Solid composition and method for producing the same

Abstract

To provide a solid composition containing acetaminophen and having sufficient hardness. SOLUTION: A solid composition containing acetaminophen, glycine, and licorice.

Description

Technical Field

[0001] The present invention broadly relates to a solid composition containing acetaminophen, glycine, and licorice, and a method for producing the same, etc.

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.

[0003] Since there are active ingredients of pharmaceuticals that lower the hardness of solid compositions, techniques for improving the hardness of solid compositions have been studied.

[0004] For example, Patent Document 1 discloses a composition that contains a disintegrant component and microfibrous cellulose and has excellent tablet hardness and disintegrability without containing an excipient.

[0005] Patent Document 2 discloses a method for improving the hardness of a tablet and suppressing the delay of the disintegration time, in which crystalline cellulose is blended in granules obtained by wet granulating a mixture containing a main drug and then tableting the granules.

[0006] Patent Document 3 discloses a solid preparation containing acetaminophen, glycine, and at least one selected from the group consisting of caffeine, ethenzamide, ibuprofen, allylisopropylacetylurea, and bromovalerylurea. Patent Document 3 discloses that such a solid preparation has sufficient hardness.

Prior Art Documents

Patent Documents

[0007]

Patent Document 1

Patent Document 2

[0008] However, the solid composition containing acetaminophen still has room for improvement from the viewpoint of reducing hardness. An object of the present invention is to provide a solid composition containing acetaminophen having sufficient hardness. [Means for Solving the Problems]

[0009] The present inventor has found that the hardness of a solid composition containing acetaminophen, glycine, and licorice is sufficiently high, and has thus completed the present invention.

[0010] That is, the present embodiment includes the following aspects. [1] A solid composition containing acetaminophen, glycine, and licorice. [2] The solid composition according to [1], containing a granulated product containing acetaminophen, glycine, and licorice. [3] The solid composition according to [1] or [2], wherein the hardness of the solid composition is 40 N or more. [4] A method for producing the solid composition according to any one of [1] to [3], including a step of mixing acetaminophen, glycine, and licorice. [5] A step of forming a granulated product containing acetaminophen, glycine, and licorice; A step of tableting the granulated product; A method for producing the solid composition according to [4], including the above steps. [Effects of the Invention]

[0011] According to the present invention, a solid composition containing acetaminophen and having sufficient hardness can be provided.

Mode for Carrying Out the Invention

[0012] 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 "more than or equal to" and "less than or equal to", and includes both numerical values at both ends.

[0013] (Solid Composition) In a first aspect, a solid composition containing acetaminophen, glycine, and licorice is provided. The solid composition is specifically a solid pharmaceutical composition.

[0014] Each component contained in the solid composition according to the present embodiment may be contained in the state of a pharmaceutically acceptable salt or may be contained as a complex with other components. "Pharmaceutically acceptable salts" include, for example, salts with bases or acids acceptable as pharmaceuticals. Non-limiting specific examples of pharmaceutically acceptable salts include addition salts of inorganic acids (hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, etc.), addition salts of organic acids (p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, p-bromophenylsulfonic acid, carboxylic acid, succinic acid, citric acid, benzoic acid, acetic acid, etc.), addition salts of inorganic bases (ammonium hydroxide or alkali or alkaline earth metal hydroxides, carbonates, bicarbonates, etc.), and addition salts of amino acids, etc. Pharmaceutically acceptable salts may be hydrates or anhydrous salts.

[0015] In the present embodiment, since the solid composition contains glycine and licorice in addition to acetaminophen, it has sufficient hardness.

[0016] The hardness of the solid composition in the present embodiment is measured by the "Tablet Hardness Measurement Method" in the Reference Information of the 18th Revised Japanese Pharmacopoeia <g6-4-180>It is the hardness measured by the method described in "」. More specifically, it may be the above hardness measured in the form of tablets obtained by tableting with a pressure of 1,000 kgf using a 9φ, 10.8R punch. The volume of the tablets when measuring the hardness is not particularly limited, but may be 300 mg per tablet. More specifically, the hardness of the solid composition in the present embodiment may be the hardness measured by the method described in the examples.

[0017] The hardness of the solid composition measured as described above is preferably 40 N or more, more preferably 40 to 200 N, still more preferably 45 to 150 N, even more preferably 50 to 140 N, yet even more preferably 60 to 130 N, and particularly preferably 70 to 120 N.

[0018] The solid composition in the present embodiment also tends to be excellent in terms of abrasion degree and / or tablet thickness.

[0019] The abrasion degree of the solid composition in the present embodiment is based on the "Tablet Abrasion Degree Test Method" in the Reference Information of the 18th Revised Japanese Pharmacopoeia <g6-5-150>It is the degree of wear measured by the method described in 「」. More specifically, it may be the degree of wear measured in the form of tablets obtained by tableting at a pressure of 1,000 kgf using a 9φ, 10.8R punch. The volume of the tablets when measuring the degree of wear is not particularly limited, but may be 300 mg per tablet. More specifically, the degree of wear of the solid composition in the present embodiment may be the hardness measured by the method described in the examples.

[0020] The degree of wear of the solid composition measured as described above is preferably 0.40% or less, more preferably 0.30% or less, and even more preferably 0.20% or less. The lower limit value of the above degree of wear is not particularly limited. For example, the above degree of wear may be 0% or more.

