Solid composition and method for producing the same

Abstract

At least one selected from the group consisting of tipepidine and its salts, having sufficient hardness To provide a solid composition containing one of the following: [Solution] At least one selected from the group consisting of tipepidine and its salts and licorice A solid composition containing the following.

Description

Technical Field

[0001] The present invention broadly relates to a solid composition containing at least one selected from the group consisting of tipepidine and its salts and kanzou, and a method for producing the same. and the like.

Background Art

[0002] Solid compositions such as tablets for oral administration disintegrate in the digestive tract, and then the active ingredients in the composition are absorbed into the body. From the viewpoints of transportability and abrasion resistance, it is extremely important in the formulation design that the solid composition has a hardness of a certain level or more. Since there are active ingredients of pharmaceuticals that reduce the hardness of solid compositions, techniques for improving the hardness of solid compositions have been studied. and the like.

[0003] For example, Patent Document 1 discloses a composition having excellent tablet hardness and disintegrability without containing a shaping agent by containing a disintegrant component and microfibrous cellulose. and the like.

[0004] In the tablets obtained by tableting granules obtained by wet granulation of a mixture containing the main drug, Patent Document 2 discloses a method for improving the hardness of the tablets and suppressing the delay of the disintegration time by blending crystalline cellulose in the granules. and the like.

[0005] and the like. and the like. and the like.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Summary of the Invention

[0007] The present inventors have developed a solid comprising at least one selected from the group consisting of tipepidine and its salts. We found that the hardness may decrease in the morphological composition. Therefore, the present invention provides sufficient hardness. A solid containing at least one selected from the group consisting of tipepidine and its salts, having a degree The objective is to provide a composition. [Means for solving the problem]

[0008] The present inventors have selected at least one from the group consisting of tipepidine and its salts, When licorice is added, at least one substance selected from the group consisting of tipepidine and its salts is obtained. We discovered that the decrease in hardness caused by [the substance] is suppressed, and thus completed the present invention.

[0009] In other words, this embodiment includes the following aspects. [1] The mixture includes at least one selected from the group consisting of tipepidine and its salts, and licorice. Solid composition. [2] The mixture includes at least one selected from the group consisting of tipepidine and its salts, and licorice. The solid composition according to [1], containing granules. [3] The solid composition according to [1] or [2], further comprising acetaminophen. [4] The solid composition according to [2], further comprising acetaminophen in the granules. [5] The hardness of the solid composition is 40 N or higher, as described in any one of [1] to [4]. Solid composition. [6] A mixture of at least one substance selected from the group consisting of tipepidine and its salts, and licorice. A method for producing the solid composition according to any one of [1] to [5], including the step of [7] The production method according to [6], including the step of further mixing acetaminophen. [8] At least one selected from the group consisting of tipepidine and its salts, and licorice, including The step of forming a granule, The step of tableting the granule, The production method according to [6], including [9] In the step of forming the granule, a granule containing at least one selected from the group consisting of tipepidine and its salts, licorice, and acetaminophen is formed. [8] The production method according to

Advantages of the Invention

[0010] According to the present invention, a solid composition containing at least one selected from the group consisting of tipepidine and its salts, having sufficient hardness, can be provided.

Modes for Carrying Out the Invention

[0011] Hereinafter, embodiments of the present invention (hereinafter referred to as "the present embodiment") will be described, but the scope of the present invention is not construed as being limited to the following embodiments. In the present embodiment, the composition can contain each component alone or in combination of two or more. In this specification, "~" indicating a numerical range represents "or more" and "or less", and includes both end values.

[0012] (Solid Composition) In a first aspect, a solid composition containing at least one selected from the group consisting of tipepidine and its salts, and licorice is provided. Specifically, the solid composition is a solid pharmaceutical composition.​​​

[0013] Each component contained in the solid composition according to this embodiment is included in a pharmaceutically acceptable salt state. It may be present on its own, or it may be included as a complex with other components. That is, in this embodiment The solid composition in question may include, for example, not only tipepidine, but also acetaminophen, and other Regarding the ingredients, it is acceptable to include salts of each ingredient. "Pharmacologically acceptable salts" are, for example, Contains salts with bases and acids that are acceptable as pharmaceuticals. Non-specific examples of pharmacologically acceptable salts include inorganic acids (hydrochloric acid, hydrobromic acid, iodide). Addition salts of hydrogen acids, sulfuric acid, phosphoric acid, etc., organic acids (p-toluenesulfonic acid, methanesulfone Acids, oxalic acid, p-bromophenylsulfonic acid, carboxylic acids, succinic acid, citric acid, benzoate Addition salts of acetic acid (such as acetic acid), inorganic bases (ammonium hydroxide or alkali or alkali) Examples include addition salts of earth metal hydroxides, carbonates, bicarbonates, etc., and addition salts of amino acids. Pharmacologically acceptable salts may be hydrated or anhydrous.

[0014] In this embodiment, the solid composition is selected from the group consisting of tipepidine and its salts. Because it contains licorice in addition to at least one of the above, it has sufficient hardness.

[0015] The hardness of the solid composition in this embodiment is as defined in the "Tablet Hardness" section of the 18th edition of the Japanese Pharmacopoeia Reference Information. Measurement method <g6-4-180>This is hardness measured by the method described in "". More specifically This is obtained by using a 9φ, 10.8R punch and compressing it in a tablet press at a pressure of 1,000 kgf. The hardness may be measured in the form of a tablet. The volume of the tablet used when measuring hardness is particularly important. Although not limited to this, one tablet may be 400 mg. More specifically, the solid in this embodiment The hardness of the composition may be the hardness measured by the method described in the examples.

[0016] The hardness of the solid composition measured as described above is preferably 40 N or higher. It is more preferably 40-250N, more preferably 50N or more, and 50 More preferably ~200N, and even more preferably 55~150N It is preferable that the temperature is 60-120N, and even more preferable that it is 65-100N. This is particularly preferable.

[0017] (At least one selected from the group consisting of tipepidine and its salts) As used herein, "tipepidine" is the CAS registry number 5169-78-8 Yes, C 15 H 17 This compound is represented by the chemical formula NS2 (molecular weight: 275.43 g / molecular weight). The salt of tipepidine is not particularly limited as long as it is pharmacologically acceptable, but tipepidine Examples include hibenzate and tipepidine citrate.

