Solid composition and method for producing same

Abstract

The invention relates to a solid composition and a method of making the same. The present invention addresses the problem of providing a solid composition that has sufficient hardness and contains at least one substance selected from the group consisting of teperidine and salts thereof. [Solution] A solid composition containing licorice and at least one substance selected from the group consisting of teperidine and salts thereof.

Description

TECHNICAL FIELD

[0001] The present application relates to a solid composition containing at least one selected from the group consisting of tipepidine and salts thereof and licorice and a manufacturing method thereof, and the like. BACKGROUND

[0002] Solid compositions such as tablets administered orally disintegrate in the digestive tract, and then the effective ingredients in the composition are absorbed into the body. From the viewpoint of transportability and wear resistance, it is extremely important for solid compositions to have a hardness of one degree or more in the design of formulations.

[0003] Since there are components in the effective ingredients of pharmaceutical products that reduce the hardness of solid compositions, techniques for improving the hardness of solid compositions have been studied.

[0004] For example, Patent Literature 1 discloses a composition that has excellent tablet hardness and disintegration even without excipients by containing a disintegrant component and a microfibrous cellulose.

[0005] Patent Literature 2 discloses a method of improving the hardness of tablets and suppressing the delay of disintegration time by incorporating crystalline cellulose into a granule (the granule is obtained by wet granulation of a mixture containing a main drug) in a tablet obtained by tableting the granule.

[0006] Prior Art Documents

[0007] Patent Literature

[0008] Patent Literature 1: International Publication No. 2020 / 022053

[0009] Patent Literature 2: Japanese Patent Application Publication No. 2005-047861 SUMMARY

[0010] Problems to be Solved by the Invention

[0011] The present inventors found that the hardness can decrease for a solid composition containing at least one selected from the group consisting of tipepidine and salts thereof. Therefore, an object of the present application is to provide a solid composition containing at least one selected from the group consisting of tipepidine and salts thereof, which has sufficient hardness.

[0012] Means for Solving the Problems

[0013] The present inventors found that if licorice is incorporated into at least one selected from the group consisting of tipepidine and salts thereof, the decrease in hardness caused by at least one selected from the group consisting of tipepidine and salts thereof can be suppressed, thereby completing the present application.

[0014] That is, the present embodiment contains the following means.

[0015] [1] A solid composition comprising: at least one selected from the group consisting of tipepidine and salts thereof; and licorice.

[0016] [2] The solid composition according to [1], which contains a granulate comprising: at least one selected from the group consisting of tipepidine and salts thereof; and licorice.

[0017] [3] The solid composition according to [1] or [2], which further comprises acetaminophen.

[0018] [4] The solid composition according to [2], wherein the aforementioned granulate further comprises acetaminophen.

[0019] [5] The solid composition according to any one of [1] to [4], wherein the aforementioned solid composition has a hardness of 40 N or more.

[0020] [6] A method for producing the solid composition according to any one of [1] to [5], which comprises a step of mixing at least one selected from the group consisting of tipepidine and salts thereof with licorice.

[0021] [7] The production method according to [6], which comprises a step of further mixing acetaminophen.

[0022] [8] The production method according to [6], which comprises:

[0023] a step of forming a granulate comprising at least one selected from the group consisting of tipepidine and salts thereof and licorice; and

[0024] a step of tableting the aforementioned granulate.

[0025] [9] The production method according to [8], wherein, in the step of forming the aforementioned granulate, a granulate comprising at least one selected from the group consisting of tipepidine and salts thereof, licorice, and acetaminophen is formed.

[0026] [1A] A solid composition comprising: at least one selected from the group consisting of tipepidine and salts thereof; and licorice,

[0027] which contains a granulate comprising: at least one selected from the group consisting of tipepidine and salts thereof; and licorice,

[0028] wherein the solid composition does not include a solid composition comprising loratadine or levocetirizine.

[0029] [2A] The solid composition according to [1A], which further comprises acetaminophen.

[0030] [3A] The solid-state composition according to [2A], wherein the aforementioned granulation further contains acetaminophen.

[0031] [4A] The solid-state composition according to any one of [1A] to [3A], wherein the aforementioned solid-state composition has a hardness of 40 N or more.

[0032] [5A] A method for producing the solid-state composition according to any one of [1A] to [4A], comprising a step of mixing at least one selected from the group consisting of tipepidine and salts thereof with licorice.

[0033] [6A] The production method according to [5A], comprising a step of further mixing acetaminophen.

[0034] [7A] The production method according to [5A], comprising:

[0035] a step of forming a granulation containing at least one selected from the group consisting of tipepidine and salts thereof and licorice; and

[0036] a step of tableting the aforementioned granulation.

[0037] [8A] The production method according to [7A], wherein, in the step of forming the granulation, a granulation containing at least one selected from the group consisting of tipepidine and salts thereof, licorice, and acetaminophen is formed.

[0038] Effects of the Invention

[0039] According to the present application, it is possible to provide a solid-state composition containing at least one selected from the group consisting of tipepidine and salts thereof, which has sufficient hardness. DETAILED DESCRIPTION

[0040] Hereinafter, an embodiment of the present application (hereinafter, referred to as "the present embodiment") will be described, but the scope of the present application is not construed as being limited to the following embodiment. In the present embodiment, the composition can contain each component alone or in combination of two or more components. In the present specification, "~" indicating a numerical range indicates the above, the below, and both the numerical values are included.

[0041] (Solid-state composition)

[0042] In the first mode, a solid-state composition is provided, which contains: at least one selected from the group consisting of tipepidine and salts thereof; and licorice.

[0043] The solid-state composition is specifically a solid-state pharmaceutical composition.

[0044] Each component included in the solid composition according to the present embodiment can be included in a state of a pharmacologically acceptable salt, or can be included as a complex with other components. That is, in the solid composition according to the present embodiment, for example, not only tipepidine, but also salts of each component can be included with respect to acetaminophen and other components. The "pharmacologically acceptable salt" includes, for example, a salt with a base or an acid that is pharmacologically acceptable.

[0045] As non-limiting specific examples of the pharmacologically acceptable salt, there are mentioned an addition salt of an inorganic acid (hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, etc.), an addition salt of an organic acid (p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, p-bromophenylsulfonic acid, carboxylic acid, succinic acid, citric acid, benzoic acid, acetic acid, etc.), an addition salt of an inorganic base (ammonium hydroxide, or an alkali metal hydroxide or an alkaline earth metal hydroxide, carbonate, bicarbonate, etc.), an addition salt of an amino acid, and the like. The pharmacologically acceptable salt can be a hydrate or an anhydrate.

