Pharmaceuticals

Abstract

To provide a pharmaceutical composition in which the enhancement of the characteristic odor derived from Geranium thunbergii or its extract during storage is suppressed. [Solution] The following components (A) and (B-1): (A) Geranium thunbergii or its extract (B-1) A pharmaceutical product comprising a pharmaceutical composition containing a magnesium ion-containing compound, packaged in an airtight container.

Description

Technical Field

[0001] The present invention relates to pharmaceuticals and the like.

Background Art

[0002] In recent years, various lifestyle-related diseases have been spreading due to changes in diet, dietary imbalances, stress, etc. One of them is gastrointestinal disorders such as stomachaches, constipation, and diarrhea caused by stress such as tension and anxiety, which cause great inconvenience in daily life.

[0003] Gen-noshoko has long been one of the representative herbs in Japan. Gen-noshoko contains ellagitannin and is said to be effective against diarrhea, constipation, sore throats, etc., and its main component is geraniin. Gen-noshoko powder obtained by drying and pulverizing the above-ground part is used as pharmaceuticals and the like.

[0004] Since crude drugs contain components with various properties, the storage stability of compositions containing crude drugs tends to be a problem. Therefore, conventionally, techniques for improving the storage stability of compositions containing crude drugs have been studied. For example, as a solid preparation capable of suppressing odor, an anti-odor solid preparation obtained by coating a solid preparation containing a drug having an odor with a film coating composition (Patent Document 1), or as a solid preparation capable of suppressing caking (solidification) and discoloration, a solid preparation containing a crude drug extract or a Kampo extract and first and second adsorbents such as calcium silicate and light anhydrous silicic acid (Patent Document 2) has been reported. However, pharmaceuticals should be stored, stored, transported, etc. under temperature-controlled conditions (at least 30°C or lower, so-called room temperature). In particular, after delivering pharmaceuticals to patients, they may be stored under conditions such as high temperature and high humidity. Therefore, from the viewpoint of providing higher-quality pharmaceuticals, ensuring storage stability is extremely important.

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] Japanese Patent Publication No. 2002-012541 [Patent Document 2] Japanese Patent Publication No. 2013-032346 [Overview of the project] [Problems that the invention aims to solve]

[0006] The inventors have found that when Geranium thunbergii is stored in airtight packaging, its characteristic odor, resembling damp earth, intensifies over time. Therefore, the object of the present invention is to provide a pharmaceutical composition in which the intensification of the characteristic odor derived from Geranium thunbergii during storage is suppressed. [Means for solving the problem]

[0007] As a result of diligent research to solve the above problems, the inventors of the present invention have found that by including a magnesium ion-containing compound or a calcium ion-containing compound together with Geranium thunbergii and sealing them in an airtight package, it is possible to suppress the enhancement of the characteristic odor derived from Geranium thunbergii when it is stored in an airtight package, and have completed the present invention.

[0008] In other words, the present invention comprises the following components (A) and (B): (A) Geranium thunbergii or its extract (B) Compounds containing divalent cations This invention provides a pharmaceutical product in which a pharmaceutical composition containing [the specified substance] is packaged in an airtight container. [Effects of the Invention]

[0009] According to the present invention, the enhancement of the characteristic odor derived from Geranium thunbergii or its extract during storage is suppressed, and a pharmaceutical product with excellent storage stability can be provided. [Modes for carrying out the invention]

[0010] The pharmaceutical composition of the present invention contains Geranium thunbergii or an extract thereof as component (A). In this invention, "Gennoshoko" refers to a crude drug derived from the plant Geranium thunbergii (Geraniaceae), but it is preferable to harvest the above-ground parts of Geranium thunbergii just before flowering and sun-dry them so that the leaves do not fall off. The form of Gennoshoko can be adjusted as needed, and for example, dried and powdered Gennoshoko powder can be used in this invention. "Geranium thunbergii extract" is obtained by subjecting Geranium thunbergii to some kind of extraction treatment. In addition to extraction, "Geranium thunbergii extract" also includes products that have undergone processing treatments such as heating, drying, and grinding. Specifically, the "Geranium thunbergii extract" of this invention also includes liquids obtained by leaching Geranium thunbergii after cutting it to an appropriate size as needed, by adding an appropriate extraction solvent, as well as concentrated liquids (soft extracts, tinctures, etc.) obtained by concentrating the leaching, and even dried versions of these (dried extracts, etc.). In the present invention, Geranium thunbergii extract, Geranium thunbergii dry extract, Geranium thunbergii powder, and Geranium thunbergii fluid extract are preferred as Geranium thunbergii or its extract, with Geranium thunbergii dry extract being more preferred.

[0011] The method for producing the extract of Geranium thunbergii is not particularly limited, and it can be produced by referring to known methods for producing plant extracts, such as those described in the sections on "Extracts," "Infusions / Decoctions," "Tinctures," and "Fluid Extracts" in the General Provisions of the Seventeenth Revised Japanese Pharmacopoeia. Specifically, it can be produced by cutting, heating, or grinding Geranium thunbergii as necessary, and then extracting it with an appropriate extraction solvent. The obtained extract may be further concentrated or dried as necessary.

