Solid pharmaceutical composition

Abstract

A solid that maintains a stable suspension state over time and suppresses the occurrence of concentration variations. To provide a pharmaceutical composition. [Solution] Sodium azulene sulfonate (a1) and sodium copper chlorophyllin A solid containing component (a) consisting of at least one of (a2) and teprenone (b). Pharmaceutical composition.

Description

Technical Field

[0001] The present invention relates to a solid pharmaceutical composition, and more particularly, to a solid pharmaceutical composition with excellent dispersibility as described below.

Background Art

[0002] In a solid pharmaceutical composition, when active pharmaceutical ingredients or excipients do not disperse properly in water, the degree of suspension may change over time, leading to uneven concentration. When uneven concentration occurs, the amount of components ingested during administration becomes non-uniform, resulting in non-uniform distribution in the stomach, residence time, and contact with digestive juices. As a result, some components are absorbed quickly, while the absorption of some components may be delayed or insufficient, which may cause variations in absorption, and there are concerns that this may affect the stability of drug efficacy. As a result, some components are absorbed quickly, while the absorption of some components may be delayed or insufficient, which may cause variations in absorption, and there are concerns that this may affect the stability of drug efficacy. As a result, some components are absorbed quickly, while the absorption of some components may be delayed or insufficient, which may cause variations in absorption, and there are concerns that this may affect the stability of drug efficacy. There are concerns that this may affect the stability of drug efficacy.

[0003] Conventionally, as a method to eliminate such concerns, for example, a method using a thickener, a suspending agent, a dispersant or the like to achieve stability of the suspended state is known (for example, Patent Document 1). Conventionally, as a method to eliminate such concerns, for example, a method using a thickener, a suspending agent, a dispersant or the like to achieve stability of the suspended state is known (for example, Patent Document 1). However, the addition of a thickener unrelated to the drug efficacy may increase the viscosity, which causes the problem of impairing the ease of swallowing during administration. There was a problem that the ease of swallowing during administration was impaired. In addition, since it is desirable to maintain suspension stability without adding extra components, the arbitrary use of thickeners and the like cannot be said to be an optimal design. In addition, since it is desirable to maintain suspension stability without adding extra components, the arbitrary use of thickeners and the like cannot be said to be an optimal design. Therefore, there is a demand for a technique that stabilizes the suspended state, prevents an excessive increase in viscosity, and ensures uniformity during administration. There is a demand for a technique that stabilizes the suspended state, prevents an excessive increase in viscosity, and ensures uniformity during administration.

[0004] On the other hand, even in the manufacturing process, if the suspended state is unstable, the content of the active ingredient in each pharmaceutical preparation lot tends to fluctuate easily. For example, if dispensing is performed without obtaining a uniform suspension, the content of the active ingredient in each pharmaceutical preparation lot tends to fluctuate easily. This means that the distribution of the active ingredient differs from lot to lot, creating a risk of variations in drug efficacy depending on the formulation. Furthermore, in quality control, the uniformity of the administered components is an important factor, as is the stability of the suspension. If the performance is low, the variability of data in clinical trials increases, and the reproducibility of the expected drug efficacy decreases. There is a risk of that happening.

[0005] Thus, in solid pharmaceutical compositions, technologies for improving the stability of the suspension state are used in manufacturing processes. Ensuring uniformity during administration, improving the stability of dosage during administration, and ultimately improving the reproducibility of drug effects. This has become an important issue from the perspective mentioned above. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] Japanese Patent Publication No. 2024-052251 [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] The present invention aims to provide a novel solid pharmaceutical composition with high stability. [Means for solving the problem]

[0008] In view of these circumstances, the present inventors have conducted extensive research and have found that in a solid pharmaceutical composition, A Low levels of sodium zulene sulfonate (a1) and sodium copper chlorophyllin (a2) By using a component (a) consisting of at least one of these components in combination with teprenone (b), the effects can be controlled over time. We have discovered that it is possible to suppress the accompanying changes in suspension degree and prevent the occurrence of concentration unevenness, and therefore, we present the present invention. It's finished.