[0046] In the present embodiment, the solid composition contains licorice in addition to at least one selected from the group consisting of tipepidine and a salt thereof, and thus has sufficient hardness.

[0047] The hardness of the solid composition according to the present embodiment is the hardness measured by the method described in "Method for measuring hardness of tablets <G6-4-180> " of the 18th edition of the Japanese Pharmacopoeia Reference Information. More specifically, it can be the hardness measured by the method described in the Examples using a 10.8R, and the hardness of the tablet obtained by tabletting using a tablet machine at a pressure of 1,000 kgf. The capacity of the tablet at the time of measuring the hardness is not particularly limited, and can be set to 400 mg per tablet. More specifically, the hardness of the solid composition according to the present embodiment can be the hardness measured by the method described in the Examples.

[0048] The hardness of the solid composition measured in the above-described manner is preferably 40 N or greater, more preferably 40 to 250 N, more preferably 50 N or greater, further more preferably 50 to 200 N, further more preferably 55 to 150 N, more further more preferably 60 to 120 N, and particularly preferably 65 to 100 N.

[0049] Note that, in the solid composition according to the present embodiment, the "solid composition containing loratadine or levocetirizine" can not be included.

[0050] Here, "levocetirizine" refers to a compound represented by the chemical formula C 21 H 25A compound represented by ClN2O3. Levocetirizine is a substance obtained by optically resolving only the R-enantiomer having a stronger physiological activity among optical isomers of cetirizine, and has a CAS registration number of 130018-77-8. In addition, in the solid composition of the present embodiment, a solid composition including a salt of levocetirizine can also be excluded. As the salt of levocetirizine, there is no particular limitation as long as it is a pharmacologically acceptable salt, and for example, a salt of an inorganic acid such as a hydrochloride, a hydrobromide, a phosphate, and a salt of an organic acid such as an acetate, an oxalate, a malonate, a succinate, a fumarate, a maleate, a lactate, a malate, a citrate, a tartrate, and a carbonate, and the like can be given, and in particular, a hydrochloride.

[0051] Here, "desloratadine" refers to a compound represented by the chemical formula C 22 H 23 A compound represented by ClN2O2, and has a CAS registration number of 79794-75-5.

[0052] In addition, in the solid composition of the present embodiment, each of the solid compositions disclosed in Japanese Patent Application Publication No. 2022-008041 and Japanese Patent Application Publication No. 2020-158487 can be excluded. The solid composition disclosed in Japanese Patent Application Publication No. 2022-008041 is a pharmaceutical composition in which the content of levocetirizine or a salt thereof is inhibited from decreasing over time even if ibuprofen and levocetirizine or a salt thereof are contained, and the solid composition disclosed in Japanese Patent Application Publication No. 2020-158487 is a solid composition in which the content of desloratadine is inhibited from decreasing over time even if ibuprofen and desloratadine are contained.

[0053] at least 1 kind selected from the group consisting of tipepidine and a salt thereof

[0054] In the present specification, "tipepidine" is a compound represented by C 15 H 17 A compound represented by the chemical formula of NS2 (molecular weight: 275.43 g / mol). As the salt of tipepidine, there is no particular limitation as long as it is pharmacologically acceptable, and for example, tipepidine hybenzoate and tipepidine citrate can be given.

[0055] The blending amount of at least 1 kind selected from the group consisting of tipepidine and a salt thereof can be appropriately adjusted depending on the use of the solid composition, the degree of the desired antitussive and expectorant effect, the degree of the desired hardness, the symptoms, age, body weight, gender, and the like of the subject to be administered. Note that the following blending amount and content of at least 1 kind selected from the group consisting of tipepidine and a salt thereof are the blending amount and content for each of tipepidine and a salt of tipepidine, and it is preferable to make the total blending amount and content of tipepidine and a salt of tipepidine fall within the range of the blending amount and content described below.

[0056] Regarding the dosage of at least one ingredient selected from the group consisting of tepedidine and its salts, for example, the daily dose administered to an adult can be adjusted within the range of 8 mg to 120 mg, more preferably 16 mg to 72 mg. In this embodiment, "adult" refers to men and women aged 15 years and older. However, the solid composition involved in this embodiment is not limited to adult use, but can also be used for children under 15 years of age. When used by children, the dosage can be reduced to 1 / 2, 2 / 3, or the daily dose for adults, depending on their age. The same applies to ingredients other than at least one ingredient selected from the group consisting of tepedidine and its salts.

[0057] The weight and dosage of the above-described solid composition are daily dosages (1-day doses). This dosage can be administered to the subject once, or it can be administered to the subject multiple times a day (e.g., 2 or 3 times, preferably 3 times). The same applies to components other than at least one selected from the group consisting of tebuconazole and its salts. Furthermore, each dosage is a total amount, therefore the content of each component in the solid composition can vary depending on the single dosage, the dosage form of the solid composition, etc.

[0058] In a specific embodiment, the solid composition is a tablet, and the above-mentioned dosage is the amount of ingredients contained in 3, 6, or 9 tablets, preferably the amount of ingredients contained in 9 tablets. In this embodiment, the dosage for adults (15 years and older) is 3 times, and the dosage for a single dose is 2, 3, or 4 tablets, preferably 3 tablets.

[0059] (Licorice)

[0060] When used in this specification, "licorice" may be any substance described in the 18th edition of the Japanese Pharmacopoeia. As licorice, for example, there are products obtained using water, 30% aqueous ethanol, etc., as extraction solvents. For example, depending on the type of extract, such as licorice extract, dried licorice extract, soft licorice extract, or fluid licorice extract, various products are sold with a conversion ratio to the original drug. Unless otherwise specified, the amounts of licorice mentioned in this specification are values ​​converted to the original drug. For example, regarding soft licorice extract, approximately 4 parts by mass of licorice are contained relative to 1 part by mass of the extraction solvent, calculated using the original drug conversion ratio. In addition to these licorice extracts, substances obtained by pulverizing extracts obtained from licorice extracted with water, 30% aqueous ethanol, etc., into powder (extract powder), as well as licorice extracts, licorice extract solutions, etc., may also be used appropriately, without particular limitation. However, the preferred extract powder is prepared by drying a dried licorice extract containing approximately 5 to 9 parts by mass, for example, 6 to 8 parts by mass, of licorice relative to 1 part by mass of the extracting solvent, calculated using a conversion ratio based on the raw herb. Water is the preferred extracting solvent.