[0012] Examples of the extraction solvents mentioned above include lower monohydric alcohols such as methanol, ethanol, isopropanol, and n-butanol (preferably linear or branched aliphatic alcohols having 1 to 6 carbon atoms); lower polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and glycerin; ethers such as diethyl ether; ketones such as acetone and ethyl methyl ketone; esters such as ethyl acetate; nitriles such as acetonitrile; alkanes such as pentane, hexane, cyclopentane, and cyclohexane; halogenoalkanes such as dichloromethane and chloroform; aromatic hydrocarbons such as benzene and toluene; amides such as dimethylformamide; sulfoxides such as dimethyl sulfoxide; and water (including hot water). These may be used individually or in combination of two or more. In the present invention, the extraction solvent is preferably a solvent containing at least water or a linear or branched aliphatic alcohol having 1 to 6 carbon atoms, more preferably a solvent selected from water, a linear or branched aliphatic alcohol having 1 to 6 carbon atoms, and a mixture of water and a linear or branched aliphatic alcohol having 1 to 6 carbon atoms, and particularly preferably a solvent selected from the group consisting of water, ethanol, and a water / ethanol mixture.

[0013] The extraction procedure is not particularly limited, and known methods used for extraction from plants can be employed, such as immersion in an extraction solvent (cold immersion, warm immersion, percolation, etc.) and extraction using supercritical or subcritical fluids. Furthermore, stirring or homogenization in the extraction solvent may be performed to increase extraction efficiency. The extraction temperature is not particularly limited and varies depending on the extraction solvent used, the extraction procedure, etc., but it is preferable to set it to a temperature between approximately 5°C and below the boiling point of the extraction solvent. The extraction time is not particularly limited and varies depending on the extraction solvent used, the extraction procedure, etc., but it is preferable to use a time of approximately 1 hour to 14 days.

[0014] In the present invention, commercially available products can be used as Geranium thunbergii or its extract. Specific examples of commercially available products include Geranium thunbergii extract, Geranium thunbergii extract-N, Geranium thunbergii dry extract-S, Geranium thunbergii powder, Geranium thunbergii fluid extract, and Geranium thunbergii fluid extract-L (all manufactured by Nippon Powder Pharmaceutical Co., Ltd.).

[0015] The content of Geranium thunbergii or its extract in the pharmaceutical composition of the present invention may be set appropriately according to the dosage form, dosage, etc., but from the viewpoint of improving stomach-strengthening, diaphoretic, and intestinal regulating effects, it is preferable to contain 0.01 to 60% by mass, more preferably 0.3 to 50% by mass, and particularly preferably 1 to 10% by mass, based on the total mass of the pharmaceutical composition. Furthermore, when the content of Geranium thunbergii or its extract is converted to the amount of crude drug, it is preferable that it be contained in an amount equivalent to 0.1 to 600% by mass of the total mass of the pharmaceutical composition, more preferably 4 to 500% by mass, and particularly preferably 30 to 50% by mass.

[0016] The pharmaceutical composition of the present invention contains a "divalent cation-containing compound" as component (B). "Divalent cation-containing compounds" are those that are pharmaceutically acceptable and contain a divalent cation as a constituent ion (for example, Mg 2+ Ions, Ca 2+ Ions, Zn 2+ Ions, Fe 2+ Ions, Mn 2+ Any compound containing ions, etc., is acceptable. Specifically, one or more compounds selected from calcium alginate, calcium ascorbate, calcium citrate, magnesium citrate, zinc citrate, calcium gluconate, ferrous gluconate, zinc gluconate, calcium succinate, zinc oxide, magnesium oxide, calcium citrate, magnesium hydroxide, magnesium carbonate, calcium pantothenate, calcium fumarate, ferrous fumarate, calcium pectin, zinc sulfate, ferrous sulfate, manganese sulfate, magnesium sulfate, etc. are acceptable. The compound may be produced by a known method or a commercially available product may be used.

[0017] From the viewpoint of suppressing the enhancement of the specific odor derived from ganoderma lucidum or its extract, etc., the content of the divalent cation-containing compound in the pharmaceutical composition of the present invention is preferably 0.01 to 60% by mass, more preferably 0.1 to 50% by mass, and particularly preferably 1 to 25% by mass based on the total mass of the pharmaceutical composition.

[0018] From the viewpoint of suppressing the enhancement of the specific odor derived from ganoderma lucidum or its extract, etc., the content mass ratio of ganoderma lucidum or its extract and the divalent cation-containing compound in the pharmaceutical composition of the present invention is preferably 0.001 to 20 parts by mass, more preferably 0.05 to 10 parts by mass, and particularly preferably 0.1 to 5 parts by mass of the divalent cation-containing compound with respect to 1 part by mass of ganoderma lucidum or its extract. Also, when the content of ganoderma lucidum or its extract is converted into the crude drug amount, preferably 0.001 to 8 parts by mass, more preferably 0.005 to 5 parts by mass, and particularly preferably 0.01 to 1 part by mass of the divalent cation-containing compound with respect to 1 part by mass of the crude drug conversion amount of ganoderma lucidum or its extract.