[0018] The amount of at least one substance selected from the group consisting of tipepidine and its salts is the solid composition The intended use of the substance, the required degree of cough suppressant and expectorant effect, the required degree of hardness, and the target recipients. The dosage is adjusted as appropriate according to the symptoms, age, weight, sex, etc. Furthermore, tipepidine and its The amount and content of at least one selected from the group consisting of salts is tipepidine and tipepidine The proportions and content of each of the salts of tipepidine are as follows: It is preferable that the amount and content of the total be within the range of the amounts and content described below.

[0019] The amount of at least one substance selected from the group consisting of tipepidine and its salts is, for example, For adults, the daily dose is, for example, 8 mg to 120 mg, more preferably. The dosage can be adjusted within the range of 16 mg to 72 mg. In this embodiment, "adult" means 15 years of age or older. This refers to men and women. However, the solid composition according to this embodiment is intended for adult consumption. It is not limited to children under 15 years of age. In such cases, the dosage should be reduced to 1 / 2 or 2 / 3 of the daily dose taken by adults, depending on the age group. It is possible to be present. At least one selected from the group consisting of tipepidine and its salts. The same applies to its components.

[0020] The weight and dosage of the above solid composition are the daily dose (daily amount), but the same amount The substance can be administered to the target in one dose, or multiple times a day, for example, two or three times, preferably in three separate doses. May be given. At least one component selected from the group consisting of tipepidine and its salts. The same applies to minutes. Also, each dosage is the total amount, so the single dose and the solid composition are different. The content of each component in the solid composition may vary depending on its shape and other factors.

[0021] In certain embodiments, the solid composition is a tablet, and the above dosage is 3 tablets, 6 tablets, or This is the amount of the ingredient contained in 9 tablets, preferably the amount of the ingredient in 9 tablets. For adults (15 years and older), the single dose is three times a day, with each dose consisting of 2 tablets, 3 tablets, or The dosage is 4 tablets, preferably 3 tablets per dose.

[0022] (Licorice) As used herein, "licorice" refers to the term as it appears in the 18th edition of the Japanese Pharmacopoeia. This can be used. For licorice, for example, water or 30% ethanol can be used as the extraction solvent. Some products use aqueous solutions of licorice, such as licorice extract and dried licorice extract. Depending on the type of extract, such as licorice soft extract or licorice fluid extract, the crude drug equivalent ratio varies. Such products are sold. The quantities of licorice described herein are not specified unless otherwise noted. The values ​​are calculated based on the equivalent amount of crude drugs. For example, licorice extract is calculated per 1 part by mass of the extraction solvent. It contains approximately 4 parts by mass of licorice in terms of crude drug equivalent. In addition, the extract of these licorice In addition to the above, there is also a powdered extract made by extracting licorice with water or a 30% ethanol aqueous solution. (Extract powder), as well as licorice extract, licorice extract solution, etc. may be used as appropriate, and there is no particular limitation It is not fixed. However, the ratio is approximately 5 to 9 parts by mass of crude drug per 1 part by mass of extraction solvent. Parts by mass, for example, about 6 to about 8 parts by mass of licorice extract containing licorice, are dried. The extract powder is preferred. The extraction solvent is preferably water.

[0023] Furthermore, licorice is selected from the group consisting of glycyrrhizic acid and its salts as its main components. It contains at least one of the following. When used herein, "glycyrrhizic acid" is The CAS registry number is 1405-86-3, and C 42 H 62 O 16 Compounds represented by the chemical formula It is (molecular weight: 822.93 g / mol). Salts of glycyrrhizic acid are pharmacodynamically acceptable. It is not particularly limited as long as it is a substance, but for example, trisodium glycyrrhizinate, glycyrrhizinate Disodium glycyrrhizate, diammonium glycyrrhizinate, monoammonium glycyrrhizinate Examples include dipotassium glycyrrhizinate and monopotassium glycyrrhizinate.

[0024] Therefore, in the solid composition according to this embodiment, licorice is replaced with and / or added Furthermore, the mixture contains at least one selected from the group consisting of glycyrrhizic acid and its salts. It is also good. Licorice is composed of glycyrrhizic acid and its salts in the dried crude drug. It may contain at least 2.0% of one species selected from the group. Licorice powder is calculated as raw At least one selected from the group consisting of glycyrrhizic acid and its salts to the dried drug It may contain 2.0% or more of it. Licorice extract may contain glycyrrhizin in proportion to the dried crude drug converted to glycyrrhizin. It may contain at least 3.6% of at least one substance selected from the group consisting of tinic acid and its salts. Licorice crude extract consists of glycyrrhizic acid and its salts, converted from the dried crude drug. The solid composition according to this embodiment may contain at least one selected from the group in an amount of 4.8% or more. In a substance, the total content of glycyrrhizic acid and its salts is referred to as the content of licorice, as will be described later. The content can be reduced to, for example, 0.01 to 0.1 times (for example, 0.02 times, 0.036 times, 0.04 times, It is acceptable to use a range that is 0.048 times the original value.

[0025] The extracted components are obtained by conventional methods, for example, by extracting the active ingredients from the crude drug using an extraction solvent. It can be obtained by the following. Examples of extraction solvents include water, hydrophilic solvents, or mixtures thereof. A solvent is often used. Examples of the hydrophilic solvent include methanol, ethanol, and prophosphate. Panol, Isopropanol, Butanol, Isobutanol, S-Butanol, T-Butanol Alcohols such as methyl cellosolve and ethyl cellosolve; cellosolves such as methyl cellosolve and ethyl cellosolve. Ketones such as acetone; ethers such as dioxane and tetrahydrofuran; pyrid N, Morpholine, Acetonitrile, N,N-dimethylformamide, Dimethylacetamide Examples include nitrogen-containing solvents such as N-methylpyrrolidone. These hydrophilic solvents are It may be used alone or as a mixture of two or more solvents.

[0026] The amount of licorice used depends on the intended use of the solid composition, the required degree of hardness, and the target of administration. The dosage is adjusted as appropriate according to symptoms, age, weight, sex, etc. For example, the amount of licorice per day Per serving, in terms of crude drug equivalent, 100 mg to 5,000 mg, preferably 200 mg to 2,0 The amount is 00 mg, more preferably in the range of 50 mg to 1,200 mg.

[0027] The amount of licorice contained in the composition administered daily is 1% by mass to 7% in terms of crude drug equivalent. 0% by mass, preferably 5% to 50% by mass, more preferably 10% to 30% by mass be.

[0028] The total amount of tipepidine and its salts contained in the composition administered daily, and the mass of licorice. The ratio is the total amount of tipepidine and its salts to the amount of licorice converted to crude drug, preferably 1: 20 to 1:1, more preferably 1:15 to 1:2, and even more preferably 1:10 to 1:3 Yes. When using licorice extract powder as licorice, the total amount of tipepidine and its salts and The mass ratio with lentil extract powder is preferably 1:2 to 10:1, more preferably 1:1 to 5 :1, more preferably 2:1 to 3:1.

