulose such as carmellose, carmellose potassium, carmellose calcium, and carmellose sodium or a salt thereof; a carboxyalkyl cellulose derivative such as croscarmellose sodium or a salt thereof; Hydroxyalkyl celluloses such as hydroxyethyl cellulose, low substituted hydroxypropyl cellulose, (not low substituted) hydroxypropyl cellulose; hydroxyalkylalkyl celluloses such as hypromellose (hydroxypropylmethylcellulose 2208, hydroxypropylmethylcellulose 2906, hydroxypropylmethylcellulose 2910, etc.); Hydroxypropyl methylcellulose acetate succinate, etc. Shi alkyl cellulose derivatives and the like. In addition, the carbon number of the alkyl group in the carboxyalkyl cellulose, carboxyalkyl cellulose derivative, hydroxyalkyl cellulose, hydroxyalkylalkyl cellulose, and hydroxyalkylalkylcellulose derivative is preferably 1 to 4.
These are known compounds and can be produced by a known method or commercially available.

Among the above cellulose derivatives or salts thereof, cellulose, carboxyalkyl cellulose or salt thereof, carboxyalkyl cellulose derivative or salt thereof, hydroxyalkyl cellulose, hydroxyalkylalkyl cellulose are preferred, hydroxyalkyl cellulose, hydroxyalkylalkyl cellulose are more preferred, Low-substituted hydroxypropylcellulose and hypromellose are more preferable. Among these, those listed in official documents established in countries and regions are preferable. The official documents include Japanese Pharmacopoeia, US Pharmacopoeia, British Pharmacopoeia, European Pharmacopoeia, Chinese Pharmacopoeia and so on. In Japan, Japanese pharmacopoeia, low-substituted hydroxypropyl cellulose, and Japanese pharmacopoeia hypromellose are particularly preferred.

The degree of substitution of the hydroxypropoxy group of the low-substituted hydroxypropylcellulose is preferably 3 to 35%, more preferably 5 to 16%.
Further, the substitution degree of the methoxy group in the hypromellose is preferably 15 to 35%, more preferably 16.5 to 30%. On the other hand, the substitution degree of the hydroxypropoxy group is preferably 3 to 35%, more preferably 4 to 32%.

When a cellulose derivative or a salt thereof is used, the content of the cellulose derivative or a salt thereof is determined based on the interaction inhibitory effect of loxoprofen or a salt thereof and butyl scopolamine bromide, the sex, age, symptoms, etc. of the user. It may be determined by appropriate examination according to the dose. The amount that can be taken 1 to 1500 mg of cellulose derivative or a salt per day is preferred, the amount that can be taken 5 to 1000 mg is more preferred, and the amount that can be taken 10 to 500 mg is more preferred.
The content of the cellulose derivative or a salt thereof is preferably 0.05 to 90% by mass, more preferably 0.1 to 80% by mass, and further preferably 0.2 to 60% by mass with respect to the total mass of the pharmaceutical composition. 5 to 55% by mass is preferable.
Further, the content ratio of loxoprofen or a salt thereof and a cellulose derivative or a salt thereof may be determined by appropriate examination according to the daily dose of each component described above, but 1 part by mass of loxoprofen or a salt thereof. The amount of cellulose derivative or salt thereof is preferably 0.003 to 150 parts by weight, more preferably 0.02 to 35 parts by weight, more preferably 0.05 to 10 parts by weight (in terms of loxoprofen sodium anhydrate). Those containing parts are more preferred.

Examples of the fats and oils used in the pharmaceutical composition of the present invention include waxes, hardened oil, hardened soybean oil and the like.
Examples of waxes include plant-derived waxes such as carnauba wax, wood wax (goose wax, urushi wax), and castor wax; animal-derived waxes such as beeswax, white beeswax, whale wax, and purified lanolin; and petroleum-derived waxes such as paraffin and microcrystalline wax. Natural waxes such as montanic acid ester wax and purified montan wax, synthetic waxes, and the like.
Fats and oils are known compounds, and can be produced by known methods, and commercially available products can be used.
Among the oils and fats as described above, carnauba wax, castor wax, beeswax, beeswax wax, paraffin, synthetic wax, hardened oil, and hardened soybean oil are preferable.

When using fats and oils, the content of fats and oils depends on the daily dose according to the inhibitory effect of the interaction between loxoprofen or a salt thereof and butylscopolamine bromide, the sex, age, symptoms, etc. of the user, What is necessary is just to consider and decide suitably. The amount that can be taken 0.1 to 1000 mg of fats and oils per day is preferred, the amount that can be taken 0.5 to 600 mg is more preferred, and the amount that can be taken 1 to 300 mg is more preferred.
The content of the fats and oils is preferably 0.001 to 70% by mass, more preferably 0.01 to 60% by mass, and still more preferably 0.1 to 55% by mass with respect to the total mass of the pharmaceutical composition.
In addition, the content ratio of loxoprofen or a salt thereof and fats and oils may be appropriately determined and determined according to the daily dose of each component described above, but 1 part by mass of loxoprofen or a salt thereof (loxoprofen sodium) (In terms of non-hydrate) the fats and oils are preferably contained in an amount of 0.0003 to 100 parts by weight, more preferably 0.002 to 20 parts by weight, and further preferably 0.005 to 5 parts by weight. preferable.

Further, in the pharmaceutical composition of the present invention, those other than capsules containing 60 mg of loxoprofen sodium, 10 mg of butyl scopolamine bromide, appropriate amount of crystalline cellulose, 10 mg of calcium carboxymethylcellulose and 1 mg of magnesium stearate and having a total mass of 150 mg are preferable. .

The pharmaceutical composition of the present invention includes drugs other than loxoprofen or a salt thereof and butylscopolamine bromide, such as antipyretic analgesics, antihistamines, antitussives, noscapine, bronchodilators, expectorants, hypnotic sedatives, vitamins, antiseptics It may contain one or more selected from the group consisting of inflammatory agents, gastric mucosal protective agents, anticholinergic agents, herbal medicines, Kampo prescriptions and the like.