[0021] The tablet thickness of the solid composition in the present embodiment varies depending on the volume of the tablets and the tableting conditions. For example, the tablet thickness measured in the form of a 300 mg tablet obtained by tableting at a pressure of 1,000 kgf using a 9φ, 10.8R punch may be 5.0 mm or less, may be 2.0 to 5.0 mm, or may be 3.0 to 4.5 mm.

[0022] (Acetaminophen) As used herein, "acetaminophen" is a compound having a CAS registration number of 103 - 90 - 2 and represented by the chemical formula C8H9NO2. The salts of acetaminophen are not particularly limited as long as they are pharmacologically acceptable.

[0023] The blending amount of acetaminophen is appropriately adjusted according to the use of the solid composition, the degree of the required antitussive and expectorant effects, the degree of the required hardness, the symptoms, age, weight, gender, etc. of the administered subject.

[0024] The dosage of acetaminophen can be adjusted, for example, in the range of 120 mg to 1200 mg, preferably 150 mg to 900 mg, more preferably 180 mg to 600 mg, as the amount per day administered to adults. In this embodiment, "adult" means men and women aged 15 years or older. However, the solid composition according to this embodiment is not limited to those for adults to take, and may be for children under 15 years old to take. When children take it, it can be used after reducing the amount taken by adults per day, such as 1 / 2 or 2 / 3, according to each age group. The same applies to components other than acetaminophen.

[0025] The weight and dosage of the above solid composition are the dosage per day (one-day dose), but the same amount may be administered to the subject once or multiple times a day, for example, 2 times or 3 times, preferably 3 times. The same applies to components other than acetaminophen. Also, since each dosage is the total amount, the content of each component contained in the solid composition may vary depending on the single dose or the dosage form of the solid composition.

[0026] In a specific embodiment, the solid composition is a tablet, and the above dosage is the amount of the component contained in 3 tablets, 6 tablets or 9 tablets, preferably the amount of the component in 9 tablets. In this embodiment, the number of times of taking for an adult (15 years old or older) is 3 times, and the single dose is 2 tablets, 3 tablets or 4 tablets, preferably the single dose is 3 tablets.

[0027] (Glycine) As used in this specification, "glycine" is a compound with a CAS registration number of 56-40-6 and represented by the chemical formula C2H5NO2. The salts of glycine are not particularly limited as long as they are pharmacologically acceptable.

[0028] The dosage of glycine varies depending on the amount of acetaminophen and the like, but as the amount per day, it can be adjusted, for example, in the range of 10 mg to 1000 mg, preferably 30 mg to 950 mg, more preferably 100 mg to 900 mg, even more preferably 180 mg to 900 mg.

[0029] The mass ratio of acetaminophen to glycine (acetaminophen: glycine) contained in the composition administered daily is preferably 4:1 to 1:3, more preferably 3:1 to 1:2, and even more preferably 2:1 to 1:1.

[0030] (Licorice Root) As used herein, "Licorice Root" can be the one listed in the 18th revised Japanese Pharmacopoeia. Examples of Licorice Root include those extracted with water, 30% aqueous ethanol solution, etc. as the extraction solvent. For example, depending on the type of extract such as Licorice Root extract, Licorice Root dry extract, Licorice Root soft extract, Licorice Root fluid extract, etc., various crude drug conversion ratios are sold. The description of the amount of Licorice Root in this specification is the value converted to crude drug unless otherwise specified. For example, Licorice Root soft extract contains about 4 parts by mass of Licorice Root in terms of crude drug conversion ratio per 1 part by mass of the extraction solvent. In addition to these extracts of Licorice Root, powders of extracts obtained by extracting Licorice Root with water, 30% aqueous ethanol solution, etc. (extract powder), Licorice Root extracts, Licorice Root extract solutions, etc. may be appropriately used and are not particularly limited. However, an extract powder obtained by drying a Licorice Root dry extract containing about 5 parts by mass to about 9 parts by mass, for example, about 6 parts by mass to about 8 parts by mass of Licorice Root in terms of crude drug conversion ratio per 1 part by mass of the extraction solvent is preferred. The extraction solvent is preferably water.

[0031] Note that Licorice Root contains at least one selected from the group consisting of glycyrrhizic acid and its salts as the main component. As used herein, "glycyrrhizic acid" has a CAS registration number of 1405-86-3 and is a compound represented by the chemical formula of 42 C 62 H 16 O (molecular weight: 822.93 g / mol). The salts of glycyrrhizic acid are not particularly limited as long as they are pharmacologically acceptable. Examples include trisodium glycyrrhizate, disodium glycyrrhizate, diammonium glycyrrhizate, monoammonium glycyrrhizate, dipotassium glycyrrhizate, and monopotassium glycyrrhizate.

[0032] Therefore, in the solid composition according to the present embodiment, at least one selected from the group consisting of glycyrrhizic acid and its salts may be blended in place of and / or in addition to licorice. Licorice may contain at least one selected from the group consisting of glycyrrhizic acid and its salts in an amount of 2.0% or more based on the dried crude drug in terms of conversion. Licorice powder may contain at least one selected from the group consisting of glycyrrhizic acid and its salts in an amount of 2.0% or more based on the dried crude drug in terms of conversion. Licorice extract may contain at least one selected from the group consisting of glycyrrhizic acid and its salts in an amount of 3.6% or more. Crude licorice extract may contain at least one selected from the group consisting of glycyrrhizic acid and its salts in an amount of 4.8% or more. In the solid composition according to the present embodiment, the total content of glycyrrhizic acid and its salts may be in the range of, for example, 0.01 to 0.1 times (for example, 0.02 times, 0.036 times, 0.04 times, 0.048 times) the content described later as the content of licorice.