[0019] The pharmaceutical composition of the present invention preferably contains, as component (B), at least one selected from the group consisting of component (B-1) magnesium ion-containing compound and (B-2) calcium ion-containing compound. A "magnesium ion-containing compound" can be any pharmaceutically acceptable compound that contains magnesium ions as a constituent ion. Specifically, examples include one or more selected from magnesium aspartate, magnesium chloride, magnesium citrate, magnesium glycinate, magnesium gluconate, magnesium aluminosilicate, magnesium silicate, magnesium oxide, magnesium hydroxide, magnesium carbonate, magnesium lactate, magnesium pyrophosphate, magnesium ascorbyl phosphate, magnesium orotate, magnesium stearate, magnesium fumarate, magnesium sulfate, etc. Among these, one or more selected from magnesium citrate, magnesium oxide, magnesium hydroxide, magnesium carbonate, and magnesium sulfate are preferred from the viewpoint of neutralizing stomach acid, helping to improve constipation, and suppressing the enhancement of the characteristic odor derived from Geranium thunbergii or its extracts, with magnesium oxide and / or magnesium hydroxide being more preferred, and magnesium hydroxide being particularly preferred. The compound may be produced by known methods, or a commercially available product may be used. Commercially available products include magnesium oxide (Sanei Gen F.F.I. Co., Ltd.), magnesium oxide (Tomita Pharmaceutical Co., Ltd.), magnesium oxide (Kyowa Chemical Industry Co., Ltd.), Kyowa Suimag (Kyowa Chemical Industry Co., Ltd.), magnesium hydroxide (Tomita Pharmaceutical Co., Ltd.), magnesium carbonate (Kyowa Chemical Industry Co., Ltd.), magnesium sulfate (Tomita Chemical Co., Ltd.), and magnesium sulfate heptahydrate (Merck KGaA).

[0020] The magnesium ion-containing compound in the pharmaceutical composition of the present invention is preferably present in an amount of 0.1 to 60% by mass, more preferably 2 to 50% by mass, and particularly preferably 5 to 20% by mass, relative to the total mass of the pharmaceutical composition, from the viewpoint of suppressing the enhancement of the characteristic odor derived from Geranium thunbergii or its extract.

[0021] In the pharmaceutical composition of the present invention, the mass ratio of Geranium thunbergii or its extract to the magnesium ion-containing compound is preferably 0.01 to 10 parts by mass, more preferably 0.5 to 5 parts by mass, and particularly preferably 1 to 3 parts by mass of the magnesium ion-containing compound per 1 part by mass of Geranium thunbergii or its extract, from the viewpoint of suppressing the enhancement of the characteristic odor derived from Geranium thunbergii or its extract. Furthermore, when the content of Geranium thunbergii or its extract is converted to the amount of crude drug, the magnesium ion-containing compound is preferably 0.001 to 5 parts by mass, more preferably 0.05 to 1 part by mass, and particularly preferably 0.1 to 0.3 parts by mass per 1 part by mass of the crude drug equivalent amount of Geranium thunbergii or its extract.

[0022] A "calcium ion-containing compound" can be any compound that is pharmaceutically acceptable and contains calcium ions as a constituent ion. Specifically, examples include one or more compounds selected from calcium ascorbate, calcium alginate, calcium carboxymethylcellulose, calcium citrate, calcium gluconate, calcium succinate, calcium citrate, calcium hydroxide, calcium stearate, calcium lactate, calcium pantothenate, calcium fumarate, calcium pectin, anhydrous calcium hydrogen phosphate, calcium sulfate, monocalcium phosphate, calcium phosphate, tricalcium phosphate, calcium dihydrogen phosphate, etc. In particular, from the viewpoint of nutritional supplementation and suppressing the enhancement of the characteristic odor derived from Geranium thunbergii or its extracts, one or more selected from calcium ascorbate, calcium alginate, calcium citrate, calcium gluconate, calcium succinate, calcium citrate, calcium lactate, calcium pantothenate, calcium fumarate, and calcium pectin are preferred, one or more selected from calcium ascorbate, calcium gluconate, calcium lactate, and calcium pantothenate are more preferred, and calcium pantothenate is especially preferred. The compound may be produced by known methods, or a commercially available product may be used. Commercially available products include calcium gluconate (Tomita Pharmaceutical Co., Ltd.), Japanese Pharmacopoeia calcium lactate hydrate (Taihei Chemical Industry Co., Ltd.), calcium lactate hydrate (Sanei Gen F.F.I. Co., Ltd.), calcium lactate hydrate (DSP Gokyo Food & Chemical Co., Ltd.), calcium pantothenate (BASF Japan Ltd.), and calcium pantothenate (Sanei Gen F.F.I. Co., Ltd.).