Examples of antipyretic analgesics include aspirin, aspirin aluminum, ibuprofen, isopropylantipyrine, ethenzamide, sazapyrine, salicylamide, sodium salicylate, thiaramide hydrochloride, lactylphenetidine and the like.

Antihistamines include, for example, azelastine hydrochloride, alimemazine tartrate, istipendil hydrochloride, iproheptin hydrochloride, epinastine hydrochloride, emedastine fumarate, carbinoxamine diphenyl disulfonate, carbinoxamine maleate, clemastine fumarate. Acid salt, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, ketotifen fumarate, dipheterol hydrochloride, dipheterol phosphate, diphenylpyraline hydrochloride, diphenylpyraline theocrate, diphenhydramine Hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, triprolidine hydrochloride, tripelenamine hydrochloride, tondilamine hydrochloride, phenetazine hydrochloride, promethazine hydrochloride, prometa Nmechiren two salicylates, mequitazine, methdilazine hydrochloride, main blanking hydro Linna Paji sills salts include emetine Das Chin fumarate salt.

Antitussives include, for example, aloclamide hydrochloride, eprazinone hydrochloride, carbetapentane enoate, cloperastine hydrochloride, cloperastine phendizoate, codeine phosphate, dihydrocodeine phosphate, dibutarate sodium, dimemorphan Examples thereof include phosphate, dextromethorphan hydrobromide, dextromethorphan / phenol phthaline salt, tipepidine citrate, and tipepidine hibenzate.

Examples of noscapine include noscapine hydrochloride and noscapine.

Examples of bronchodilators include trimethquinol hydrochloride, phenylpropanolamine hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, methylephedrine, dl-methylephedrine hydrochloride, l-methylephedrine hydrochloride, dl -Methylephedrine saccharin salt, methoxyphenamine hydrochloride and the like.

As an expectorant, for example, ambroxol hydrochloride, ammonia fennel, ethylcysteine hydrochloride, ammonium chloride, carbocysteine, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, bromhexine hydrochloride, methylcysteine hydrochloride, Examples thereof include l-menthol and lysozyme hydrochloride.
Examples of the hypnotic sedative include allyl isopropyl acetyl urea and bromvalerylurea.

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). Nitrates, dicetiamine hydrochloride, sethiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octothiamine, chicotiamine, thiamine disulfide, bisbutiamine, bisbenchamine, prosultiamine, benfotiamine, riboflavin, riboflavin phosphate Esters, riboflavin butyrate, sodium riboflavin phosphate, panthenol, panthetin, calcium pantothenate, sodium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate, cyanocobalamin, mecobara Min, ascorbic acid, sodium ascorbate, calcium ascorbate, hesperidin, etc.).

Examples of the anti-inflammatory agent include glycyrrhizic acid and derivatives thereof and salts thereof (for example, dipotassium glycyrrhizinate and monoammonium glycyrrhizinate), seaprose, semi-alkaline proteinase, serrapeptase, proctase, pronase, bromelain and the like.

Examples of the gastric mucosa protective agent include aminoacetic acid, aldioxa, gefarnate, sucralfate, cetraxate hydrochloride, sofalcone, teprenone, copper chlorophyllin potassium, copper chlorophyllin sodium, methylmethionine sulfonium chloride and the like.

Examples of the anticholinergic agent include oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, datsura extract, tipedium bromide, methyl atropine bromide, methyl anisotropin bromide, methyl scopolamine bromide, methyl- l-hyostiamine bromide, methylbenactidium bromide, pirenzepine hydrochloride, belladonna alkaloid, belladonna extract, belladonna total alkaloid, iodide isopropamide, diphenylpiperidinomethyldioxolane iodide, funnel extract, funnel root, funnel root total alkaloid Examples include acid salts.

Herbal medicines include, for example, akamegashiwa (red buds), asenyaku (asenyaku), inyoukaku (horny lamb), fennel (yuka), turmeric (depressed gold), engosaku (yenkogyo), enmaiso (extended herb), ogon (yellow jade) ), Ousei (yellow spirit), Oubak (yellow twilight), Spruce (cherry skin), Auren (yellow ream), Onji (distant), Gajutsu (we), Ganoderma (deer herb), Chamomile, Caronin (Karojin), Licorice (licorice), Kyo-kyo (kikyo), Kyo-nin (Kyojin), Kukoshi (coconut), Kuko-yo (Kashiwa), Keihi (Kinko), Ketsumeishi (Katsumeko), Gentiana, Gennoshouko (current evidence), Koubushi (Katsukiko), Gooh (beef yellow), Goshi (Gomiko), Saishin (Spicy), Salamander (Sansho), Zion (Purple), Zykopi (Peel), Peonies (Glue), Musk, Shajin, Shazenshi (car front child), Shazenso (car front grass), Beast gall (including Yutan (bear gall)), Shakyo (ginger), Giryu (land dragon), Xinyi ), Sexan (Ishizuchi), Senega, Senkyu (Ryukyu), Zenko (Mae-Hu), Senburi (Senshu), Sojutsu (蒼朮), Sohakuhi (Mulberry white skin), Soyo (Soba), Taisan (Oiso), Chixetsu carrot (bamboo ginseng), clove (clove), chimpi (chonse), touki (to home), tokong (napping root), Nantenjitsu (southern), carrot (carrot), baimo (shellfish), bacmond (wheat) Gate winter), mint (thin load), Hange (half-summer), bankouka (Banka), Hampi (anti-nose), peony (white bean), peanut (white moth), bukuryo (茯苓), button pi (peony skin), maou (Mao), herbal medicines such as Lokujo (deer) These extracts (extract, tincture, dry extract, etc.) and the like can be mentioned.

