solid components

Abstract

To provide a solid composition containing ibuprofen in which changes in color or properties are suppressed. [Solution] A solid composition comprising the following components: (A) at least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of dextromethorphan and its salts, and (C) at least one selected from the group consisting of tranexamic acid and its salts (excluding those containing at least one selected from the group consisting of guaifenesin or its salts, and diphenhydramine or its salts); the following components: (A) at least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of noscapine and its salts, and (C) tranexamic acid or its salts, A solid composition comprising at least one selected from the group consisting of acetaminophen or a salt thereof, clemastine or a salt thereof, citric acid or a salt thereof, stearic acid or a salt thereof, and sodium bicarbonate; or a solid composition comprising the following components: (A) at least one selected from the group consisting of ibuprofen and a salt thereof, (B) at least one selected from the group consisting of noscapine and a salt thereof, (C) at least one selected from the group consisting of dextromethorphan and a salt thereof, and (D) at least one selected from the group consisting of chlorpheniramine or a salt thereof, caffeine or a salt thereof, croscarmellose sodium, silicon dioxide, and talc.

Description

[Technical Field]

[0001] This disclosure broadly relates to solid compositions comprising, for example, at least one selected from the group consisting of ibuprofen and its salts, at least one selected from the group consisting of dextromethorphan and its salts, and at least one selected from the group consisting of tranexamic acid and its salts.

[0002] This disclosure broadly relates to solid compositions comprising, for example, at least one selected from the group consisting of ibuprofen and its salts, at least one selected from the group consisting of noscapine and its salts, and at least one selected from the group consisting of tranexamic acid or its salts, acetaminophen or its salts, clemastine or its salts, citric acid or its salts, stearic acid or its salts, and sodium bicarbonate.

[0003] This disclosure broadly relates to solid compositions comprising, for example, at least one selected from the group consisting of ibuprofen and its salts, at least one selected from the group consisting of noscapine and its salts, at least one selected from the group consisting of dextromethorphan and its salts, and at least one selected from the group consisting of chlorpheniramine or its salts, caffeine or its salts, croscarmellose sodium, silicon dioxide, and talc. [Background technology]

[0004] Ibuprofen is widely used as a nonsteroidal anti-inflammatory drug (NSAID). However, solid compositions containing ibuprofen may undergo changes in properties over time due to the addition of other components, such as discoloration, solidification, aggregation, moisture absorption, separation, paste formation, swelling, and adhesion to the walls of storage containers. Therefore, efforts are being made to suppress these changes in properties.

[0005] Furthermore, dextromethorphan is widely used as a morphinane-based drug with sedative and antitussive effects. Noscapine is an isoquinoline alkaloid with antitussive effects and is used in cold medicines, etc. Solid compositions containing ibuprofen or noscapine (e.g., cold medicines) have been developed.

[0006] Patent Document 1 discloses a solid dosage form comprising granules containing (a1) ibuprofen or a salt thereof or a solvate thereof, (a2) magnesium oxide, (a3) ​​sodium lauryl sulfate, and (a4) one or more disintegrants selected from low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, carmellose, carmellose calcium, crospovidone, and croscarmellose sodium.

[0007] Patent Document 2 discloses a pharmaceutical solid composition containing component (A): total belladonna alkaloids, component (B): dextromethorphan hydrobromide hydrate, component (C): ambroxol hydrochloride, and component (D): at least one of tranexamic acid and crystalline cellulose.

[0008] Patent Document 3 discloses a pharmaceutical composition containing ibuprofen, diphenhydramine or a salt thereof, dextromethorphan or a salt thereof, and tranexamic acid or a salt thereof. [Prior art documents] [Patent Documents]

[0009] [Patent Document 1] Japanese Patent Publication No. 2022-087085 [Patent Document 2] Japanese Patent Publication No. 2023-103978 [Patent Document 3] Japanese Patent Publication No. 2021-075528 [Overview of the project] [Problems that the invention aims to solve]

[0010] Solid compositions containing ibuprofen still have room for improvement in terms of color change over time. The present inventors have newly discovered that a significant color change occurs when at least one substance selected from the group consisting of ibuprofen and its salts is combined with at least one substance selected from the group consisting of dextromethorphan and its salts. One aspect of this disclosure is to provide a solid composition containing ibuprofen that suppresses the color change that occurs when at least one substance selected from the group consisting of ibuprofen and its salts is combined with at least one substance selected from the group consisting of dextromethorphan and its salts.

[0011] Furthermore, solid compositions containing ibuprofen may undergo changes in properties over time, such as discoloration, solidification, aggregation, moisture absorption, separation, paste formation, expansion, and adhesion to the walls of storage containers, depending on the addition of other components. Therefore, solid compositions containing ibuprofen still have room for improvement in terms of changes in properties. The inventors have newly discovered that a significant change in properties occurs when at least one substance selected from the group consisting of ibuprofen and its salts is combined with at least one substance selected from the group consisting of noscapine and its salts. The inventors have also newly discovered that a significant change in properties occurs when at least one substance selected from the group consisting of ibuprofen and its salts is combined with at least one substance selected from the group consisting of noscapine and its salts, and at least one substance selected from the group consisting of dextromethorphan and its salts.

[0012] One aspect of this disclosure aims to provide an ibuprofen-containing solid composition in which the changes in properties caused by combining at least one selected from the group consisting of ibuprofen and its salts with at least one selected from the group consisting of noscapine and its salts are suppressed. Another aspect of this disclosure aims to provide an ibuprofen-containing solid composition in which the changes in properties caused by combining at least one selected from the group consisting of ibuprofen and its salts with at least one selected from the group consisting of noscapine and its salts, and at least one selected from the group consisting of dextromethorphan and its salts are suppressed. [Means for solving the problem]

[0013] The present inventors have discovered that the color change that occurs when at least one substance selected from the group consisting of ibuprofen and its salts is combined with at least one substance selected from the group consisting of dextromethorphan and its salts can be suppressed by further combining it with at least one substance selected from the group consisting of tranexamic acid and its salts, thereby completing an invention relating to one aspect of this disclosure.

[0014] Furthermore, the present inventors have discovered that the change in properties that occurs when at least one substance selected from the group consisting of ibuprofen and its salts is combined with at least one substance selected from the group consisting of noscapine and its salts can be suppressed by further combining it with at least one substance selected from the group consisting of tranexamic acid or its salt, acetaminophen or its salt, clemastine or its salt, citric acid or its salt, stearic acid or its salt, and sodium bicarbonate, thus completing the invention relating to one aspect of this disclosure.

[0015] Furthermore, the present inventors have found that the property change caused by blending at least one selected from the group consisting of noscapine and salts thereof and at least one selected from the group consisting of dextromethorphan and salts thereof, with respect to at least one selected from the group consisting of ibuprofen and salts thereof, can be suppressed by further blending at least one selected from the group consisting of chlorpheniramine or salts thereof, caffeine or salts thereof, croscarmellose sodium, silicon dioxide, and talc. This has led to the completion of the invention according to one aspect of the present disclosure.

[0016] That is, the present application includes the following inventions. [1] The following components: (A) at least one selected from the group consisting of ibuprofen and salts thereof, (B) at least one selected from the group consisting of dextromethorphan and salts thereof, (C) at least one selected from the group consisting of tranexamic acid and salts thereof, A solid composition comprising the above (excluding those comprising at least one selected from the group consisting of guaifenesin or salts thereof and diphenhydramine or salts thereof). [2] The solid composition according to [1], comprising a crystal composed of the (A) ibuprofen and the (C) tranexamic acid. [3] The solid composition according to [2], wherein the molar ratio of the (A) ibuprofen to the (C) tranexamic acid in the crystal is 1:1. [4] The solid composition according to any one of [1] to [3], wherein the mass ratio of (A) to (B) in the solid composition is 20:1 to 5:1 ((A):(B)). [5] The solid composition according to any one of [1] to [4], wherein the mass ratio of (A) to (C) in the solid composition is 1:0.5 to 1:2.5 ((A):(C)). [6] The solid composition according to any one of [1] to [5], wherein the mass ratio of (B) to (C) in the solid composition is 1:3 to 1:32 ((B):(C)). [7] A color change inhibitor for a solid composition comprising (A) at least one selected from the group consisting of ibuprofen and its salts, and (B) at least one selected from the group consisting of dextromethorphan and its salts, (C) A color change inhibitor comprising at least one selected from the group consisting of tranexamic acid and its salts. [8] The following ingredients: (A) At least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of noscapine and its salts, (C) At least one selected from the group consisting of tranexamic acid or its salt, acetaminophen or its salt, clemastine or its salt, citric acid or its salt, stearic acid or its salt, and sodium bicarbonate. A solid composition containing the following: [9] The solid composition according to [8], comprising crystals consisting of (A) ibuprofen and (C) tranexamic acid.

[10] The solid composition according to [9], wherein the molar ratio of (A) ibuprofen to (C) tranexamic acid in the crystal is 1:1.

[11] The solid composition according to any one of [8] to

[10] , wherein the mass ratio of (A) to (B) in the solid composition is 1:0.01 to 1:0.4 ((A):(B)).

[12] The solid composition according to any one of [8] to

[11] , wherein the mass ratio of (A) to (C) in the solid composition is 1:0.01 to 1:10 ((A):(C)).

[13] The solid composition according to any one of [8] to

[12] , wherein the mass ratio of (B) to (C) in the solid composition is 1:0.1 to 1:150 ((B):(C)).

[14] A solid composition property change inhibitor comprising (A) at least one selected from the group consisting of ibuprofen and its salts, and (B) at least one selected from the group consisting of noscapine and its salts, (C) A property change inhibitor comprising at least one selected from the group consisting of tranexamic acid or a salt thereof, acetaminophen or a salt thereof, clemastine or a salt thereof, citric acid or a salt thereof, stearic acid or a salt thereof, and sodium bicarbonate.

[15] The following ingredients: (A) At least one selected from the group consisting of ibuprofen and its salts, (B) At least one selected from the group consisting of noscapine and its salts, (C) at least one selected from the group consisting of dextromethorphan and its salts, and (D) At least one selected from the group consisting of chlorpheniramine or its salt, caffeine or its salt, croscarmellose sodium, silicon dioxide, and talc. A solid composition containing the following:

[16] (D) The solid composition according to

[15] , comprising at least one selected from the group consisting of chlorpheniramine or a salt thereof, caffeine or a salt thereof, and silicon dioxide.

[17] (D) The solid composition according to

[15] , comprising silicon dioxide.

[18] The solid composition according to any one of

[15] to

[17] , wherein the mass ratio of (A) to (B) in the solid composition is 1:0.01 to 1:0.4 ((A):(B)).

[19] The solid composition according to any one of

[15] to

[18] , wherein the mass ratio of (A) to (C) in the solid composition is 1:0.01 to 1:0.4 ((A):(C)).

[20] The solid composition according to any one of

[15] to

[19] , wherein the mass ratio of (A) to (D) in the solid composition is 1:0.001 to 1:10 ((A):(D)). [twenty one] A property change inhibitor for a solid composition comprising (A) at least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of noscapine and its salts, and (C) at least one selected from the group consisting of dextromethorphan and its salts, wherein the property change inhibitor further comprises (D) at least one selected from the group consisting of chlorpheniramine or its salts, caffeine or its salts, croscarmellose sodium, silicon dioxide, and talc. [Effects of the Invention]

[0017] According to the present invention, a solid composition containing ibuprofen can be provided in which changes in color or properties are suppressed. [Brief explanation of the drawing]

[0018] [Figure 1] The results of differential scanning calorimetry (DSC) in crystals of ibuprofen and tranexamic acid are shown. [Modes for carrying out the invention]

[0019] The following describes embodiments of the present invention (hereinafter referred to as "these embodiments"), but the scope of the present invention is not limited to these embodiments. In these embodiments, each component may be included individually or in combination of two or more. In this specification, the "~" indicating a numerical range represents "greater than or equal to" and "less than or equal to," and includes both values ​​at either end.

[0020] (solid composition) In the first embodiment, the following components: (A) At least one selected from the group consisting of ibuprofen and its salts, (B) At least one selected from the group consisting of dextromethorphan and its salts, (C) At least one selected from the group consisting of tranexamic acid and its salts, Solid compositions containing (excluding those containing at least one selected from the group consisting of guaifenesin or its salts, and diphenhydramine or its salts). It will be provided. The solid composition is specifically a solid pharmaceutical composition.