[0023] The content of the calcium ion-containing compound in the pharmaceutical composition of the present invention is preferably 0.1 to 60% by mass, more preferably 0.5 to 50% by mass, and particularly preferably 1 to 10% by mass, based on the total mass of the pharmaceutical composition, from the viewpoint of suppressing the enhancement of the characteristic odor derived from Geranium thunbergii or its extract.

[0024] In the pharmaceutical composition of the present invention, the mass ratio of Geranium thunbergii or its extract to the calcium ion-containing compound is preferably 0.01 to 10 parts by mass, more preferably 0.05 to 3 parts by mass, and particularly preferably 0.1 to 1 part by mass of the calcium ion-containing compound per 1 part by mass of Geranium thunbergii or its extract, from the viewpoint of suppressing the enhancement of the characteristic odor derived from Geranium thunbergii or its extract. Furthermore, when the content of Geranium thunbergii or its extract is converted to the amount of crude drug, the amount of calcium ion-containing compound is preferably 0.001 to 5 parts by mass, more preferably 0.005 to 1 part by mass, and particularly preferably 0.01 to 0.5 parts by mass, per 1 part by mass of the crude drug equivalent amount of Geranium thunbergii or its extract.

[0025] In the present invention, the pharmaceutical composition may be in any form: solid, semi-solid, or liquid, and may be in any form commonly used in pharmaceuticals, quasi-drugs, etc., depending on its intended use. For example, it may be in the form of solid preparations such as tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolvable tablets, oral tablets (including lozenges, sublingual tablets, buccal tablets, adhesive tablets, and gums)), capsules, granules (including effervescent granules), powders, and pills; liquid preparations such as oral solutions (including elixirs, suspensions, emulsions, and limonades), syrups, and oral solutions; or semi-solid preparations such as oral jellies and semi-solid oral preparations, as described in the General Provisions for Preparations of the Seventeenth Edition of the Japanese Pharmacopoeia. In the present invention, from the viewpoint of formulation stability, ease of administration, and production efficiency, a solid composition is preferred, a dosage form selected from the group consisting of tablets, capsules, granules, powders, and pills is more preferred, and tablets are particularly preferred.

[0026] The pharmaceutical compositions of the present invention can be manufactured according to methods known in the pharmaceutical field, the quasi-drug field, etc., depending on the shape and dosage form described above, for example, according to methods described in the General Provisions for Preparations of the Seventeenth Edition of the Japanese Pharmacopoeia.

[0027] In addition to the components (A) and (B) described above, the pharmaceutical composition of the present invention may also contain carriers (pharmaceutical additives) used in the pharmaceutical field, quasi-drug field, etc. Examples of such pharmaceutical additives include excipients, binders, disintegrants, lubricants, colorants, film-forming agents, powders, poorly water-soluble polymers, antioxidants, pH adjusters, and flavoring agents. In the present invention, these can be used individually or in combination of two or more. The content of such formulation additives can be appropriately set within a range that does not impair the objective of the present invention.

[0028] Examples of excipients include inorganic excipients such as aluminum silicate, anhydrous sodium sulfate, sodium chloride, calcium silicate, light anhydrous silicic acid, heavy anhydrous silicic acid, calcium carbonate, calcium hydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, and sodium dihydrogen phosphate; and organic excipients such as syrup powder, starch (wheat starch, rice starch, corn starch, partially pregelatinized starch, etc.), fructose, caramel, agar, xylitol, paraffin, crystalline cellulose, sucrose, maltose, lactose, lactose monohydrate, sucrose, glucose, pullulan, polyoxyethylene hydrogenated castor oil, maltitol, reduced maltose syrup, powdered reduced maltose syrup, erythritol, sorbitol, mannitol, lactitol, trehalose, reduced palatinose, aminoalkyl methacrylate copolymer E, and polyvinyl acetal diethylaminoacetate.

[0029] Examples of binders include oils and fats such as hydrogenated beef tallow, hydrogenated oil, hydrogenated vegetable oil, hydrogenated soybean oil, carnauba wax, bleached beeswax, beeswax, and Japanese wax, as well as methylcellulose, hydroxypropylcellulose, hypromellose, sodium carmellose, starch (wheat starch, rice starch, corn starch, partially pregelatinized starch, etc.), dextrin, pullulan, acacia gum, agar, gelatin, tragacanth, sodium alginate, povidone, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, and polyvinyl acetal diethylaminoacetate.

[0030] Examples of disintegrants include super disintegrants such as sodium carboxymethyl starch, sodium croscarmellose, and crospovidone, as well as carmellose, carmellose calcium, starch, sucrose fatty acid esters, gelatin, sodium bicarbonate, dextrin, dehydroacetic acid and its salts, povidone, and polyoxyethylene hydrogenated castor oil 60.