Kampo prescriptions include, for example, Kakkon-yu, Katsue-yu, Koso-san, Saiko-Kei-do, Sho-saiko-to, Shosei-ryu, Mumon-tou-yu, Hanka-kopaku-to, Mao-to, and the like.

In the present invention, since the pharmaceutical composition of the present invention contains loxoprofen or a salt thereof and butyl scopolamine bromide, from the viewpoint of being used as an antipyretic analgesic or the like, as a drug other than loxoprofen or a salt thereof and butyl scopolamine bromide, isopropyl Drugs such as antipyretic analgesics such as antipyrine and etenzamid, and gastric mucosa protective agents such as methylmethioninesulfonium chloride are preferred.
The pharmaceutical composition of the present invention is preferably used as an antipyretic analgesic or the like. Therefore, its effects are as follows: headache, toothache, post-extraction pain, sore throat, ear pain, joint pain, neuralgia, low back pain, muscle pain, shoulder pain, bruise pain, fracture pain, sprain pain, menstrual pain (physiology) Pain), pain relief of trauma, antipyretic during chills / fever, relief of cold symptoms (throat pain, chills, fever, headache, joint pain, muscle pain).

In addition, it is desirable that the pharmaceutical composition of the present invention is in a packaging form that prevents intrusion of liquid or solid foreign matters in a normal handling or storage state. Examples of the packaging form include bottle packaging, SP packaging (Stripe Package) packaging, PTP (Press Through Package) packaging, and stick packaging.

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 (1)
Loxoprofen sodium hydrate 204.3 parts by mass and butyl scopolamine bromide 30 parts by mass were mixed, put in a glass bottle and stored at 60 ° C. (Reference Example A). As comparative controls, loxoprofen sodium hydrate alone (Control Example 1) and butyl scopolamine bromide alone (Control Example 2) were similarly placed in glass bottles and stored at 60 ° C.
About these reference examples A and control examples 1 and 2, the state in the glass bottle immediately after the start of storage, one day later, two days later and one week later was evaluated. The results are shown in Table 1.

As shown in Table 1, there was no change in the storage of either loxoprofen sodium hydrate or butyl scopolamine bromide alone, and it remained as a white powder (Control Examples 1 and 2).
In contrast, when a mixture of loxoprofen sodium hydrate and butyl scopolamine bromide was stored, the mixture solidified after one day (Reference Example A).
From this, it was found that the state change of the mixture was a result of the interaction between loxoprofen or a salt thereof and butyl scopolamine bromide.

Test Example 2 Examination of interaction (2)
The compositions of Reference Example B and Reference Examples 1 to 16 below were obtained, put in glass bottles, and stored at 60 ° C.
Reference Example B: Loxoprofen sodium hydrate 204.3 parts by mass and butyl scopolamine bromide 30 parts by mass were mixed to obtain a composition.
Reference Example 1: 204.3 parts by mass of loxoprofen sodium hydrate, 30 parts by mass of butyl scopolamine bromide and 250 parts by mass of anhydrous caffeine were mixed to obtain a composition.
Reference Example 2: A composition was obtained in the same manner as in Reference Example 1 except that caffeine anhydride was changed to 750 parts by mass of tranexamic acid.
Reference Example 3: A composition was obtained in the same manner as in Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of magnesium aluminate silicate.
Reference Example 4: A composition was obtained in the same manner as in Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of magnesium aluminate metasilicate.
Reference Example 5: A composition was obtained in the same manner as Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of calcium silicate.
Reference Example 6: A composition was obtained in the same manner as in Reference Example 1 except that the anhydrous caffeine was replaced with 234.3 parts by weight of light anhydrous silicic acid.
Reference Example 7: A composition was obtained in the same manner as in Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of hydrous magnesium silicate (natural).
Reference Example 8: A composition was obtained in the same manner as Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of precipitated calcium carbonate.
Reference Example 9: A composition was obtained in the same manner as in Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of anhydrous calcium hydrogen phosphate.
Reference Example 10: A composition was obtained in the same manner as Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of magnesium hydroxide.
Reference Example 11: A composition was obtained in the same manner as in Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of magnesium oxide.
Reference Example 12 A composition was obtained in the same manner as in Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of titanium oxide.
Reference Example 13: A composition was obtained in the same manner as in Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of low-substituted hydroxypropylcellulose.
Reference Example 14 A composition was obtained in the same manner as in Reference Example 1, except that anhydrous caffeine was replaced with 234.3 parts by mass of hypromellose (hydroxypropylmethylcellulose 2910).
Reference Example 15: A composition was obtained in the same manner as in Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by weight of Carnauba wax.
Reference Example 16: A composition was obtained in the same manner as in Reference Example 1 except that anhydrous caffeine was replaced with 234.3 parts by mass of hydrogenated oil.
For the compositions of Reference Example B and Reference Examples 1 to 16, the conditions in the glass bottles immediately after the start of storage, 1 day, 2 days, and 1 week were evaluated. The results are shown in Table 2.

As apparent from Table 2, when the state of the loxoprofen sodium hydrate and butyl scopolamine bromide mixture after storage at 60 ° C. for 1 week was confirmed, as in Test Example 1, the interaction resulted in 1 After a day, it became solidified (Reference Example B).
In contrast, in addition to a mixture of loxoprofen sodium hydrate and butyl scopolamine bromide, anhydrous caffeine (Reference Example 1), tranexamic acid (Reference Example 2), magnesium aluminate silicate (Reference Example 3), and aluminate metasilicate. Magnesium silicate (reference example 4), calcium silicate (reference example 5), light anhydrous silicic acid (reference example 6), hydrous magnesium silicate (natural) (reference example 7), precipitated calcium carbonate (reference example 8), anhydrous Calcium hydrogen phosphate (Reference Example 9), magnesium hydroxide (Reference Example 10), magnesium oxide (Reference Example 11), titanium oxide (Reference Example 12), low-substituted hydroxypropylcellulose (Reference Example 13), hypromellose (Reference A composition containing Example 14), Carnauba wax (Reference Example 15) or hydrogenated oil (Reference Example 16) was retained even after 1 week. Maintaining the same state as immediately after the start, the change did not occur (the slightly yellow in Reference Example 15 is the color derived from carnauba wax, not caused by the interaction).
Therefore, the interaction that occurs between loxoprofen or a salt thereof and butyl scopolamine bromide can be converted into a xanthine derivative, tranexamic acid or a salt thereof, a silicic acid compound, a carbonic acid compound, a phosphoric acid compound, a hydroxide, a metal oxide, a cellulose derivative or a salt thereof. And oils and fats were found to be suppressed.