[0033] The extraction component can be obtained by a conventional method, for example, by extracting the active ingredient from the crude drug with an extraction solvent. As the extraction solvent, for example, water, a hydrophilic solvent, or a mixed solvent thereof is often used. Examples of the hydrophilic solvent include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, s-butanol, and t-butanol; cellosolves such as methyl cellosolve and ethyl cellosolve; ketones such as acetone; ethers such as dioxane and tetrahydrofuran; nitrogen-containing solvents such as pyridine, morpholine, acetonitrile, N,N-dimethylformamide, dimethylacetamide, and N-methylpyrrolidone. These hydrophilic solvents may be used alone or as a mixed solvent of two or more.

[0034] The dosage of licorice is appropriately adjusted according to the use of the solid composition, the required degree of hardness, the symptoms, age, weight, gender, etc. of the subject to be administered. The dosage of licorice is in terms of the crude drug equivalent, for example, in the range of 100 mg to 5,000 mg, preferably 200 mg to 2,000 mg, more preferably 50 mg to 1,200 mg per day.

[0035] The content of licorice in the composition administered daily is, in terms of the crude drug equivalent, 1% by mass to 70% by mass, preferably 5% by mass to 50% by mass, more preferably 10% by mass to 30% by mass.

[0036] The mass ratio of acetaminophen to licorice in the composition administered daily is the ratio of acetaminophen to licorice converted to the crude drug, preferably 1:10 to 2:1, more preferably 1:7 to 2:1, still more preferably 1:7 to 1:1. When using licorice extract powder as licorice, the mass ratio of acetaminophen to licorice extract powder is preferably 1:2 to 10:1, more preferably 1:2 to 7:1, still more preferably 1:1 to 7:1.

[0037] From the viewpoint of further increasing the hardness of the solid composition according to the present embodiment, licorice is preferably contained in the same granule as acetaminophen and / or glycine. That is, the solid composition according to the present embodiment preferably contains a granule containing acetaminophen and / or glycine and licorice, and preferably contains a granule obtained by granulating a mixed powder containing acetaminophen and / or glycine and licorice. From the same viewpoint, licorice is preferably contained in the same granule as acetaminophen and glycine. That is, the solid composition according to the present embodiment preferably contains a granule containing acetaminophen, glycine, and licorice, and preferably contains a granule obtained by granulating a mixed powder containing acetaminophen, glycine, and licorice. The solid composition according to the present embodiment may be a tablet obtained by tableting these granules that are the granulated products.

[0038] However, the solid composition according to the present embodiment may be a tablet produced by a direct compression method in which a mixed powder containing acetaminophen, glycine, and licorice is directly compressed, or a tablet obtained by dissolving acetaminophen, glycine, and licorice in a solvent, drying and distilling off the solvent to obtain a powder, and optionally granulating the powder and then compressing it.

[0039] In such an embodiment, acetaminophen, glycine, and licorice exist in a proximate state in the solid composition, and the hardness of the solid composition tends to be further improved.

[0040] (Other components) The solid composition according to the present embodiment may contain components other than the above components according to its use. When the solid composition is intended to relieve various symptoms of a cold, such as runny nose, nasal congestion, sneezing, sore throat, cough, phlegm, chill, fever, headache, joint pain, muscle pain, etc., in addition to bromhexine and meloxicam, antipyretic analgesics, particularly active ingredients such as non-steroidal anti-inflammatory drugs (NSAIDs), and other pharmacologically acceptable components may be formulated.

[0041] Non-steroidal anti-inflammatory drugs are roughly classified into COX-2 non-selective inhibitors such as ibuprofen, diclofenac, loxoprofen, zaltoprofen, pranoprofen, oxaprozin, tiaprofenic acid, naproxen, lornoxicam, ampiroxicam, piroxicam, nabumetone, indomethacin, sulindac, mofezolac, mefenamic acid, etc., and COX-2 selective inhibitors such as meloxicam, etodolac, celecoxib, etc. Meloxicam may be formulated in the composition as a non-steroidal anti-inflammatory drug. The non-steroidal anti-inflammatory drug is preferably a COX-2 non-selective inhibitor. The non-steroidal anti-inflammatory drug may be in the form of a salt.

[0042] As other pharmacologically acceptable components, antihistamines, antipyretic analgesics, antitussive expectorants, anti-inflammatory drugs, central nervous stimulants, vitamins, anticholinergics, antiplasmin agents, etc., which are formulated in general cold medicines, antipyretic analgesics, rhinitis medicines, etc., may be additionally formulated.

[0043] For example, antihistamines include isopentyl hydrochloride, dipheteol hydrochloride, tripelennamine hydrochloride, tonzylamine hydrochloride, phenethazine hydrochloride, methdilazine hydrochloride, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, carbinoxamine diphenyl disulfonate, diphenylpyraline hydrochloride, diphenylpyraline theoclate, diphenhydramine hydrochloride, diphenhydramine salicylate, alimemazine tartrate, diphenhydramine tannate, triprolidine hydrochloride hydrate, mebumhydroline napadisilate, promethazine methylene disalicylate, carbinoxamine maleate, dipheteol phosphate, clemastine fumarate, mequitazine, and the like.