[0061] It should be noted that licorice contains at least one component selected from the group consisting of glycyrrhizic acid and its salts. In the context of this specification, "glycyrrhizic acid" is defined as CAS Registry No. 1405-86-3, and is produced by C... 42 H 62 O 16 The chemical formula of the compound is given (molecular weight: 822.93 g / mol). Salts of glycyrrhizic acid are not particularly limited as long as they are pharmacologically permissible; examples include trisodium glycyrrhizate, disodium glycyrrhizate, diammonium glycyrrhizate, monoammonium glycyrrhizate, dipotassium glycyrrhizate, and monopotassium glycyrrhizate.

[0062] Therefore, in the solid composition according to this embodiment, licorice can be used instead of glycyrrhizic acid, and / or at least one of the group consisting of glycyrrhizic acid and its salts in addition to licorice. Licorice may contain at least 2.0% or more of the group consisting of glycyrrhizic acid and its salts relative to the dried weight of the converted crude drug. Licorice powder may contain at least 2.0% or more of the group consisting of glycyrrhizic acid and its salts relative to the dried weight of the converted crude drug. Licorice extract may contain at least 3.6% or more of the group consisting of glycyrrhizic acid and its salts relative to the dried weight of the converted crude drug. Crude licorice extract may contain at least 4.8% or more of the group consisting of glycyrrhizic acid and its salts relative to the dried weight of the converted crude drug. In the solid composition of this embodiment, the total content of glycyrrhizic acid and its salt can be set within a range of, for example, 0.01 to 0.1 times (e.g., 0.02 times, 0.036 times, 0.04 times, 0.048 times) of the content of licorice, which is described below.

[0063] The active ingredients can be extracted from the aforementioned crude drugs using conventional methods, such as extraction solvents. Common extraction solvents include, for example, water, hydrophilic solvents, or mixtures thereof. Examples of such hydrophilic solvents include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, sec-butanol, and tert-butanol; cellolytic agents such as methyl and ethyl cellolytic agents; ketones such as acetone; ethers such as dioxane and tetrahydrofuran; and nitrogen-containing solvents such as pyridine, morpholine, acetonitrile, N,N-dimethylformamide, dimethylacetamide, and N-methylpyrrolidone. These hydrophilic solvents can be used alone or as a mixture of two or more solvents.

[0064] The dosage of licorice can be appropriately adjusted according to the intended use of the solid composition, the required hardness, the symptoms, age, weight, and sex of the recipient. For example, the dosage of licorice, converted from raw herb, is in the range of 100 mg to 5,000 mg per day, preferably in the range of 200 mg to 2,000 mg, and more preferably in the range of 50 mg to 1,200 mg.

[0065] The composition administered within one day contains licorice in a content of 1% to 70% by mass, preferably 5% to 50% by mass, and more preferably 10% to 30% by mass, based on the amount of raw herb.

[0066] The mass ratio of teperidine and its salts to licorice in the composition administered within one day, expressed as the total amount of teperidine and its salts to the amount of licorice in its original form, is preferably 1:20 to 1:1, more preferably 1:15 to 1:2, and even more preferably 1:10 to 1:3. When using licorice extract powder as licorice, the mass ratio of teperidine and its salts to licorice extract powder is preferably 1:2 to 10:1, more preferably 1:1 to 5:1, and even more preferably 2:1 to 3:1.

[0067] From the viewpoint of further improving the hardness of the solid composition according to this embodiment, licorice is preferably included in the same granule as at least one of the group consisting of tebuconazole and its salts. That is, the solid composition according to this embodiment preferably includes a granule containing at least one of the group consisting of tebuconazole and its salts and licorice, preferably including a granule obtained by granulating a mixed powder containing at least one of the group consisting of tebuconazole and its salts and licorice. The solid composition according to this embodiment can be a tablet obtained by compressing the granules as such. However, the solid composition according to this embodiment can be a tablet manufactured by direct compression using a direct compression method that directly compresses a mixed powder containing at least one of the group consisting of tebuconazole and its salts and licorice, or a tablet obtained by dissolving at least one of the group consisting of tebuconazole and its salts and licorice in a solvent and drying and distilling off the solvent, and optionally granulating the powder and then compressing it. In such an embodiment, at least one of the group consisting of tebuconazole and its salts exists in a state similar to that of licorice in the solid composition, which tends to more effectively exert the hardness-enhancing effect of licorice on the solid composition containing at least one of the group consisting of tebuconazole and its salts.

[0068] (acetaminophen)

[0069] The solid composition described in this embodiment may further contain acetaminophen. By further containing acetaminophen, there is a tendency to further increase the hardness of the solid composition. As used in this specification, "acetaminophen" is a compound with CAS Registry No. 103-90-2 and the chemical formula C8H9NO2. There are no particular limitations on the salts of acetaminophen, provided they are pharmacologically permissible.

[0070] The dosage of acetaminophen can be appropriately adjusted according to the intended use of the solid composition, the required hardness, the symptoms, age, weight, and sex of the recipient. The dosage containing acetaminophen varies depending on the amount of at least one of the groups consisting of tebufenozide and its salts, and as a daily dose, it can be adjusted within the range of 120 mg to 1200 mg, preferably 150 mg to 900 mg, and more preferably 180 mg to 600 mg.

[0071] The mass ratio of teperidine and its salts to acetaminophen in the composition administered within one day, expressed as the ratio of teperidine and its salts to acetaminophen, is preferably 1:10 to 3:1, more preferably 1:5 to 2:1, and even more preferably 1:2 to 1:1.

[0072] From the viewpoint of further improving the hardness of the solid composition according to this embodiment, acetaminophen is preferably contained in the same granule as at least one of the group consisting of tebuconazole and its salts, and preferably in the same granule as at least one of the group consisting of tebuconazole and its salts and licorice. That is, the solid composition according to this embodiment preferably contains a granule containing at least one of the group consisting of tebuconazole and its salts, licorice, and acetaminophen, and preferably contains a granule obtained by granulating a mixed powder containing at least one of the group consisting of tebuconazole and its salts, licorice, and acetaminophen. The solid composition according to this embodiment can be a tablet obtained by compressing the granules as such. From the same perspective, the solid composition involved in this embodiment can be a tablet manufactured by direct compression using a method that directly compresses a mixed powder containing at least one of the group consisting of tebuconazole and its salts, licorice, and acetaminophen; or it can be a powder obtained by dissolving at least one of the group consisting of tebuconazole and its salts, licorice, and acetaminophen in a solvent and then drying and distilling off the solvent; and optionally, a tablet obtained by granulating the powder and then compressing it. In such an embodiment, at least one of the group consisting of tebuconazole and its salts, licorice, and acetaminophen exist in a similar state in the solid composition, which tends to further increase the hardness of the solid composition.