[0031] Examples of lubricants include magnesium stearate, sodium stearyl fumarate, and sucrose fatty acid esters.

[0032] Examples of coloring agents include tar dyes and iron oxide.

[0033] Examples of film-forming agents include alkylcelluloses such as methylcellulose and ethylcellulose; alginic acid or its salts such as sodium alginate; carrageenan; carboxyalkylcelluloses such as sodium carboxymethylcellulose, potassium carboxymethylcellulose, carboxymethylcellulose, and carboxymethylethylcellulose; xanthan gum; hydroxyalkylcelluloses such as hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and hypromellose (hydroxypropylmethylcellulose); hydroxyalkylcellulose phthalates such as hydroxypropylmethylcellulose phthalate; pullulan; polyvinyl acetate; polyvinyl acetate phthalate; and polyvinylpyrrolidone.

[0034] Examples of powders include organic or inorganic powders such as talc, titanium dioxide, yellow iron(III) oxide, iron(III) oxide, and legally approved dyes.

[0035] Examples of poorly water-soluble polymers include carboxyvinyl polymers and aminoalkyl methacrylate copolymers.

[0036] Examples of antioxidants include ascorbic acid, sodium bisulfite, sodium sulfite, sodium edetate, erythorbic acid, tocopherol acetate, dibutylhydroxytoluene, natural vitamin E, tocopherol, and butylhydroxyanisole.

[0037] Examples of pH adjusters include organic acids or their salts such as citric acid, sodium citrate, anhydrous citric acid, malic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, sodium tartrate, lactic acid, sodium lactate, acetic acid, sodium acetate, and glacial acetic acid; inorganic acids or their salts such as hydrochloric acid, sulfuric acid, phosphoric acid, sodium hydrogen phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, sodium carbonate, and sodium bicarbonate; alkali hydroxides such as sodium hydroxide and potassium hydroxide; and amines such as triethanolamine, diethanolamine, and diisopropanolamine.

[0038] Examples of flavoring agents include terpenes such as limonene, pinene, camphene, cymene, cineole, citronellol, geraniol, nerol, linalool, menthol, terpineol, rodinol, borneol, isoborneol, menthone, camphor, eugenol, and synzeyranol; essential oils containing terpenes such as spruce oil, orange oil, peppermint oil, camphor oil, eucalyptus oil, turpentine oil, lemon oil, ginger oil, clove oil, cinnamon oil, lavender oil, fennel oil, chamomile oil, perilla oil, and spearmint oil; and acidulants such as ascorbic acid, tartaric acid, citric acid, malic acid, saccharin and their salts, aspartame, stevia, sucralose, thaumatin, and acesulfame potassium.

[0039] Furthermore, the pharmaceutical composition of the present invention may optionally contain other pharmacoactive ingredients in addition to the above-mentioned components (A) and (B), provided that such ingredients do not impair the effects of the present invention. Such pharmacoactive ingredients are not particularly limited and can be appropriately considered and selected depending on the disease or symptoms to which the pharmaceutical composition is applied. Examples include local anesthetics, digestive agents (choleretics), digestive enzymes, gastric mucosal repair agents (mucosal protective components), intestinal regulators, herbal ingredients, and antacids. In the present invention, one or more of these pharmacoactive ingredients can be appropriately combined and formulated. The content of such pharmacoactive ingredients can be appropriately set within a range that does not impair the objective of the present invention.

[0040] Examples of local anesthetics include ethyl aminobenzoate and oxethazaine. Examples of digestive agents (cholagogues) include ursodeoxycholic acid and animal bile (bear bile, bovine bile). Examples of digestive enzymes include starch-digesting enzymes (biodiastase, takadiastase) and fat-digesting enzymes (lipase). Examples of gastric mucosal repair agents (mucosal protective components) include copper chlorophyll sodium, copper chlorophyll potassium, cetraxate hydrochloride, sofalcone, gefarnate, trimebutine maleate, sodium azulene sulfonate, aldioxa, and methylmethionine sulfonium chloride. Examples of intestinal regulators include intestinal regulating bacteria components such as bifidobacteria, lactic acid bacteria, butyrate-producing bacteria, and saccharifying bacteria, as well as dimethylpolysiloxane. Examples of herbal ingredients include catechu, aniseed, aloe, fennel, turmeric, basil, cinnamon, Corydalis, Enmeisou, scutellaria, phellodendron, Coptis japonica, processed garlic, zedoary, cuckoo, kale root, ginger, licorice, citrus fruit, kudzu, cinnamon, cassia, gentian, ginseng, evodia, pepper, gallnut, colombo, conzurango, hawthorn, sansho, lilac, perilla, and peony. Examples of crude drugs and their extracts include cardamom, ginger, cardamom, green bark, red bud oak, sweet flag, Centaurium grass, gentian, atractylodes lancea, hibiscus, star anise, rhubarb, bamboo shoot ginseng, clove, dried tangerine peel, chili pepper, spruce, quatica, nutmeg, ginseng, mint, long pepper, long pepper, hops, venus, water lily, yakuchi, basil, gentian, and lily lily. Examples of antacids include proton pump inhibitors such as omeprazole, lansoprazole, and rabeprazole sodium; H2 receptor antagonists such as cimetidine, ranitidine hydrochloride, and famotidine; inorganic salts such as magnesium aluminometasilicate, synthetic aluminum silicate, synthetic hydrotalcite, sodium bicarbonate, and precipitated calcium carbonate; and cuttlefish bone, oyster shell, oyster shell, and aminoacetic acid.