Test Example 3 Examination of interaction (3)
The compositions of Comparative Example 1 and Example 1 below were obtained, put in glass bottles, and stored at 50 ° C.
Comparative Example 1: Loxoprofen sodium hydrate 68.1 parts by mass, 29.2 parts by mass of macrogol 6000, corn starch 24.3 parts by mass and butyl scopolamine bromide 10 parts by mass were mixed.
Example 1: 68.1 parts by weight of loxoprofen sodium hydrate, 29.2 parts by weight of macrogol 6000 and 24.3 parts by weight of corn starch were stirred in a glass beaker on a 65 ° C water bath and then cooled. Thereafter, the mixture was sieved with a No. 18 sieve to obtain a granulated product. The granulated product thus obtained was mixed with 10 parts by weight of butyl scopolamine bromide to obtain a granular preparation.
And about the composition of the said Example 1 and the comparative example 1, the state in the glass bottle immediately after a storage start, 1 day, 2 days later, and 1 week after was evaluated, respectively. The results are shown in Table 3.

As can be seen from Table 3, when a mixture of loxoprofen sodium hydrate and butyl scopolamine bromide stored at 50 ° C. was stored at 50 ° C., an interaction occurred, resulting in the mixture becoming wet one day after the start of storage. The state became (Comparative Example 1).
On the other hand, the granule obtained by mixing loxoprofen sodium hydrate with the granulated product prepared by mixing butyl scopolamine bromide maintained the same state as at the start even after 1 week. (Example 1).
From this result, it is understood that the interaction can be suppressed by containing loxoprofen sodium hydrate and butyl scopolamine bromide so as not to substantially contact each other.