[0021] Each component contained in the solid composition according to this embodiment may be included in the form of a pharmaceutically acceptable salt, or it may be included as a complex with other components. That is, the solid composition according to this embodiment may contain salts of each component, not only of components (A) to (C), but also of other components. "Pharmacologically acceptable salt" includes, for example, salts with pharmaceutically acceptable bases or acids. Non-specific examples of pharmacologically acceptable salts include addition salts of inorganic acids (hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, etc.), addition salts of organic acids (p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, p-bromophenylsulfonic acid, carboxylic acids, succinic acid, citric acid, benzoic acid, acetic acid, etc.), addition salts of inorganic bases (ammonium hydroxide or alkali or alkaline earth metal hydroxides, carbonates, bicarbonates, etc.), and addition salts of amino acids. Pharmacologically acceptable salts may be hydrated or anhydrous.

[0022] In this embodiment, in addition to components (A) and (B), component (C) is also included, which suppresses color changes in the solid composition, particularly color changes over time.

[0023] "Suppressed color change" means that color change is less likely to occur, but for example, color change may be suppressed when compared to a solid composition that does not contain the above component (C).

[0024] The solid composition according to this embodiment may have suppressed property changes other than color changes. Property changes other than color changes are not particularly limited, but include, for example, aggregation, solidification, separation, and liquefaction. Therefore, the solid composition according to this embodiment may have suppressed aggregation, solidification, separation, and liquefaction that occur over time. "Property changes are suppressed" means that property changes are less likely to occur, but for example, property changes may be suppressed when compared to a solid composition that does not contain the above component (C).

[0025] The solid composition according to this embodiment may have suppressed color changes under high-temperature conditions. The solid composition according to this embodiment may also have suppressed property changes other than color changes under high-temperature conditions. High-temperature conditions may be, for example, 30 to 100°C or 40 to 90°C.

[0026] "Color change over time" refers to a change in color that occurs over time, and may be, for example, a change in color that occurs over a period of 12 hours or more, 18 hours or more, 24 hours or more, 1 week or more, or 2 weeks or more after manufacturing or after being placed in a specific environment (e.g., a high-temperature and / or high-humidity environment). In the solid composition according to this embodiment, there is no particular limit to the period during which color change and changes in properties other than color change are suppressed, but may be, for example, 12 hours or more, 18 hours or more, 24 hours or more, 1 week or more, or 2 weeks or more.

[0027] In this embodiment, "solid compositions comprising at least one selected from the group consisting of guaifenesin or a salt thereof, and diphenhydramine or a salt thereof" are excluded.

[0028] Guaifenesin is manufactured and sold commercially by known methods. For example, guaifenesin conforming to the Japanese Pharmacopoeia is available.

[0029] "Diphenhydramine or its salts" includes diphenhydramine and its pharmaceutically acceptable salts, as well as solvates of diphenhydramine and its pharmaceutically acceptable salts with water, alcohol, etc. Examples of diphenhydramine or its salts include diphenhydramine, diphenhydramine hydrochloride, diphenhydramine citrate, diphenhydramine salicylate, diphenhydramine tannate, and diphenhydramine lauryl sulfate. These are manufactured by known methods and are commercially available. Examples of diphenhydramine or its salts include diphenhydramine or its salts conforming to the Japanese Pharmacopoeia.

[0030] Furthermore, the solid compositions according to this embodiment exclude the pharmaceutical compositions disclosed in Japanese Patent Publication No. 2021-075530 and Japanese Patent Publication No. 2021-075528, respectively. The solid composition disclosed in Japanese Patent Publication No. 2021-075530 is a pharmaceutical composition that suppresses wetting and / or dissolution due to interactions when ibuprofen, dextromethorphan or a salt thereof and guaifenesin are simultaneously compounded, thereby suppressing deterioration of appearance quality. The solid composition disclosed in Japanese Patent Publication No. 2021-075528 is a pharmaceutical composition that suppresses wetting and / or dissolution due to interactions when ibuprofen, diphenhydramine or a salt thereof and dextromethorphan or a salt thereof are simultaneously compounded, thereby suppressing deterioration of appearance quality. However, the solid composition according to this embodiment is a solid composition containing ibuprofen that suppresses color changes that may occur when at least one selected from the group consisting of ibuprofen and a salt thereof is compounded with at least one selected from the group consisting of dextromethorphan and a salt thereof.

[0031] (A) At least one selected from the group consisting of ibuprofen and its salts As used herein, "ibuprofen" refers to the CAS registry number 15687-27-1, C 13 H 18It is a compound represented by the chemical formula O2. Ibuprofen is used as an active ingredient in anti-inflammatory, analgesic, and antipyretic agents. The salts of ibuprofen are not particularly limited as long as they are pharmacologically acceptable, and examples include alkali metal salts such as sodium salt and potassium salt, and alkaline earth metal salts such as calcium salt. The amount and content of at least one selected from the group consisting of ibuprofen and its salts are the amount and content of ibuprofen and ibuprofen salts respectively, but it is preferable that the total amount and content of ibuprofen and ibuprofen salts be within the range of the amounts and content described below.

[0032] The amount of at least one substance selected from the group consisting of ibuprofen and its salts is appropriately adjusted according to the use of ibuprofen in the solid composition, the symptoms of the person being administered to, age, weight, sex, etc. For example, when ibuprofen is included as a nonsteroidal anti-inflammatory drug, the daily amount of at least one substance selected from the group consisting of ibuprofen and its salts administered to adults can be adjusted in ibuprofen equivalent to, for example, 30 mg to 2000 mg, preferably 100 mg to 1000 mg, more preferably 200 mg to 600 mg. In this specification, "adult" means men and women aged 15 years or older. However, the solid composition according to this disclosure is not limited to those for adult use, and may also be used by children under 15 years of age. When used by children, the amount can be reduced to 1 / 2 or 2 / 3 of the amount taken by adults per day, depending on the age group. The same applies to components other than component (A).

[0033] The above dosages are examples, and the content of at least one selected from the group consisting of ibuprofen and its salts per solid composition administered daily is, for example, about 1% to about 70% by mass, preferably about 5% to about 50% by mass, and more preferably about 10% to about 30% by mass.

[0034] In this embodiment, the content of at least one substance selected from the group consisting of ibuprofen and its salts contained in the composition administered daily is 1% to 70% by mass, preferably 5% to 50% by mass, and more preferably 10% to 30% by mass.

[0035] The description herein regarding the amount of at least one selected from the group consisting of ibuprofen and its salts may refer to the total amount of tranexamic acid and at least one selected from the group consisting of crystalline ibuprofen and non-crystalline ibuprofen and its salts.

[0036] The solid composition may contain tranexamic acid and crystalline ibuprofen, and at least one selected from the group consisting of tranexamic acid and non-crystalline ibuprofen and its salts.

[0037] The content of at least one substance selected from the group consisting of tranexamic acid and non-crystallized ibuprofen and its salts in the solid composition may be, for example, 0 to 100% by mass, 10 to 99% by mass, 20 to 95% by mass, or 30 to 90% by mass, relative to the total amount of ibuprofen and its salts. The content of at least one substance selected from the group consisting of tranexamic acid and non-crystallized ibuprofen and its salts in the solid composition may be, within the above range, for example, 8% by mass or less, 5% by mass or less, 3% by mass or less, 1% by mass or less, or 0.1% by mass or less, relative to the total amount of ibuprofen and its salts. The content of at least one substance selected from the group consisting of tranexamic acid and non-crystallized ibuprofen and its salts in the solid composition may be, within the above range, for example, 40% by mass or more, 50% by mass or more, 60% by mass or more, 70% by mass or more, or 80% by mass or more, relative to the total amount of ibuprofen and its salts.

[0038] The weight and dosage of the solid composition described above are daily doses (daily amounts), but the same amount may be administered to the subject in one dose, or divided into multiple doses per day, for example, two or three times, preferably three times. The same applies to components other than component (A). Furthermore, since each dosage is a total amount, the content of each component contained in the solid composition may vary depending on the single dose and the dosage form of the solid composition.

[0039] In certain embodiments, the solid composition is a tablet, and the above dosage is the amount of the ingredient contained in 3, 6, or 9 tablets, preferably the amount of the ingredient in 9 tablets. In this embodiment, the number of doses per day for adults (15 years of age or older) is 3, and the amount per dose is 2, 3, or 4 tablets, preferably 3 tablets per dose.

[0040] (B) At least one selected from the group consisting of dextromethorphan and its salts As used herein, "dextromethorphan" refers to the CAS registry number 125-71-3, C 18 H 25 Dextromethorphan is a compound represented by the chemical formula NO (molecular weight: 271.40 g / mol). Dextromethorphan is used as an active ingredient in cough suppressants and other medications. The salts of dextromethorphan are not particularly limited as long as they are pharmacodynamically acceptable, but examples include dextromethorphan hydrobromide hydrate and dextromethorphan phenolphthalein salt. The following amounts and contents of at least one selected from the group consisting of dextromethorphan and its salts refer to the amounts and contents of dextromethorphan and dextromethorphan salts respectively, but it is preferable that the total amount and content of dextromethorphan and dextromethorphan salts be within the range of amounts and contents described below.

[0041] The amount of at least one component selected from the group consisting of component (B) dextromethorphan and its salts is appropriately adjusted according to the intended use of the solid composition, the required degree of antitussive effect, the symptoms of the recipient, age, weight, sex, etc. The daily amount of at least one component selected from the group consisting of dextromethorphan and its salts varies depending on the amount of component (A), etc., but can be adjusted in the range of, for example, 8 mg to 120 mg, preferably 16 mg to 72 mg, in terms of dextromethorphan equivalent.

[0042] The content of at least one substance selected from the group consisting of dextromethorphan and its salts in the solid composition administered daily is 0.01% to 99% by mass, preferably 0.1% to 20% by mass, and more preferably 0.2% to 8% by mass.

[0043] The mass ratio ((A):(B)) of the total amount of component (A) to the total amount of component (B) in the solid composition according to this embodiment is preferably 20:1 to 5:1, more preferably 20:1 to 7:1, and even more preferably 20:1 to 8:1 in the solid composition administered daily. The mass ratio of ibuprofen to dextromethorphan salt may be within the above range, and the mass ratio of ibuprofen to dextromethorphan hydrobromide may be within the above range. When the mass ratio of components (A) to (B) is within the above range, color changes tend to be further suppressed.

[0044] (C) At least one selected from the group consisting of tranexamic acid and its salts As used herein, "tranexamic acid" refers to the C8H compound with CAS registry number 1197-18-8. 15It is a compound represented by the chemical formula NO2 (molecular weight: 157.21 g / mol). Tranexamic acid is used as an active ingredient in anti-inflammatory drugs and the like. The salts of tranexamic acid are not particularly limited as long as they are pharmacologically acceptable. The amounts and contents of at least one selected from the group consisting of tranexamic acid and its salts below refer to the amounts and contents of tranexamic acid and tranexamic acid salts respectively, but it is preferable that the total amount and content of tranexamic acid and tranexamic acid salts be within the range of amounts and contents described below.

[0045] The amount of tranexamic acid is appropriately adjusted according to the intended use of the solid composition, the desired degree of anti-inflammatory effect, the symptoms of the recipient, age, weight, sex, etc. The amount of at least one selected from the group consisting of tranexamic acid and its salts varies depending on the amount of component (A), etc., but for example, the daily amount can be adjusted in the range of 10 mg to 3000 mg, preferably 100 mg to 1500 mg, and more preferably 200 mg to 1000 mg, in terms of tranexamic acid.

[0046] The content of at least one substance selected from the group consisting of tranexamic acid and its salts in the solid composition administered daily is 1% to 70% by mass, preferably 5% to 50% by mass, and more preferably 10% to 30% by mass.

[0047] The mass ratio ((A):(C)) of the total amount of component (A) to the total amount of component (C) in the solid composition according to this embodiment is preferably 1:0.5 to 1:2.5, more preferably 1:0.5 to 1:2.2, and even more preferably 1:0.6 to 1:1.8 in the solid composition administered daily. The mass ratio of ibuprofen to tranexamic acid may also be within the above range. When the mass ratio of components (A) to (C) is within the above range, color changes tend to be further suppressed.