[0041] The route of administration of the pharmaceutical composition is not particularly limited and can be determined as appropriate depending on the disease to be treated, the type of preparation, the gender, age, and symptoms of the user. However, oral administration is preferred from the viewpoint of ease of administration. The pharmaceutical composition can also be taken in 1 to 4 divided doses per day, such as before meals, between meals, after meals, or before bedtime. The above dosage is, for example, an amount that allows for the administration of 10 to 3000 mg of component (A) per day, preferably 50 to 1500 mg, and more preferably 100 to 500 mg. In terms of crude drug equivalent, it is an amount that allows for the administration of 30 to 4000 mg, preferably 500 to 2000 mg, and more preferably 1000 to 1500 mg. Furthermore, the amount is such that 10 to 2500 mg of component (B) can be taken, preferably 20 to 1000 mg, more preferably 30 to 500 mg, and particularly preferably 100 to 400 mg.

[0042] The pharmaceutical composition of the present invention is further contained in an airtight package. In this invention, the pharmaceutical composition may also be provided with packaging other than the airtight package, and the pharmaceutical composition may be contained directly or indirectly in the airtight package. One example of an indirectly contained form in an airtight packaging is a form in which the pharmaceutical composition is contained in the "other packaging" and then contained in an airtight packaging.

[0043] In this specification, "airtight packaging" means packaging that can prevent the intrusion of solid or liquid foreign matter under normal handling, transportation, or storage conditions, and is a concept that encompasses "airtight containers" and "sealed containers" as defined in the General Rules of the 17th Revised Japanese Pharmacopoeia. Airtight packaging can be either fixed-shaped or irregular-shaped, and specific examples include bottle packaging, SP (Strip Package) packaging, PTP (Press Through Package) packaging, pillow packaging, stick packaging, etc. Airtight packaging may also be a combination of multiple types of these, for example, by first packaging a pharmaceutical composition in PTP packaging and then further packaging this in pillow packaging.

[0044] The packaging material (material) for the airtight packaging is not particularly limited, and for example, materials used in the pharmaceutical field, such as glass, plastics (polyesters such as polyethylene terephthalate and polyethylene naphthalate; polyethylene (including low-density (LDPE), medium-density (MDPE), and high-density (HDPE))), polyolefins such as polypropylene; polycarbonate; polystyrene, etc.), and metals (aluminum, etc.), can be used individually or in combination of two or more as appropriate.

[0045] For example, the packaging materials used for bottle packaging are not particularly limited and include the above-mentioned glass, plastic, metal, etc., and one or more of these can be combined as appropriate. As for the material for bottle packaging, from the viewpoint of suppressing the enhancement of the characteristic odor derived from Geranium thunbergii or its extract, glass, polyethylene, and polypropylene are preferred, glass, low-density polyethylene (LDPE), high-density polyethylene (HDPE), and polypropylene are more preferred, glass, high-density polyethylene (HDPE), and polypropylene are even more preferred, and glass is particularly preferred. When packaging in bottles, for example, an appropriate quantity of the pharmaceutical composition can be placed in the bottle, and then sealed with a suitable stopper or cap. The size of the bottle should be appropriately selected according to the quantity of composition to be stored, and the bottle capacity is, for example, about 10 to 600 mL, preferably 30 to 400 mL, and more preferably 150 to 350 mL.

[0046] Furthermore, the packaging materials used in SP packaging, PTP packaging, pillow packaging, stick packaging, etc., are not particularly limited. Examples include biaxially oriented polypropylene (OPP), biaxially oriented polyester (PET), glycol-modified PET (PET-G), biaxially oriented nylon (ONy, PA), cellophane, paper, low-density polyethylene (LDPE), linear low-density polyethylene (L-LDPE), ethylene-vinyl acetate copolymer (EVA), unoriented polypropylene (CPP, IPP), and ionomer resin (IO). Examples include resins such as ethylene-methacrylic acid copolymer (EMAA), polyacrylonitrile (PAN), biaxially oriented polyvinylidene chloride (PVDC), ethylene-vinyl alcohol copolymer resin (EVOH), polyvinyl chloride (PVC), cyclic polyolefin (COC), unoriented nylon (CNy), polycarbonate (PC), polystyrene (PS), and rigid polyvinyl chloride (VSC), as well as metal foils such as aluminum foil (AL). One or more of these can be appropriately combined.