[0029] From the viewpoint of further increasing the hardness of the solid composition according to this embodiment, licorice contains tipepidine and It is preferable that at least one selected from the group consisting of those salts be included in the same granules. In other words, the solid composition according to this embodiment is made from the group consisting of tipepidine and its salts. Preferably, the granules contain at least one selected ingredient and licorice, and tipepidine A mixed powder containing at least one selected from the group consisting of and salts thereof, and licorice is granulated. It is preferable to include granules obtained by the process. The solid composition according to this embodiment contains the granules. The solid composition according to this embodiment may be a tablet obtained by compressing certain granules. A mixture containing at least one selected from the group consisting of tipepidine and its salts, and licorice. The tablets may be manufactured by a direct compression method in which the combined powder is directly compressed, and may contain tipepidine and its salts. At least one selected from the group consisting of and licorice is dissolved in a solvent, and the solvent is dried by distillation. Even if the powder obtained by removing the residue, and even if the powder is optionally granulated and then compressed into tablets, Good. In such embodiments, at least one selected from the group consisting of tipepidine and its salts. Both the licorice and the licorice will be present in close proximity in the solid composition. Solid composition containing at least one selected from the group consisting of tipepidine and its salts. The effect of increasing the hardness of materials tends to be even more pronounced.

[0030] (Acetaminophen) The solid composition according to this embodiment may further contain acetaminophen. The inclusion of minofen tends to further improve the hardness of the solid composition. When used in detailed documents, "acetaminophen" has CAS registry number 103-90-2. It is a compound represented by the chemical formula C8H9NO2. Acetaminophen salts are used as medicines. It is not particularly limited as long as it is permissible in theory.

[0031] The amount of acetaminophen to be included depends on the intended use of the solid composition, the required degree of hardness, and the dosage. The dosage is adjusted as appropriate depending on the symptoms, age, weight, sex, etc. of the person being treated. Contains acetaminophen. If used, the amount of at least one selected from the group consisting of tipepidine and its salts. The amount varies depending on the quantity, but the daily amount is 120mg to 1200mg, preferred The dosage is adjusted to a range of 150 mg to 900 mg, more preferably 180 mg to 600 mg. obtain.

[0032] The total amount of tipepidine and its salts and acetaminophen contained in the composition administered daily The mass ratio of tipepidine and its salt to acetaminophen is preferably the ratio of the total amount of tipepidine and its salt to acetaminophen. 1:10 to 3:1, more preferably 1:5 to 2:1, and even more preferably 1:2 to 1:1 be.

[0033] From the viewpoint of further increasing the hardness of the solid composition according to this embodiment, acetaminophen is used. It is contained in the same granule as at least one selected from the group consisting of pepidine and its salts. Preferably, at least one selected from the group consisting of tipepidine and its salts and It is preferable that it be contained in the same granules as licorice. That is, the solid according to this embodiment. The composition consists of at least one selected from the group consisting of tipepidine and its salts, and licorice. Preferably, it contains granules containing acetaminophen, and tipepidine and its salts. A mixed powder containing at least one selected from the group, licorice, and acetaminophen is prepared. It is preferable to include granules obtained by granulation. The solid composition according to this embodiment is the granules The tablet may be obtained by compressing granules, which are a physical substance. From a similar viewpoint, the embodiment described herein The solid composition consists of at least one selected from the group consisting of tipepidine and its salts, and licorice. These tablets are manufactured by a direct compression method, in which a mixture containing u and acetaminophen is directly compressed into tablets. However, it is also fine to have at least one selected from the group consisting of tipepidine and its salts and licorice A powder obtained by dissolving acetaminophen in a solvent and drying off the solvent, and the The tablets may be formed by selectively granulating a powder and then compressing it into tablets. In such embodiments, At least one selected from the group consisting of tipepidine and its salts, licorice, and acetone Minofen and other substances are present in close proximity in the solid composition, and the hardness of the solid composition The degree tends to improve even further.

[0034] (Other ingredients) The solid composition according to this embodiment may contain components other than those listed above, depending on its intended use. The solid composition relieves various cold symptoms, such as runny nose, nasal congestion, sneezing, sore throat, cough, and For the purpose of relieving chills, fever, headache, joint pain, muscle pain, etc., bromhexyl In addition to meloxicam, antipyretic analgesics, especially nonsteroidal anti-inflammatory drugs (NSAIDs) ) and other pharmacologically acceptable ingredients may be included.

[0035] Nonsteroidal anti-inflammatory drugs include ibuprofen, diclofenac, loxoprofen, and za Lutoprofen, pranoprofen, oxaprozin, tiaprofenic acid, naproxen , lornoxicam, ampiroxicam, piroxicam, nabumetone, indomethacin, s COX-2 nonselective inhibitors such as lindac, mofezolac, and mefenamic acid, and meloxicam. These are broadly classified into COX-2 selective inhibitors such as etodolac and celecoxib. Meloxicam is It may be incorporated into the composition as a nonsteroidal anti-inflammatory drug. Nonsteroidal anti-inflammatory drugs are C It is preferable that it be an OX-2 nonselective inhibitor. Nonsteroidal anti-inflammatory drugs are in the form of salts. That's fine.

[0036] Other pharmacologically acceptable ingredients include those found in combination cold medicines, antipyretic analgesics, and rhinitis medications. Antihistamines, antipyretics and analgesics, cough suppressants and expectorants, anti-inflammatory drugs, central nervous system stimulants, vitamins The drug may also be formulated with other agents such as anticholinergics and antiplasmins.

[0037] For example, antihistamines include isopendyl hydrochloride, difeterol hydrochloride, and triphosphate hydrochloride. Perenamin, tondiamine hydrochloride, phenetazine hydrochloride, methidilazine hydrochloride, dl-chlor Pheniramine maleate, d-chlorpheniramine maleate, diphenyl disulfone Carbinoxamine phosphate, diphenylpyraline hydrochloride, diphenylpyraline theoclate, Diphenhydramine hydrochloride, diphenhydramine salicylate, alimethazine tartrate, Diphenhydramine iodine, triprolidine hydrochloride hydrate, mebhydrolysine napadisylate N, promethazine methylene disalicylate, carbinoxamine maleate, diphosphate Examples include terol, clemastine fumarate, and mequitazine.