[0009] In other words, the present invention has the following aspects. [1] Sodium azulenesulfonate (a1) and sodium copper chlorophyllin (a 2), which is component (a) comprising at least one of the two, and teprenone (b), a solid pharmaceutical composition containing the same. [2] The mass ratio of the teprenone (b) to the component (a) comprising at least one of the sodium azulenesulfonate (a1) and copper sodium chlorophyllin (a2), (b / a) is in the range of 0.1 to 200, the solid pharmaceutical composition according to [1]. [3] The solid pharmaceutical composition according to [1] or [2], further comprising menthol (c). 物。 [4] The solid pharmaceutical composition according to any one of [1] to [3], wherein the form of the solid pharmaceutical composition is granules. 形医薬組成物。 [5] Sodium azulenesulfonate (a1) and sodium copper chlorophyllin (a 2), which is component (a) comprising at least one of the two, teprenone (b), and menthol (c), a solid pharmaceutical composition containing the same, wherein the mass ratio of the teprenone (b) to the component (a) comprising at least one of the sodium azulenesulfonate (a1) and copper chloro phyllin sodium (a2) (b / a) is in the range of 0.1 to 200, the menthol (c) is contained in an amount of 0.0005 to 12 mass% relative to the total mass of the solid pharmaceutical composi tion, and the form of the solid pharmaceutical composition is granules, the solid pharmaceutical composition. Effects of the Invention

[0010] The present invention uses the component (a) comprising at least one of sodium azulenesulfonate (a1) and sodium copper chlorophyllin (a2) in combination with teprenone (b). Therefore, excellent suspension stability can be obtained, and a uniform concentration can be maintained even after a lapse of time . As a result, variation in dosage at the time of administration is reduced, and excessive addition of a thickener is avoided while achieving suspension stability, and uniform distribution in the manufacturing process can be performed without impairing ease of ingestion . [Mode for Carrying Out the Invention]

[0011] Hereinafter, the present invention will be described based on examples of modes for carrying out the present invention. However, the present invention is not limited to the embodiments described below.

[0012] In the present specification, "x and / or y (x and y are any constituents)" means at least one of x and y, and refers to three cases: x only, y only, and x and y . In the present specification, when expressed as "X to Y" (X and Y are any numbers), unless otherwise specified, it means "X or more and Y or less", and also includes the meaning of "preferably greater than X" or "preferably less than Y". In the present specification, when expressed as "X or more" (X is any number) or "Y or less" (Y is any number), it also includes the meaning of "preferably greater than X" or "preferably less than Y". Regarding the numerical ranges described stepwise in the present specification, the upper limit value or lower limit value of a numerical range in one step may be arbitrarily combined with the upper limit value or lower limit value of a numerical range in another step. Further, in the numerical ranges described in the present specification, the upper limit value or lower limit value of the numerical range may be replaced with the values shown in the Examples.

[0013] ​<<Solid drug composition>> A solid pharmaceutical composition according to one embodiment of the present invention is sodium azulene sulfonate (a1) and component (a) consisting of at least one of copper chlorophyllin sodium (a2), and This is a solid pharmaceutical composition containing prenon (b). The individual components are described below.

[0014] <Ingredients (a)> In this embodiment, component (a) refers to sodium azulene sulfonate (a1) and This means at least one of copper chlorophyllin sodium (a2), and azure Sodium chlorophyllin (a1) and / or sodium copper chlorophyllin (a2) To possess means the same thing. In other words, component (a) consists only of sodium azulene sulfonate (a1), copper chlorophate Sodium chlorophosphate (a2) only, sodium azulene sulfonate (a1) and copper chlorophosphate. This includes substances containing both phylline sodium (a2).

[0015] In this embodiment, the content of component (a) is determined to be solid in order to fully exert its effectiveness. Preferably, it contains 0.01 to 10% by mass of the total mass of the pharmaceutical composition, and 0.02 to It is more preferable to contain 8% by mass, and even more preferable to contain 0.03 to 5% by mass. Furthermore, the content of component (a) is 0.0005% by mass relative to the total mass of the solid pharmaceutical composition. or more, 0.001 mass% or more, 0.005 mass% or more, 0.01 mass% or more, 0.05 quality It may be % by volume or more, 0.1% by mass or more, 0.5% by mass or more, or 1% by mass or more, and 50% by mass % by mass or less, 40% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15 quality It may be less than or equal to a certain amount, less than or equal to 10% by mass, less than or equal to 5% by mass, or less than or equal to 1% by mass.

[0016] <Sodium azulene sulfonate (a1)> The azulene sulfonate sodium (a1) has a sulfone group (-SO3N) attached to the azulene ring. It is a water-soluble compound having (a). The sodium azulene sulfonate (a1) is a stomach It is known to act directly on the mucous membrane, suppressing inflammation and promoting tissue repair. ru.