[0048] The mass ratio ((B):(C)) of the total amount of component (B) to the total amount of component (C) in the solid composition according to this embodiment is preferably 1:3 to 1:32, more preferably 1:4 to 1:24, and even more preferably 1:5 to 1:16 in the solid composition administered daily. The mass ratio of dextromethorphan salt to tranexamic acid may be within the above range, and the mass ratio of dextromethorphan hydrobromide to tranexamic acid may be within the above range. When the mass ratio of components (B) to (C) is within the above range, color changes tend to be further suppressed.

[0049] In the solid composition, tranexamic acid may form crystals with ibuprofen. The description herein regarding the amount of at least one selected from the group consisting of tranexamic acid and its salts may be the total amount of tranexamic acid crystallized with ibuprofen and at least one selected from the group consisting of ibuprofen and non-crystallized tranexamic acid and its salts.

[0050] The solid composition may contain ibuprofen and crystalline tranexamic acid, and ibuprofen and at least one selected from the group consisting of non-crystalline tranexamic acid and its salts.

[0051] The content of at least one substance selected from the group consisting of ibuprofen and non-crystallized tranexamic acid and its salts in the solid composition may be, for example, 0 to 100% by mass, 10 to 99% by mass, 20 to 95% by mass, or 30 to 90% by mass, relative to the total amount of tranexamic acid and its salts. The content of at least one substance selected from the group consisting of ibuprofen and non-crystallized tranexamic acid and its salts in the solid composition may be, within the above range, for example, 8% by mass or less, 5% by mass or less, 3% by mass or less, 1% by mass or less, or 0.1% by mass or less, relative to the total amount of tranexamic acid and its salts. The content of at least one substance selected from the group consisting of ibuprofen and non-crystallized tranexamic acid and its salts in the solid composition may be, within the above range, for example, 40% by mass or more, 50% by mass or more, 60% by mass or more, 70% by mass or more, or 80% by mass or more, relative to the total amount of tranexamic acid and its salts.

[0052] The solid composition according to this embodiment preferably contains crystals composed of ibuprofen and tranexamic acid. That is, in the solid composition according to this embodiment, it is preferable that ibuprofen and tranexamic acid form crystals. The formation of crystals between ibuprofen and tranexamic acid further suppresses color changes.

[0053] In a crystal composed of ibuprofen and tranexamic acid, ibuprofen and tranexamic acid may exist in a 1:1 molar ratio. Furthermore, in the above crystal, ibuprofen and tranexamic acid may form a crystalline unit cell consisting of four molecules each.

[0054] In the above crystal, hydrogen bonds may be formed between the carboxylic acid group of ibuprofen and the carboxylic acid group of tranexamic acid, and between the carboxylic acid group of ibuprofen and the amino group of tranexamic acid.

[0055] The above crystal may have an endothermic peak around 180°C in differential scanning calorimetry (DSC). "Around 180°C" may refer to a range such as 180°C ± 20°C or 180°C ± 10°C. Note that in the DSC of the above crystal, the fusion heat peak around 75°C characteristic of ibuprofen may disappear.

[0056] The above crystal may have, for example, the crystal structure shown in Figure 1 of Japanese Patent Publication No. 2022-70674, and may have the X-ray diffraction pattern shown in Figure 2 of the same publication. The above crystal may have seven main peaks (2θ = 6.3, 8.4, 16.2, 18.5, 19.1, 21.1, 25.6 ± 0.5°) in its X-ray diffraction pattern.

[0057] Crystals composed of ibuprofen and tranexamic acid can be produced, for example, by the method described in Japanese Patent Publication No. 2022-070674. Three representative production methods described in the same publication are listed below.

[0058] A method for producing crystals consisting of ibuprofen and tranexamic acid, A method comprising: (1) producing ibuprofen in a fluid form by adding a solvent or heating; (2) mixing the obtained fluid ibuprofen with tranexamic acid; and (3) producing crystals from the obtained mixture.

[0059] A method for producing crystals consisting of ibuprofen and tranexamic acid, A method comprising (1) obtaining tranexamic acid in a fluid form, (2) mixing the obtained fluid tranexamic acid with ibuprofen, or ibuprofen in a fluid form obtained by adding a solvent or heating, and (3) generating crystals from the obtained mixture.

[0060] A method for producing crystals consisting of ibuprofen and tranexamic acid, A method comprising: (1) adding ibuprofen and tranexamic acid to a solvent to obtain a solution or dispersion; (2) spraying and drying the obtained solution or dispersion; or (3) allowing the solution obtained in step (1) to stand, filtering the product obtained after standing, and drying the product.

[0061] (solid composition) In the second embodiment, the following components: (A) At least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of noscapine and its salts, (C) At least one selected from the group consisting of tranexamic acid or its salt, acetaminophen or its salt, clemastine or its salt, citric acid or its salt, stearic acid or its salt, and sodium bicarbonate. Solid composition containing It will be provided. The solid composition is specifically a solid pharmaceutical composition.

[0062] Each component contained in the solid composition according to this embodiment may be included in the form of a pharmaceutically acceptable salt, or it may be included as a complex with other components. That is, the solid composition according to this embodiment may contain salts of each component, not only of components (A) to (C), but also of other components. "Pharmacologically acceptable salt" includes, for example, salts with pharmaceutically acceptable bases or acids. The above are examples of non-specific pharmacologically acceptable salts.

[0063] In this embodiment, in addition to (A) at least one selected from the group consisting of ibuprofen and its salts, and (B) at least one selected from the group consisting of noscapine and its salts, the above component (C) is also included, thereby suppressing changes in the properties of the solid composition, particularly changes in properties over time.

[0064] In this specification, "change in properties" means a change in the nature and / or state of the material, including at least discoloration, solidification, aggregation, moisture absorption, separation, pasteurization, expansion, and adhesion to the walls of the storage container. Therefore, the solid composition according to this embodiment may have suppressed discoloration, solidification, aggregation, moisture absorption, separation, pasteurization, expansion, and adhesion to the walls of the storage container that occur over time. Furthermore, in this embodiment, "suppression of changes in properties" means that changes in properties are less likely to occur, but for example, changes in properties may be suppressed when compared to a solid composition that does not contain component (C).

[0065] The solid composition according to this embodiment may have its properties suppressed under high-temperature conditions. High-temperature conditions may be, for example, 30 to 100°C or 40 to 90°C.

[0066] In this specification, "changes in properties over time" means changes in properties that occur over time, and may include changes in properties that occur over a period of 12 hours or more, 18 hours or more, 24 hours or more, 1 week or more, or 2 weeks or more after manufacturing or after being placed in a specific environment (e.g., a high-temperature and / or high-humidity environment). The period over which changes in properties are suppressed in the solid composition relating to this disclosure is not particularly limited, but may be, for example, 12 hours or more, 18 hours or more, 24 hours or more, or 48 hours or more.

[0067] (A) At least one selected from the group consisting of ibuprofen and its salts The amounts and contents of at least one selected from the group consisting of ibuprofen and its salts are the amounts and contents for ibuprofen and ibuprofen salts respectively, but it is preferable that the total amount and contents of ibuprofen and ibuprofen salts be within the range of the amounts and contents described below.

[0068] The amount of ibuprofen included in the solid composition is adjusted as appropriate depending on the intended use of ibuprofen, the symptoms of the recipient, age, weight, sex, etc. For example, when ibuprofen is included as a nonsteroidal anti-inflammatory drug, the daily amount of ibuprofen administered to an adult may be adjusted in ibuprofen equivalent to, for example, 30 mg to 2000 mg, preferably 100 mg to 1000 mg, and more preferably 200 mg to 600 mg.

[0069] The above dosages are examples, and the content of at least one selected from the group consisting of ibuprofen and its salts per solid composition administered daily is, for example, about 1% to about 70% by mass, preferably about 5% to about 50% by mass, and more preferably about 10% to about 30% by mass.

[0070] In this embodiment, the content of at least one substance selected from the group consisting of ibuprofen and its salts contained in the composition administered daily is 1% to 70% by mass, preferably 5% to 50% by mass, and more preferably 10% to 30% by mass.

[0071] If the solid composition contains tranexamic acid or a salt thereof, the solid composition may also contain at least one selected from the group consisting of tranexamic acid and crystalline ibuprofen, and tranexamic acid and non-crystalline ibuprofen and salts thereof.

[0072] The content of at least one substance selected from the group consisting of tranexamic acid and non-crystallized ibuprofen and its salts in the solid composition may be, for example, 0 to 100% by mass, 10 to 99% by mass, 20 to 95% by mass, or 30 to 90% by mass, relative to the total amount of ibuprofen and its salts. The content of at least one substance selected from the group consisting of tranexamic acid and non-crystallized ibuprofen and its salts in the solid composition may be, within the above range, for example, 8% by mass or less, 5% by mass or less, 3% by mass or less, 1% by mass or less, or 0.1% by mass or less, relative to the total amount of ibuprofen and its salts. The content of at least one substance selected from the group consisting of tranexamic acid and non-crystallized ibuprofen and its salts in the solid composition may be, within the above range, for example, 40% by mass or more, 50% by mass or more, 60% by mass or more, 70% by mass or more, or 80% by mass or more, relative to the total amount of ibuprofen and its salts.

[0073] The weight and dosage of the solid composition described above are for a day, but the same amount may be administered to the subject in one dose, or divided into multiple doses per day, for example, two or three times, preferably three times. The same applies to components other than ibuprofen. Furthermore, since each dosage is a total amount, the content of each component contained in the solid composition may vary depending on the single dose and the dosage form of the solid composition.

[0074] In certain embodiments, the solid composition is a tablet, and the above dosage is the amount of the ingredient contained in 3, 6, or 9 tablets, preferably the amount of the ingredient in 9 tablets. In this embodiment, the number of doses per day for adults (15 years of age or older) is 3, and the amount per dose is 2, 3, or 4 tablets, preferably 3 tablets per dose.

[0075] (B) At least one selected from the group consisting of noscapine and its salts As used herein, "noscapine" refers to the noscapine with CAS Registry Number 128-62-1, C 22 H 23It is a compound represented by the chemical formula NO7. Noscapine is used as an active ingredient in cough suppressants and other medications. The salts of noscapine are not particularly limited as long as they are pharmacologically acceptable, but noscapine hydrochloride is an example.

[0076] The amount of at least one substance selected from the group consisting of noscapine and its salts is appropriately adjusted according to the intended use of the solid composition, the required degree of antitussive effect, the required degree of stability, the symptoms of the recipient, age, weight, sex, etc. The amounts and contents of at least one substance selected from the group consisting of noscapine and its salts described below are the amounts and contents for noscapine and noscapine salts respectively, but it is preferable that the total amount and content of noscapine and noscapine salts be within the range of the amounts and contents described below.

[0077] The daily amount of at least one substance selected from the group consisting of noscapine and its salts can be adjusted in noscapine equivalent to, for example, 8 mg to 120 mg, preferably 16 mg to 72 mg.

[0078] The content of at least one substance selected from the group consisting of noscapine and its salts in the solid composition administered daily is 0.1% to 90% by mass, preferably 0.2% to 30% by mass, and more preferably 0.3% to 10% by mass.

[0079] The amount of at least one component selected from the group consisting of noscapine and its salts may vary depending on the amount of at least one component selected from the group consisting of ibuprofen and its salts, etc. For example, the mass ratio ((A):(B)) of the total amount of component (A):(B) in the solid composition according to this embodiment is preferably 1:0.01 to 1:0.4, more preferably 1:0.03 to 1:0.3, and even more preferably 1:0.05 to 1:0.2 in the solid composition administered per day. The mass ratio of ibuprofen to noscapine may be within the above range. When the mass ratio of components (A) to (B) is within the above range, changes in properties tend to be further suppressed.

[0080] (C) at least one selected from the group consisting of tranexamic acid or a salt thereof, acetaminophen or a salt thereof, clemastine or a salt thereof, citric acid or a salt thereof, stearic acid or a salt thereof, and sodium hydrogen carbonate The solid composition according to the present embodiment further comprises at least one (C) selected from the group consisting of tranexamic acid or a salt thereof, acetaminophen or a salt thereof, clemastine or a salt thereof, citric acid or a salt thereof, stearic acid or a salt thereof, and sodium hydrogen carbonate. These components may be contained singly, or two or more thereof may be contained.