[0038] Examples of antipyretic analgesics other than nonsteroidal anti-inflammatory drugs include aspirin and ethenzame. D, salicylamide, lactylphenethidine, isopropylantipyrine, etc. These are some examples.

[0039] Cough suppressants and expectorants include noscapine, noscapine hydrochloride hydrate, and dextromethorphan. Hydrobromide hydrate, bromhexine, dihydrocodeine phosphate, dl-methyl ephedrine Dorin hydrochloride, dl-methylephedrine saccharin salt, pseudoephedrine hydrochloride, Examples include ambroxol hydrochloride and L-carbocysteine.

[0040] Anti-inflammatory drugs include glycyrrhizic acid and its derivatives and their salts (for example, glycyrrhizic acid and its derivatives and salts). Dipotassium lycyrrhizinate, monoammonium glycyrrhizate, etc., tranexamic acid, etc. These are some examples.

[0041] Examples of central nervous system stimulants include caffeine and anhydrous caffeine.

[0042] Vitamin supplements include vitamin B1 and its derivatives and their salts (e.g., Benf Othiamine, vitamin B2 and its derivatives and their salts (e.g., riboflavin) Vitamin C and its derivatives and their salts (e.g., ascorbic acid), hesperidin Examples include ions and their derivatives, as well as salts thereof.

[0043] Anticholinergic agents include scopolamine hydrobromide, datura extract, and methylscopolamine. Bromides, methyl-l-hyoscyamine bromide, pirenzepine hydrochloride, butylscopolamine Bromides, belladonna alkaloids, belladonna extract, total belladonna alkaloids, iodine Isopropamide, diphenylpiperidinomethyldioxolane iodide, belladonna extract, ro Examples include belladonna root, belladonna root total alkaloid citrate, etc.

[0044] The solid composition according to this embodiment may be further modified by adding a formulation additive as needed. Possible alternatives include pharmaceutically acceptable carriers, such as excipients, binders, and disintegrants. Disintegration aids, glossing agents, foaming agents, moisture-proofing agents, surfactants, stabilizers, antioxidants, fillers, Sweeteners, flavoring agents, cooling agents, fragrances, air fresheners, coloring agents, bases, coating agents, sugar coating agents, etc. Examples include plasticizers, dispersants, defoamers, fluidizers, and flavoring agents / fragrances, etc., as well as conventionally known solid formulations. Pharmaceutical additives that can be used for the above purposes may be used for the above purposes.

[0045] Excipients include, for example, sugar powder, gum arabic, powdered gum arabic, cocoa butter, caramel. Sodium carboxymethyl starch, hydrated silicon dioxide, anhydrous amorphous silicon dioxide, Xylitol, magnesium aluminosilicate, calcium silicate, magnesium silicate Light anhydrous silicic acid, crystalline cellulose, crystalline cellulose-carmellose sodium, crystalline cellulose Lurose (fine particles), crystalline cellulose (granules), powdered cellulose, synthetic aluminum silicate Synthetic aluminum silicate, hydroxypropyl starch, crystalline cellulose, wheat cellulose Pun, rice flour, rice starch, heavy anhydrous silicic acid, refined white sugar, refined white sugar spherical granules, gelatin, D-sorbitol, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low degree of substitution Hydroxypropylcellulose, dextrin, corn starch, corn Starch granules, trehalose, silicon dioxide, lactose monohydrate, lactose granules, sucrose, potato Sweet potato starch, hydroxypropyl starch, partially pregelatinized starch, powdered sugar, powdered candy, powdered syrup Original maltose syrup, powdered cellulose, pectin, polyoxyethylene hydrogenated castor oil, polio Xyethylene hydrogenated castor oil 60, maltitol, D-mannitol, aluminum metasilicate Examples include magnesium sulfate, calcium sulfate, erythritol, glucose, and fructose.

[0046] Examples of binders include gum arabic, gum arabic powder, kanbai flour, gelatin, and ceramic. Hydroxypropyl starch, hydroxypropyl cellulose, hypromellose, Lulan, povidone, polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified) (Diluted methacrylate), methacrylate copolymer L, methacrylate copolymer LD, methacrylate Copolymer S, butyl methacrylate / methyl methacrylate copolymer, methylcellulose Examples include polyvinyl alcohol-acrylic acid-methyl methacrylate copolymers.

[0047] Examples of disintegrants include sodium carboxymethyl starch, carmellose, and caramel. Mellose calcium, croscarmellose sodium, croscarmellose sodium, Crospovidone, low-substituted hydroxypropyl cellulose, hydroxypropyl starch Examples include partially pregelatinized starch.

[0048] Examples of disintegration aids include carboxymethyl starch sodium, carmellose, Carmellose calcium, croscarmellose sodium, light anhydrous silicic acid, crystalline cellulose Sodium bicarbonate, precipitated calcium carbonate, lactose monohydrate, hydroxypropyl starch -ch, polysorbate 40, polysorbate 60, polysorbate 80, macrogol 1 Examples include 500 and macrogol 4000.

[0049] Examples of glossing agents include carnauba wax, bleached beeswax, refined shellac, and macromolecules. Goal 400, Macro Goal 1500, Macro Goal 4000, Macro Goal 6000, Examples include macrogol 6000NF and beeswax.

[0050] Examples of foaming agents include anhydrous sodium carbonate, tartaric acid, potassium bitartrate, and carbonated water. Examples include sodium chloride and anhydrous citric acid.

[0051] Examples of moisture-proofing agents include ethylcellulose, olive oil, and dried aluminum hydroxide gel. Glycerin, magnesium silicate, light anhydrous silicic acid, hydrogenated oil, synthetic aluminum silicate sucrose fatty acid ester, stearic acid, magnesium stearate, refined shellac, Refined sugar, talc, neutral anhydrous sodium sulfate, precipitated calcium carbonate, fumaric acid, stearin Acid, polyvinyl acetal diethylaminoacetate, hydroxypropyl methylcellulose -2910 mixture, polyvinyl acetal diethylaminoacetate, aluminum metasilicate Examples include magnesium methyl phosphate.

[0052] Examples of surfactants include sucrose fatty acid esters and polyoxyethylene hydrogenated castor oil. Oil 20, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether , polyoxyethylene cetyl ether, polyoxyethylene sorbitan monolaurate, Polyoxyethylene sorbitan beeswax, polyoxyethylene nonylphenyl ether, Polyoxyethylene (20) polyoxypropylene (20) glycol, polyoxyethylene Poly(105)polyoxypropylene(5)glycol, polyoxyethylene(120) Polyoxypropylene (40) glycol, polyoxyethylene (160) polyoxypropylene Polypropylene (30) glycol, polyoxyethylene (10) polyoxypropylene (4) Cetyl ether, polysorbate 20, polysorbate 60, polysorbate 80, macro Logol 400, sorbitan monooleate, glyceryl monostearate, monostearate Examples include sorbitan phosphate, sorbitan monolaurate, and sodium lauryl sulfate. ru.