[0044] Examples of antipyretic analgesics other than non-steroidal anti-inflammatory drugs include aspirin, ethenzamide, salsalate, salicylamide, lactylphenetidine, isopropylantipyrine, and the like.

[0045] Antitussive and expectorant drugs include noscapine, noscapine hydrochloride hydrate, tipepidine hibenzate, dextromethorphan hydrobromide hydrate, bromhexine, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, pseudoephedrine hydrochloride, ambroxol hydrochloride, L-carbocysteine, and the like.

[0046] Anti-inflammatory drugs include glycyrrhizic acid and its derivatives and their salts (for example, dipotassium glycyrrhizate, monoammonium glycyrrhizate, etc.), tranexamic acid, and the like.

[0047] Central nervous system stimulants include caffeine, anhydrous caffeine, and the like.

[0048] Examples of the vitamin agents include vitamin B1 and its derivatives and their salts (for example, benfotiamine), vitamin B2 and its derivatives and their salts (for example, riboflavin), vitamin C and its derivatives and their salts (for example, ascorbic acid), hesperidin and its derivatives and their salts, and the like.

[0049] Examples of the anticholinergic agents include scopolamine hydrobromide, datura extract, methylscopolamine bromide, methyl-l-hyoscyamine bromide, pirenzepine hydrochloride, butylscopolamine bromide, belladonna alkaloid, belladonna extract, belladonna total alkaloid, isopropamide iodide, diphenylpiperidinomethyl dioxolane iodide, rhubarb extract, rhubarb root, rhubarb root total alkaloid citrate, and the like.

[0050] For the solid composition according to this embodiment, pharmaceutical additives may be further added as needed. Examples of the pharmaceutical additives include pharmaceutically acceptable carriers such as excipients, binders, disintegrants, disintegration aids, glidants, foaming agents, moisture-proof agents, surfactants, stabilizers, antioxidants, fillers, sweeteners, flavoring agents, cooling agents, fragrances, aromatic agents, coloring agents, bases, coating agents, sugar coating agents, plasticizers, dispersants, defoaming agents, fluidizing agents, and flavoring agents and fragrances, and pharmaceutical additives that can be used in conventionally known solid preparations can be used for the above purposes.

[0051] Examples of excipients include, for example, starch syrup, gum arabic, powdered gum arabic, cacao butter, caramel, sodium carboxymethyl starch, hydrated silicon dioxide, anhydrous amorphous silicon dioxide, xylitol, magnesium aluminum silicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, crystalline cellulose, crystalline cellulose - sodium carboxymethylcellulose, crystalline cellulose (fine particles), crystalline cellulose (granules), powdered cellulose, synthetic aluminum silicate, synthetic aluminum silicate - hydroxypropyl starch - crystalline cellulose, wheat starch, rice flour, glutinous rice starch, heavy anhydrous silicic acid, refined sugar, refined sugar spherical granules, gelatin, D - sorbitol, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low - degree - substituted hydroxypropyl cellulose, dextrin, corn starch, granulated corn starch, trehalose, silicon dioxide, lactose hydrate, granulated lactose, sucrose, potato starch, hydroxypropyl starch, partially - pregelatinized starch, powdered sugar, powdered maltose, powdered reduced maltose syrup starch syrup, powdered cellulose, pectin, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 60, maltitol, D - mannitol, magnesium aluminum metasilicate, calcium sulfate, erythritol, glucose, fructose, and the like.

[0052] Examples of binders include, for example, gum arabic, powdered gum arabic, ume plum powder, gelatin, shellac, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose, pullulan, povidone, polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified), methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, butyl methacrylate - methyl methacrylate copolymer, methyl cellulose, polyvinyl alcohol - acrylic acid - methyl methacrylate copolymer, and the like.

[0053] Examples of disintegrants include sodium carboxymethyl starch, carmellose, carmellose calcium, croscarmellose sodium, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, hydroxypropyl starch, partially pre-gelatinized starch, etc.

[0054] Examples of disintegration aids include sodium carboxymethyl starch, carmellose, carmellose calcium, croscarmellose sodium, light anhydrous silicic acid, crystalline cellulose, sodium hydrogen carbonate, precipitated calcium carbonate, lactose hydrate, hydroxypropyl starch, polysorbate 40, polysorbate 60, polysorbate 80, macrogol 1500, macrogol 4000, etc.

[0055] Examples of brightening agents include carnauba wax, bleached beeswax, purified shellac, macrogol 400, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, beeswax, etc.

[0056] Examples of foaming agents include sodium carbonate anhydrous, tartaric acid, potassium hydrogen tartrate, sodium hydrogen carbonate, citric acid anhydrous, etc.

[0057] Examples of moisture-proof agents include ethyl cellulose, olive oil, aluminum hydroxide gel dried, glycerin, magnesium silicate, light anhydrous silicic acid, hardened oil, synthetic aluminum silicate, sucrose fatty acid ester, stearic acid, magnesium stearate, purified shellac, refined sugar, talc, sodium sulfate anhydrous neutral, precipitated calcium carbonate, fumaric acid - stearic acid - polyvinyl acetal diethylaminoacetate - hydroxypropyl methylcellulose 2910 mixture, polyvinyl acetal diethylaminoacetate, magnesium aluminometasilicate, etc.