[0073] (Other ingredients)

[0074] The solid composition described in this embodiment may contain other components besides those mentioned above, depending on its intended use. In cases where the purpose is to relieve various symptoms of the common cold, such as runny nose, nasal congestion, sneezing, sore throat, cough, phlegm, chills, fever, headache, joint pain, and muscle pain, in addition to bromhexine and meloxicam, antipyretic analgesics, especially nonsteroidal anti-inflammatory drugs (NSAIDs), and other pharmacologically permissible components may be added.

[0075] Nonsteroidal anti-inflammatory drugs (NSAIDs) are broadly classified into: non-selective COX-2 inhibitors such as ibuprofen, diclofenac, loxoprofen, zaltoprofen, pranoprofen, oxaprazin, tiprofenicol, naproxen, lornoxicam, ampicillin, piroxicam, nabumetone, indomethacin, sulindac, mofuzolic acid, and mefenamic acid; and selective COX-2 inhibitors such as meloxicam, etodoxacin, and celecoxib. Meloxicillin can be incorporated into compositions as an NSAID. Non-selective COX-2 inhibitors are preferred. NSAIDs can be in salt form.

[0076] As other pharmacologically permissible ingredients, it can be added in combination with compound cold medicines, antipyretic analgesics, rhinitis medicines, etc., as well as antihistamines, antipyretic analgesics, antitussives and expectorants, anti-inflammatory drugs, central nervous system stimulants, vitamins, anticholinergics, antifibrinolytics, etc.

[0077] For example, antihistamines include isoxependyne hydrochloride, difeterol hydrochloride, trapyrimidine diamine hydrochloride, fenethazine hydrochloride, methaqualone hydrochloride, racemic chlorpheniramine maleate, d-chlorpheniramine maleate, carbixamine diphenyl disulfonic acid, diphenylpyraline hydrochloride, diphenylpyraline teoclate, diphenhydramine hydrochloride, diphenhydramine salicylate, alimazine tartrate, diphenhydramine tannate, triprolidine hydrochloride hydrate, methaqualone naphthalene disulfonic acid, methylene disalicylic acid promethazine, carbixamine maleate, difeterol phosphate, chlormastine fumarate, and mequinatazine.

[0078] Antipyretic analgesics other than nonsteroidal anti-inflammatory drugs include, for example, aspirin, ethylsalicylate, salicylates, salicylamide, lactylphenethylamine, and isopropylantipyrine.

[0079] Examples of antitussive and expectorant drugs include noscarbene, noscarbene hydrochloride hydrate, dextromethorphan hydrobromide hydrate, bromhexine, codeine dihydrophosphate, racemic methylephedrine hydrochloride, racemic methylephedrine saccharin salt, pseudoephedrine hydrochloride, ambroxol hydrochloride, and L-carboxycysteine.

[0080] As anti-inflammatory drugs, glycyrrhizic acid and its derivatives and their salts (e.g., dipotassium glycyrrhizate, monoammonium glycyrrhizate, etc.), tranexamic acid, etc. can be cited.

[0081] Examples of central nervous system stimulants include caffeine and anhydrous caffeine.

[0082] Examples of vitamin supplements include vitamin B1 and its derivatives and their salts (e.g., phenylphosphine), 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, etc.

[0083] Examples of anticholinergic agents include scopolamine hydrobromide, datura extract, methyl scopolamine bromide, methyl-l-hyoscyamine bromide, pirenzepine hydrochloride, butyl scopolamine bromide, belladonna alkaloids, belladonna extract, total belladonna alkaloids, isoproiodine, diphenylpiperidine methyldioxolane iodide, hyoscyamine extract, hyoscyamine root, and total hyoscyamine root alkaloids citrate.

[0084] For the solid composition involved in this embodiment, formulation additives may be further added as needed. Examples of pharmaceutically permissible carriers include excipients, binders, disintegrants, disintegration aids, gloss enhancers, foaming agents, moisture-proofing agents, surfactants, stabilizers, antioxidants, fillers, sweeteners, flavoring agents, cooling agents, fragrances, aromas, colorants, matrices, coating agents, sugar coatings, plasticizers, dispersants, defoamers, flow agents, and flavoring agents / fragrances. For the purposes described above, conventionally known formulation additives usable in solid dosage forms may be used.

[0085] Examples of excipients include powdered sugar, gum arabic, gum arabic powder, cocoa butter, caramel, sodium carboxymethyl starch, hydrated silica, anhydrous amorphous silica, xylitol, magnesium aluminum silicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, crystalline cellulose, crystalline cellulose·sodium carboxymethyl cellulose, crystalline cellulose (microparticles), 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, purified white sugar, purified white sugar spheres. Granular components, gelatin, D-sorbitol, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, dextrin, corn starch, corn starch granules, trehalose, silicon dioxide, lactose hydrate, lactose granules, white sugar, potato starch, hydroxypropyl starch, partially α-substituted starch, powdered sugar, powdered sugar, powdered reduced maltose syrup, powdered cellulose, pectin, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 60, maltitol, D-mannitol, magnesium aluminum metasilicate, calcium sulfate, erythritol, glucose, fructose, etc.

[0086] Examples of adhesives include gum arabic, gum arabic powder, plum powder, gelatin, shellac, hydroxypropyl starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, 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.

[0087] Examples of disintegrants include sodium carboxymethyl starch, carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, croscarmellose sodium, croscarmellose sodium, croscarmellose, low-substituted hydroxypropyl cellulose, hydroxypropyl starch, and partially α-substituted starch.

[0088] Examples of disintegration aids include sodium carboxymethyl starch, carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium carboxymethyl cellulose, light anhydrous silica, crystalline cellulose, sodium bicarbonate, precipitated calcium carbonate, lactose hydrate, hydroxypropyl starch, polysorbate 40, polysorbate 60, polysorbate 80, polyethylene glycol 1500, and polyethylene glycol 4000.