[0017] In this embodiment, the content of sodium azulene sulfonate (a1) is such that the effectiveness is To ensure optimal efficacy, the solid pharmaceutical composition should contain 0.01 to 0.5% by mass of the active ingredient. It is preferable to contain 0.02 to 0.4% by mass, and more preferably 0.03 to 0 It is even more preferable to contain 0.2% by mass. Also, sodium azulene sulfonate (a1 The content of ) is 0.0005% by mass or more and 0.001% by mass relative to the total mass of the solid pharmaceutical composition. Mass% or more, 0.005 mass% or more, 0.01 mass% or more, 0.05 mass% or more, 0.1 It may be 0.5% by mass or more, 1% by mass or more, and 50% by mass or less, or 40% by mass. % by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10 quality % or less, 5% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less. That's fine.

[0018] The daily dose of sodium azulene sulfonate (a1) is determined based on the patient's symptoms and age. The dosage is adjusted as appropriate depending on age, weight, administration method, etc., but is 0.5 to 10 mg, more preferably, The amount can be 0.8 to 8 mg, more preferably 1 to 6 mg.

[0019] <Sodium copper chlorophyllin (a2)> The aforementioned copper chlorophyllin sodium (a2) is a chlorophyll derivative, and carboxy This is a water-soluble compound in which the cy group is stabilized as a sodium salt. Lilium (a2) is known to have a function that helps repair damaged gastric mucosa.

[0020] In this embodiment, the content of copper chlorophyllin sodium (a2) is such that the effectiveness is sufficient. To ensure optimal performance, the composition should contain 0.1 to 10% by mass relative to the total mass of the solid pharmaceutical composition. Preferably, it contains 0.5 to 8% by mass, more preferably 1 to 5% by mass. This is even more preferable. Also, the content of copper chlorophyllin sodium (a2) is the solid drug compound. 0.0005% or more by mass, 0.001% or more by mass, and 0.005% by mass relative to the total mass of the finished product. % or more, 0.01 mass% or more, 0.05 mass% or more, 0.1 mass% or more, 0.5 mass% or more The above may be 1% by mass or more, 50% by mass or less, 40% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, 5% by mass or less, 1 It may be less than or equal to a mass percent.

[0021] The daily dose of copper chlorophyllin sodium (a2) is determined based on the patient's symptoms and age. The dosage is adjusted as appropriate depending on body weight, administration method, etc., but preferably 20-200 mg, more preferably The amount can be 30 to 150 mg, more preferably 40 to 120 mg. .

[0022] In this embodiment, component (a) is sodium azulene sulfonate (a1) and copper It is preferable to have both chlorophyllin sodium (a2), and in particular copper chlorophyllin Mass ratio of sodium filin (a2) to sodium azulene sulfonate (a1) (a2 / a1) is preferably in the range of 1 to 200, and more preferably 3 to 18 0, more preferably 6 to 120. Also, copper chlorophyllin sodium (a2) The mass ratio (a2 / a1) of a2 to sodium azulene sulfonate (a1) is 0.00 0.5 or higher, 0.001 or higher, 0.005 or higher, 0.01 or higher, 0.05 or higher, 0.1 or higher It may be 0.5 or more, 1 or more, 5 or more, 10 or more, and 1000 or less, 500 or less. , 450 or less, 400 or less, 350 or less, 300 or less, 250 or less, 200 or less, 150 The following may also be 100 or less, or 50 or less.

[0023] <Teprenone (b)> The teprenone (b) used in this embodiment is also called geranylgeranylacetone. Lupenoid compounds (C 23 H 38 O) The aforementioned teprenone (b) increases mucus. It is known to promote the regeneration of the gastric mucosa and provide protection from stomach acid.

[0024] In this embodiment, the amount of teprenone (b) is considered to be sufficient in order to fully exert its effectiveness. Furthermore, it is preferable that it be contained in an amount of 0.1 to 20% by mass relative to the total mass of the solid pharmaceutical composition, and 0.5 It is more preferable to contain ~10% by mass, and even more preferable to contain 1~5% by mass. Furthermore, the teprenone (b) content is 0.0005% of the total mass of the solid pharmaceutical composition. % by weight or more, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.0 It may be 5% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 1% by mass or more, 5 0 mass% or less, 40 mass% or less, 30 mass% or less, 25 mass% or less, 20 mass% or less, 1 It may be 5% by mass or less, 10% by mass or less, or 5% by mass or less.