Production Example 1
Loxoprofen sodium hydrate 204.3 parts, hypromellose 16.2 parts, croscarmellose sodium 24.3 parts, light anhydrous silicic acid 8.1 parts and crystalline cellulose 17.1 parts After kneading with water and granulating, granulation was performed to obtain a granulated product. On the other hand, 30 parts by mass of butyl scopolamine bromide, 420 parts by mass of tranexamic acid, 16.2 parts by mass of hydroxypropyl cellulose, 24.3 parts by mass of croscarmellose sodium and 17.1 parts by mass of lactose hydrate were mixed and ethanol was used. After kneading and granulating, granulation was performed to obtain a granulated product. 32.4 parts by mass of talc was added to and mixed with the two types of granules obtained to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 2
Loxoprofen sodium hydrate 204.3 parts, hypromellose 16.2 parts, croscarmellose sodium 24.3 parts, light anhydrous silicic acid 8.1 parts, and crystalline cellulose 115.2 parts After kneading with water and granulating, granulation was performed to obtain a granulated product. On the other hand, 30 parts by mass of butyl scopolamine bromide, 240 parts by mass of anhydrous caffeine, 16.2 parts by mass of hydroxypropyl cellulose, 24.3 parts by mass of croscarmellose sodium and 115.2 parts by mass of lactose hydrate were mixed, and ethanol was added. The mixture was kneaded and granulated, and then granulated to obtain a granulated product. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 3
Loxoprofen sodium hydrate 204.3 parts, hypromellose 16.2 parts, carmellose 24.3 parts, calcium silicate 8.1 parts and crystalline cellulose 34.7 parts are mixed and purified water is used. After kneading and granulating, granulation was performed to obtain a granulated product. On the other hand, 30 parts by weight of butyl scopolamine bromide, 240 parts by weight of anhydrous caffeine, 180 parts by weight of allylisopropylacetylurea, 16.2 parts by weight of hardened oil and 40 parts by weight of D-mannitol were mixed and kneaded using ethanol. After granulation, the granules were sized to obtain a granulated product. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 4
Loxoprofen sodium hydrate 204.3 parts, hydroxypropylcellulose 16.2 parts, carmellose calcium 24.3 parts, calcium silicate 8.1 parts and crystalline cellulose 25.2 parts After kneading and granulating with water, the granules were sized to obtain a granulated product. On the other hand, 30 parts by mass of butyl scopolamine bromide, 420 parts by mass of tranexamic acid, 180 parts by mass of allyl isopropyl acetylurea, 16.2 parts by mass of hydroxypropyl cellulose, 24.3 parts by mass of crospovidone and 25.2 parts by mass of lactose hydrate After mixing, kneading with ethanol and granulating, the granules were sized to obtain a granulated product. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 5
Loxoprofen sodium hydrate 204.3 parts, hydroxypropylcellulose 16.2 parts, croscarmellose sodium 24.3 parts, hydrous silicon dioxide 8.1 parts and crystalline cellulose 194.7 parts, After kneading and granulating with purified water, granulation was performed to obtain a granulated product. On the other hand, after mixing 30 parts by weight of butyl scopolamine bromide, 100 parts by weight of magnesium aluminate metasilicate, 16.2 parts by weight of hydroxypropylcellulose and 200 parts by weight of lactose hydrate, kneading with ethanol and granulating And granulated to obtain a granulated product. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 6
Loxoprofen sodium hydrate 204.3 parts, hydroxypropylcellulose 16.2 parts, low substituted hydroxypropylcellulose 24.3 parts, calcium silicate 8.1 parts and crystalline cellulose 170.4 parts The mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. On the other hand, 30 parts by mass of butyl scopolamine bromide, 100 parts by mass of anhydrous calcium hydrogen phosphate, 16.2 parts by mass of hydroxypropylcellulose, 24.3 parts by mass of crospovidone and 200 parts by mass of lactose hydrate were mixed and ethanol was used. After kneading and granulating, granulation was performed to obtain a granulated product. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 7
Loxoprofen sodium hydrate 204.3 parts by mass, hydroxypropylcellulose 16.2 parts by mass, carboxymethyl starch sodium 24.3 parts by mass, calcium silicate 8.1 parts by mass and crystalline cellulose 50.4 parts by mass, After kneading and granulating with purified water, granulation was performed to obtain a granulated product. On the other hand, 30 parts by mass of butyl scopolamine bromide, 750 parts by mass of tranexamic acid, 16.2 parts by mass of hydroxypropyl cellulose, 24.3 parts by mass of carmellose calcium and 60 parts by mass of lactose hydrate were mixed and kneaded using ethanol. And after granulating, it sized and obtained the granulated material. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 8
Loxoprofen sodium hydrate 204.3 parts, hydroxypropylcellulose 16.2 parts, carmellose 24.3 parts, carnauba wax 8.1 parts and crystalline cellulose 4.4 parts are mixed and purified water is used. After kneading and granulating, granulation was performed to obtain a granulated product. On the other hand, 30 parts by mass of butyl scopolamine bromide, 750 parts by mass of tranexamic acid, 100 parts by mass of magnesium aluminate metasilicate, 16.2 parts by mass of hydroxypropylcellulose, 24.3 parts by mass of croscarmellose sodium and 6 parts by mass of lactose hydrate Were mixed, kneaded using ethanol, granulated, and then granulated to obtain a granulated product. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 9
Loxoprofen sodium hydrate 204.3 parts, hydroxypropylcellulose 16.2 parts, croscarmellose sodium 24.3 parts, light anhydrous silicic acid 8.1 parts and crystalline cellulose 65.2 parts The mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. On the other hand, 30 parts by mass of butyl scopolamine bromide, 240 parts by mass of anhydrous caffeine, 100 parts by mass of magnesium aluminate metasilicate, 16.2 parts by mass of hydroxypropyl cellulose, 24.3 parts by mass of carmellose calcium and 65.2 of lactose hydrate Mass parts were mixed, kneaded using ethanol, granulated, and then granulated to obtain a granulated product. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 10
Loxoprofen sodium hydrate 204.3 parts by mass, hydroxypropylcellulose 16.2 parts by mass, croscarmellose sodium 24.3 parts by mass, light anhydrous silicic acid 8.1 parts by mass and lactose hydrate 95.2 parts by mass After mixing, kneading with purified water, granulating, and granulating, a granulated product was obtained. On the other hand, 30 parts by mass of butyl scopolamine bromide, 180 parts by mass of allyl isopropyl acetyl urea, 100 parts by mass of magnesium aluminate metasilicate, 16.2 parts by mass of hydroxypropyl cellulose, 24.3 parts by mass of low-substituted hydroxypropyl cellulose and 95 of crystalline cellulose .2 parts by mass was mixed, kneaded with ethanol, granulated, and then granulated to obtain a granulated product. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 11
Loxoprofen sodium hydrate 204.3 parts, hydroxypropylcellulose 16.2 parts, carmellose calcium 24.3 parts, calcium silicate 8.1 parts and crystalline cellulose 185.2 parts After kneading with water and granulating, granulation was performed to obtain a granulated product. On the other hand, 30 parts by mass of butyl scopolamine bromide, 100 parts by mass of anhydrous calcium hydrogen phosphate, 16.2 parts by mass of hydroxypropyl cellulose, 24.3 parts by mass of carmellose calcium and 185.2 parts by mass of lactose hydrate were mixed together. The mixture was kneaded and granulated, and then granulated to obtain a granulated product. 16.2 parts by mass of magnesium stearate was added to and mixed with the obtained two types of granulated products to obtain granules for tableting.
The obtained granules for tableting were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 12
23.1 parts by mass of hypromellose and 0.9 part by mass of macrogol 6000 are dissolved in 240 parts by mass of purified water, and 0.3 parts by mass of titanium oxide and 5.7 parts by mass of talc are dispersed therein to form a film coating solution. Was prepared. Using the coating apparatus, the above-mentioned film coating solution was sprayed and coated to have a film layer of 10 mg per tablet (plain tablet) obtained in Production Examples 1 to 11. Subsequently, glazing was applied with carnauba wax (trace amount), and film-coated tablets were obtained for each of the tablets obtained in Production Examples 1 to 11.

Production Example 13
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. The resulting granulated product was mixed with 10 parts by weight of butyl scopolamine bromide, 81 parts by weight of carmellose calcium, 589.3 parts by weight of lactose hydrate and 8.1 parts by weight of magnesium stearate, and then tableted. A tablet capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butylscopolamine bromide was obtained.

Production Example 14
In the same manner except that Macrogol 6000 was replaced with hydrogenated oil, a tablet capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day was obtained.

Production Example 15
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. 10 parts by mass of butyl scopolamine bromide, 81 parts by mass of carmellose calcium, 294.7 parts by mass of lactose hydrate, 294.6 parts by mass of crystalline cellulose, and 8.1 parts by mass of magnesium stearate were mixed with the obtained granulated product. Thereafter, tablets were tableted to obtain tablets capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 16
10 parts by weight of butyl scopolamine bromide, 3.4 parts by weight of macrogol 6000 and 2.9 parts by weight of corn starch were stirred in a glass beaker on a 65 ° C. water bath, then cooled, and then passed through a No. 18 sieve. Thus, a granulated product was obtained. The obtained granulated product was mixed with 68.1 parts by mass of loxoprofen sodium hydrate, 81 parts by mass of carmellose calcium, 636.5 parts by mass of lactose hydrate and 8.1 parts by mass of magnesium stearate, and then tableted. Thus, a tablet capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day was obtained.