[0089] Examples of gloss enhancers include carnauba wax, white beeswax, purified shellac, polyethylene glycol 400, polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, and beeswax.

[0090] Examples of foaming agents include dried sodium carbonate, tartaric acid, potassium bitartrate, sodium bicarbonate, and anhydrous citric acid.

[0091] Examples of moisture-proofing agents include ethyl cellulose, olive oil, dried aluminum hydroxide gel, glycerin, magnesium silicate, light anhydrous silicic acid, hydrogenated oil, synthetic aluminum silicate, sucrose fatty acid esters, stearic acid, magnesium stearate, purified shellac, purified white sugar, 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 aluminum metasilicate.

[0092] Examples of surfactants include sucrose fatty acid esters, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearate, polyoxyethylene cetyl ether, polyoxyethylene dehydrated sorbitol monolaurate, polyoxyethylene sorbitol beeswax, polyoxyethylene nonylphenyl ether, polyoxyethylene (20) polyoxypropylene (20) diol, polyoxyethylene (105) polyoxypropylene (5) diol, polyoxyethylene (120) polyoxypropylene (40) diol, polyoxyethylene (160) polyoxypropylene (30) diol, polyoxyethylene (10) polyoxypropylene (4) cetyl ether, polysorbate 20, polysorbate 60, polysorbate 80, polyethylene glycol 400, monooleic acid dehydrated sorbitol ester, glyceryl monostearate, monostearate dehydrated sorbitol ester, monolauric acid dehydrated sorbitol ester, and sodium dodecyl sulfate.

[0093] Examples of stabilizers include, for example, 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, calcium disodium edetate, sodium edetate, tetrasodium edetate, tetrasodium edetate tetrahydrate, zinc chloride, ammonium chloride, calcium chloride hydrate, hexadecylpyridinium chloride, ferric chloride, sodium chloride, magnesium chloride, cysteine ​​hydrochloride, histidine hydrochloride, cocoa butter, carboxyvinyl polymers, and calcium carboxymethyl cellulose. 1. Hydrous silica, sodium carboxymethyl cellulose, dried sodium carbonate, glycine, glycerol, fatty acid glycerides, calcium gluconate hydrate, sodium gluconate, magnesium gluconate, potassium L-glutamate, monosodium L-glutamate, L-glutamic acid, L-lysine, light anhydrous silica, crystalline sodium dihydrogen phosphate, sodium chondroitin sulfate, zinc oxide, L-cysteine, L-cysteine, tartaric acid, sucrose fatty acid esters, stearic acid, purified gelatin, purified soybean lecithin, gelatin, gelatin hydrolysate, dehydrated sorbitol fatty acid esters, taurine, talc, calcium carbonate, potassium bicarbonate, carbon Sodium bicarbonate, sodium carbonate hydrate, magnesium carbonate, natural vitamin E, tocopherol, tocopheryl acetate, lactose, concentrated glycerin, povidone, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearate, 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 fatty glyceride (7E) .O.), polysorbate 20, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 4000, anhydrous citric acid, anhydrous sodium citrate, anhydrous sodium monohydrogen phosphate, anhydrous sodium dihydrogen phosphate, magnesium aluminum metasilicate, methylcellulose, l-menthol, glyceryl monostearate, pharmaceutical 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.

[0094] Examples of antioxidants include ascorbic acid, L-ascorbic acid stearate, citric acid hydrate, soybean lecithin, natural vitamin E, tocopherol, tocopheryl acetate, ascorbic acid palmitate, and sodium metabisulfite. In the case of a solid composition containing acetaminophen, it is preferable to omit tocopherols as antioxidants or stabilizers.

[0095] Examples of fillers include RSS No.1 raw rubber, acrylic starch 1000, hydrated silica, titanium dioxide, silica, and dicalcium phosphate.

[0096] Examples of sweeteners include aspartame, acesulfame potassium, gancha, gancha powder, reduced malt syrup, xylitol, dipotassium glycyrrhizate, disodium glycyrrhizate, saccharin, sodium saccharin hydrate, sucralose, stevia extract, purified stevia extract, purified white sugar, fructose, white sugar, maltitol, D-mannitol, erythritol, etc.

[0097] Examples of flavoring agents include, for example, sodium chloride, phellodendron bark powder, cherry bark extract, coptis root, coptis root powder, orange, orange oil, cocoa powder, fructose, caramel, xylitol, calcium citrate, citrate hydrate, sodium citrate hydrate, L-glutamic acid, monosodium glutamate, grapefruit extract, brown sugar, cinnamon powder, cinnamon oil, saccharin, sodium saccharin hydrate, Sichuan pepper powder, tartaric acid, D-tartaric acid, potassium hydrogen tartrate, sodium DL-tartrate, and ginger. Powder, sucralose, stevia extract, purified stevia extract, angelica, D-sorbitol, tannic acid, clove oil, tangerine peel tincture, chili pepper, chili powder, spruce powder, trehalose hydrate, bitterwood powder, plum extract, fructooligosaccharides, powdered sugar, peppermint powder, D-mannitol, dl-menthol, l-menthol, menthol powder, borneol, borneol powder, green tea powder, DL-malic acid, sodium DL-malate, lemon oil, rose oil, etc.

[0098] Examples of cooling agents include, for example, fennel oil, d-camphor, dl-camphor, cinnamon oil, peppermint water, peppermint oil, and l-menthol.

[0099] Examples of flavorings include orange flavoring, guarana extract, sweet orange, strawberry, brown sugar flavoring, strawberry flavoring, cherry flavoring, banana powder flavoring, peach essence, fruit flavoring, mint, melon powder flavoring, L-menthol, and peppermint oil.

[0100] Examples of aromatic agents include, for example, anise powder, anise oil, ethyl vanillin, d-camphor, dl-camphor, cinnamon powder, cinnamon oil, ginger oil, agarwood powder, spearmint oil, clove oil, turpentine oil, chili powder, pineapple powder spice 51357, pineapple powder spice 59492, peppermint water, peppermint oil, vanilla powder spice 54286, vanillin, bergamot oil, d-borneol, dl-borneol, dl-menthol, l-menthol, eucalyptus oil, rose water, rose oil, etc.