[0025] The daily dose of teprenone (b) is determined based on the patient's symptoms, age, weight, administration method, etc. The amount is adjusted as appropriate, but preferably 50-200 mg, more preferably 75-1 The amount can be 70 mg, and more preferably 100 to 150 mg.

[0026] The mass ratio (b / a1) of teprenone (b) to component (a1) is effective. From the perspective of ensuring sufficient performance, it is preferable that the value be in the range of 10 to 200, and more preferably, 12 to 150, more preferably 15 to 125. Also, the teprenone (b) The mass ratio (b / a1) to the above component (a1) is 0.1 or more, 0.5 or more, 1 or more, 5 or more, 10 or more, 15 or more, 30 or more, 70 or more, 100 or more, 120 or more, Also good: under 1000, under 500, under 450, under 400, under 350, under 300 Even if it is 250 or less, 200 or less, 150 or less, 100 or less, 50 or less, or 25 or less good.

[0027] The mass ratio (b / a2) of teprenone (b) to component (a2) is effective. From the standpoint of ensuring sufficient performance, it is preferable that the value be in the range of 0.1 to 10, and more preferably, 0.3 to 7, more preferably 0.7 to 5. Also, the preceding teprenone (b) The mass ratio (b / a2) to the component (a2) is 0.0005 or greater, 0.001 or greater, 0 0.005 or higher, 0.01 or higher, 0.05 or higher, 0.1 or higher, 0.5 or higher, 1 or higher, 3 or higher , may be 500 or less, 400 or less, 300 or less, 100 or less, 50 or less, 25 The following may also be 10 or less, 5 or less, 3 or less.

[0028] The solid pharmaceutical composition in this embodiment comprises component (a), teprenone (b), and In addition, because it can further improve dispersibility, it contains menthol (c). This is preferable. Examples of the menthol (c) include l-menthol and dl-menthol. However, l-menthol is preferred due to its superior stability over time. These are one type Alternatively, two or more types can be used in combination. Furthermore, in systems containing menthol (c), the issue of dispersibility tends to become apparent. However, this embodiment has the advantage of being able to achieve a stable suspension state even in such systems. It is for use.

[0029] When this embodiment contains menthol (c), it offers an excellent balance with improved taste sensation. From this perspective, it is preferable that the solid pharmaceutical composition contain 0.0005 to 12% by mass of the total mass. It is more preferable to contain 0.005 to 10% by mass, and more preferably 0.01 to 5% by mass. It is even more preferable that it contains 0.03 to 1.5% by mass. The menthol (c) content is 0.0005% by mass or more, relative to the total mass of the solid pharmaceutical composition. , 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass The above may be 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, and 50% by mass Below, 40% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass The following amounts may be 10% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less.

[0030] If this embodiment contains menthol (c), the menthol relative to component (a1) It is preferable that the mass ratio of Thor (c) (c / a1) is in the range of 0.1 to 65, and more Preferably 0.5 to 45, more preferably 1 to 30, and even more preferably The range is 4-25. Also, the mass ratio of menthol (c) to component (a1) (c / a1) This includes values ​​of 0.001 or higher, 0.005 or higher, 0.01 or higher, 0.05 or higher, 0.1 or higher, and 0. It may be 5 or more, 1 or more, 5 or more, 10 or more, 20 or more, and 500 or less, 400 or less. Below, 300 or less, 200 or less, 100 or less, 50 or less, 25 or less, 10 or less, 5 or less. It's okay to have it.

[0031] If this embodiment contains menthol (c), the menthol relative to component (a2) It is preferable that the mass ratio of Thor (c) (c / a²) is in the range of 0.005 to 3. Preferably 0.02 to 2, more preferably 0.05 to 1.5, and even more Preferably, it is 0.1 to 1. Also, the mass ratio of menthol (c) to component (a2) (c / a2) is 0.0005 or higher, 0.001 or higher, 0.005 or higher, 0.01 or higher, It may be 0.05 or higher, 0.1 or higher, 0.5 or higher, and 500 or less, 400 or less, 3 00 or less, 200 or less, 100 or less, 50 or less, 20 or less, 10 or less, 5 or less, 2 or less, It may be less than 1.