Production Example 17
Loxoprofen sodium hydrate 68.1 parts by mass, hydroxypropylcellulose 24.3 parts by mass, carmellose calcium 81 parts by mass and crystalline cellulose 618.5 parts by mass were kneaded using purified water and granulated. Thereafter, the mixture was sized to obtain a granulated product. 791.9 parts by mass of the obtained granulated product, 10 parts by mass of butyl scopolamine bromide and 8.1 parts by mass of magnesium stearate were mixed and then tableted to obtain 204.3 mg of loxoprofen sodium hydrate per day, butyl scopolamine. A tablet capable of taking 30 mg of bromide was obtained.

Production Example 18
10 parts by weight of butyl scopolamine bromide, 24.3 parts by weight of hydroxypropyl cellulose, 81 parts by weight of carmellose calcium and 618.5 parts by weight of crystalline cellulose are mixed, kneaded with purified water, granulated, and then granulated. To obtain a granulated product. After mixing 733.8 parts by mass of the obtained granulated product, 68.1 parts by mass of loxoprofen sodium hydrate and 8.1 parts by mass of magnesium stearate, the mixture was tableted to give 204. loxoprofen sodium hydrate per day. The tablet which can take 3 mg and 30 mg of butyl scopolamine bromide was obtained.

Production Example 19
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hydroxypropylcellulose, 40.5 parts by mass of carmellose calcium and 280.2 parts by mass of crystalline cellulose, they were kneaded with purified water, After granulation, the granules were sized to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hydroxypropyl cellulose, 40.5 parts by mass of carmellose calcium and 338.3 parts by mass of crystalline cellulose were mixed, kneaded using purified water, and granulated. Thereafter, the mixture was sized to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 20
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. The obtained granulated product was mixed with 10 parts by weight of butyl scopolamine bromide, 81 parts by weight of low-substituted hydroxypropyl cellulose, 589.3 parts by weight of lactose hydrate and 8.1 parts by weight of magnesium stearate, and then tableted. A tablet capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day was obtained.

Production Example 21
Butyl scopolamine bromide 10 parts by mass Hypromellose 24.3 parts by mass, carmellose calcium 81 parts by mass, lactose hydrate 418.5 parts by mass and crystalline cellulose 200 parts by mass, kneaded with purified water, granulated And then granulated to obtain a granulated product. After mixing 733.8 parts by mass of the obtained granulated product, 68.1 parts by mass of loxoprofen sodium hydrate and 8.1 parts by mass of magnesium stearate, the mixture was tableted to give 204. loxoprofen sodium hydrate per day. The tablet which can take 3 mg and 30 mg of butyl scopolamine bromide was obtained.

Production Example 22
Butyl scopolamine bromide 10 parts by mass Hypromellose 24.3 parts by mass, carmellose calcium 81 parts by mass and anhydrous calcium hydrogen phosphate 618.5 parts by mass, kneaded with purified water, granulated, and granulated To obtain a granulated product. After mixing 733.8 parts by mass of the obtained granulated product, 68.1 parts by mass of loxoprofen sodium hydrate and 8.1 parts by mass of magnesium stearate, the mixture was tableted to give 204. loxoprofen sodium hydrate per day. The tablet which can take 3 mg and 30 mg of butyl scopolamine bromide was obtained.

Production Example 23
Butyl scopolamine bromide 10 parts by mass Hypromellose 24.3 parts by mass, carmellose calcium 81 parts by mass, lactose hydrate 370 parts by mass, crystalline cellulose 218.5 parts by mass and magnesium metasilicate aluminate 30 parts by mass The mixture was kneaded and granulated, and then granulated to obtain a granulated product. After mixing 733.8 parts by mass of the obtained granulated product, 68.1 parts by mass of loxoprofen sodium hydrate and 8.1 parts by mass of magnesium stearate, the mixture was tableted to give 204. loxoprofen sodium hydrate per day. The tablet which can take 3 mg and 30 mg of butyl scopolamine bromide was obtained.

Production Example 24
Butyl scopolamine bromide 10 parts by mass Hypromellose 24.3 parts by mass, carmellose calcium 81 parts by mass, lactose hydrate 370 parts by mass, crystalline cellulose 218.5 parts by mass and light anhydrous silicic acid 30 parts by mass The mixture was kneaded and granulated, and then granulated to obtain a granulated product. After mixing 733.8 parts by mass of the obtained granulated product, 68.1 parts by mass of loxoprofen sodium hydrate and 8.1 parts by mass of magnesium stearate, the mixture was tableted to give 204. loxoprofen sodium hydrate per day. The tablet which can take 3 mg and 30 mg of butyl scopolamine bromide was obtained.