[0101] Examples of coloring agents include yellow iron oxide, yellow ferric oxide, orange flavoring, brown iron oxide, carbon black, caramel, β-carotene, gold leaf, black iron oxide, titanium dioxide, ferric oxide, diazo yellow, edible blue No. 1, edible yellow No. 4, edible yellow No. 5, edible blue No. 2 aluminum lake, edible yellow No. 4 aluminum lake, edible red No. 2, edible red No. 3, edible red No. 102, ferric oxide / glycerol suspension, sodium copper chlorophyllin, copper chlorophyllin, phenol red, malachite green, methylene blue, pharmaceutical charcoal, riboflavin, riboflavin butyrate, sodium riboflavin phosphate, green tea powder, rose oil, etc.

[0102] Examples of matrices include gum arabic powder, α-starch, ethyl cellulose, cocoa butter, carnauba wax, carboxyvinyl polymers, carboxymethyl cellulose, sodium carboxymethyl cellulose, reduced malt syrup, hydrated silica, dried aluminum hydroxide gel, agar, agar powder, xanthan gum, glycine, glycerol, fatty acid glycerides, light anhydrous silicate, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, synthetic magnesium silicate sodium, titanium dioxide, tartaric acid, sucrose fatty acid esters, 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 glycerol, potato starch, and hydroxypropyl. Cellulose, hydroxypropyl methylcellulose, pullulan, pectin, povidone, polysorbate 60, polysorbate 80, polyvinyl alcohol (partial saponification), microcrystalline wax, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, polyethylene glycol 20000, D-mannitol, glyceryl monostearate, sorbitol monostearate, squalene monostearate, propylene glycol monostearate, polyethylene glycol monostearate, sodium dodecyl sulfate, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, etc.

[0103] Examples of coating agents include, for instance, ethyl acrylate-methyl methacrylate copolymer dispersions, aminoalkyl methacrylate copolymers E, aminoalkyl methacrylate copolymers RS, gum arabic, gum arabic powder, ethyl cellulose, ethyl cellulose aqueous dispersions, carnauba wax, carboxyvinyl polymers, gold foil, silver foil, triethyl citrate, glycerol, fatty acid glycerides, hydrogenated oil, titanium dioxide, sucrose fatty acid esters, stearyl alcohol, stearic acid, magnesium stearate, purified gelatin, purified shellac, gelatin, D-sorbitol, talc, calcium carbonate, magnesium carbonate, medium gold foil, precipitated calcium carbonate, concentrated glycerol, white shellac, hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose 2910-titanium dioxide-polyethylene glycol 400 mixture, hydroxypropyl methylcellulose, fumaric acid-stearic acid-polyvinyl acetal diethylaminoacetate-hydroxypropyl methylcellulose 2 Mixture 910, pullulan, polysorbate 80, polyvinyl acetal diethylaminoacetate, povidone, polyvinyl alcohol (partially saponified), polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, polyethylene glycol 20000, polyethylene glycol 35000, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, magnesium aluminum metasilicate, methyl acrylate-methacrylic acid-methyl methacrylate copolymer, methyl cellulose, methyl 2-methyl-5-vinylpyridine acrylate-methacrylic acid copolymer, aluminum monostearate, glyceryl monostearate, dehydrated sorbitol monostearate, dehydrated sorbitol monolaurate, calcium sulfate, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, etc.

[0104] Examples of sugar coating agents include gum arabic, gum arabic powder, ethyl cellulose, carnauba wax, sodium carboxymethyl cellulose, titanium dioxide, stearic acid, polyoxyethylene stearate 40, purified gelatin, purified shellac, purified white sugar, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, white sugar, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, pullulan, povidone, polyvinyl alcohol (partially saponified), polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, calcium hydrogen phosphate hydrate, calcium dihydrogen phosphate hydrate, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, etc.

[0105] Examples of plasticizers include triethyl citrate, glycerol, fatty acid glycerides, D-sorbitol, medium-chain fatty acid triglycerides, glyceryl triacetate, concentrated glycerol, castor oil, polyoxyethylene hydrogenated castor oil 60, propylene glycol, polyoxyethylene (105)polyoxypropylene (5) glycol, polysorbate 80, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, glyceryl monostearate, isopropyl linoleate, and liquid paraffin.

[0106] Examples of dispersants include aminoalkyl methacrylate polymers (RS), gum arabic, gum arabic powder, carboxyvinyl polymers, sodium carboxymethyl starch, agar powder, citric acid hydrate, sodium citrate hydrate, glycerol, fatty acid glycerides, magnesium silicate, light alumina, light anhydrous silicate, crystalline cellulose, titanium dioxide, sucrose fatty acid esters, stearic acid, magnesium stearate, D-sorbitol, soybean lecithin, low-substituted hydroxypropyl cellulose, dextrin, corn starch, lactose hydrate, concentrated glycerol, potato starch, hydroxyethyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and 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, polyethylene glycol 300, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 6000NF, anhydrous sodium citrate, magnesium aluminum metasilicate, methylcellulose, glyceryl monooleate, dehydrated sorbitol monooleate, aluminum monostearate, glyceryl monostearate, dehydrated sorbitol monostearate, dehydrated sorbitol monopalmitate, dehydrated sorbitol monolaurate, sodium lauryl sulfate, etc.

[0107] Examples of defoaming agents include ethanol, glycerol fatty acid esters, dimethyl polysiloxane (for internal use), a mixture of dimethyl polysiloxane and silica, sucrose fatty acid esters, silicone defoamers, silicone oil, dehydrated sorbitol fatty acid esters, and polysorbate 80.

[0108] Examples of fluidizing agents include hydrated silica, light anhydrous silicic acid, synthetic aluminum silicate, heavy anhydrous silicic acid, magnesium aluminum hydroxide, stearic acid, calcium stearate, magnesium stearate, calcium phosphate, talc, magnesium aluminum metasilicate, and granulated dicalcium phosphate.

[0109] Examples of flavoring agents and fragrances include, for example, anise powder, anise oil, ethyl vanillin, orange, orange extract, orange essence, orange oil, chamomile oil, caramel, d-camphor, dl-camphor, cinnamon powder, cinnamon oil, lemongrass oil, sugar flavoring, spearmint oil, cherry flavoring, clove oil, chili flavoring, spruce tincture, spruce oil, pine oil, peppermint oil, vanilla flavoring, vanillin, bittering essence, vitamin base, Himalayan cedar oil, fruit flavoring, G1 flavoring, hesperidin peppermint extract, bergamot oil, bergamot flavoring, d-borneol, dl-borneol, matcha, mixed flavorings, peppermint flavoring, dl-menthol, l-menthol, eucalyptus oil, lavender oil, borneol, borneol powder, lemon powder, lemon oil, rose water, rose oil, peppermint oil, etc.