[0032] If this embodiment contains menthol (c), the teprenone (b) The mass ratio (c / b) of menthol (c) is preferably in the range of 0.005 to 5. More preferably 0.01 to 3, and even more preferably 0.1 to 1. The mass ratio of menthol (c) to non (b) (c / b) is 0.0005 or greater, or 0.0 0.1 or higher, 0.005 or higher, 0.01 or higher, 0.05 or higher, 0.1 or higher, 0.5 or higher, It's okay if there are some, under 1000, under 500, under 450, under 400, under 350, 30 0 or less, 250 or less, 200 or less, 150 or less, 100 or less, 50 or less, 10 or less, 1 or less It could also be "below."

[0033] The solid pharmaceutical composition of this implementation may contain optional components in addition to the above components. Examples of optional ingredients include antacids, stomachic agents, digestive agents, intestinal regulators, antidiarrheals, and analgesics / antispasmodics. Examples include agents, mucosal repair agents, additives, and herbal ingredients. These may be used individually or in combination of two or more. It can be used.

[0034] Examples of the aforementioned antacids include sodium bicarbonate, potassium bicarbonate, and sodium carbonate. M, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, silicate Magnesium luminate, magnesium aluminometasilicate, magnesium silicate, oxidation Magnesium, magnesium hydroxide, alumina magnesium hydroxide, magnesium carbonate, Inorganic salts such as aldioxa, synthetic aluminum silicate, and synthetic hydrotalcite; cuttlefish bone, Examples include oyster shell, oyster shell, and aminoacetic acid. These are used individually or in combination of two or more. It is possible.

[0035] Examples of the aforementioned stomachic agents include Japanese red oak extract, aniseed fruit, aloe, fennel, Turmeric, edible herb, longevity herb, golden scutellaria, phellodendron, cinnamon, processed garlic, zedoary, kale Kou, Calamus root, dried ginger, bitter orange, kijitsu, keihi, gentian, koujin, kouboku, go Shuyu, pepper, Colombo, Conzlango, Sansho, Yamana, Shisoshi, Shukusha, Sho Ukyo, Shozuku, Aokawa, Ishikagen, Centaurum, Swertia, Soyou, Anemone Rhubarb, ginseng, clove, dried tangerine peel, chili pepper, spruce, bitter oak, kudzu Carrots, mint (including peppermint), long pepper, atractylodes, hot Pu, Homika extract, Suisaiyo (water lily leaf), Mokkou, Yakuchi, Ryutan, Ryoki Crude drugs such as ginger or their extracts, ginger oil, cardamom oil, clove oil, spruce oil Animal bile (including bear bile), betaine hydrochloride, glutamate hydrochloride, carnitine chloride, salt Examples include betanazole and dried yeast. These are used individually or in combination of two or more. It is possible.

[0036] Examples of the aforementioned digestive agents include ursodeoxycholic acid, oxycoranates, and ko It contains lic acid, bile powder, bile extract (powder), dehydrocholic acid, animal bile (including bear bile), etc. These can be used individually or in combination of two or more types.

[0037] Examples of the aforementioned intestinal regulators include red oak, catechu, jasmine, cassia seed, and geranium. Examples include herbal medicines such as turmeric or their extracts, and intestinal bacteria components (lactic acid bacteria, butyric acid bacteria, natto bacteria, etc.). These can be used individually or in combination of two or more types.

[0038] Examples of the aforementioned antidiarrheal agents include catechu, basil, phellodendron bark, coptis japonica, kudzu, and geranium. Herbal medicines such as gallnut, hawthorn, swertia japonica, and hibiscus, or their extracts, Clinol, berberine chloride, guaiacol, creosote, phenyl salicylate, carbonic acid Guaiacol, berberine tannate, bismuth subsalicylate, bismuth subnitrate, subcarbonate Bismuth, bismuth subgallate, tannic acid, tannic acid albumin, methylenemol Tannins, kaolin, natural aluminum silicate, aluminum hydroxynaphthoate, pe Examples include kuchin, medicinal charcoal, and calcium lactate. These are used individually or in combination of two or more. It can be used.

[0039] Examples of the aforementioned analgesic and antispasmodic agents include Corydalis, Licorice, Peony, Belladonna, etc. Herbal medicine or its extract, oxyphencycline hydrochloride, dicyclomine hydrochloride, mexic acid Thixene, hydrobromic acid, scopolamine, methylatropine bromide, methylanisotropine bromide Methylscopolamine bromide, methyl-l-hyoscyamine bromide, methylbenactide bromide Um, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, Papa hydrochloride Examples include berine and ethyl aminobenzoate. These can be used individually or in combination of two or more. It is possible to be there.