[0053] Examples of stabilizers include adipic acid, L-aspartic acid, and L-aspartic acid sodium. Thorium, DL-alanine, L-alanine, L-arginine, L-arginine hydrochloride, A Sodium benzoate, propylene glycol alginate, benzoic acid, sodium benzoate Thorium, ethylenediamine, calcium disodium edetate, sodium edetate, Tetrasodium edetate, tetrasodium edetate tetrahydrate, zinc chloride, ammonium chloride, salt Calcium chloride hydrate, cetylpyridinium chloride, ferric chloride, sodium chloride, magnesium chloride Nesium, cysteine ​​hydrochloride, L-histidine hydrochloride, cocoa butter, carboxyvinyl polymer , carmellose calcium, hydrated silicon dioxide, carmellose sodium, dried sodium carbonate Glycine, Glycerin, Glycerin fatty acid ester, Calcium gluconate hydrate Substances, sodium gluconate, magnesium gluconate, potassium L-glutamate, L- Sodium glutamate, L-lysine glutamate, light anhydrous silicic acid, crystalline phosphate diphosphate Sodium hydrogen, sodium chondroitin sulfate, zinc oxide, L-cysteine, L-cysteine Ingredients: tartaric acid, sucrose fatty acid ester, stearic acid, refined gelatin, refined soy lecithin Gelatin, gelatin hydrolysate, sorbitan fatty acid ester, taurine, talc, carbonic acid Calcium, potassium bicarbonate, sodium bicarbonate, sodium carbonate hydrate, magnesium carbonate Cholesterol, natural vitamin E, tocopherol, tocopherol acetate, lactose, concentrated Lycerin, povidone, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stear Lyl ether, polyoxyethylene cetyl ether, polyoxyethylene nonylphenyl Ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene (42) polyoxyp Polypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39 ) Glycol, polyoxyethylene (160) polyoxypropylene (30) glycol , polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxy Ethylene coconut oil glyceryl (7E.O.), polysorbate 20, polysorbate 60, Polysorbate 80, Polyvinyl alcohol (partially saponified), Macrogol 30 0, Macrogol 400, Macrogol 4000, Anhydrous Citric Acid, Anhydrous Sodium Citrate M, anhydrous sodium monohydrogen phosphate, anhydrous sodium dihydrogen phosphate, aluminometasilicate Magnesium, methylcellulose, l-menthol, glyceryl monostearate, medicinal Carbon, magnesium sulfate hydrate, DL-malic acid, sodium hydrogen phosphate hydrate, diphosphate Potassium hydrogen, calcium dihydrogen phosphate hydrate, L-leucine, polyvinyl alcohol. Examples include acrylic acid / methyl methacrylate copolymers.

[0054] Examples of antioxidants include ascorbic acid, L-ascorbic acid, and steate. Ingredients: Citric acid hydrate, soy lecithin, natural vitamin E, tocopherol tocopherol acetate, ascorbic acid palmitate, sodium pyrosulfite, etc. Examples include: In the case of a solid composition containing acetaminophen, an antioxidant or stabilizer. It is preferable not to include tocopherols.

[0055] Examples of fillers include RSS No. 1 raw rubber, starch acrylate 1000, and Examples include silicon dioxide, titanium dioxide, silicon dioxide, and calcium monohydrogen phosphate.

[0056] Examples of sweeteners include aspartame, acesulfame potassium, amacha, and ama. Tea powder, reduced maltose syrup, xylitol, dipotassium glycyrrhizinate, glycyrrhizin Disodium saccharin, saccharin sodium hydrate, sucralose, stevia Stevia extract, refined stevia extract, refined sucrose, fructose, sucrose, maltitol, D-mannitol Examples include erythritol.

[0057] Examples of flavoring agents include sodium chloride, Phellodendron bark powder, Parmesan extract, Coptis japonica, and others. Uren powder, orange, orange oil, cocoa powder, fructose, caramel, xylitol, citric acid Calcium, citric acid hydrate, sodium citrate hydrate, L-glutamic acid, L-glutamic acid Sodium thamate, grapefruit extract, brown sugar, cinnamon powder, cinnamon oil, saccharin Ingredients: Sodium saccharin hydrate, Japanese pepper powder, tartaric acid, D-tartaric acid, potassium bitartrate. Um, DL-sodium tartrate, ginger powder, sucralose, stevia extract, ste Via extract refined product, Swertia japonica, D-sorbitol, tannic acid, clove oil, citrus peel tincture Chili pepper, chili pepper powder, spruce powder, trehalose hydrate, porcini powder, plum extract, Fructooligosaccharides, powdered sugar, peppermint powder, D-mannitol, dl-menthol l-menthol, menthol powder, dragon's mane, dragon's mane powder, green tea powder, DL- Examples include ngolic acid, DL-sodium malate, lemon oil, and rose oil.

[0058] Examples of cooling agents include fennel oil, d-camphor, dl-camphor, and cinnamon oil. Examples include peppermint water, peppermint oil, and l-menthol.

[0059] Flavorings include, for example, orange flavor, guarana extract, sweet orange, and Strawberry, brown sugar flavor, strawberry flavor, cherry flavor, banana powder Dark flavor, peach essence, fruit essence, peppermint, melon powder Examples include flavorings, l-menthol, and peppermint oil.

[0060] Examples of fragrances include fennel powder, fennel oil, ethyl vanillin, and d-camphor. dl-camphor, cinnamon powder, cinnamon oil, ginger oil, agarwood powder, spearmint Oil, clove oil, turpentine oil, chili pepper powder, pineapple powder, flavoring 51357, pineapple Apple powder flavoring 59492, peppermint water, peppermint oil, vanilla powder flavoring 54286, vanillin Bergamot oil, d-borneol, dl-borneol, dl-menthol, l- Examples include ethanol, eucalyptus oil, rose water, and rose oil.