[0058] Examples of the surfactant include sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan beeswax, polyoxyethylene nonylphenyl ether, polyoxyethylene (20) polyoxypropylene (20) glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (10) polyoxypropylene (4) cetyl ether, polysorbate 20, polysorbate 60, polysorbate 80, macrogol 400, sorbitan monooleate, glycerin monostearate, sorbitan monostearate, sorbitan monolaurate, sodium lauryl sulfate, and the like.

[0059] Examples of stabilizers include adipic acid, L-aspartic acid, sodium L-aspartate, DL-alanine, L-alanine, L-arginine, L-arginine hydrochloride, sodium alginate, propylene glycol alginate, benzoic acid, sodium benzoate, ethylenediamine, calcium disodium edetate, sodium edetate, tetrasodium edetate, tetrasodium edetate tetrahydrate, zinc chloride, ammonium chloride, calcium chloride hydrate, cetylpyridinium chloride, ferric chloride, sodium chloride, magnesium chloride, cysteine hydrochloride, L-histidine hydrochloride, cacao butter, carboxyvinyl polymer, calcium carmellose, hydrous silicon dioxide, sodium carmellose, anhydrous sodium carbonate, glycerin, glycerin fatty acid ester, calcium gluconate hydrate, sodium gluconate, magnesium gluconate, potassium L-glutamate, sodium L-glutamate, L-lysine L-glutamate, light anhydrous silicic acid, crystalline sodium dihydrogen phosphate, sodium chondroitin sulfate, zinc oxide, L-cystine, L-cysteine, tartaric acid, sucrose fatty acid ester, stearic acid, purified gelatin, purified soy lecithin, gelatin, hydrolyzed gelatin, sorbitan fatty acid ester, taurine, talc, calcium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium carbonate hydrate, magnesium carbonate, natural vitamin E, tocopherol, tocopherol acetate, lactose, concentrated glycerin, povidone, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxyethylene nonyl phenyl 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 acid glyceryl (7 E.O.) Polysorbate 20, Polysorbate 60, Polysorbate 80, polyvinyl alcohol (partially saponified), Macrogol 300, Macrogol 400, Macrogol 4000, anhydrous citric acid, sodium anhydrous citrate, sodium hydrogen phosphate anhydrous, sodium dihydrogen phosphate anhydrous, magnesium aluminum metasilicate, methylcellulose, l-menthol, glycerin monostearate, medicinal charcoal, magnesium sulfate hydrate, DL-malic acid, sodium hydrogen phosphate hydrate, potassium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, L-leucine, polyvinyl alcohol·acrylic acid·methyl methacrylate copolymer, etc. can be mentioned.

[0060] As antioxidants, for example, ascorbic acid, L-ascorbic acid stearate, citric acid hydrate, soy lecithin, natural vitamin E, natural vitamin E, tocopherol, tocopherol acetate, ascorbyl palmitate, sodium pyrosulfite, etc. can be mentioned. In the case of a solid composition containing acetaminophen, it is preferable not to blend tocopherols as antioxidants or stabilizers.

[0061] As fillers, for example, RSS No.1 raw rubber, starch acrylate 1000, hydrous silicon dioxide, titanium oxide, silicon dioxide, calcium hydrogen phosphate, etc. can be mentioned.

[0062] As sweeteners, for example, aspartame, acesulfame potassium, amacha, amacha powder, reduced maltose syrup, xylitol, dipotassium glycyrrhizinate, disodium glycyrrhizinate, saccharin, sodium saccharin hydrate, sucralose, stevia extract, purified stevia extract, refined sugar, fructose, sucrose, maltitol, D-mannitol, erythritol, etc. can be mentioned.

[0063] Examples of flavoring agents include sodium chloride, Chinese magnoliavine powder, evodia extract, Chinese cinnamon, Chinese cinnamon powder, orange, orange oil, cocoa powder, fructose, caramel, xylitol, calcium citrate, citric acid hydrate, sodium citrate hydrate, L-glutamic acid, sodium L-glutamate, grapefruit extract, brown sugar, cinnamon powder, cinnamon oil, saccharin, sodium saccharin hydrate, sansho powder, tartaric acid, D-tartaric acid, potassium hydrogen tartrate, sodium DL-tartrate, ginger powder, sucralose, stevia extract, purified stevia extract, assemblage, D-sorbitol, tannic acid, clove oil, chinpi chinchi, capsicum, capsicum powder, torreya powder, trehalose hydrate, bitter orange powder, umeboshi extract, fructooligosaccharide, 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.

[0064] Examples of cooling agents include perilla oil, d-camphor, dl-camphor, cinnamon oil, peppermint water, peppermint oil, l-menthol, etc.

[0065] Examples of fragrances include orange flavor, guarana extract, sweet orange, strawberry, brown sugar flavor, strawberry flavor, cherry flavor, banana powder flavor, peach essence, fruit essence, peppermint, melon powder flavor, l-menthol, peppermint oil, etc.

[0066] Examples of aromatic agents include Chinese wild ginger powder, Chinese wild ginger oil, ethyl vanillin, d-camphor, dl-camphor, cinnamon powder, cinnamon oil, ginger oil, ginseng powder, spearmint oil, clove oil, turpentine oil, capsicum powder, pineapple powder fragrance 51357, pineapple powder fragrance 59492, peppermint water, peppermint oil, vanilla powder fragrance 54286, vanillin, bergamot oil, d-borneol, dl-borneol, dl-menthol, l-menthol, eucalyptus oil, rose water, rose oil, etc.