[0040] Examples of the mucosal repair agent include crude drugs such as red oak, Corydalis, and licorice, or Extract, aldioxa, glycyrrhizic acid and its salts, L-glutamine, copper chlorophyll Potassium phosphate, histidine hydrochloride, porcine gastric wall pepsin hydrolysate, porcine gastric wall acid hydrolysate, Tylmethionine sulfonium chloride, gefarnate, cetraxate hydrochloride, sucrose Examples include Ralfate hydrate (sucrose sulfate aluminum salt) and Sofalcone. These can be used individually or in combination of two or more types.

[0041] Examples of the aforementioned additives include excipients, stabilizers, surfactants, lubricants, and other additives. Solvents, buffers, sweeteners, bases, adsorbents, flavoring agents, binders, suspending agents, curing agents, Antioxidants, glossing agents, fragrances, coating agents, coating agents, humectants, humectants, fillers, defoaming agents Agents, cooling agents, chewing agents, antistatic agents, flavoring agents / fragrances, coloring agents, sugar coating agents, isotonic agents, softeners Reacting agents, emulsifiers, adhesives, tack enhancers, viscosity modifiers, foaming agents, pH adjusters, dispersants, disintegrants Agents, disintegrating agents, fragrances, moisture-proofing agents, preservatives, solvents, solubilizers, solvents, fluidizers Examples include various agents. These can be used individually or in combination of two or more.

[0042] Examples of the aforementioned excipients include refined sucrose, glucose, trehalose, lactose, and maltose. Sugars such as , or starches such as potato starch and corn starch are preferred. sugars such as rubitol, xylitol, mannitol, erythritol, and granitol Calls are also preferred. These can be used individually or in combination of two or more.

[0043] If this embodiment contains sugars or sugar alcohols, from the viewpoint of improving the feeling of taking the medicine, solid Preferably, it contains 5 to 90% by mass of the total mass of the pharmaceutical composition, and preferably 10 to 80% by mass. It is more preferable to have it, and even more preferable to contain 15 to 70% by mass.

[0044] If this embodiment contains sugars or sugar alcohols, the sugars relative to component (a) The mass ratio is preferably 1.5 to 300, more preferably 5 to 250. More preferably, it is between 15 and 200.

[0045] Specific examples of the aforementioned additives include, for example, refined sucrose, glucose, trehalose, lactose, ma Lutos, mannitol, sorbitol, xylitol, erythritol, granulose Sodium saccharin, aspartame, acesulfame potassium, sucralose, Licorice extract, stevia extract, monk fruit extract, corn starch, potato Starch, wheat starch, sodium chloride, crystalline cellulose, methylcellulose, eth Cellulose, hypromellose, hydroxypropylcellulose, carboxymethylcellulose Rose, sodium carboxymethylcellulose, calcium carboxymethylcellulose Carmellose calcium, croscarmellose sodium, hypromellose phthalate Ester, cellulose acetate phthalate, dextrin, pregelatinized starch, A Labia gum, gelatin, sodium alginate, polyvinylpyrrolidone, crospovidone Polyvinyl alcohol, polyethylene glycol, casein, sodium caseinate, Ruboxyvinyl polymer, tartaric acid, light anhydrous silicic acid, hydrated silicic acid dioxide, stearic acid Gnesium, calcium stearate, sodium stearate, sodium lauryl sulfate Ingredients: talc, hydrogenated vegetable oil, macrogol, silicone oil, agar, shellac, glycerin N, aromatic essential oils, water-soluble food coloring, yellow iron oxide, yellow iron(III) oxide, iron(III) oxide, brown iron oxide Iron, black iron oxide, titanium dioxide, lake dye, benzoic acid, sodium benzoate, parahydroxy Benzoic acid, cyclodextrin, polysorbate 80, glycerin fatty acid ester, pro Pyrene glycol fatty acid ester, lecithin, bleached beeswax, medium-chain triglyceride Ascorbic acid, tocopherol, sodium thiosulfate, sodium edetate, plants Derived flavorings (fruit flavors such as orange and lemon, coffee flavors, tea flavors), chocolate Flavorings: yogurt-based, milk-based, peppermint oil, spearmint oil, spice Examples include plant essential oils such as syrup. These can be used individually or in combination of two or more. Cut.