[0081] The solid composition according to the present embodiment may contain a crystal formed of ibuprofen and tranexamic acid. That is, when the solid composition according to the present embodiment contains tranexamic acid, ibuprofen and tranexamic acid may form a crystal. The crystal, characteristics thereof, and method for producing the same are as described above.

[0082] 90% by mass or more of the tranexamic acid contained in the solid composition, for example 90% by mass, 91% by mass, 92% by mass, 93% by mass, 94% by mass, 95% by mass, 96% by mass, 97% by mass, 98% by mass, 99% by mass, or 100% by mass may be crystallized with ibuprofen.

[0083] As used herein, "acetaminophen" is a compound having a CAS Registry Number of 103-90-2 and represented by the chemical formula C8H9NO2 (molecular weight: 151.16 g / mol). The salt of acetaminophen is not particularly limited as long as it is pharmacologically acceptable.

[0084] As used herein, "clemastine" is a compound having a CAS Registry Number of 17-7-4 and represented by the chemical formula C 21 H 26 ClNO (molecular weight: 343.89 g / mol). The salt of clemastine is not particularly limited as long as it is pharmacologically acceptable, and examples thereof include clemastine fumarate.

[0085] As used herein, "citric acid" refers to the compound with CAS registry number 77-92-9 and the chemical formula C6H8O7 (molecular weight: 192.12 g / mol). The salt of citric acid is not particularly limited as long as it is pharmacodynamically acceptable, but examples include alkali metal salts or alkaline earth metal salts of citric acid, such as sodium citrate. Furthermore, citric acid may be included in the solid composition in the form of anhydrous citric acid.

[0086] As used herein, "stearic acid" refers to the CAS registry number 57-11-4, C 18 H 36 It is a compound represented by the chemical formula O2 (molecular weight: 284.48 g / mol). Stearic acid is not particularly limited as long as it is pharmacologically acceptable, but examples include metal salts of stearic acid such as calcium stearate, magnesium stearate, and aluminum monostearate, especially alkaline earth metal salts.

[0087] As used herein, "sodium bicarbonate" refers to the compound with CAS registry number 144-55-8 and the chemical formula NaHCO3 (molecular weight: 84.01 g / mol).

[0088] The amount and content of ingredient (C) may be determined independently.

[0089] The amount of tranexamic acid or its salt included is, for example, in the range of 10 mg to 3000 mg, preferably 100 mg to 1500 mg, and more preferably 200 mg to 1000 mg per day in terms of tranexamic acid equivalent.

[0090] The amount of tranexamic acid or its salt contained in the solid composition administered daily is, for example, 1% to 70% by mass, preferably 5% to 50% by mass, and more preferably 10% to 30% by mass.

[0091] The amount of acetaminophen or its salt included is, for example, in the range of 120 mg to 1200 mg, preferably 150 mg to 900 mg, and more preferably 180 mg to 600 mg per day in terms of acetaminophen equivalent.

[0092] The amount of acetaminophen or a salt thereof contained in the solid composition administered daily is, for example, 0.1% to 99% by mass, preferably 1% to 50% by mass, and more preferably 2% to 10% by mass.

[0093] The amount of clemastine or its salt included is, for example, in the range of 0.01 mg to 10 mg, preferably 0.1 mg to 5 mg, and more preferably 1 mg to 2 mg per day in terms of clemastine equivalent.

[0094] The amount of clemastine or its salt contained in the solid composition administered daily is, for example, 0.0001% to 10% by mass, preferably 0.001% to 1% by mass, and more preferably 0.01% to 0.2% by mass.

[0095] The amount of citric acid or its salt added is, for example, in the range of 0.1 mg to 7000 mg, preferably 1 mg to 1000 mg, and more preferably 10 mg to 300 mg per day in terms of citric acid equivalent.

[0096] The amount of citric acid or its salt contained in the solid composition administered daily is, for example, 0.1% to 50% by mass, preferably 0.5% to 10% by mass, and more preferably 1% to 5% by mass.

[0097] The amount of stearic acid or its salt added is, for example, in the range of 0.1 mg to 3000 mg, preferably 1 mg to 500 mg, and more preferably 5 mg to 200 mg, in terms of stearic acid per day.

[0098] The amount of stearic acid or its salt contained in the solid composition administered daily is, for example, 0.1% to 30% by mass, preferably 0.3% to 10% by mass, and more preferably 0.5% to 5% by mass.

[0099] The amount of sodium bicarbonate used is, for example, in the range of 0.1 mg to 2000 mg per day, preferably 1 mg to 800 mg, and more preferably 10 mg to 200 mg.

[0100] The amount of sodium bicarbonate contained in the solid composition administered daily is, for example, 0.1% to 90% by mass, preferably 0.5% to 10% by mass, and more preferably 1% to 5% by mass.

[0101] The amounts and content of tranexamic acid, acetaminophen, clemastine fumarate, magnesium stearate, anhydrous citric acid, or sodium bicarbonate may be within the above ranges.

[0102] The mass ratio of component (A) to (C) in the solid composition according to this embodiment (the mass ratio of the total amount of component (A) to component (C)) is not particularly limited, but is preferably 1:0.01 to 1:10 ((A):(C)), more preferably 1:0.01 to 1:5 ((A)):((C)), and even more preferably 1:0.02 to 1:2 ((A)):((C)). The mass ratio of the total amount of component (A) contained in the solid composition to each component (C) may be within the above range, and the mass ratio of ibuprofen to each component (C) may be within the above range.

[0103] The mass ratio of component (B) to (C) in the solid composition according to this embodiment (the mass ratio of the total amount of component (B) to component (C)) is not particularly limited, but is preferably 1:0.1 to 1:150 ((B):(C)), more preferably 1:0.1 to 1:100 ((B)):((C)), and even more preferably 1:0.1 to 1:60 ((B)):((C)). The mass ratio of the total amount of component (B) contained in the solid composition to each component (C) may be within the above range, and the mass ratio of noscapine to each component (C) may be within the above range.

[0104] (solid composition) In a third embodiment, the following components: (A) At least one selected from the group consisting of ibuprofen and its salts, (B) At least one selected from the group consisting of noscapine and its salts, (C) at least one selected from the group consisting of dextromethorphan and its salts, and (D) At least one selected from the group consisting of chlorpheniramine or its salt, caffeine or its salt, croscarmellose sodium, silicon dioxide, and talc. Solid composition containing It will be provided. The solid composition is specifically a solid pharmaceutical composition.

[0105] Each component contained in the solid composition according to this embodiment may be included in the form of a pharmaceutically acceptable salt, or it may be included as a complex with other components. That is, the solid composition according to this embodiment may contain salts of not only components (A) to (D), but also other components. "Pharmacologically acceptable salt" includes, for example, salts with pharmaceutically acceptable bases or acids. The above are examples of non-specific pharmacologically acceptable salts.

[0106] In this embodiment, in addition to (A) at least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of noscapine and its salts, and (C) at least one selected from the group consisting of dextromethorphan and its salts, the above component (D) is also included, thereby suppressing changes in the properties of the solid composition, particularly changes in properties over time.

[0107] "Changes in properties" and "changes in properties over time" are as described above. In this embodiment, "changes in properties are suppressed" means that changes in properties are less likely to occur, but for example, changes in properties may be suppressed when compared to a solid composition that does not contain component (D).

[0108] The solid composition according to this embodiment may have its properties suppressed under high-temperature conditions. High-temperature conditions may be, for example, 30 to 100°C or 40 to 90°C.

[0109] (A) At least one selected from the group consisting of ibuprofen and its salts The amounts and contents of at least one selected from the group consisting of ibuprofen and its salts are the amounts and contents for ibuprofen and ibuprofen salts respectively, but it is preferable that the total amount and contents of ibuprofen and ibuprofen salts be within the range of the amounts and contents described below.

[0110] The amount of at least one substance selected from the group consisting of ibuprofen and its salts is appropriately adjusted according to the use of ibuprofen in the solid composition, the symptoms of the recipient, age, weight, sex, etc. For example, when ibuprofen is included as a nonsteroidal anti-inflammatory drug, the daily amount of at least one substance selected from the group consisting of ibuprofen and its salts administered to an adult may be adjusted in ibuprofen equivalent to, for example, 30 mg to 2000 mg, preferably 100 mg to 1000 mg, and more preferably 200 mg to 600 mg.

[0111] The above dosages are examples, and the content of at least one selected from the group consisting of ibuprofen and its salts per solid composition administered daily is, for example, about 1% to about 70% by mass, preferably about 5% to about 50% by mass, and more preferably about 10% to about 30% by mass.

[0112] In this embodiment, the content of at least one substance selected from the group consisting of ibuprofen and its salts contained in the composition administered daily is 1% to 70% by mass, preferably 5% to 50% by mass, and more preferably 10% to 30% by mass.

[0113] The weight and dosage of the solid composition described above are for a day, but the same amount may be administered to the subject in one dose, or divided into multiple doses per day, for example, two or three times, preferably three times. The same applies to components other than ibuprofen. Furthermore, since each dosage is a total amount, the content of each component contained in the solid composition may vary depending on the single dose and the dosage form of the solid composition.

[0114] In certain embodiments, the solid composition is a tablet, and the above dosage is the amount of the ingredient contained in 3, 6, or 9 tablets, preferably the amount of the ingredient in 9 tablets. In this embodiment, the number of doses per day for adults (15 years of age or older) is 3, and the amount per dose is 2, 3, or 4 tablets, preferably 3 tablets per dose.

[0115] (B) At least one selected from the group consisting of noscapine and its salts The amount of at least one substance selected from the group consisting of noscapine and its salts is appropriately adjusted according to the intended use of the solid composition, the required degree of antitussive effect, the required degree of stability, the symptoms of the recipient, age, weight, sex, etc. The amounts and contents of at least one substance selected from the group consisting of noscapine and its salts described below are the amounts and contents for noscapine and noscapine salts respectively, but it is preferable that the total amount and content of noscapine and noscapine salts be within the range of the amounts and contents described below.

[0116] The daily amount of at least one substance selected from the group consisting of noscapine and its salts can be adjusted in noscapine equivalent to, for example, 8 mg to 120 mg, preferably 16 mg to 72 mg.

[0117] The content of at least one substance selected from the group consisting of noscapine and its salts in the solid composition administered daily is 0.1% to 90% by mass, preferably 0.2% to 30% by mass, and more preferably 0.3% to 10% by mass.

[0118] The amount of at least one component selected from the group consisting of noscapine and its salts may vary depending on the amount of at least one component selected from the group consisting of ibuprofen and its salts, etc. For example, the mass ratio ((A):(B)) of the total amount of component (A):(B) in the solid composition according to this embodiment is preferably 1:0.01 to 1:0.4, more preferably 1:0.03 to 1:0.3, and even more preferably 1:0.05 to 1:0.2 in the solid composition administered per day. The mass ratio of ibuprofen to noscapine may be within the above range. When the mass ratio of components (A) to (B) is within the above range, changes in properties tend to be further suppressed.

[0119] (C) At least one selected from the group consisting of dextromethorphan and its salts The amounts and contents of at least one selected from the group consisting of dextromethorphan and its salts are the amounts and contents of dextromethorphan and dextromethorphan salts, respectively, but it is preferable that the total amount and content of dextromethorphan and dextromethorphan salts be within the range of the amounts and contents described below.

[0120] The amount of at least one substance selected from the group consisting of dextromethorphan and its salts is appropriately adjusted according to the intended use of the solid composition, the required degree of antitussive effect, the symptoms of the recipient, age, weight, sex, etc. The daily amount of at least one substance selected from the group consisting of dextromethorphan and its salts varies depending on the amount of component (A), etc., but can be adjusted in the range of, for example, 8 mg to 120 mg, preferably 16 mg to 72 mg, in terms of dextromethorphan equivalent.

[0121] The content of at least one substance selected from the group consisting of dextromethorphan and its salts in the solid composition administered daily is 0.1% to 90% by mass, preferably 0.2% to 30% by mass, and more preferably 0.3% to 10% by mass.

[0122] The mass ratio of component (A) to (C) in the solid composition according to this embodiment (the mass ratio of the total amount of component (A) to component (C)) is not particularly limited, but is preferably 1:0.01 to 1:0.4 ((A):(C)), more preferably 1:0.03 to 1:0.3 ((A):((C)), and even more preferably 1:0.05 to 1:0.2 ((A):((C)). The mass ratio of ibuprofen to dextromethorphan salt may be within the above range, and the mass ratio of ibuprofen to dextromethorphan hydrobromide may be within the above range. When the mass ratio of component (A) to (C) is within the above range, changes in properties tend to be further suppressed.