[0061] Examples of coloring agents include yellow iron oxide, yellow iron(III) oxide, orange essence, and brown iron oxide. Iron, carbon black, caramel, beta-carotene, gold leaf, black iron oxide, titanium dioxide, tri-dioxide Iron compounds, dizuazo yellow, food blue No. 1, food yellow No. 4, food yellow No. 5, food blue No. 2 Aluminum lake, Food Yellow No. 4, Aluminum lake, Food Red No. 2, Food Red No. 3, Food Red No. 102, iron(III) oxide / glycerin suspension, copper chlorophyllin sodium, copper chlorophyllin Lofil, phenol red, malachite green, methylene blue, medicinal charcoal, riboflavin Bottle, riboflavin butyrate, riboflavin sodium phosphate, green tea powder, ro Examples include oils and other similar substances.

[0062] The base ingredients are acacia powder, pregelatinized starch, ethylcellulose, and cocoa butter. Carnauba wax, carboxyvinyl polymer, carmellose, carmellose sodium Reduced maltose syrup, hydrated silicon dioxide, dried aluminum hydroxide gel, agar, can Ten powder, xanthan gum, glycine, glycerin, glycerin fatty acid ester, light anhydrous Silicic acid, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, synthetic magnesium silicate Thorium, titanium dioxide, tartaric acid, sucrose fatty acid ester, silicone oil, stearic acid, sucrose Magnesium thearate, gelatin, D-sorbitol, talc, calcium carbonate, tofu Sorghum starch, lactic acid, ethyl lactate, calcium lactate hydrate, lactic acid / glycolic acid copolymer Combined ingredients, concentrated glycerin, potato starch, hydroxypropylcellulose, hypromello Polysorbate 60, Polysorbate 80, Poly Vinyl alcohol (partially saponified), microcrystalline wax, macrogol 20 0, Macrogol 300, Macrogol 400, Macrogol 1000, Macrogol 1 500, Macrogol 1540, Macrogol 4000, Macrogol 6000, Macro Gol 6000NF, Macrogol 20000, D-mannitol, Monostearate Lycerin, sorbitan monostearate, batyl monostearate, pryl monostearate Polyethylene glycol, polyethylene glycol monostearate, sodium lauryl sulfate Examples include polyvinyl alcohol, acrylic acid, and methyl methacrylate copolymers.

[0063] Examples of coating agents include ethyl acrylate / methyl methacrylate copolymer. Dispersion, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate Polymer RS, gum arabic, gum arabic powder, ethylcellulose, ethylcellulose water Dispersion, carnauba wax, carboxyvinyl polymer, gold leaf, silver leaf, triethyl citrate Glycerin, glycerin fatty acid ester, hydrogenated oil, titanium dioxide, sucrose fatty acid ester , stearyl alcohol, stearic acid, magnesium stearate, refined gelatin, Shellac, gelatin, D-sorbitol, talc, calcium carbonate, magnesium carbonate Gold leaf, precipitated calcium carbonate, concentrated glycerin, white shellac, hydroxypropyl cellulose Rose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl Pyrmethylcellulose 2910, titanium dioxide, macrogol 400 mixture, hypromellol S, fumaric acid, stearic acid, polyvinyl acetal diethylaminoacetate, hydro Xypropylmethylcellulose 2910 mixture, pullulan, polysorbate 80, polypropylmethylcellulose Nylacetal diethylaminoacetate, povidone, polyvinyl alcohol (partially hydrated) (Monster), Macrogol 300, Macrogol 400, Macrogol 600, Macrogol 1500, Macrogol 1540, Macrogol 4000, Macrogol 6000, Mac Logol 6000NF, Macrogol 20000, Macrogol 35000, Methacrylic Acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, metasilicic acid Magnesium aluminate, methyl acrylate, methacrylic acid, methyl methacrylate Tocopolymer, methylcellulose, 2-methyl-5-vinylpyridine methyl acrylate • Methacrylic acid copolymer, aluminum monostearate, glyceryl monostearate N, sorbitan monostearate, sorbitan monolaurate, calcium sulfate, polyvinyl sulfate Examples include a copolymer of methyl methacrylate, acrylic acid, and methyl alcohol.

[0064] Examples of sugar coating agents include gum arabic, gum arabic powder, ethylcellulose, and carnauba. Uva wax, carboxymethylcellulose sodium, titanium dioxide, stearic acid, polyoxy stearate Sil-40, refined gelatin, refined shellac, refined white sugar, gelatin, shellac, talc, precipitate Calcium carbonate, white shellac, sucrose, hydroxypropylcellulose, hypromellose Pullulan, povidone, polyvinyl alcohol (partially saponified), macrogol 1500 Macrogol 4000, Macrogol 6000, Macrogol 6000NF, Hydrophosphate Calcium hydrate, calcium dihydrogen phosphate hydrate, polyvinyl alcohol, acrylic Examples include acid-methyl methacrylate copolymers.

[0065] Examples of plasticizers include triethyl citrate, glycerin, and glycerin fatty acid ester. Lu, D-sorbitol, medium-chain triglyceride, triacetin, concentrated glycerin, castor oil Castor oil, polyoxyethylene hydrogenated castor oil 60, propylene glycol, polyoxyethylene (105) Polyoxypropylene (5) Glycol, Polysorbate 80, Macroglucose Lu 400, Macrogol 600, Macrogol 1500, Macrogol 4000, Macro Gol 6000, Macrogol 6000NF, Glyceryl Monostearate, Linoleic Acid Examples include isopropyl alcohol and liquid paraffin.

[0066] Dispersants include aminoalkyl methacrylate polymer RS, acacia gum, and arabic Agumon powder, carboxyvinyl polymer, sodium carboxymethyl starch, agar Powder, citric acid hydrate, sodium citrate hydrate, glycerin, glycerin fatty acid ester Magnesium silicate, light aluminum oxide, light anhydrous silicic acid, crystalline cellulose, acid Titanium dioxide, sucrose fatty acid ester, stearic acid, magnesium stearate, D-sol Bitol, soy lecithin, low-substituted hydroxypropyl cellulose, dextrin, Corn starch, lactose monohydrate, concentrated glycerin, potato starch, hydroxyethyl Cellulose, hydroxypropyl starch, hydroxypropylcellulose, hypromene Rose, povidone, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 40, Polyoxyethylene hydrogenated castor oil 50, Polyoxyethylene hydrogenated castor oil 60, Resorbate 20, Polysorbate 60, Polysorbate 80, Microcrystalline Macrogol, Macrogol 300, Macrogol 4000, Macrogol 6000, Macrogol 6000NF, anhydrous sodium citrate, magnesium aluminometasilicate, methyl Cellulose, glyceryl monooleate, sorbitan monooleate, monostearin Aluminum phosphate, glyceryl monostearate, sorbitan monostearate, monopal Examples include sorbitan mitinate, sorbitan monolaurate, and sodium lauryl sulfate. ru.