[0110] These ingredients may be a single ingredient or two or more.

[0111] (Dosage Form)

[0112] The solid composition of this embodiment can be formulated into dosage forms such as those described in the 18th edition of the Japanese Pharmacopoeia, including oral administration formulations (tablets (including intraorally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets, etc.), capsules, granules, and powders), and oral formulations (including oral tablets, lozenges, sublingual tablets, oral lozenges, adhesive tablets, and gels). The solid composition of this embodiment is preferably an oral solid composition.

[0113] Examples of dosage forms for the solid compositions of this embodiment include tablets, capsules, pills, granules, and fine granules. These solid compositions can be coated using known methods, such as sugar coating or film coating, as needed. Tablets are preferred as the dosage form of the solid composition. Specific examples of tablets include plain tablets, film-coated tablets, and sugar-coated tablets.

[0114] The solid composition of this embodiment can be temporarily packaged and airtightly stored in bottles, PTP packages, bags, strips, or SP packages. It can also be further packaged in pillow-like containers or stored in boxes. There are no particular limitations on the materials used in pillow-like packaging; for example, resin films such as polypropylene film, polyethylene terephthalate film, and polyethylene film, or materials made by attaching aluminum foil to these resin films, can be used. It should be noted that, if there are concerns about moisture absorption, desiccants or similar substances can be stored simultaneously inside the bottle packaging or the pillow-like packaging.

[0115] The solid composition of this embodiment can be contained within a packaging container to form a package. For example, the solid composition of this embodiment can be contained in an airtight package. By forming a package, for example, the convenience of using the solid composition can be improved. Specifically, the package in this embodiment is a pharmaceutical product.

[0116] As packaging forms for solid dosage forms, solid compositions can be temporarily packaged and airtightly preserved using bottles, PTP (Press Through Package), pouches, strips, and SP (Strip Package). They can also be further packaged in pillow-like containers or stored in boxes. Furthermore, from the viewpoint of reducing moisture absorption by the solid composition, desiccants can be stored simultaneously within the bottle or pillow-like packaging container.

[0117] Materials used in SP packaging, PTP packaging, strip packaging, pillow packaging, etc., include, for example, resin films such as polypropylene film, polyethylene terephthalate film, and polyethylene film, and materials made by attaching aluminum foil to these resin films. Any of single-layer films and multi-layer films (e.g., laminated films) can be used.

[0118] Furthermore, the materials constituting the packaging container preferably include materials that are not easily affected by moisture. Examples of such packaging include packaging formed from at least one of moisture-proof materials and gas-barrier materials.

[0119] As a moisture-proof material, a combination of PTP (polypropylene) and polyethylene aluminum pillow packaging can be cited as an example. Furthermore, when the solid composition is a tablet, considering factors such as inhibiting the rise in moisture content of the tablet, tablet storage stability, and tablet stability after opening, PTP packaging (Al-Al packaging) using aluminum on both sides can be used as a moisture-proof material.

[0120] As a gas barrier material, known materials can be used, such as laminates with functional barrier layers, or materials that also function as moisture-proof materials, or materials that are used together with moisture-proof materials.

[0121] In addition, packaging containers can be made in an environmentally conscious way. For example, environmentally friendly raw materials such as recycled plastics, biomass plastics, and biodegradable plastics can be used in part or all of the packaging materials.

[0122] (Manufacturing method)

[0123] In a second approach, a method for manufacturing a solid composition is provided, comprising the step of mixing at least one selected from the group consisting of tebuconazole and its salts with licorice.

[0124] The method for manufacturing the solid composition involved in this embodiment may include a step of further mixing acetaminophen.

[0125] The solid composition can be manufactured using known techniques. The components are added in any step, eventually coming into contact with each other. Solvents and binders can be added to the mixture after contact and kneaded, resulting in a kneaded compound as the solid composition.

[0126] The obtained kneaded mixture can also be further dried and granulated to produce granules. In this case, granules containing each component can be prepared separately. Granulation can be wet or dry.

[0127] The resulting granules can be used directly, or additives can be added to the granules and compressed into tablets to produce uncoated tablets, or they can be further coated with a film.

[0128] For example, when the solid composition is a tablet, it can be manufactured in accordance with the "Tablets" section of the General Rules for Preparations in the Japanese Pharmacopoeia. Specifically, tablets can be manufactured by granulating a mixed powder containing at least one of the group consisting of at least tebecidine and its salts, licorice, and optionally acetaminophen, to obtain granules (granules), and then compressing the obtained granules and optional extragranule components into tablets. Alternatively, a mixed powder containing at least one of the group consisting of tebecidine and its salts can be granulated to obtain a first granule, and a mixed powder containing licorice can be granulated to obtain a second granule, and these two granules and appropriate extragranule components can be compressed into tablets, thereby manufacturing a tablet. From the viewpoint of improving the hardness of the solid composition, it is preferable to granulate a mixed powder containing at least one of the group consisting of at least tebecidine and its salts and licorice to form granules (granules), so that the two components are contained in the same granule, and more preferably, acetaminophen is further contained in the same granule.

[0129] When a solid dosage form contains extragranular ingredients, subsequent ingredients can be added to the granulated granules in a manner that forms the exterior of the granules, and the mixture is compressed into tablets, thereby manufacturing tablets. Alternatively, the extragranular ingredients can be formed into granules. For example, a first granule can be manufactured containing at least one ingredient selected from the group consisting of tepedidine and its salts, and licorice, and a second granule can be manufactured containing other active ingredients. In this case, a first granule containing at least one ingredient selected from the group consisting of tepedidine and its salts, and licorice, and a second granule containing other active ingredients can be separately manufactured, such that the ingredients in the first granule and other active ingredients in the second granule do not substantially come into contact. Other active ingredients can be included in the first granule or in the second granule in a manner that yields a suitable formulation.

[0130] It should be noted that the granules obtained from the above process can be used directly as granules.

[0131] To illustrate the invention in more detail, embodiments are described below, but the invention is not limited to these.

[0132] Example

[0133] 1. Raw materials

[0134] In this embodiment, the following raw materials are used. It should be noted that the licorice extract powder described below is obtained by converting the raw herb to a 7:1 ratio, that is, by concentrating the raw herb 7 times.