[0123] (D) At least one selected from the group consisting of chlorpheniramine or its salt, caffeine or its salt, croscarmellose sodium, silicon dioxide, and talc. The solid composition according to this embodiment further comprises (D) at least one selected from the group consisting of chlorpheniramine or a salt thereof, caffeine or a salt thereof, croscarmellose sodium, silicon dioxide, and talc. These components may be present individually or in groups of two or more.

[0124] As used herein, "chlorpheniramine" refers to the CAS registry number 132-22-9, C 16 H 19 It is a compound represented by the chemical formula ClN2 (molecular weight: 274.79 g / mol). The salts of chlorpheniramine are not particularly limited as long as they are pharmacologically acceptable, but chlorpheniramine maleate (especially d-chlorpheniramine maleate) is an example.

[0125] As used herein, "caffeine" refers to C8H2, which has CAS Registry Number 58-08-2. 10 It is a compound represented by the chemical formula N4O2 (molecular weight: 194.19 g / mol). The salt of caffeine is not particularly limited as long as it is pharmacodynamically acceptable. Caffeine may also be included in the solid composition in the form of anhydrous caffeine.

[0126] As used herein, "croscarmellose sodium" is the compound represented by CAS registry number 74811-65-7.

[0127] As used herein, "silicon dioxide" refers to a compound represented by the chemical formula SiO2, and includes, for example, silica with CAS registry number 7631-86-9. In this embodiment, "silicon dioxide" may be a component mainly comprising a compound represented by the chemical formula SiO2, for example, light anhydrous silicic acid listed in the 18th edition of the Japanese Pharmacopoeia and / or hydrated silicon dioxide listed in the Japanese Standards for Pharmaceutical Additives 2018. Light anhydrous silicic acid contains 98.0% or more silicon dioxide (SiO2), and hydrated silicon dioxide contains 95.0% or more silicon dioxide (SiO2). In this embodiment, silicon dioxide may be hydrated silicon dioxide and / or light anhydrous silicic acid, and is preferably light anhydrous silicic acid.

[0128] In this embodiment, when light anhydrous silicic acid is used, the specific surface area of ​​the light anhydrous silicic acid is not particularly limited, but for example, 100 to 350 m². 2 It is preferable that the amount is / g. Here, the specific surface area of ​​light anhydrous silicic acid is measured by the BET multi-point method described in 3.02 Specific Surface Area Measurement Method of the 18th Edition of the Japanese Pharmacopoeia.

[0129] As used herein, "talc" refers to the talc with CAS Registry Number 14807-96-6. Mg3Si4O 10 It is a compound represented by the chemical formula (OH)2 (molecular weight: 379.26 g / mol).

[0130] The amount and content of ingredient (D) may be determined independently.

[0131] The amount of chlorpheniramine or its salt included is, for example, in the range of 0.5 mg to 15 mg, preferably 1 mg to 10 mg, and more preferably 1.5 mg to 8 mg per day in terms of chlorpheniramine equivalent.

[0132] The amount of chlorpheniramine or its salt contained in the solid composition administered daily is, for example, 0.001% to 10% by mass, preferably 0.01% to 2% by mass, and more preferably 0.02% to 1% by mass.

[0133] The amount of caffeine or its salt added is, for example, in the range of 15 mg to 600 mg, preferably 20 mg to 450 mg, and more preferably 30 mg to 300 mg per day in caffeine equivalent.

[0134] The amount of caffeine or its salt contained in the solid composition administered daily is, for example, 0.1% to 90% by mass, preferably 0.3% to 40% by mass, and more preferably 0.5% to 25% by mass.

[0135] The amount of croscarmellose sodium included is, for example, in the range of 0.1 mg to 640 mg per day, preferably 1 mg to 100 mg, and more preferably 20 mg to 80 mg.

[0136] The amount of croscarmellose sodium contained in the solid composition administered daily is, for example, 0.001% to 80% by mass, preferably 0.01% to 30% by mass, and more preferably 0.1% to 10% by mass.

[0137] The amount of silicon dioxide included is, for example, in the range of 1 mg to 300 mg per day, preferably 5 mg to 200 mg, and more preferably 15 mg to 160 mg.

[0138] The silicon dioxide contained in the solid composition administered daily is, for example, 0.01% to 90% by mass, preferably 0.1% to 30% by mass, and more preferably 0.2% to 15% by mass.

[0139] The amount of talc included is, for example, in the range of 1 mg to 3500 mg per day, preferably 10 mg to 1000 mg, and more preferably 50 mg to 300 mg.

[0140] The amount of talc contained in the solid composition administered daily is, for example, 0.01% to 50% by mass, preferably 0.1% to 10% by mass, and more preferably 0.2% to 3% by mass.

[0141] The amounts and content of chlorpheniramine maleate, anhydrous caffeine, croscarmellose sodium, light anhydrous silicic acid, or talc may be within the above ranges.

[0142] The mass ratio of components (A) and (D) in the solid composition according to this embodiment (the mass ratio of the total amount of component (A) to component (D)) is not particularly limited, but is preferably 1:0.001 to 1:10 ((A):(D)), more preferably 1:0.002 to 1:5 ((A)):((D)), and even more preferably 1:0.003 to 1:1 ((A)):((D)). The mass ratio of the total amount of component (A) contained in the solid composition to each component (D) may be within the above range, and the mass ratio of ibuprofen to each component (D) may be within the above range.

[0143] (Other ingredients) The solid compositions according to this embodiment, namely the solid composition according to the first embodiment, the solid composition according to the second embodiment, and the solid composition according to the third embodiment, may each contain components other than those listed above, depending on their intended use. When the solid composition is intended to alleviate various symptoms of the common cold, such as runny nose, nasal congestion, sneezing, sore throat, cough, phlegm, chills, fever, headache, joint pain, muscle pain, etc., in addition to bromhexine, meloxicam, and acetaminophen, antipyretic analgesics, particularly active ingredients such as nonsteroidal anti-inflammatory drugs (NSAIDs), and other pharmacologically acceptable components may be included. The components listed above in any of the solid compositions according to the first embodiment, the solid composition according to the second embodiment, and the solid composition according to the third embodiment may also be described below.

[0144] Nonsteroidal anti-inflammatory drugs (NSAIDs) are broadly classified into COX-2 nonselective inhibitors such as diclofenac, loxoprofen, zaltoprofen, pranoprofen, oxaprozin, tiaprofenic acid, naproxen, lornoxicam, ampiroxicam, piroxicam, nabumetone, indomethacin, sulindac, mofezolac, and mefenamic acid, and COX-2 selective inhibitors such as meloxicam, etodolac, and celecoxib. Meloxicam may be included in the composition as a NSAID. It is preferable that the NSAID is a COX-2 nonselective inhibitor. The NSAID may also be in salt form.

[0145] Other pharmacologically acceptable ingredients that may be added include antihistamines, antipyretic analgesics, cough and expectorant agents, anti-inflammatory drugs, central nervous system stimulants, vitamins, anticholinergics, and antiplasmins, which are commonly found in combination cold medicines, antipyretic analgesics, and rhinitis medicines.

[0146] For example, antihistamines include isopendyl hydrochloride, difeterol hydrochloride, triperenamine hydrochloride, tondiamine hydrochloride, phenetazine hydrochloride, methodilazine hydrochloride, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, carbinoxamine diphenyldisulfonate, diphenylpyraline hydrochloride, diphenylpyraline theoclate, diphenhydramine hydrochloride, diphenhydramine salicylate, alimazine tartrate, diphenhydramine tannate, triprolidine hydrochloride hydrate, mebhydroline napadisylate, promethazine methylene disalicylate, carbinoxamine maleate, difeterol phosphate, clemastine fumarate, and mequitazine.

[0147] Examples of antipyretic analgesics other than nonsteroidal anti-inflammatory drugs include aspirin, acetaminophen, ethenzamide, sazapyrine, salicylamide, lactylphenetidine, and isopropylantipyrine. Acetaminophen may be included in the composition as an antipyretic analgesic.

[0148] Examples of cough suppressants and expectorants include noscapine, noscapine hydrochloride hydrate, tipepidine hibenzate, dextromethorphan hydrobromide hydrate, bromhexine, bromhexine hydrochloride, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, pseudoephedrine hydrochloride, ambroxol hydrochloride, and L-carbocysteine.

[0149] Examples of anti-inflammatory drugs include glycyrrhizic acid and its derivatives and their salts (e.g., dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.), and tranexamic acid.

[0150] Examples of central nervous system stimulants include caffeine and anhydrous caffeine.

[0151] Examples of vitamin supplements include vitamin B1 and its derivatives and their salts (e.g., benfotiamine), vitamin B2 and its derivatives and their salts (e.g., riboflavin), vitamin C and its derivatives and their salts (e.g., ascorbic acid), hesperidin and its derivatives and their salts, and so on.

[0152] Examples of anticholinergic agents include scopolamine hydrobromide, datura extract, methylscopolamine bromide, methyl-l-hyoscyamine bromide, pirenzepine hydrochloride, butylscopolamine bromide, belladonna alkaloids, belladonna extract, total belladonna alkaloids, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, belladonna extract, belladonna root, and total belladonna root alkaloid citrate.

[0153] Pharmaceutical additives may be added to the solid composition according to this embodiment as needed. Examples of pharmaceutical additives include pharmaceutically acceptable carriers, such as excipients, binders, disintegrants, disintegration aids, glossing agents, foaming agents, moisture-proofing agents, surfactants, stabilizers, antioxidants, fillers, sweeteners, flavoring agents, cooling agents, fragrances, aromatics, colorants, bases, coating agents, sugar coating agents, plasticizers, dispersants, defoaming agents, fluidizing agents, and flavoring agents / fragrances. Pharmaceutical additives that are conventionally known and can be used in solid compositions can be used for the above purposes.

[0154] Excipients include, for example, sugar powder, gum arabic, gum arabic powder, cocoa butter, caramel, sodium carboxymethyl starch, hydrated silicon dioxide, anhydrous amorphous silicon dioxide, xylitol, magnesium aluminosilicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, crystalline cellulose, crystalline cellulose / carmellose sodium, crystalline cellulose (fine particles), crystalline cellulose (granules), powdered cellulose, synthetic aluminum silicate, synthetic aluminum silicate / hydroxypropyl starch / crystalline cellulose, wheat starch, rice flour, rice starch, heavy anhydrous silicic acid, refined sucrose, refined sucrose spherical granules, gelatin, D-sorbitol, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, and low-substituted hydroxypropyl cellulose. Examples include dextrin, corn starch, corn starch granules, trehalose, silicon dioxide, lactose monohydrate, lactose granules, sucrose, potato starch, hydroxypropyl starch, partially pregelatinized starch, powdered sugar, powdered candy, powdered reduced maltose syrup, powdered cellulose, pectin, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 60, maltitol, D-mannitol, magnesium aluminometasilicate, calcium sulfate, erythritol, glucose, fructose, etc.

[0155] Examples of binders include gum arabic, gum arabic powder, kanbai flour, gelatin, shellac, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose, pullulan, povidone, polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified), methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, butyl methacrylate / methyl methacrylate copolymer, methylcellulose, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, etc.

[0156] Examples of disintegrants include sodium carboxymethyl starch, carmellose, carmellose calcium, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, hydroxypropyl starch, and partially pregelatinized starch.

[0157] Examples of disintegration aids include sodium carboxymethyl starch, carmellose, carmellose calcium, croscarmellose sodium, light anhydrous silicic acid, crystalline cellulose, sodium bicarbonate, precipitated calcium carbonate, lactose monohydrate, hydroxypropyl starch, polysorbate 40, polysorbate 60, polysorbate 80, macrogol 1500, macrogol 4000, and the like.

[0158] Examples of glossing agents include carnauba wax, bleached beeswax, refined shellac, macrogol 400, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, and beeswax.

[0159] Examples of foaming agents include anhydrous sodium carbonate, tartaric acid, potassium bitartrate, sodium bicarbonate, and anhydrous citric acid.