[0067] Examples of the coloring agent include, for example, iron oxide yellow, iron sesquioxide yellow, orange essence, iron oxide brown, carbon black, caramel, β-carotene, gold leaf, iron oxide black, titanium oxide, iron sesquioxide, disazo 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 sesquioxide-glycerin suspension, copper chlorophyllin sodium, copper chlorophyll, phenol red, malachite green, methylene blue, medicinal charcoal, riboflavin, riboflavin butyrate, riboflavin phosphate sodium, green tea powder, rose oil and the like.

[0068] Examples of the base include gum arabic powder, α - starch, ethyl cellulose, cacao butter, carnauba wax, carboxyvinyl polymer, carmellose, sodium carmellose, reduced maltose syrup, hydrous silicon dioxide, dried aluminum hydroxide gel, agar, agar powder, xanthan gum, glycerin, glycerin fatty acid ester, light anhydrous silicic acid, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, synthetic magnesium sodium silicate, titanium oxide, tartaric acid, sucrose fatty acid ester, silicone oil, stearic acid, magnesium stearate, gelatin, D - sorbitol, talc, calcium carbonate, corn starch, lactic acid, ethyl lactate, calcium lactate hydrate, lactic acid - glycolic acid copolymer, concentrated glycerin, potato starch, hydroxypropyl cellulose, hypromellose, pullulan, pectin, povidone, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), microcrystalline wax, macrogol 200, macrogol 300, macrogol 400, macrogol 1000, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 6000NF, macrogol 20000, D - mannitol, glycerin monostearate, sorbitan monostearate, batyl monostearate, propylene glycol monostearate, polyethylene glycol monostearate, sodium lauryl sulfate, polyvinyl alcohol - acrylic acid - methyl methacrylate copolymer, etc.

[0069] Examples of coating agents include, for example, ethyl acrylate-methyl methacrylate copolymer dispersion, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, gum arabic, gum arabic powder, ethyl cellulose, ethyl cellulose aqueous dispersion, carnauba wax, carboxyvinyl polymer, gold foil, silver foil, triethyl citrate, glycerin, glycerin fatty acid ester, hardened oil, titanium oxide, sucrose fatty acid ester, 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 glycerin, white shellac, hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose 2910-titanium oxide-macrogol 400 mixture, hypromellose, fumaric acid-stearic acid-polyvinyl acetal diethylaminoacetate-hydroxypropyl methylcellulose 2910 mixture, pullulan, polysorbate 80, polyvinyl acetal diethylaminoacetate, povidone, polyvinyl alcohol (partially saponified), macrogol 300, macrogol 400, macrogol 600, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 6000NF, macrogol 20000, macrogol 35000, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, magnesium aluminometasilicate, methyl acrylate-methacrylic acid-methyl methacrylate copolymer, methyl cellulose, 2-methyl-5-vinylpyridine methyl acrylate-methacrylic acid copolymer, aluminum monostearate, glycerin monostearate, sorbitan monostearate, sorbitan monolaurate, calcium sulfate, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, and the like.

[0070] Examples of sugar coating agents include gum arabic, powdered gum arabic, ethyl cellulose, carnauba wax, sodium carboxymethyl cellulose, titanium oxide, stearic acid, polyoxyl 40 stearate, purified gelatin, purified shellac, purified sucrose, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, sucrose, hydroxypropyl cellulose, hypromellose, pullulan, povidone, polyvinyl alcohol (partially saponified), macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, calcium hydrogen phosphate hydrate, calcium dihydrogen phosphate hydrate, polyvinyl alcohol - acrylic acid - methyl methacrylate copolymer, and the like.

[0071] Examples of plasticizers include triethyl citrate, glycerin, glycerin fatty acid ester, D - sorbitol, medium - chain fatty acid triglyceride, triacetin, concentrated glycerin, castor oil, polyoxyethylene hydrogenated castor oil 60, propylene glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polysorbate 80, macrogol 400, macrogol 600, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, glycerin monostearate, isopropyl linoleate, liquid paraffin, and the like.

[0072] Examples of the dispersant include aminoalkyl methacrylate polymer RS, gum arabic, powdered gum arabic, carboxyvinyl polymer, sodium carboxymethyl starch, agar powder, citric acid hydrate, sodium citrate hydrate, glycerin, glycerin fatty acid ester, magnesium silicate, light aluminum oxide, light anhydrous silicic acid, crystalline cellulose, titanium oxide, sucrose fatty acid ester, stearic acid, magnesium stearate, D-sorbitol, soy lecithin, low-substituted hydroxypropyl cellulose, dextrin, corn starch, lactose hydrate, concentrated glycerin, potato starch, hydroxyethyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose, povidone, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polysorbate 20, polysorbate 60, polysorbate 80, microcrystalline wax, macrogol 300, macrogol 4000, macrogol 6000, macrogol 6000NF, sodium anhydrous citrate, magnesium aluminometasilicate, methyl cellulose, glycerin monooleate, sorbitan monooleate, aluminum monostearate, glycerin monostearate, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, sodium lauryl sulfate, and the like.

[0073] Examples of the antifoaming agent include ethanol, glycerin fatty acid ester, dimethylpolysiloxane (for oral use), dimethylpolysiloxane-silicon dioxide mixture, sucrose fatty acid ester, silicone antifoaming agent, silicone oil, sorbitan fatty acid ester, polysorbate 80, and the like.