[0135] [Table 1]

[0136] Raw material Trade name Manufacturer Tipepidine hydrochloride ASTRAZAN H San Chemical Co., Ltd. Glycyrrhiza extract powder Glycyrrhiza extract powder-A Nippon Powder Medicine Co., Ltd. Acetaminophen Acetaminophen Yamamoto Chemical Industry Co., Ltd. Lactose Lactose hydrate Armor Pharma Crystalline cellulose Ceolus UF-702 Asahi Kasei Co., Ltd. Corn starch Corn starch Matsutani Chemical Industry Co., Ltd. D-mannitol D-mannitol Bussan Food Science Co., Ltd. Magnesium stearate Magnesium stearate Taihei Chemical Industry Co., Ltd.

[0137] 2. Manufacturing of granules

[0138] Granulations containing teperidine syrup, licorice extract powder, or acetaminophen are prepared as follows: Appropriate amounts of ethanol are added to each raw material, and the mixture is granulated using a mortar and pestle. The granules are then vacuum-dried and sieved through a 30-mesh sieve. It should be noted that, as shown in Tables 2 and 3, for the co-granulation of teperidine syrup and licorice extract powder, the raw materials are formulated in a mass ratio of teperidine syrup to licorice extract powder of 2:1 (or 2:7 when converting licorice to its raw form). Furthermore, for the co-granulation of teperidine syrup, licorice extract powder, and acetaminophen, the raw materials are formulated in a mass ratio of teperidine syrup: licorice extract powder: acetaminophen of 1:1:1 (or 1:7:1 when converting licorice to its raw form).

[0139] 3. Tablet manufacturing and hardness determination

[0140] Weigh each raw material according to the proportions in Tables 2 and 3 to make a total of 2.5g, mix them evenly in a bottle, and prepare each tablet powder. The proportions of each component in Tables 2 and 3 are expressed in parts by mass. For each tablet powder, use... A 10.8R tablet was compressed using a manual tableting machine (Riken Seiki) at a pressure of 1,000 kgf to produce tablets of 400 mg each. It should be noted that in Tables 2 and 3, the components labeled "granules" are granules obtained using the method described in "2. Manufacturing of Granules". Specifically, when using Examples 1 and 2 described in Table 2, for example, Example 1 used 40 parts by weight of teperidine hyaluronic acid powder and 20 parts by weight of licorice extract powder; in contrast, Example 2 used 60 parts by weight of a co-granule containing teperidine hyaluronic acid powder and licorice extract powder in a 2:1 mass ratio.

[0141] For each tablet, the hardness (unit: N) was measured using a load-sensor type tablet hardness tester, Tablet Tester 8M (manufactured by Pharmatron). The measured values ​​are recorded in Tables 2 and 3.

[0142] [Table 2]

[0143]

[0144] [Table 3]

[0145]

[0146] As shown in Table 2, solid compositions containing at least one of the group consisting of ibuprofen and its salts, and licorice, have higher hardness than solid compositions without licorice. Furthermore, solid compositions containing granules formed by co-granulating at least one of the group consisting of ibuprofen and its salts with licorice have particularly high hardness.

[0147] Furthermore, as shown in Table 3, solid compositions containing at least one of the group consisting of tebuconazole and its salts, licorice, and acetaminophen have higher hardness than solid compositions without licorice. Additionally, solid compositions formed by co-granulation of at least one of the group consisting of tebuconazole and its salts, licorice, and acetaminophen have particularly high hardness.

[0148] The following are examples of solid dosage forms. It should be noted that in the following dosage form examples, glycyrrhizic acid, which is the main component of licorice, is added instead of licorice, but licorice can also be added instead of glycyrrhizic acid.

[0149] [Table 4]

[0150] Combined amount (mg) in 1 day amount Preparation Example 1 Preparation Example 2 Preparation Example 3 Preparation Example 4 Preparation Example 5 Ibuprofen 450 450 450 450 450 Clemastine fumarate 1.34 1.34 1.34 1.34 1.34 Tipepidine hydrochloride 75 75 75 75 75 Noscapine 48 48 48 48 48 L-carbocisteine 750 750 750 750 750 Glycyrrhizic acid 39 39 39 39 39 Anhydrous caffeine 75 75 75 75 75 Hydroxypropyl methyl cellulose 167 242 34 36 90 Polyoxyethylene hydrogenated castor oil 235 319 92 225 45 Crystalline cellulose 182 91 630 285 488 D-mannitol 460 275 52 43 156 Sodium croscarmellose 65 48 29 210 134 Hydroxypropyl cellulose 35 26 280 190 72 Light anhydrous silicic acid 19 56 8 42 24 Talc 62 28 15 73 186 Polyvinyl alcohol (partially saponified) 30 146 27 105 68 Hydroxypropyl methyl cellulose 18 11 69 68 23 Triethyl citrate 3 32 21 15 8 Titanium oxide 40 44 59 23 23 Carnauba wax Trace amount Trace amount Trace amount Trace amount Trace amount Trace amount

[0151] [Table 5]

[0152]

[0153] The preferred embodiments and examples of the present invention have been described above, but the present invention is not limited thereto. Additions, omissions, substitutions, and other modifications to the configuration can be made without departing from the spirit of the present invention.

Claims

1. A solid composition comprising: at least one selected from the group consisting of tipepidine and salts thereof; and licorice.

2. The solid composition according to claim 1, which contains a granulate comprising: at least one selected from the group consisting of tipepidine and salts thereof; and licorice.

3. The solid composition according to claim 1, further comprising acetaminophen.

4. The solid state composition of claim 2, wherein, The granulate further comprises acetaminophen.

5. The solid state composition of any one of claims 1-4, wherein, The hardness of the solid composition is 40 N or more.

6. A method for producing the solid composition according to any one of claims 1 to 4, comprising a step of mixing at least one selected from the group consisting of tipepidine and salts thereof with licorice.

7. The production method according to claim 6, comprising a further step of mixing acetaminophen.

8. The production method according to claim 6, comprising: a step of forming a granulate comprising at least one selected from the group consisting of tipepidine and salts thereof and licorice; and a step of tableting the granulate. In the step of forming the granulate, a granulate comprising at least one selected from the group consisting of tipepidine and salts thereof, licorice, and acetaminophen is formed.

9. The production method as claimed in claim 8, wherein, ​

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