[0160] Examples of moisture-proofing agents include ethylcellulose, olive oil, dried aluminum hydroxide gel, glycerin, magnesium silicate, light anhydrous silicic acid, hydrogenated oil, synthetic aluminum silicate, sucrose fatty acid ester, stearic acid, magnesium stearate, refined shellac, refined sucrose, talc, neutral anhydrous sodium sulfate, precipitated calcium carbonate, a mixture of fumaric acid, stearic acid, polyvinyl acetal diethylaminoacetate, and hydroxypropyl methylcellulose 2910, polyvinyl acetal diethylaminoacetate, and magnesium aluminometasilicate.

[0161] Examples of surfactants include sucrose fatty acid esters, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan beeswax, polyoxyethylene nonylphenyl ether, polyoxyethylene (20) polyoxypropylene (20) glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (10) polyoxypropylene (4) cetyl ether, polysorbate 20, polysorbate 60, polysorbate 80, macrogol 400, sorbitan monooleate, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, and sodium lauryl sulfate.

[0162] Examples of stabilizers include adipic acid, L-aspartic acid, sodium L-aspartate, DL-alanine, L-alanine, L-arginine, L-arginine hydrochloride, sodium alginate, propylene glycol alginate, benzoic acid, sodium benzoate, ethylenediamine, disodium calcium edetate, sodium edetate, tetrasodium edetate, tetrasodium edetate tetrahydrate, zinc chloride, ammonium chloride, calcium chloride hydrate, cetylpyridinium chloride, and dichloride. Iron, sodium chloride, magnesium chloride, cysteine ​​hydrochloride, L-histidine hydrochloride, cocoa butter, carboxyvinyl polymer, carmellose calcium, hydrated silicon dioxide, carmellose sodium, anhydrous sodium carbonate, glycine, glycerin, glycerin fatty acid ester, calcium gluconate hydrate, sodium gluconate, magnesium gluconate, potassium L-glutamate, sodium L-glutamate, L-lysine L-glutamate, light anhydrous silicic acid, crystalline sodium dihydrogen phosphate, chondrone Sodium leutin sulfate, zinc oxide, L-cystine, L-cysteine, tartaric acid, sucrose fatty acid ester, stearic acid, refined gelatin, refined soy lecithin, gelatin, gelatin hydrolysate, sorbitan fatty acid ester, taurine, talc, calcium carbonate, potassium bicarbonate, sodium bicarbonate, sodium carbonate hydrate, magnesium carbonate, natural vitamin E, tocopherol, tocopherol acetate, lactose, concentrated glycerin, povidone, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene Nonstearyl ether, polyoxyethylene cetyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene (42) polyoxypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxyethylene coconut oil fat glyceryl (7E.O.)Examples include polysorbate 20, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), macrogol 300, macrogol 400, macrogol 4000, anhydrous citric acid, anhydrous sodium citrate, anhydrous sodium monohydrogen phosphate, anhydrous sodium dihydrogen phosphate, magnesium aluminometasilicate, methylcellulose, l-menthol, glyceryl monostearate, medicinal charcoal, magnesium sulfate hydrate, DL-malic acid, sodium hydrogen phosphate hydrate, potassium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, L-leucine, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, etc.

[0163] Examples of antioxidants include ascorbic acid, L-ascorbic acid stearate, citric acid hydrate, soy lecithin, natural vitamin E, tocopherol, tocopherol acetate, ascorbic palmitate, and sodium pyrosulfite. In the case of a solid composition containing acetaminophen, it is preferable not to include tocopherols as antioxidants or stabilizers.

[0164] Examples of fillers include RSS No. 1 raw rubber, starch acrylate 1000, hydrated silicon dioxide, titanium dioxide, silicon dioxide, and calcium monohydrogen phosphate.

[0165] Examples of sweeteners include aspartame, acesulfame potassium, amacha, amacha powder, reduced maltose syrup, licorice, licorice extract, licorice powder, xylitol, dipotassium glycyrrhizinate, disodium glycyrrhizinate, saccharin, sodium saccharin hydrate, sucralose, stevia extract, stevia extract, refined sucrose, fructose, sucrose, maltitol, D-mannitol, and erythritol.

[0166] Examples of flavoring agents include sodium chloride, Phellodendron bark powder, Parmesan extract, Coptis japonica, Coptis japonica powder, orange, orange oil, cocoa powder, fructose, caramel, licorice, licorice extract, licorice powder, xylitol, calcium citrate, citric acid hydrate, sodium citrate hydrate, L-glutamic acid, sodium L-glutamate, grapefruit extract, brown sugar, cinnamon powder, cinnamon oil, saccharin, sodium saccharin hydrate, Japanese pepper powder, tartaric acid, D-tartaric acid, potassium bitartrate, DL-tartaric acid Examples include sodium glycyrrhizate, ginger powder, sucralose, stevia extract, stevia extract, swertia japonica, D-sorbitol, tannic acid, clove oil, citrus peel tincture, chili pepper, chili pepper powder, spruce powder, trehalose hydrate, porcini powder, plum extract, fructooligosaccharides, powdered sugar, peppermint powder, D-mannitol, dl-menthol, l-menthol, menthol powder, bonito flakes, bonito flakes powder, green tea powder, DL-malic acid, sodium DL-malate, lemon oil, rose oil, etc.

[0167] Examples of cooling agents include fennel oil, d-camphor, dl-camphor, cinnamon oil, peppermint water, peppermint oil, and l-menthol.

[0168] Examples of flavorings include orange flavor, guarana extract, sweet orange, strawberry, brown sugar flavor, cherry flavor, banana powder flavor, peach essence, fruit essence, peppermint, melon powder flavor, l-menthol, and peppermint oil.

[0169] Examples of fragrances include fennel powder, fennel oil, ethyl vanillin, d-camphor, dl-camphor, cinnamon powder, cinnamon oil, ginger oil, agarwood powder, spearmint oil, clove oil, turpentine oil, chili pepper powder, pineapple powder fragrance 51357, pineapple powder fragrance 59492, peppermint water, peppermint oil, vanilla powder fragrance 54286, vanillin, bergamot oil, d-borneol, dl-borneol, dl-menthol, l-menthol, eucalyptus oil, rose water, and rose oil.

[0170] Examples of coloring agents include yellow iron oxide, yellow ferric oxide, orange essence, brown iron oxide, carbon black, caramel, β-carotene, licorice extract, gold leaf, black iron oxide, titanium dioxide, ferric oxide, dizazo yellow, food blue No. 1, food yellow No. 4, food yellow No. 5, food blue No. 2 aluminum lake, food yellow No. 4 aluminum lake, food red No. 2, food red No. 3, food red No. 102, ferric oxide / glycerin suspension, copper chlorophyllin sodium, copper chlorophyll, phenol red, malachite green, methylene blue, medicinal charcoal, riboflavin, riboflavin butyrate, riboflavin phosphate sodium, green tea powder, rose oil, etc.

[0171] The base ingredients include: acacia powder, pregelatinized starch, ethylcellulose, cocoa butter, carnauba wax, carboxyvinyl polymer, carmellose, carmellose sodium, reduced maltose syrup, hydrated silicon dioxide, dried aluminum hydroxide gel, agar, agar powder, xanthan gum, glycine, glycerin, glycerin fatty acid ester, light anhydrous silicic acid, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, synthetic magnesium sodium silicate, titanium dioxide, tartaric acid, sucrose fatty acid ester, silicone oil, stearic acid, magnesium stearate, gelatin, D-sorbitol, talc, calcium carbonate, corn starch, lactic acid, ethyl lactate, calcium lactate hydrate, lactic acid / glycolic acid copolymer, concentrated glycerin, potato starch. Examples include hydroxypropylcellulose, hypromellose, pullulan, pectin, povidone, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), microcrystalline wax, macrogol 200, macrogol 300, macrogol 400, macrogol 1000, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 6000NF, macrogol 20000, D-mannitol, glyceryl monostearate, sorbitan monostearate, batyl monostearate, propylene glycol monostearate, polyethylene glycol monostearate, sodium lauryl sulfate, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, etc.

[0172] Examples of coating agents include: ethyl acrylate / methyl methacrylate copolymer dispersion, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, gum arabic, gum arabic powder, ethyl cellulose, ethyl cellulose aqueous dispersion, carnauba wax, carboxyvinyl polymer, gold leaf, silver leaf, triethyl citrate, glycerin, glycerin fatty acid ester, hydrogenated oil, titanium dioxide, sucrose fatty acid ester, stearyl alcohol, stearic acid, magnesium stearate, purified gelatin, purified shellac, gelatin, D-sorbitol, talc, calcium carbonate, magnesium carbonate, medium gold leaf, precipitated calcium carbonate, concentrated glycerin, white shellac, hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose 2910 / titanium dioxide / macrogol 400 mixture, hypromellose, fumaric acid / stearic acid / polyvinyl acetal diethylaminoacetate / Hypermethylcellulose Examples include droxypropyl methylcellulose 2910 mixture, pullulan, polysorbate 80, polyvinyl acetal diethylaminoacetate, povidone, polyvinyl alcohol (partially saponified), macrogol 300, macrogol 400, macrogol 600, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 6000NF, macrogol 20000, macrogol 35000, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, magnesium aluminometasilicate, methyl acrylate / methacrylic acid / methyl methacrylate copolymer, methylcellulose, 2-methyl-5-vinylpyridine methyl acrylate / methacrylic acid copolymer, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, calcium sulfate, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, etc.

[0173] Examples of sugar coating agents include gum arabic, gum arabic powder, ethylcellulose, carnauba wax, carboxymethylcellulose sodium, titanium dioxide, stearic acid, polyoxyl 40 stearate, purified gelatin, purified shellac, purified sucrose, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, sucrose, hydroxypropylcellulose, hypromellose, pullulan, povidone, polyvinyl alcohol (partially saponified), macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, calcium hydrogen phosphate hydrate, calcium dihydrogen phosphate hydrate, and polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer.

[0174] Examples of plasticizers include triethyl citrate, glycerin, glycerin fatty acid esters, D-sorbitol, medium-chain triglyceride, triacetin, concentrated glycerin, castor oil, polyoxyethylene hydrogenated castor oil 60, propylene glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polysorbate 80, macrogol 400, macrogol 600, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, glyceryl monostearate, isopropyl linoleate, and liquid paraffin.

[0175] The dispersants include aminoalkyl methacrylate polymer RS, gum arabic, gum arabic powder, carboxyvinyl polymer, sodium carboxymethyl starch, agar powder, citric acid hydrate, sodium citrate hydrate, glycerin, glycerin fatty acid ester, magnesium silicate, light aluminum oxide, light anhydrous silicic acid, crystalline cellulose, titanium dioxide, sucrose fatty acid ester, stearic acid, magnesium stearate, D-sorbitol, soy lecithin, and low-substituted hydroxypropyl cellulose. Examples include dextrin, corn starch, lactose monohydrate, concentrated glycerin, potato starch, hydroxyethylcellulose, hydroxypropyl starch, hydroxypropylcellulose, hypromellose, povidone, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polysorbate 20, polysorbate 60, polysorbate 80, microcrystalline wax, macrogol 300, macrogol 4000, macrogol 6000, macrogol 6000NF, anhydrous sodium citrate, magnesium aluminometasilicate, methylcellulose, glyceryl monooleate, sorbitan monooleate, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, sodium lauryl sulfate, etc.

[0176] Examples of defoaming agents include ethanol, glycerin fatty acid esters, dimethylpolysiloxane (for oral use), dimethylpolysiloxane / silicon dioxide mixture, sucrose fatty acid esters, silicone defoaming agents, silicone oil, sorbitan fatty acid esters, and polysorbate 80.

[0177] Examples of fluidizing agents include hydrated silicon dioxide, light anhydrous silicic acid, synthetic aluminum silicate, heavy anhydrous silicic acid, magnesium aluminum hydroxide, stearic acid, calcium stearate, magnesium stearate, tricalcium phosphate, talc, magnesium aluminometasilicate, and calcium hydrogen phosphate granules.

[0178] Examples of fragrances and scentings include fennel powder, fennel oil, ethyl vanillin, orange, orange extract, orange essence, orange oil, chamomile oil, caramel, licorice powder, d-camphor, dl-camphor, cinnamon powder, cinnamon oil, citronella oil, sugar flavor, spearmint oil, cherry flavor, clove oil, chili flavor, spruce tincture, spruce oil, pine oil, peppermint oil, vanilla flavor, vanillin, bitter essence, Vitabase, cedarwood oil, fruit flavor, Flavor G1, hesperidin peppermint essence, bergamot oil, vermouth flavor, d-borneol, dl-borneol, matcha, mixed flavor, mint flavor, dl-menthol, l-menthol, eucalyptus oil, lavender oil, bonito flakes, bonito flakes powder, lemon powder, lemon oil, rose water, rose oil, peppermint oil, etc.