Production Example 25
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. 10 parts by mass of butyl scopolamine bromide, 81 parts by mass of carmellose calcium, 30 parts by mass of magnesium aluminate, 559.3 parts by mass of lactose hydrate, and 8.1 parts by mass of magnesium stearate were mixed with the obtained granulated product. Thereafter, tableting was carried out to obtain a tablet capable of taking 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 26
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. After mixing 10 parts by mass of butylscopolamine bromide, 81 parts by mass of carmellose calcium, 30 parts by mass of magnesium silicate, 559.3 parts by mass of lactose hydrate, and 8.1 parts by mass of magnesium stearate to the obtained granulated product. The tablets were tableted to give 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 27
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. After mixing 10 parts by mass of butyl scopolamine bromide, 81 parts by mass of carmellose calcium, 30 parts by mass of magnesium oxide, 559.3 parts by mass of lactose hydrate and 8.1 parts by mass of magnesium stearate to the obtained granulated product, The tablets were tableted to give 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 28
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. After mixing 10 parts by mass of butyl scopolamine bromide, 81 parts by mass of carmellose calcium, 30 parts by mass of magnesium hydroxide, 559.3 parts by mass of lactose hydrate, and 8.1 parts by mass of magnesium stearate to the obtained granulated product. The tablets were tableted to give 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 29
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. After mixing 10 parts by weight of butyl scopolamine bromide, 81 parts by weight of carmellose calcium, 30 parts by weight of precipitated calcium carbonate, 559.3 parts by weight of lactose hydrate, and 8.1 parts by weight of magnesium stearate to the resulting granulated product. The tablets were tableted to give 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 30
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. After mixing 10 parts by weight of butyl scopolamine bromide, 81 parts by weight of carmellose calcium, 30 parts by weight of hydrous silicon dioxide, 559.3 parts by weight of lactose hydrate and 8.1 parts by weight of magnesium stearate to the resulting granulated product. The tablets were tableted to give 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 31
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. After mixing 10 parts by mass of butyl scopolamine bromide, 81 parts by mass of carmellose calcium, 30 parts by mass of calcium silicate, 559.3 parts by mass of lactose hydrate, and 8.1 parts by mass of magnesium stearate with the obtained granulated product. The tablets were tableted to give 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 32
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. After mixing 10 parts by mass of butyl scopolamine bromide, 81 parts by mass of carmellose calcium, 30 parts by mass of hardened oil, 559.3 parts by mass of lactose hydrate and 8.1 parts by mass of magnesium stearate to the obtained granulated product, The tablets were tableted to give 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 33
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. After mixing 10 parts by mass of butyl scopolamine bromide, 81 parts by mass of carmellose calcium, 10 parts by mass of titanium oxide, 579.3 parts by mass of lactose hydrate, and 8.1 parts by mass of magnesium stearate to the obtained granulated product, The tablets were tableted to give 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 34
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. The resulting granulated product was mixed with 10 parts by weight of butyl scopolamine bromide, 81 parts by weight of crospovidone, 589.3 parts by weight of lactose hydrate and 8.1 parts by weight of magnesium stearate, and then tableted to give loxoprofen per day. The tablet which can take 204.3 mg of sodium hydrate and 30 mg of butyl scopolamine bromide was obtained.

Production Example 35
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. The resulting granulated product was mixed with 10 parts by weight of butyl scopolamine bromide, 81 parts by weight of crospovidone, 581.2 parts by weight of lactose hydrate and 16.2 parts by weight of talc, then tableted, and loxoprofen sodium water per day. A tablet capable of taking 204.3 mg of the Japanese product and 30 mg of butyl scopolamine bromide was obtained.

Production Example 36
After loxoprofen sodium hydrate 68.1 parts by weight, 29.2 parts by weight Macrogol 6000 and corn starch 24.3 parts by weight in a glass beaker on a 65 ° C. water bath, and then cooled, No. 18 Sieving with a sieve gave a granulated product. After mixing 10 parts by mass of butyl scopolamine bromide, 81 parts by mass of crospovidone, 581.2 parts by mass of lactose hydrate, 8.1 parts by mass of carnauba wax and 8.1 parts by mass of magnesium stearate to the obtained granulated product, The tablets were tableted to give 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide per day.

Production Example 37
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 180.2 parts by mass of lactose hydrate and 100 parts by mass of crystalline cellulose, purified water is used. After kneading and granulating, granulation was performed to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 238.3 parts by mass of lactose hydrate, and 100 parts by mass of crystalline cellulose were mixed and then purified using purified water. After granulation, granulation was performed to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 38
Purification after mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of low-substituted hydroxypropylcellulose, 180.2 parts by mass of lactose hydrate and 100 parts by mass of crystalline cellulose After kneading with water and granulating, granulation was performed to obtain a granulated product. Also, after mixing 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of low-substituted hydroxypropylcellulose, 238.3 parts by mass of lactose hydrate and 100 parts by mass of crystalline cellulose, purified water is added. The mixture was kneaded and granulated, and then granulated to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 39
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of crospovidone, 180.2 parts by mass of lactose hydrate and 100 parts by mass of crystalline cellulose, purified water is used. After kneading and granulating, granulation was performed to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of crospovidone, 238.3 parts by mass of lactose hydrate and 100 parts by mass of crystalline cellulose were mixed and then kneaded using purified water. And after granulating, it sized and obtained the granulated material. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 40
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium and 280.2 parts by mass of anhydrous calcium hydrogen phosphate, kneading with purified water, After granulation, the granules were sized to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium and 338.3 parts by mass of anhydrous calcium hydrogen phosphate were mixed and then kneaded using purified water, and granulated. And then granulated to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 41
Loxoprofen sodium hydrate 68.1 parts by mass, hypromellose 12.1 parts by mass, carmellose calcium 40.5 parts by mass, magnesium aluminate silicate 30 parts by mass, corn starch 150.2 parts by mass and crystalline cellulose 100 parts by mass After mixing, the mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. Also, after mixing 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of magnesium aluminate silicate, 208.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose. The mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 42
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of magnesium silicate, 150.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose. The mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of magnesium silicate, 208.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose were purified. After kneading and granulating with water, the granules were sized to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 43
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of magnesium oxide, 150.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose, After kneading and granulating with purified water, granulation was performed to obtain a granulated product. Further, after mixing 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of magnesium oxide, 208.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose, purified water The mixture was kneaded and granulated, and then granulated to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 44
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of magnesium hydroxide, 150.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose. The mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of magnesium hydroxide, 208.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose were purified. After kneading with water and granulating, granulation was performed to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 45
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of precipitated calcium carbonate, 150.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose. The mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of precipitated calcium carbonate, 208.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose were purified. After kneading with water and granulating, granulation was performed to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 46
Loxoprofen sodium hydrate 68.1 parts by mass, hypromellose 12.1 parts by mass, carmellose calcium 40.5 parts by mass, magnesium metasilicate aluminate 30 parts by mass, corn starch 150.2 parts by mass and crystalline cellulose 100 parts by mass After mixing, the mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. Further, after mixing 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of magnesium aluminate metasilicate, 208.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose. The mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 47
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of hydrous silicon dioxide, 150.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose. The mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of hydrous silicon dioxide, 208.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose were purified. After kneading with water and granulating, granulation was performed to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 48
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of calcium silicate, 150.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose. The mixture was kneaded with purified water, granulated, and then granulated to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 30 parts by mass of calcium silicate, 208.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose were purified. After kneading with water and granulating, granulation was performed to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 49
Loxoprofen sodium hydrate 68.1 parts by mass, hypromellose 12.1 parts by mass, carmellose calcium 40.5 parts by mass, light anhydrous silicic acid 30 parts by mass, corn starch 150.2 parts by mass and crystalline cellulose 100 parts by mass Then, after kneading and granulating using purified water, granulation was performed to obtain a granulated product. Further, after mixing 10 parts by weight of butyl scopolamine bromide, 12.1 parts by weight of hypromellose, 40.5 parts by weight of carmellose calcium, 30 parts by weight of light anhydrous silicic acid, 208.3 parts by weight of corn starch and 100 parts by weight of crystalline cellulose, After kneading and granulating with purified water, granulation was performed to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 50
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 10 parts by mass of hardened oil, 170.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose, After kneading and granulating with purified water, granulation was performed to obtain a granulated product. Further, after mixing 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 10 parts by mass of hardened oil, 228.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose, purified water The mixture was kneaded and granulated, and then granulated to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 51
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 10 parts by mass of titanium oxide, 170.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose, After kneading and granulating with purified water, granulation was performed to obtain a granulated product. Further, after mixing 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 10 parts by mass of titanium oxide, 228.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose, purified water The mixture was kneaded and granulated, and then granulated to obtain a granulated product. After mixing 400.9 parts by mass and 8.2 parts by mass of magnesium stearate with each of the obtained two types of granulated products, tableting was performed, and 204.3 mg of loxoprofen sodium hydrate per day, and butyl scopolamine bromide were added. The tablet which can be taken | dosed 30 mg was obtained.