[0067] Antifoaming agents include ethanol, glycerin fatty acid ester, and dimethylpolysiloxane. (For oral use), dimethylpolysiloxane / silicon dioxide mixture, sucrose fatty acid ester, sil Examples include antifoaming agents, silicone oil, sorbitan fatty acid esters, and polysorbate 80. ru.

[0068] Examples of fluidizing agents include hydrated silicon dioxide, light anhydrous silicic acid, and synthetic aluminum silicate. Um, heavy anhydrous silicic acid, aluminum magnesium hydroxide, stearic acid, calcium stearate Cium, magnesium stearate, tricalcium phosphate, talc, aluminum metasilicate Examples include magnesium phosphate and calcium hydrogen phosphate granules.

[0069] Examples of fragrances and scentings include fennel powder, fennel oil, ethyl vanillin, and oleo. Orange, orange extract, orange essence, orange oil, chamomile oil, caramel, d- Camphor, dl-camphor, cinnamon powder, cinnamon oil, citronella oil, sugar flavor Spearmint oil, cherry flavor, clove oil, chili flavor, spearmint tincture, Spruce oil, pine oil, peppermint oil, vanilla flavor, vanillin, bitter essence, Vitabase, cedarwood oil, fruit flavor, Flavor G1, hesperidin pepper - Mint essence, bergamot oil, vermouth flavor, d-borneol, dl -Borneol, matcha, mixed flavor, mint flavor, dl-menthol l-menthol, eucalyptus oil, lavender oil, bonito flakes, bonito flakes powder, lemon powder Examples include dah, lemon oil, rose water, rose oil, and peppermint oil.

[0070] These components may be present individually or in combination of two or more types.

[0071] (Dosage form) The solid composition of this embodiment is, for example, an orally administered preparation (tablet (orally disintegrating tablet, tubular disintegrating tablet, tubular disintegrating tablet)). (Including Abul tablets, effervescent tablets, dispersible tablets, dissolvable tablets, etc.), capsules, granules, and powders, etc.) Preparations for oral application (oral tablets, lozenges, sublingual tablets, buccal tablets, adhesive tablets, gums) This includes, etc. ) and other dosage forms as described in the General Provisions for Preparations of the 18th Revised Japanese Pharmacopoeia, etc. The solid composition of this embodiment is preferably an oral solid composition.

[0072] The dosage forms of the solid composition in this embodiment include, for example, tablets, capsules, pills, granules, and Examples include fine granules. These solid compositions may be sugar-coated or by known methods as needed. It may be coated with a film coating or the like. The dosage form of the solid composition is preferably It is a tablet. Specific examples of tablets include uncoated tablets, film-coated tablets, and sugar-coated tablets. It can be done.

[0073] The solid composition of this embodiment is packaged in bottles, PTP packaging, pouches, sticks, and SPs. They can be packaged and stored airtight. They can also be pillow-wrapped. These may be stored in boxes or the like. The materials used for pillow packaging are not particularly limited. For example, polypropylene film, polyethylene terephthalate film, polyethylene The materials used include resin films such as film, and resin films to which aluminum foil has been attached. It can be placed inside the bottle packaging or pillow packaging if moisture absorption is a concern. It may also be saved internally at the same time.

[0074] The solid composition of this embodiment may be contained in a packaging container to form a package. The solid composition may be contained, for example, in an airtight package. By using a package, For example, it can improve the convenience of using solid compositions. Packaging in this embodiment Specifically, these are pharmaceuticals.

[0075] As for the packaging form of solid dosage forms, the solid composition can be packaged in bottles, PTP packaging (Press Through Packaging). Once packaged, it is packaged in a pouch, stick, or strip package (SP). They may be stored in an airtight container. Furthermore, they may be pillow-wrapped and stored in a box or similar container. Alternatively, from the viewpoint of reducing moisture absorption of the solid composition, a desiccant may be placed inside the bottle packaging, pillow packaging, etc. They may be stored together in the same packaging container.

[0076] Examples of materials used in SP packaging, PTP packaging, stick packaging, pillow packaging, etc. include: For example, polypropylene film, polyethylene terephthalate film, polyethylene film Examples include resin films such as acrylic, and those made by attaching aluminum foil to these resin films. It can be made from either a single-layer film or a multi-layer film (e.g., laminate film). You may use it.

[0077] Furthermore, it is preferable that the materials constituting the packaging container include materials that are less susceptible to the effects of moisture. Such packaging is formed of at least one of a moisture-proof material and a gas barrier material. Examples of packaging include [mention specific packaging].

[0078] For example, PTP (polypropylene) and polyethylene aluminum pillow - A combination of packaging is an example. Also, when the solid composition is a tablet, Considering the suppression of moisture content increase, the storage stability of tablets, and the stability of tablets after opening, as a moisture-proof material Alternatively, PTP packaging (Al-Al packaging) using aluminum on both sides may be used.

[0079] As the gas barrier material, known materials may be used, for example, materials having a functional barrier layer It may also be a laminate film, which serves the same function as the above moisture-proof material, or in combination with the above moisture-proof material. They may be used together.

[0080] Furthermore, packaging containers may be made with environmentally friendly materials. For example, recycled plastics or bio-based materials. Environmentally friendly materials such as mass plastics and biodegradable plastics are used as part of the packaging material or It can be used for all of them.

[0081] (Manufacturing method) In a second embodiment, at least one selected from the group consisting of tipepidine and its salts A method for producing a solid composition is provided, which includes the step of mixing with licorice.

[0082] The method for producing the solid composition according to this embodiment involves a step of further mixing acetaminophen. It may include.

[0083] The production of the solid composition can be carried out using known techniques. Each component can be produced in any step. They are added and finally come into contact with each other. After contact, a solvent and binder are added to the mixture and kneaded together. The resulting mixture may be used as a solid composition.

[0084] The resulting mixture is further subjected to drying and granulation processes to produce granules (granulated material). This is also possible. In this case, granules (granulated materials) containing each component may be prepared separately. Granulation is It can be either wet or dry.

[0085] The resulting granules (granulated material) can be used as is, or the granules can be mixed with additives and then compressed into tablets. The tablets can be molded and manufactured without a protective film, or they can be further coated with a film. .