[0179] These components may be present individually or in combination of two or more types.

[0180] (Dosage form) The solid compositions according to this embodiment, namely the solid composition according to the first embodiment, the solid composition according to the second embodiment, and the solid composition according to the third embodiment, can all be in dosage forms described in the 18th edition of the Japanese Pharmacopoeia, General Provisions for Preparations, etc., such as oral preparations (tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolvable tablets, etc.), capsules, granules, and powders), and preparations applied orally (including oral tablets, lozenges, sublingual tablets, buccal tablets, adhesive tablets, gums, etc.). The solid compositions according to this embodiment are preferably oral solid compositions.

[0181] Dosage forms of the solid composition according to this embodiment include, for example, tablets, capsules, pills, granules, and fine granules. These solid compositions may be coated by known methods such as sugar coating or film coating as needed. The dosage form of the solid composition is preferably a tablet. Specific examples of tablets include uncoated tablets, film-coated tablets, and sugar-coated tablets.

[0182] The solid composition according to this embodiment may be initially packaged in bottle packaging, PTP packaging, pouch packaging, stick packaging, or SP packaging and stored airtight. Furthermore, they may be pillow-packaged, or stored in boxes or the like. The material used for pillow packaging is not particularly limited, and for example, resin films such as polypropylene film, polyethylene terephthalate film, polyethylene film, or resin films with aluminum foil attached can be used. If hygroscopicity is a concern, a desiccant may be stored simultaneously in the bottle packaging or pillow packaging.

[0183] The solid composition according to this embodiment may be contained in a packaging container to form a package. The solid composition according to this embodiment may be contained in, for example, an airtight package. By forming a package, the convenience of use of the solid composition can be improved. Specifically, the package in this embodiment is a pharmaceutical product.

[0184] As for the packaging form of the solid composition, the solid composition may be initially packaged in a bottle, PTP (Press Through Package), pouch, stick, or SP (Strip Package) and stored airtight. Furthermore, these may be pillow-packed, or stored in a box or similar container. In addition, from the viewpoint of reducing moisture absorption of the solid composition, a desiccant may be stored simultaneously in the packaging container, such as the bottle or pillow packaging.

[0185] Materials used in SP packaging, PTP packaging, stick packaging, pillow packaging, etc., include, for example, resin films such as polypropylene film, polyethylene terephthalate film, and polyethylene film, as well as resin films to which aluminum foil is attached. Either single-layer films or multi-layer films (e.g., laminate films) may be used.

[0186] Furthermore, it is preferable that the materials constituting the packaging container include materials that are less susceptible to the effects of moisture. Examples of such packaging include packaging formed from at least one of a moisture-proof material and a gas barrier material.

[0187] Examples of moisture-proof materials include a combination of PTP (polypropylene) and polyethylene aluminum pillow packaging. Furthermore, when the solid composition is a tablet, PTP packaging with aluminum on both sides (Al-Al packaging) may be used as a moisture-proof material, considering factors such as suppressing the rise in moisture content of the tablet, the storage stability of the tablet, and the stability of the tablet after opening.

[0188] Known materials may be used as the gas barrier material, for example, a laminate film having a functional barrier layer, and may be used to serve the same purpose as the moisture barrier material, or in combination with the moisture barrier material.

[0189] Furthermore, the packaging containers may be made environmentally friendly. For example, environmentally friendly materials such as recycled plastics, biomass plastics, and biodegradable plastics may be used in part or all of the packaging materials.

[0190] (Manufacturing method) In a fourth embodiment, a method for producing a solid composition is provided, comprising the step of contacting (A) at least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of dextromethorphan and its salts, and (C) at least one selected from the group consisting of tranexamic acid and its salts.

[0191] The crystals comprising ibuprofen and tranexamic acid may be produced in accordance with the method for producing a mixture containing both components, as described in Japanese Patent Publication No. 2022-40057 (shown above).

[0192] In a fifth embodiment, a method for producing a solid composition is provided, comprising the step of contacting (A) at least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of noscapine and its salts, and (C) at least one selected from the group consisting of tranexamic acid or its salts, acetaminophen or its salts, clemastine or its salts, citric acid or its salts, stearic acid or its salts, and sodium bicarbonate.

[0193] In a sixth embodiment, a method for producing a solid composition is provided, comprising the step of contacting (A) at least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of noscapine and its salts, (C) at least one selected from the group consisting of dextromethorphan and its salts, and (D) at least one selected from the group consisting of chlorpheniramine or its salts, caffeine or its salts, croscarmellose sodium, silicon dioxide, and talc.

[0194] The production of the solid composition according to the above embodiment can be carried out using known techniques. Each component can be added in any step and finally brought into contact with each other. A solvent and a binder may be added to the mixture after contact and kneaded, and the resulting kneaded product may be used as the solid composition.

[0195] The resulting mixture can be further subjected to drying and granulation processes to produce granules. In this case, granules containing each component may be prepared separately. Granulation can be carried out wet or dry.

[0196] The obtained granules (granulated material) can be used as is, or additives can be added to the granules, and then compressed into tablets to produce uncoated tablets, or these can be further coated with a film.

[0197] (Color change inhibitor) In a seventh embodiment, a color change inhibitor for a solid composition is provided, comprising (A) at least one selected from the group consisting of ibuprofen and its salts, and (B) at least one selected from the group consisting of dextromethorphan and its salts, wherein the inhibitor further comprises (C) at least one selected from the group consisting of tranexamic acid and its salts.

[0198] (C) At least one selected from the group consisting of tranexamic acid and its salts is as described in component (C) of the solid composition according to the first embodiment, and (A) At least one selected from the group consisting of ibuprofen and its salts and (B) At least one selected from the group consisting of dextromethorphan and its salts are as described in components (A) and (B) of the solid composition according to the first embodiment, respectively.

[0199] The above-mentioned color change inhibitor is preferably used in such an amount that the amount of at least one selected from the group consisting of (C) tranexamic acid and its salts relative to component (A) or (B) falls within the range described as the preferred content of component (C) of the solid composition according to the first embodiment. Furthermore, it is preferable that tranexamic acid is added to the solid composition after crystallization with ibuprofen (in a crystallized state).

[0200] (Property change inhibitor) In the eighth embodiment, a property change inhibitor for a solid composition is provided, comprising (A) at least one selected from the group consisting of ibuprofen and salts thereof, and (B) at least one selected from the group consisting of noscapine and salts thereof, wherein the inhibitor further comprises (C) at least one selected from the group consisting of tranexamic acid or a salt thereof, acetaminophen or a salt thereof, clemastine or a salt thereof, citric acid or a salt thereof, stearic acid or a salt thereof, and sodium bicarbonate.

[0201] (C) Tranexamic acid or its salt, acetaminophen or its salt, clemastine or its salt, citric acid or its salt, stearic acid or its salt, and sodium bicarbonate are as described in component (C) of the solid composition according to the second embodiment, and components (A) and (B) are as described in components (A) and (B) of the solid composition according to the second embodiment.

[0202] The above-mentioned property change inhibitor is preferably used in such an amount relative to component (A) or (B) that the amount of at least one selected from the group consisting of (C) tranexamic acid or a salt thereof, acetaminophen or a salt thereof, clemastine or a salt thereof, citric acid or a salt thereof, stearic acid or a salt thereof, and sodium bicarbonate is within the range described as the preferred content of component (C) of the solid composition according to the second embodiment.

[0203] In the ninth embodiment, a property change inhibitor for a solid composition is provided, comprising (A) at least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of noscapine and its salts, and (C) at least one selected from the group consisting of dextromethorphan and its salts, wherein the inhibitor further comprises (D) at least one selected from the group consisting of chlorpheniramine or its salts, caffeine or its salts, croscarmellose sodium, silicon dioxide, and talc.

[0204] (D) Chlorpheniramine or its salt, caffeine or its salt, croscarmellose sodium, silicon dioxide, and talc are as described in component (D) of the solid composition according to the third embodiment, and components (A) to (C) are as described in components (A) to (C) of the solid composition according to the third embodiment.

[0205] The above-mentioned property change inhibitor is preferably used in such an amount that the amount of (D) chlorpheniramine or its salt, caffeine or its salt, croscarmellose sodium, silicon dioxide, and talc relative to component (A), (B), or (C) falls within the range described as the preferred content of component (D) of the solid composition according to the third embodiment.

[0206] To illustrate the present invention in more detail, test examples and embodiments are described below, but the present invention is not limited thereto. [Examples]

[0207] [First Embodiment] 1.Raw materials In this example, unless otherwise specified, the following raw materials were used. [Table 1]

[0208] 2. Preparation of the solid composition (Comparative Example 1) 50g of ibuprofen (manufactured by Albemar) and 50g of dextromethorphan hydrobromide hydrate were weighed out, mixed in a bag 100 times, sieved through a 42-mesh sieve, and mixed in a bag 100 more times to obtain a physical mixture powder. 2g of the obtained physical mixture powder was weighed into a 1K glass bottle, sealed tightly, and then adjusted to a uniform thickness to obtain the sample for Comparative Example 1.

[0209] (Comparative Examples 2-3) 5.0 g of the physical mixture powder obtained in Comparative Example 1 and 2.5 g each of tartaric acid or anhydrous citric acid were weighed into a 6K glass bottle and mixed 100 times to obtain the physical mixture powder. 2 g of each obtained physical mixture powder was weighed into a 1K glass bottle, sealed tightly, and adjusted to a uniform thickness to obtain the sample for Comparative Example 2 or 3.

[0210] (Example 1) 10 g of ibuprofen (manufactured by Albemar), 10 g of dextromethorphan hydrobromide hydrate, and 7.6 g of tranexamic acid (manufactured by Kyowa Pharma Chemical) were weighed out, mixed in a bag 100 times, sieved through a 42-mesh sieve, and mixed in a bag 100 more times to obtain a physical mixture powder. 2 g of the obtained physical mixture powder was weighed into a 1K glass bottle, sealed tightly, and adjusted to a uniform thickness to obtain the sample for Example 1.

[0211] (Example 2) 240.0 g of ibuprofen (manufactured by Yonezawa Hamari) and 182.9 g of tranexamic acid (manufactured by AMI) were charged into a stirring and mixing granulator (Vertical Granulator VG-5 (manufactured by Powrec)) and mixed to obtain a mixed powder. 69 g of a mixture of ethanol (purity 99.5%) (manufactured by Kanto Chemical) and purified water (mass ratio 8:2) was added to this mixed powder and kneaded and granulated to obtain a paste. The paste was wet-milled using a power mill (manufactured by Dalton) at low speed and 32 mesh. After that, it was stored in a constant temperature bath at 70°C for 89 hours to obtain crystals consisting of ibuprofen and tranexamic acid.

[0212] Six mg of the obtained crystals were placed in an aluminum pan, and the temperature range of 25 to 350°C was measured at a rate of 60°C per minute using a differential scanning calorimeter DSC3+ (Mettler Toledo). The results are shown in Figure 1. As shown in Figure 1, the peak derived from ibuprofen around 75°C disappeared, and a peak derived from the crystal composed of ibuprofen and tranexamic acid appeared around 180°C, confirming that crystals with a molar ratio of ibuprofen to tranexamic acid of 1:1 were obtained.

[0213] Next, 17.6 g of the obtained crystals and 10 g of dextromethorphan hydrobromide hydrate were weighed out, mixed 100 times in a bag, sieved through a 42-mesh sieve, and mixed 100 more times in a bag to obtain the physical mixture powder. 2 g of the obtained physical mixture powder was weighed into a 1K glass bottle, sealed tightly, and adjusted to a uniform thickness to obtain the sample for Example 2.

[0214] The mixing ratios (mass ratios) of each sample are shown in the table below. In the table below, "IB-TXA crystals" refers to crystals composed of ibuprofen and tranexamic acid. [Table 2]

[0215] 3. Evaluation of color changes in solid compositions Samples from Examples 1 and 2, and Comparative Examples 1 to 3, were stored at 80°C for 24 hours, and the color change before and after storage was evaluated visually.