Production Example 52
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 180.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose, the mixture is purified using purified water. After granulation, granulation was performed to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 238.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose were mixed and then kneaded using purified water. After granulation, the granules were sized to obtain a granulated product. 400.9 parts by mass and 8.2 parts by mass of talc were mixed with each of the obtained two types of granulated products, and then tableted. 204.3 mg of loxoprofen sodium hydrate and 30 mg of butyl scopolamine bromide were taken per day. Tablets that can be obtained.

Production Example 53
After mixing 68.1 parts by mass of loxoprofen sodium hydrate, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 180.2 parts by mass of corn starch and 100 parts by mass of crystalline cellulose, the mixture is purified using purified water. After granulation, granulation was performed to obtain a granulated product. Further, 10 parts by mass of butyl scopolamine bromide, 12.1 parts by mass of hypromellose, 40.5 parts by mass of carmellose calcium, 238.3 parts by mass of corn starch and 100 parts by mass of crystalline cellulose were mixed and then kneaded using purified water. After granulation, the granules were sized to obtain a granulated product. After mixing 400.9 parts by mass, 5.2 parts by mass of magnesium stearate and 3 parts by mass of carnauba wax, the obtained two types of granulated products were tableted, and 204.3 mg of loxoprofen sodium hydrate per day was mixed. The tablet which can take 30 mg of butyl scopolamine bromide was obtained.

Production Example 54
A film coating solution is prepared by dissolving 23.1 parts by mass of hypromellose and 0.9 part by mass of macrogol 6000 in 240 parts by mass of purified water, and dispersing 0.3 parts by mass of titanium oxide and 5.7 parts by mass of talc. Was prepared. Using the coating apparatus, the above-mentioned film coating solution was sprayed and coated to have a film layer of 10 mg per tablet (plain tablet) obtained in Production Examples 13 to 53. Subsequently, glazing was applied with carnauba wax (trace amount), and film-coated tablets were obtained for each of the tablets obtained in Production Examples 13 to 53.

According to the present invention, a pharmaceutical composition comprising loxoprofen or a salt thereof and butyl scopolamine bromide having excellent storage stability can be provided.

Claims (9)

1. A pharmaceutical composition containing loxoprofen or a salt thereof and butyl scopolamine bromide so as not to substantially contact each other.
2. A pharmaceutical composition comprising a granular material containing loxoprofen or a salt thereof and butyl scopolamine bromide, wherein loxoprofen or a salt thereof and butyl scopolamine bromide are contained so as not to substantially contact each other.
3. A pharmaceutical composition comprising a granular material containing butyl scopolamine bromide and loxoprofen or a salt thereof, wherein loxoprofen or a salt thereof and butyl scopolamine bromide are contained so as not to substantially contact each other.
4. A pharmaceutical composition comprising a granule containing loxoprofen or a salt thereof and a granule containing butyl scopolamine bromide, wherein loxoprofen or a salt thereof and butyl scopolamine bromide are contained so as not to substantially contact each other.
5. The pharmaceutical composition according to any one of claims 1 to 4, wherein loxoprofen or a salt thereof is loxoprofen sodium hydrate.
6. The pharmaceutical composition according to any one of claims 1 to 5, comprising loxoprofen or a salt thereof in an amount of 10 to 300 mg as a daily dose in terms of anhydrous loxoprofen sodium.
7. The pharmaceutical composition according to any one of claims 1 to 6, comprising 3 to 1000 mg of butyl scopolamine bromide as a daily dose.
8. The pharmaceutical composition according to any one of claims 1 to 7, which is a solid preparation.
9. The pharmaceutical composition according to any one of claims 1 to 8, wherein the dosage form is a tablet, capsule, pill, granule, fine granule, powder, dry syrup or oral jelly.