[0046] The aforementioned crude drug components include, for example, the crude drug itself (primitive drug), as well as the primary drug in powder form. Extraction of crude drug powder, crude drugs, or crude drug powder using water, organic solvents such as ethanol, or mixtures thereof. Examples include extracts derived from the extract itself, and concentrated extracts made from the extract. This includes any form, such as an extract or a dried extract obtained by drying a soft extract. These can be used individually or in combination of two or more types.

[0047] The solid pharmaceutical composition of this embodiment contains sodium azulene sulfonate (a1) and copper Component (a) consisting of at least one of lorophilin sodium (a2) and teprenone ( b) and, if necessary, other components can be obtained by mixing them in a conventional manner. Cut. Specifically, sodium azulene sulfonate (a1) and sodium copper chlorophyllin. A component (a) consisting of at least one of (a2) is mixed with teprenone (b), and this mixture You may mix other ingredients into the substance, or the above sodium azulene sulfonate A component consisting of at least one of (a1) and copper chlorophyllin sodium (a2) (a) and all the ingredients, including teprenone (b), may be mixed together at once. Furthermore, these mixed ingredients can be dried, granulated, and subjected to other processes.

[0048] According to the solid pharmaceutical composition of this embodiment, excellent suspension stability is obtained, even after time has passed. A uniform concentration can be maintained. Therefore, variations in dosage during administration are reduced, and excessive addition of thickeners, etc., is avoided. It can improve suspension stability while maintaining drinkability during the manufacturing process. It allows for uniform distribution.

[0049] The shape (dosage form) of the solid pharmaceutical composition in this embodiment is not particularly limited. However, for example, tablets (oral disintegrating tablets, chewable tablets, effervescent tablets, lozenges, jelly-like tablets) (Including suppositories, etc.), granules, fine granules, powders, hard capsules, soft capsules, dry syrup Examples of known forms such as formulations and chewable tablets can be given. Among these, tablets, granules, fine granules, and powders are preferred because they offer the potential for immediate action. The preparations are hard capsules, dry syrups, and more preferably tablets, granules, fine granules, and powders. As a medication, powder or granule form is most preferable due to its excellent balance with ease of administration. .

[0050] When the dosage form of the solid pharmaceutical composition in this embodiment is granules, the preferred average particle size is 0 The thickness is 0.01 to 5.0 mm, more preferably 0.02 to 0.75 mm, and 0.0 A thickness of 5 to 0.5 mm is even more preferable. Furthermore, when the dosage form of the solid pharmaceutical composition of this embodiment is a powder, the preferred average particle size The diameter is 0.01 to 5 mm, more preferably 0.02 to 0.75 mm, and 0.0 A thickness of 5 to 0.5 mm is even more preferable. The average particle size of the solid pharmaceutical composition was measured using a laser diffraction particle size distribution analyzer. It is the value.

[0051] The solid pharmaceutical composition of this embodiment contains a water-insoluble pharmacoactive ingredient and / or excipient, as described above. Useful for solid pharmaceutical compositions containing 30% or more by mass of the total mass, and for those containing 50% or more by mass. It is useful depending on the product, and is even more useful when it contains 55% by mass or more, and 60% by mass It is even more useful when it contains % or more. In this specification, "insoluble in water" means that 1 mL in pure water (pH 7.0) at 25°C is insoluble in water. This means that less than 1 mg dissolves in water.

[0052] Formulation into these dosage forms can be carried out using conventional methods, depending on the formulation. Various forms of formulations can be prepared.

[0053] The dosage of the solid pharmaceutical composition in this embodiment depends on its form, method of administration, purpose of administration, and The dosage of the composition is set appropriately depending on the age, weight, symptoms, and physical condition of the person receiving the composition, and is not fixed. stomach. Furthermore, the administration of the solid pharmaceutical composition in this embodiment is within the desired dosage range. It can be administered as a single dose per day or divided into several doses, before, between, after, or with meals. They may be administered simultaneously. Furthermore, the term "administration" in this specification is intended to include "taking" or "taking." [Examples]

[0054] The present invention will be described in more detail below with reference to examples, but the present invention will not exceed its gist. The following examples are not limited to the above. Note that in the examples, "%" indicates that there is no particular indication. Unless otherwise specified, it refers to the mass basis.