[0216] Next, the color changes were evaluated according to the following criteria. Color change: A: No change, B: Slight discoloration, C: Discoloration present, D: Significant discoloration

[0217] The following table shows the results of color changes compared to the start of high-temperature storage. Significant color changes were observed in Comparative Examples 1-3. Specifically, the samples of Comparative Examples 1-3 turned yellow. On the other hand, although the sample of Example 1 turned light yellow, the color change was significantly suppressed compared to Comparative Examples 1-3. Furthermore, no discoloration was observed in the sample of Example 2. From the above, it was shown that at least one substance selected from the group consisting of tranexamic acid and its salts can suppress the color change under high-temperature conditions of at least one substance selected from the group consisting of ibuprofen and its salts and at least one substance selected from the group consisting of dextromethorphan and its salts, and that this effect is particularly pronounced when crystals consisting of ibuprofen and tranexamic acid are formed.

[0218] [Table 3]

[0219] [Second Example] 1.Raw materials In this example, the following raw materials were used. [Table 4]

[0220] 2. Preparation of the solid composition (Comparative Example 1) 3.0 g of ibuprofen (SI Group) and 3.0 g of noscapine were weighed out, mixed 100 times in a bag, sieved through a 42-mesh sieve, and mixed 100 more times in a bag to obtain a physical mixture powder. 2 g of the obtained physical mixture powder was weighed into a 1K glass bottle, sealed tightly, and adjusted to a uniform thickness to prepare the sample.

[0221] (Example 1) 2.5g of ibuprofen (SI Group), 2.5g of noscapine, and 1.9g of tranexamic acid (Hunan Dongting Pharmaceutical) were weighed into a 5K glass bottle, mixed 100 times, sieved through a 22-mesh sieve, and then mixed 100 more times in the 5K glass bottle to obtain a physical mixture powder. 2g of the obtained physical mixture powder was weighed into a 1K glass bottle, sealed tightly, and adjusted to a uniform thickness to prepare the sample.

[0222] (Examples 2 and 3) 2.5 g of ibuprofen (manufactured by SI Group), 2.5 g of noscapine, and 2.5 g each of acetaminophen or clemastine fumarate were weighed into a 5K glass bottle, mixed 100 times, sieved through a 30-mesh sieve, and then mixed 100 times again in the 5K glass bottle to obtain a physical mixture powder. 2 g of the obtained physical mixture powder was weighed into a 1K glass bottle, sealed tightly, and adjusted to a uniform thickness to obtain the sample for Example 2 or 3.

[0223] (Examples 4-6) 2.5g of ibuprofen (manufactured by SI Group), 2.5g of noscapine, and 2.5g each of magnesium stearate, anhydrous citric acid, or sodium bicarbonate were weighed into a 5K glass bottle, mixed 100 times, sieved through a 22-mesh sieve, and then mixed 100 times again in the 5K glass bottle to obtain the physical mixture powder. 2g of the obtained physical mixture powder was weighed into a 1K glass bottle, sealed tightly, and adjusted to a uniform thickness to obtain the samples for Examples 4-6.

[0224] (Example 7) Similar to Example 2 of Example 1, crystals consisting of ibuprofen and tranexamic acid were obtained. 4.4 g of the obtained crystals and 2.5 g of noscapine were weighed into a 5K glass bottle, mixed 100 times, sieved through a 22-mesh sieve, and then mixed 100 more times in the 5K glass bottle to obtain a physical mixture powder. 2 g of the obtained physical mixture powder was weighed into a 1K glass bottle, sealed tightly, and adjusted to a uniform thickness to prepare the sample.

[0225] The mixing ratios (mass ratios) of each sample are shown in the table below. In the table below, "IB-TXA crystals" refers to crystals composed of ibuprofen and tranexamic acid.

[0226] [Table 5]

[0227] 3. Evaluation of changes in the properties of the solid composition Each sample from Examples 1-7 and Comparative Example 1 was left to stand at 80°C for 24 hours, and changes in color and state were evaluated. Changes in state included solidification, moisture absorption, separation, paste formation, expansion, and adhesion to the wall of a standard bottle. For color changes, it was confirmed whether a change in color was visible before and after standing. For changes in state, it was confirmed whether the changes in state after standing were suppressed compared to Comparative Example 1.

[0228] Next, the color changes were evaluated according to the following criteria. Color change: A: No change, B: Slight change, C: Change present, D: Significant change

[0229] The following table shows the results of color changes compared to the start of high-temperature storage. Comparative Example 1 showed significant changes in both color and state. Specifically, Comparative Example 1 separated into two layers: yellow and white.

[0230] On the other hand, in Examples 1 to 7, color tone change was suppressed. Specifically, although a change in color tone to pale yellow was observed in Examples 1 to 6, the color tone change was significantly suppressed as compared with Comparative Example 1. No color tone change was observed in Example 7.

[0231]

Table 6

[0232] Further, in the Examples, state change was suppressed as compared with Comparative Example 1. For example, although partial solidification occurred in Example 1, state change was suppressed as compared with Comparative Example 1. Although partial formation of a paste occurred in Examples 2 and 3, state change was suppressed as compared with Comparative Example 1. No state change was observed in Example 7.

[0233] From these results, it was shown that by blending at least one selected from the group consisting of tranexamic acid or a salt thereof, acetaminophen or a salt thereof, clemastine or a salt thereof, citric acid or a salt thereof, stearic acid or a salt thereof, and sodium bicarbonate, in addition to at least one selected from the group consisting of ibuprofen and salts thereof, and at least one selected from the group consisting of noscapine and salts thereof, change in properties of a solid composition containing at least one selected from the group consisting of ibuprofen and salts thereof, and at least one selected from the group consisting of noscapine and salts thereof, particularly change in properties under high temperature, can be suppressed.

[0234] [Third Example] 1. Raw materials In the present Example, the following raw materials were used.

Table 7

[0235] 2. Preparation of solid composition (Comparative Example 1) 50 g of ibuprofen and 50 g of noscapine were weighed out, mixed in a bag 100 times, sieved through a 42-mesh sieve, and further mixed in the bag 100 times to obtain a physically mixed powder. 5.0 g of the obtained physically mixed powder and 2.5 g of dextromethorphan hydrobromide hydrate were weighed into a 6K glass bottle, mixed 100 times, then 2.0 g of the obtained mixed powder was weighed into a 1K glass bottle, sealed, adjusted to have a uniform thickness, and used as a sample.

[0236] (Examples 1 to 3, 5) 2.0 g of ibuprofen, 2.0 g of noscapine, 2.0 g of dextromethorphan hydrobromide hydrate, and 2.0 g each of d-chlorpheniramine maleate, anhydrous caffeine, croscarmellose sodium, or talc were weighed into a 5K glass bottle, mixed 100 times, sieved through a 22-mesh sieve, and further mixed 100 times in a 5K glass bottle to obtain a physically mixed powder. 2 g of the obtained physically mixed powder was weighed into a 1K glass bottle, sealed, adjusted to have a uniform thickness, and used as the samples of Examples 1 to 3 and 5, respectively.

[0237] (Example 4) 2.0 g of ibuprofen, 2.0 g of noscapine, 2.0 g of dextromethorphan hydrobromide hydrate, and 0.5 g of light anhydrous silicic acid were weighed into a 5K glass bottle, mixed 100 times, sieved through a 22-mesh sieve, and further mixed 100 times in a 5K glass bottle to obtain a physically mixed powder. 2 g of the obtained physically mixed powder was weighed into a 1K glass bottle, sealed, adjusted to have a uniform thickness, and used as a sample.

[0238] The blending ratios (mass ratios) of the respective samples are shown in the table below.

[0239]

Table 8

[0240] 3. Evaluation of property change of solid composition Each sample from Examples 1-5 and Comparative Example 1 was left to stand at 80°C for 24 hours, and changes in color and state were evaluated. Changes in state included solidification, aggregation, moisture absorption, and separation of the powder. The changes in color and state after standing were checked to see if they were suppressed compared to Comparative Example 1.

[0241] Compared to the initial state at the start of high-temperature storage, Comparative Example 1 showed significant changes in color and state. Specifically, Comparative Example 1 separated into two layers: red and white.

[0242] On the other hand, color changes and property changes were suppressed in Examples 1 to 5. Specifically, in Examples 1 and 2, color changes were suppressed compared to Comparative Example 1. In Examples 3 and 5, although aggregation and solidification occurred, the change in state was suppressed compared to Comparative Example 1. In Example 4, although aggregation and solidification occurred, the color change and the change in state were significantly suppressed compared to Comparative Example 1.

[0243] These results demonstrate that by combining at least one selected from the group consisting of ibuprofen and its salts, at least one selected from the group consisting of noscapine and its salts, and at least one selected from the group consisting of dextromethorphan and its salts, with at least one selected from the group consisting of chlorpheniramine or its salt, caffeine or its salt, croscarmellose sodium, silicon dioxide, and talc, it is possible to suppress changes in the properties of a solid composition containing at least one selected from the group consisting of ibuprofen and its salts, at least one selected from the group consisting of noscapine and its salts, and at least one selected from the group consisting of dextromethorphan and its salts, particularly changes in properties at high temperatures.

[0244] Although preferred embodiments and examples of the present invention have been described above, the present invention is not limited thereto. Additions, omissions, substitutions, and other modifications to the configuration are possible without departing from the spirit of the present invention.

Claims

1. The following ingredients: (A) At least one selected from the group consisting of ibuprofen and its salts, (B) At least one selected from the group consisting of dextromethorphan and its salts, (C) At least one selected from the group consisting of tranexamic acid and its salts, Solid compositions containing (excluding those containing at least one selected from the group consisting of guaifenesin or its salts, and diphenhydramine or its salts).

2. The solid composition according to claim 1, comprising crystals comprising (A) ibuprofen and (C) tranexamic acid.

3. The solid composition according to claim 2, wherein the molar ratio of (A) ibuprofen to (C) tranexamic acid in the crystal is 1:

1.

4. The solid composition according to any one of claims 1 to 3, wherein the mass ratio of (A) to (B) in the solid composition is 20:1 to 5:1 ((A):(B)).

5. The solid composition according to any one of claims 1 to 3, wherein the mass ratio of (A) to (C) in the solid composition is 1:0.5 to 1:2.5 ((A):(C)).

6. The solid composition according to any one of claims 1 to 3, wherein the mass ratio of (B) to (C) in the solid composition is 1:3 to 1:32 ((B):(C)).

7. The following ingredients: (A) At least one selected from the group consisting of ibuprofen and its salts, (B) at least one selected from the group consisting of noscapine and its salts, (C) At least one selected from the group consisting of tranexamic acid or a salt thereof, acetaminophen or a salt thereof, clemastine or a salt thereof, citric acid or a salt thereof, stearic acid or a salt thereof, and sodium bicarbonate. A solid composition containing the following:

8. The solid composition according to claim 7, comprising crystals comprising (A) ibuprofen and (C) tranexamic acid.

9. The solid composition according to claim 8, wherein the molar ratio of (A) ibuprofen to (C) tranexamic acid in the crystal is 1:

1.

10. The solid composition according to any one of claims 7 to 9, wherein the mass ratio of (A) to (B) in the solid composition is 1:0.01 to 1:0.4 ((A):(B)).

11. The solid composition according to any one of claims 7 to 9, wherein the mass ratio of (A) to (C) in the solid composition is 1:0.01 to 1:10 ((A):(C)).

12. The solid composition according to any one of claims 7 to 9, wherein the mass ratio of (B) to (C) in the solid composition is 1:0.1 to 1:150 ((B):(C)).

13. The following ingredients: (A) At least one selected from the group consisting of ibuprofen and its salts, (B) At least one selected from the group consisting of noscapine and its salts, (C) At least one selected from the group consisting of dextromethorphan and its salts, (D) At least one selected from the group consisting of chlorpheniramine or its salt, caffeine or its salt, croscarmellose sodium, silicon dioxide, and talc. A solid composition containing the following:

14. The solid composition according to claim 13, wherein the mass ratio of (A) to (B) in the solid composition is 1:0.01 to 1:0.4 ((A):(B)).

15. The solid composition according to claim 13, wherein the mass ratio of (A) to (C) in the solid composition is 1:0.01 to 1:0.4 ((A):(C)).

16. The solid composition according to claim 13, wherein the mass ratio of (A) to (D) in the solid composition is 1:0.001 to 1:10 ((A):(D)).

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