[0074] Examples of the fluidizing agent include, for example, hydrous silicon dioxide, light anhydrous silicic acid, synthetic aluminum silicate, heavy anhydrous silicic acid, magnesium aluminum hydroxide, stearic acid, calcium stearate, magnesium stearate, tricalcium phosphate, talc, magnesium aluminometasilicate, calcium hydrogen phosphate granule, and the like.

[0075] Examples of the fragrance agent and perfume include, for example, powdered star anise, star anise oil, ethyl vanillin, 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, torreya tincture, torreya oil, pine oil, peppermint oil, vanilla flavor, vanilla, bitter essence, vita base, Himalayan cedarwood oil, fruit flavor, flavor G1, hesperidin peppermint essence, bergamot oil, bergamot flavor, d-borneol, dl-borneol, matcha, mixed flavor, mint flavor, dl-menthol, l-menthol, eucalyptus oil, lavender oil, dragon's blood, powdered dragon's blood, lemon powder, lemon oil, rose water, rose oil, peppermint oil, etc.

[0076] These components may be contained singly or in combination of two or more.

[0077] (Dosage form) The solid composition of the present embodiment can be made into dosage forms described in the General Rules of Pharmaceutical Forms of the Japanese Pharmacopoeia, Eighteenth Revision, etc., such as preparations for oral administration (tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, soluble tablets, etc.), capsules, granules, and powders, etc.), preparations for application in the oral cavity (including oral tablets, troches, sublingual tablets, buccal tablets, adherent tablets, gums, etc.). The solid composition of the present embodiment is preferably an oral solid composition.

[0078] Examples of the dosage form of the solid composition of the present embodiment include tablets, capsules, pills, granules, and fine granules. These solid compositions may be coated with sugar coating, film coating, etc. by known methods as necessary. The dosage form of the solid composition is preferably a tablet. Specific examples of the tablet include plain tablets, film-coated tablets, and sugar-coated tablets.

[0079] The solid composition of this embodiment may be once packaged by bottle packaging, PTP packaging, pouch packaging, stick packaging, or SP packaging and stored airtightly. Further, they may be pillow-packaged, or they may be stored in a box or the like. The material used for pillow packaging is not particularly limited, and for example, resin films such as polypropylene films, polyethylene terephthalate films, and polyethylene films, or those obtained by attaching aluminum foil to these resin films can be used. When there are concerns about hygroscopicity, a desiccant or the like may be stored simultaneously inside the bottle packaging or inside the pillow packaging.

[0080] The solid composition of this embodiment may be contained in a packaging container to form a package. The solid composition of this embodiment may be contained in, for example, an airtight package. By forming a package, for example, the convenience during use of the solid composition can be improved. The package in this embodiment is specifically a pharmaceutical product.

[0081] As the packaging form of the solid preparation, the solid composition may be once packaged by bottle packaging, PTP packaging (Press Through Package), pouch packaging, stick packaging, SP packaging (Strip Package), etc. and stored airtightly. Further, they may be pillow-packaged, or they may be stored in a box or the like. Also, from the viewpoint of reducing the moisture absorption of the solid composition, a desiccant or the like may be stored simultaneously inside the packaging container such as inside the bottle packaging or inside the pillow packaging.

[0082] Examples of the materials used for SP packaging, PTP packaging, stick packaging, pillow packaging, etc. include resin films such as polypropylene films, polyethylene terephthalate films, and polyethylene films, and those obtained by attaching aluminum foil to these resin films. Either a single-layer film or a multi-layer film (for example, a laminate film) may be used.

[0083] Further, the material constituting the packaging container preferably includes a material that is less susceptible to the influence of moisture. Examples of such packaging include packaging formed by at least one of a moisture-proof material and a gas barrier material.

[0084] Examples of the moisture-proof material include, for example, a combined packaging of PTP (polypropylene) and a polyethylene aluminum pillow. Further, when the solid composition is a tablet, considering suppression of an increase in the moisture value in the tablet, storage stability of the tablet, tablet stability after opening, etc., as the moisture-proof material, a PTP packaging (Al-Al packaging) using aluminum on both sides may be used.

[0085] Known materials may be used as the gas barrier material. For example, it may be a laminated film having a functional barrier layer, and may be used in combination with or in addition to the above moisture-proof material while also serving the role of the above moisture-proof material.

[0086] Further, the packaging container may be environmentally friendly. For example, environmentally friendly materials such as recycled plastics, biomass plastics, and biodegradable plastics may be used for part or all of the packaging material.

[0087] (Manufacturing method) In a second aspect, there is provided a method for producing a solid composition, which includes a step of mixing acetaminophen, glycine, and licorice.

[0088] The production of the solid composition can be carried out using known techniques. Each component is added in an arbitrary step and finally brought into contact with each other. A solvent or a binder may be added to the mixture after contact and kneaded, and the obtained kneaded product may be used as the solid composition.

[0089] The obtained kneaded product can also be further subjected to a drying step or a granulation step to produce granules (granulated products). In this case, the granules (granulated products) containing each component may be prepared separately. The granulation may be wet or dry.

[0090] The obtained granules (granulated products) as they are, or additives are blended into the granules, and these can be tabletted and molded to produce tablets, and further, these can be film-coated.