[0055] First, the following components (materials) were prepared to create examples, comparative examples, and reference examples. • Sodium azulene sulfonate (a1): Manufactured by Alps Pharmaceutical Co., Ltd. • Sodium copper chlorophyllin (a2): Manufactured by Tokyo Chemical Industry Co., Ltd. • Teprenone (b): Manufactured by Tokyo Chemical Industry Co., Ltd. • Menthol (c): L-Menthol JP (manufactured by Takasago International Corporation) • Excipient: A mixture of lactose and corn starch in a 7:3 (mass ratio) mixture. Lactose: Lactose Pharmatose 100M (manufactured by DFEpharma) Corn starch: Pharmacopoeia-grade Matsutani corn starch (manufactured by Matsutani Chemical Industry Co., Ltd.)

[0056] [Examples 1-2, Comparative Examples 1-4] These components are weighed according to the formulations shown in Table 1, and then mixed and homogenized using conventional methods. A powdered solid pharmaceutical composition (powder) was obtained.

[0057] The obtained solid pharmaceutical composition (powder) and 10 mL of water were each placed into a turbidimeter tube. Then, cover the turbidimeter tube and move it up and down by hand with an amplitude of approximately 15 cm at least 5 times per second. Stir for 30 seconds, and measure the turbidity immediately after stirring and after standing for 3 minutes using a turbidimeter (model number: 2100). Measurements were taken using an AN (HACH) instrument, and the turbidity change rate was calculated according to the following formula. The results obtained... The results are shown in Table 1.

[0058] (Method for calculating the rate of change in turbidity) Turbidity change rate (%) = {(D0 - D1) / (D0)} × 100 D0: Turbidity immediately after stirring [NTU] D1: Turbidity [NTU] after standing for 3 minutes

[0059] [Table 1]

[0060] As shown in Table 1, sodium azulene sulfonate (a1) or copper chlorophyllin Example 1 and Example 2, which use at least one of thorium (a2) and teprenone (b) in combination. In Example 2, the dispersibility in water was improved.

[0061] [Examples 3-5, Comparative Example 5] Furthermore, additional studies were conducted on the turbidity changes of the solid pharmaceutical composition of the present invention. In other words, in this additional study, the only difference was that the standing time immediately after stirring was set to 10 seconds, as in Example 1~ The evaluation was carried out under the same conditions as in Comparative Examples 2 and 1-4. Note that Example 4 had the same formulation as Example 1, and Comparative Example 5 had the same formulation as Comparative Example 2. The results for Examples 3-5 and Comparative Example 5 are shown in Table 2.

[0062] [Table 2]

[0063] As shown in Table 2, even under conditions where the standing time after stirring was 10 seconds, Azulens At least one of sodium chlorophyllin (a1) or sodium copper chlorophyllin (a2) In Examples 3-5, where method (b) and teprenone (b) were used in combination, the dispersibility in water was improved. there was. [Industrial applicability]

[0064] The solid pharmaceutical composition of the present invention has improved dispersibility and stabilized suspension, and when taken, It is useful for ensuring uniformity and stabilizing quality during manufacturing.

Claims

1. Sodium azulene sulfonate (a1) and sodium copper chlorophyllin (a2) Component (a) consisting of at least one of the following, A solid pharmaceutical composition containing teprenone (b).

2. The teprenone (b), the sodium azulene sulfonate (a1), and copper chloro The mass ratio (b / ) of component (a) to component (a) which consists of at least one of the phyllin sodium (a2) a) The solid pharmaceutical composition according to claim 1, wherein the value of a) is in the range of 0.1 to 200.

3. Furthermore, the solid pharmaceutical composition according to claim 1 or 2 contains menthol (c).

4. The solid pharmaceutical composition according to claim 1 or 2, wherein the solid pharmaceutical composition is in the form of granules.

5. Sodium azulene sulfonate (a1) and sodium copper chlorophyllin (a2) Component (a) consisting of at least one of the following, Teprenone (b) and, A solid pharmaceutical composition containing menthol (c), The teprenone (b), the sodium azulene sulfonate (a1), and copper chloro The mass ratio (b / ) of component (a) to component (a) which consists of at least one of the phyllin sodium (a2) a) is in the range of 0.1 to 200, The solid pharmaceutical composition contains 0.0005 to 12% by mass of menthol (c). Re, A solid pharmaceutical composition wherein the solid pharmaceutical composition is in the form of granules.

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