[0047] When producing SP packaging, PTP packaging, pillow packaging, stick packaging, etc., the packaging can be manufactured using a sheet made of one or more of the above-mentioned packaging materials by a known method, and in this case, a multilayer structure can be formed by appropriately combining the packaging materials. One method for creating a multilayer structure using two or more types of packaging materials as a sheet is to produce a laminated sheet by laminating the packaging materials. Laminated sheets can be manufactured by known methods such as extrusion lamination, dry lamination, co-extrusion lamination, thermal lamination, wet lamination, non-solvent lamination, and heat lamination. In addition, commercially available sheets known to be used for SP packaging, PTP packaging, pillow packaging, and stick packaging can also be used.

[0048] In the above-mentioned sheets, single-layer sheets using one type of packaging material include PVC sheets and CPP sheets, and laminated sheets using two or more types of packaging materials include, for example, sheets laminated with PVC and PVDC (PVC / PVDC; hereinafter abbreviated similarly), PVC / PVDC / PE / PVC, PVC / PVDC / PE / PVDC / PVC, CPP / COC / CPP, PVC / PCTFE, CPP / PCTFE, PVC / AL / PA, PVC / AL, CPP / AL, CPP / CPP / CPP (the above sheets use two or more types of CPP), but are not limited to these.

[0049] One form of PTP packaging involves forming a desired number of pockets in a resin sheet or the like using a known method, storing one composition or one dose unit in each pocket, and then sealing the package with a sheet made of metal foil such as aluminum foil as the lid material. Alternatively, a so-called double-sided aluminum PTP packaging may be used, where the sheet forming the pockets is also made of aluminum foil. SP packaging, pillow packaging, and stick packaging methods include packaging the composition one unit or one dose unit at a time using a sheet made of resin sheet or aluminum foil as a constituent material, using known methods. When using SP packaging, pillow packaging, or stick packaging, it is preferable to use a sheet made of aluminum foil as a constituent material.

[0050] In this specification, the occupancy rate (volume ratio) of a pharmaceutical composition within the packaging of a pharmaceutical product is typically 25-90%, preferably 28-75%, and more preferably 30-50% when the packaging is a bottle. When the packaging is SP packaging, PTP packaging, pillow packaging, or stick packaging, the occupancy rate is typically 30-98%, preferably 40-95%, more preferably 45-93%, and particularly preferably 50-90%. In this case, the occupancy rate refers to the occupancy rate of the composition relative to the total volume inside the packaging, and packing materials or stoppers used to prevent damage to the composition stored inside the packaging are not considered when calculating the space occupancy rate.

[0051] As airtight packaging, commercially available packaging may be used as is, or commercially available packaging materials may be processed and used. Examples of commercially available bottle packaging include glass bottles (manufactured by Isoya Glass Industry Co., Ltd.), tablet bottles (manufactured by Tokyo Glass Co., Ltd.), and the Z-series (manufactured by Hanshin Chemical Industries, Ltd.). Examples of commercially available pillow packaging include Lamizip (registered trademark) (manufactured by Seisan Nipponsha Co., Ltd.). Furthermore, examples of packaging materials for SP packaging, PTP packaging, pillow packaging, and stick packaging include Sumilight VSS, Sumilight VSL, Sumilight NS, Sumilight FCL (all manufactured by Sumitomo Bakelite Co., Ltd.), the TAS series (manufactured by Taisei Chemical Co., Ltd.), PTP vinyl foil, PTP super foil (both manufactured by Mitsubishi Plastics, Inc.), Nippaku aluminum foil (manufactured by Nippon Foil Co., Ltd.), and plain silver aluminum foil (manufactured by Yamato Chemical Industry Co., Ltd.).

[0052] The method for containing the pharmaceutical composition in an airtight package is not particularly limited and can be achieved by placing the composition inside the package by appropriate means, such as introducing the composition into the package. In this case, a means of introducing a desiccant (for example, cylindrical (tablet-type) or sheet-type) together with the composition inside the package may also be used.

[0053] The pharmaceutical composition of the present invention contains Geranium thunbergii or an extract thereof, and can be used as a prescription drug or an over-the-counter drug. Specifically, it has efficacy or effects such as regulating bowel movements, loose stools, constipation, diarrhea, bloating, indigestion, food poisoning, stomach upset, weak stomach, loss of appetite, overeating, excessive drinking, nausea, vomiting, heartburn, chest tightness, stomach discomfort, stomach heaviness, excessive stomach acid, belching, and stomach pain, and is useful as a gastrointestinal medicine.

[0054] Furthermore, the present invention relates to the following components (A) and (B): (A) Geranium thunbergii or its extract (B) Compounds containing divalent cations The present invention also relates to a method for stabilizing component (A) in a pharmaceutical composition when it is sealed in an airtight package and stored, which includes the step of incorporating the two into the same pharmaceutical composition (preferably a method for suppressing the enhancement of the odor of Geranium thunbergii or its extract in the pharmaceutical composition during storage). In such embodiments of the invention, the order of the steps of incorporating component (A) and component (B) is not particularly limited, and it is sufficient that a composition containing component (A) and component (B) is produced directly or indirectly. In this embodiment of the invention, the meaning of various terms, the amounts of each component, etc., are all the same as those explained for the pharmaceutical composition described above.