[0086] For example, when the solid composition is a tablet, the term "tablet" is used in accordance with the "Tablets" section of the General Provisions of the Japanese Pharmacopoeia. It is possible to produce this. Specifically, from the group consisting of at least tipepidine and its salts. At least one selected, as well as licorice and optionally acetaminophen, After granulating the mixed powder containing the ingredients to obtain granules (granular material), the obtained granules and optionally the granules Tablets may be manufactured by compressing the external components into tablets. Alternatively, tipepidine and its salts may be used. A mixed powder containing at least one selected from the group is granulated to obtain a first granule, A mixture containing elephant is granulated to obtain a second type of granule, and these two types of granules and appropriate extragranular components are used. Tablets may be manufactured by compressing them. From the viewpoint of increasing the hardness of the solid composition, At least one selected from the group consisting of tipepidine and its salts, and licorice A mixed powder containing these components is granulated to form a granular material, and both components are included in the same granular material. It is preferable to include acetaminophen in the same granules. It's nice.

[0087] When a solid dosage form contains extragranular components, the granulated granules are treated to form an extragranular component. Tablets may be manufactured by adding ingredients and compressing these mixtures into tablets. The components may be in granular form. For example, from the group consisting of at least tipepidine and its salts. A granulated granule containing at least one selected ingredient, as well as licorice, is manufactured as the first granule. Granulated granules containing other active ingredients may be prepared as a second granule. In this case, tipep At least one selected from the group consisting of gin and its salts, and a first comprising licorice The first granule and the second granule containing other active ingredients are provided separately, and the components within the first granule A solid dosage form is manufactured so as not to come into substantial contact with the other active ingredients within the second granule. It may be manufactured. Other active ingredients may be included in the first granule so as to obtain a suitable formulation. It may be done this way, or it may be included in the second granule.

[0088] The granules obtained in the above process may be used as is as a granular material.

[0089] Examples are described below to illustrate the present invention in more detail, but the present invention is not limited to these examples. It is not something that should be done. [Examples]

[0090] 1. Raw materials In this example, the following raw materials were used. Note that the licorice extract powder listed below is calculated on a crude drug basis. The ratio is 7:1, meaning it is a 7-fold concentrated form of the crude drug. [Table 1]

[0091] 2. Manufacturing of granulated products Granules containing tipepidine hibenzate, licorice extract powder, or acetaminophen are It was prepared as follows: An appropriate amount of ethanol was added to each raw material and then a mortar and pestle were used. The mixture is then kneaded and granulated, the granulated material is vacuum-dried, and then sieved through a 30-mesh sieve to produce the final granule. Furthermore, as shown in Tables 2 and 3, tipepidine hibenzate and licorice extract powder The combined granules contain tipepidine hibenzate and licorice extract powder in a mass ratio of 2:1 (licorice extract). The raw materials were blended so that the ratio (in terms of crude drug equivalents) was 2:7. Additionally, tipepidine hibenzic acid was used. The co-formed granules of salt, licorice extract powder, and acetaminophen contain tipepidine hibenzate. Licorice extract powder:Acetaminophen in a mass ratio of 1:1:1 (calculated based on the raw material equivalent of licorice) Therefore, the ingredients were blended in a ratio of 1:7:1.

[0092] 3. Manufacturing of tablets and measurement of hardness Weigh each ingredient to a total of 2.5g according to the mixing ratios in Tables 2 and 3, and mix them uniformly in the bottle. Each tablet powder was prepared. The mixing ratio of each component in Tables 2 and 3 is expressed in parts by mass. The tablet powder was pressed using a 9φ, 10.8R punch and a hand press tablet press (manufactured by Riken Seiki) at a rate of 1,000 Tablets were prepared by compressing them under a pressure of 0 kgf to create 400 mg tablets. Note that in Tables 2 and 3, "Preparation For ingredients labeled "granules," granules obtained by the method described in "2. Manufacturing of Granules" are added. That is, to explain in detail using, for example, Examples 1 and 2 described in Table 2, In Example 1, 40 parts by mass of tipepidine hibenzate powder and 20 parts by mass of licorice extract were used. In contrast to the first example which used the powder, in Example 2, tipepidine hibenzate and licorice extract powder were used. Sixty parts by mass of a co-formed granule containing the ingredients in a mass ratio of 2:1 was used. For each tablet, a load cell type tablet hardness tester, Tablet Tester 8M (pha The hardness (unit: N) of the tablets was measured using a rmatron (manufactured by rmatron). The measured values ​​are shown in Tables 2 and 3. It was described there.

[0093] [Table 2]

[0094] [Table 3]

[0095] As shown in Table 2, at least one selected from the group consisting of tipepidine and its salts A solid composition containing licorice has a higher hardness than a solid composition that does not contain licorice. It was. Also, at least one selected from the group consisting of tipepidine and its salts and licorice The solid composition containing granules formed by co-granulating these materials exhibited particularly high hardness. Furthermore, as shown in Table 3, at least one selected from the group consisting of tipepidine and its salts. A solid composition containing one type of licorice and acetaminophen, a solid composition that does not contain licorice. It had a higher hardness than the composition. Furthermore, it was selected from the group consisting of tipepidine and its salts. A solid composition obtained by co-granulating at least one of the following: licorice and acetaminophen, is particularly It possessed high hardness.

[0096] Examples of solid dosage forms are shown below. Note that in the following examples of formulations, licorice is replaced with licorice. The main ingredient, glycyrrhizic acid, is added, but instead of glycyrrhizic acid, licorice is used. You may add U.

[0097] [Table 4]

[0098] [Table 5]

[0099] Although preferred embodiments and examples of the present invention have been described above, the present invention is not limited to these. This does not mean adding, omitting, substituting, or otherwise modifying the configuration without departing from the spirit of the present invention. It is possible to change this.

Claims

1. The mixture includes at least one selected from the group consisting of tipepidine and its salts, and licorice. Solid composition.

2. The mixture includes at least one selected from the group consisting of tipepidine and its salts, and licorice. The solid composition according to claim 1, comprising granules.

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

4. The solid composition according to claim 2, wherein the granules further contain acetaminophen.

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

6. A mixture of at least one substance selected from the group consisting of tipepidine and its salts, and licorice. A method for producing the solid composition according to any one of claims 1 to 4, comprising the step of [doing something].

7. The manufacturing method according to claim 6, further comprising the step of mixing acetaminophen.

8. At least one selected from the group consisting of tipepidine and its salts, and licorice. The process of forming granules, The process of compressing the granules into tablets, The manufacturing method according to claim 6, including

9. In the process of forming the granules, a selection is made from the group consisting of tipepidine and its salts. A claim to form granules comprising at least one licorice and acetaminophen. The manufacturing method described in 8.

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