[0091] For example, when the solid composition is a tablet, the tablet can be manufactured in accordance with the section "Tablets" in the General Rules for Preparations of the Japanese Pharmacopoeia. Specifically, after granulating a mixed powder containing acetaminophen and / or glycine and licorice to obtain a granulated product (granules), the obtained granulated product and optionally an extra-granular component can be tabletted to manufacture a tablet. Alternatively, a mixed powder containing at least one of acetaminophen, glycine, and licorice is granulated to obtain a first granule, and a mixed powder containing at least one of acetaminophen, glycine, and licorice is granulated to obtain a second granule, and these two types of granules and appropriately an extra-granular component are tabletted to manufacture a tablet. At this time, it is preferable that acetaminophen, glycine, and licorice are contained in either the first granule or the second granule. From the viewpoint of increasing the hardness of the solid composition, it is preferable to granulate a mixed powder containing acetaminophen, glycine, and licorice to form a granulated product (granules) and include these components in the same granulated product.

[0092] When the solid preparation contains an extra-granular component, a tablet can be manufactured by adding a post-powder component to the granulated granules so as to form the outside of the granulated granules and tabletting these mixtures. Also, the extra-granular component may be in granular form. For example, granulated granules containing acetaminophen, glycine, and licorice may be manufactured as the first granule, and granulated granules containing other active ingredients may be manufactured as the second granule. In this case, the first granule containing acetaminophen, glycine, and licorice and the second granule containing other active ingredients are provided separately, and the solid preparation may be manufactured so that the components in the first granule and the other active ingredients in the second granule do not substantially contact each other. The other active ingredients may be included in the first granule or the second granule so as to obtain an appropriate preparation.

[0093] Note that the granules obtained in the above steps may be used as they are as granules.

[0094] In order to explain the present invention in more detail, examples are described below, but the present invention is not limited thereto.

Examples

[0095] 1. Raw materials In this example, the following raw materials were used. The following licorice extract powder has a crude drug conversion ratio of 7:1, that is, the crude drug is concentrated 7 times. Also, since glycine has a large particle size, it was pulverized with an agate mortar and pestle, and then sieved through a 100-mesh sieve before use. [Table 1]

[0096] 2. Production of granules Granules containing glycine, licorice extract powder, or acetaminophen were prepared as follows. An appropriate amount of ethanol was added to each raw material, and kneading granulation was carried out using a mortar and pestle. After the granules were vacuum dried, they were sieved through a 30-mesh sieve to obtain the granules. As shown in Table 2, for the co-granules of acetaminophen, glycine, and licorice extract powder, the raw materials were blended so that the mass ratio of acetaminophen:glycine:licorice extract powder was 1:1:1 (when the licorice is converted to crude drug, it is 1: 1:7 ).

[0097] 3. Production of tablets and measurement of physical properties Each raw material was weighed to a total of 2.5 g according to the blending ratio in Table 2 and uniformly mixed in a bottle to prepare each tableting powder. The blending ratios of the respective components in Table 2 are expressed in parts by mass. Each tableting powder was tableted at a pressure of 1,000 kgf using a 9φ, 10.8R punch on a hand press tableting machine (manufactured by Riken Seiki Co., Ltd.) to produce 300-mg tablets. In Table 2, the component marked as "granules" was added with the granules obtained by the method described in "2. Production of granules". That is, for example, specifically explained using Examples 1 and 3 described in Table 2, in Example 1, 20 parts by mass of acetaminophen powder, 20 parts by mass of glycine powder, and 20 parts by mass of licorice extract powder were used, whereas in Example 3, 60 parts by mass of co-granules containing acetaminophen, glycine, and licorice extract powder in a mass ratio of 1:1:1 were used.

[0098] For each tablet, the hardness of the tablet was measured using a load cell type tablet hardness tester Tablet Tester 8M (manufactured by Pharmatron). Next, for 5 tablets of each of Examples 1 to 3, the abrasion degree (percentage of the reduced mass with respect to the initial mass) after 100 rotations was calculated using an abrasion degree measuring device (manufactured by PHARMA TEST). Also, for each tablet of Examples 1 to 3, the thickness of the tablet was measured using calipers. The measured values of each measurement are shown in Table 2.

[0099]

Table 2

[0100] As shown in Table 2, the solid composition containing acetaminophen, glycine, and licorice had a sufficiently high hardness. The solid composition containing the granulated product obtained by co-granulating acetaminophen, glycine, and licorice had a particularly high hardness. Also, the solid composition containing acetaminophen, glycine, and licorice had excellent abrasion degree and tablet thickness, and the solid composition containing the granulated product obtained by co-granulating acetaminophen, glycine, and licorice had particularly excellent abrasion degree and tablet thickness.

[0101] As described above, the preferred embodiments and examples of the present invention have been explained, but the present invention is not limited thereto. Additions, omissions, substitutions, and other modifications of the configuration are possible without departing from the spirit of the present invention.

Claims

1. containing acetaminophen, glycine, and licorice root; containing a granule containing acetaminophen, glycine, and licorice root; a tablet.

2. The tablet according to claim 1, wherein the hardness of the tablet is 40 N or more.

3. A method for producing the tablet according to claim 1 or 2, comprising a step of mixing acetaminophen, glycine, and licorice root.

4. A method for producing the tablet according to claim 3, comprising a step of forming a granule containing acetaminophen, glycine, and licorice root, and a step of tableting the granule. ​

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