[0055] This specification is not limited to these, but discloses, for example, the following embodiments. [1A] The following components (A) and (B): (A) Geranium thunbergii or its extract (B) Compounds containing divalent cations A pharmaceutical product comprising a pharmaceutical composition containing the above, packaged in an airtight container. [2A] Component (B) is (B-1) and (B-2) below (B-1) Magnesium ion-containing compound (B-2) Calcium ion-containing compounds A pharmaceutical product described in [1A], which is one or more selected from the group. [3A] The pharmaceutical product described in [1A], wherein component (B) is one or more selected from the group consisting of magnesium oxide, magnesium hydroxide, and calcium pantothenate. [4A] A pharmaceutical product according to [1A] to [3A], wherein the dosage form of the pharmaceutical composition is a tablet, capsule, granule, powder, or pill. [5A] The following components (A) and (B): (A) Geranium thunbergii or its extract (B) Compounds containing divalent cations A method for suppressing the enhancement of odor when component (A) in a pharmaceutical composition is sealed in an airtight package and stored, comprising the step of including the same component (A) in the same pharmaceutical composition. [Examples]

[0056] The present invention will be described in more detail below with reference to examples, but the present invention is not limited in any way thereto.

[0057] [Sample 1] 2g of Geranium thunbergii (Geranium thunbergii dried extract-S, manufactured by Nippon Powdered Pharmaceuticals Co., Ltd.) was placed in an open glass bottle (2K standard bottle) and used as Sample 1.

[0058] [Sample 2] 2g of Geranium thunbergii (Geranium thunbergii dried extract-S, manufactured by Nippon Powdered Pharmaceuticals Co., Ltd.) was placed in a glass bottle (2K standard bottle) and sealed to create Sample 2.

[0059] [Sample 3] A mixture was obtained by mixing 1 part by mass of Geranium thunbergii (Geranium thunbergii dried extract-S, manufactured by Nippon Powdered Pharmaceuticals Co., Ltd.) with 1 part by mass of magnesium hydroxide (Kyowa Suimag, manufactured by Kyowa Chemical Industry Co., Ltd.). 2 g of the obtained mixture was placed in a glass bottle (2K standard bottle), sealed, and designated as Sample 3.

[0060] [Sample 4] A mixture was obtained by mixing 1 part by mass of Geranium thunbergii (Geranium thunbergii dry extract-S, manufactured by Nippon Powdered Pharmaceuticals Co., Ltd.) with 1 part by mass of calcium pantothenate (calcium pantothenate, manufactured by BASF Japan Ltd.). 2 g of the obtained mixture was placed in a glass bottle (2K standard bottle) and sealed to obtain Sample 4.

[0061] [Test Example 1] Storage Stability Test Each sample was prepared and stored at 40°C and 75% RH for one day. Two panelists performed a sensory evaluation of the odor before storage and after one day of storage (checking for any increase in the characteristic odor (a damp, earthy smell)). The results are shown in Table 1.

[0062] [Table 1]

[0063] As shown in Table 1, in Sample 1, which consisted only of Geranium thunbergii and was not sealed in airtight packaging, no increase in the characteristic odor was observed even after storage. On the other hand, in Sample 2, which consisted only of Geranium thunbergii and was sealed in airtight packaging, an increase in the characteristic odor was observed after storage. In contrast, in Sample 3, which was Sample 2 with added magnesium hydroxide, and in Sample 4, which was sampled with added calcium pantothenate, no enhancement of the characteristic odor was observed after storage at 40°C and 75% RH for one day.

[0064] The above test results clearly show that the enhancement of the distinctive odor derived from Geranium thunbergii, which occurs when Geranium thunbergii is stored in airtight packaging, is relatively suppressed by incorporating components (B), such as magnesium hydroxide and calcium pantothenate.

Claims

1. The following components (A) and (B-1): (A) Geranium thunbergii or its extract (B-1) Magnesium ion-containing compounds A pharmaceutical product comprising a pharmaceutical composition containing the above, packaged in an airtight container.

2. The pharmaceutical product according to claim 1, wherein component (B-1) is magnesium oxide and / or magnesium hydroxide.

3. The pharmaceutical product according to claim 1 or 2, wherein the dosage form of the pharmaceutical composition is a tablet, capsule, granule, powder, or pill.

4. The following components (A) and (B-1): (A) Geranium thunbergii or its extract A method for suppressing the enhancement of odor when component (A) in a pharmaceutical composition is sealed in an airtight package and stored, comprising the step of including (B-1) a magnesium ion-containing compound in the same pharmaceutical composition.

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