Pharmaceutical composition

Abstract

To provide a pharmaceutical composition containing Citrus unshiu peel, exhibiting reduced occurrence of solidification caused by high-temperature storage.SOLUTION: A pharmaceutical composition comprises the following components (A) and (B): (A) Citrus unshiu peel or an extract thereof; and (B) itopride or a salt thereof.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition.

Background Art

[0002] Chimpi (Chenpi) is the mature pericarp of tangerine. Chimpi is known to have pharmacological effects such as strengthening the stomach, relieving cough, and reducing phlegm, and is widely used as a crude drug in pharmaceuticals. Since crude drugs contain components with various properties, the storage stability of pharmaceuticals containing crude drugs tends to be a problem. Therefore, conventionally, techniques for improving the storage stability of pharmaceuticals containing crude drugs have been studied. For example, 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 1) 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 pharmaceuticals are delivered to patients, they may be stored under high-temperature conditions in some cases. Therefore, from the viewpoint of providing higher-quality pharmaceuticals, ensuring storage stability under high-temperature conditions is extremely important.

[0003] By the way, itopride promotes the release of acetylcholine (ACh) by its dopamine D2 receptor antagonistic action, and further has an acetylcholinesterase (AChE) inhibitory action, inhibiting the decomposition of the released ACh. By these cooperative actions, it shows a gastrointestinal motility enhancing action. In Japan, a preparation containing itopride hydrochloride in tablet form is approved as a gastrointestinal motility activator having an action of enhancing gastric motility, enhancing the ability to discharge gastric contents, and relieving vomiting. However, there has been no report on what kind of influence itopride has on the storage stability of compositions containing crude drugs such as Chimpi.

Prior Art Documents

Patent Documents

[0004] Patent Document 1 Japanese Patent Application Laid-Open No. 2013-32346 Summary of the Invention Problems to be Solved by the Invention

[0005] The present inventor has studied to develop a pharmaceutical composition containing chinpi as a crude drug, and has found that solidification occurs under high-temperature storage. Accordingly, an object of the present invention is to provide a pharmaceutical composition containing chinpi in which solidification under high-temperature storage is suppressed. Means for Solving the Problems

[0006] As a result of intensive studies to solve the above problems, the present inventor has found that, surprisingly, solidification under high-temperature storage is suppressed by containing itopride together with chinpi or an extract thereof, and has completed the present invention.

[0007] That is, the present invention provides the following components (A) and (B): (A) Chinpi or an extract thereof (B) Itopride or a salt thereof and provides a pharmaceutical composition containing the same. Effects of the Invention

[0008] According to the present invention, it is possible to provide a pharmaceutical composition containing chinpi or an extract thereof and itopride, in which solidification under high-temperature storage is suppressed and the storage stability is good. Modes for Carrying Out the Invention

[0009] The pharmaceutical composition of the present invention contains chinpi or an extract thereof as component (A). In the present invention, "Chenpi" refers to the mature pericarp of Citrus unshiu Marcowicz or Citrus reticulata Blanco (Rutaceae). Chenpi can be adjusted in its form as needed, and the whole crude drug can be cut, crushed or pulverized into small pieces, small lumps, or powder. For example, "Chenpi powder" obtained by pulverizing Chenpi can be used in the present invention. The "extract of Chenpi" is obtained by subjecting Chenpi to some extraction treatment. In addition, the "extract of Chenpi" also includes those obtained by subjecting to processing treatments such as heating, drying, and pulverizing in addition to the extraction treatment. Specifically, after Chenpi is made into an appropriate size as needed, a suitable extraction solvent is added for leaching, the leaching solution, a concentrated solution of the leaching solution (soft extract, tincture, etc.), and further those obtained by drying these (dry extract, etc.) are also included in the "extract of Chenpi" of the present invention. In the present invention, as Chenpi or its extract, Chenpi dry extract is preferred.

[0010] The method for producing the extract of Chenpi is not particularly limited. For example, it can be produced with reference to the production methods of known plant extracts, such as the descriptions in the sections of "Extracts", "Infusions and Decoctions", "Tinctures", and "Liquid Extracts" in the General Rules of Preparations of the 17th Revised Japanese Pharmacopoeia. Specifically, it can be produced by cutting, heating, pulverizing, etc. Chenpi as needed and then adding a suitable extraction solvent for extraction. The obtained extract may be further concentrated, dried, etc. as needed.

[0011] Examples of the extraction solvent 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; water (including hot water), and the like. These may be used alone 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 / 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.

[0012] The extraction operation is not particularly limited, and known methods used for extraction operations from plants can be employed. Examples include immersion in an extraction solvent (cold extraction, warm extraction, percolation, etc.), extraction using a supercritical fluid or a subcritical fluid, and the like. In addition, in order to increase the extraction efficiency, stirring, homogenization in the extraction solvent, or the like may be performed. The extraction temperature is not particularly limited and varies depending on the extraction solvent used, the extraction operation, etc., but it is preferably about 5°C to a temperature 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 operation, etc., but it is preferably about 1 hour to 14 days.

[0013] In the present invention, commercially available products can be used as chinpi or its extract. Specific commercially available products include chinpi dry extract (manufactured by Alps Pharmaceutical Co., Ltd.), chinpi extract (manufactured by Nippon Powder Chemical Co., Ltd.), and the like.

[0014] The content of chinpi or its extract in the pharmaceutical composition of the present invention may be appropriately set according to the dosage form, dosage, etc. From the viewpoint of improving physiological activity, it is preferably contained in an amount of 0.001 to 20% by mass, more preferably 0.01 to 10% by mass, still more preferably 0.03 to 5% by mass, and particularly preferably 0.05 to 1% by mass based on the total mass of the pharmaceutical composition. Further, when the content of chinpi or its extract is converted into the crude drug amount, it is preferably contained in an amount of 0.001 to 30% by mass, more preferably 0.01 to 15% by mass, still more preferably 0.04 to 7% by mass, and particularly preferably 0.07 to 2% by mass in terms of the crude drug conversion amount based on the total mass of the pharmaceutical composition.

[0015] The pharmaceutical composition of the present invention contains itopride or a salt thereof as component (B). The itopride used in the present invention has the chemical name N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide and the molecular formula C 20 H 26 N 2 O 4 and is a compound of. The compound can be produced, for example, according to the method described in Japanese Patent Publication No. 5-37982. The salt of itopride may be a pharmaceutically acceptable salt, and examples thereof include acid addition salts with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, citric acid, tartaric acid, picric acid, methanesulfonic acid, p-toluenesulfonic acid, and glutamic acid. Among them, the hydrochloride is preferably used. Itopride or a salt thereof may be a solvate or a non-solvate, and both are included. In the present invention, preferred examples of the solvate include hydrates, alcoholates, or acetoneates.

[0016] The content of itopride or its salt in the pharmaceutical composition of the present invention may be appropriately set according to the dosage form, dosage, etc. From the viewpoint of suppressing solidification of component (A) and exerting the physiological action of itopride, it is preferably contained in an amount of 0.1 to 60% by mass, more preferably 1 to 30% by mass, and particularly preferably 2 to 10% by mass based on the total mass of the pharmaceutical composition.

[0017] In the pharmaceutical composition of the present invention, the content mass ratio of component (A) to component (B) is preferably 0.05 to 15 parts by mass, more preferably 0.1 to 5 parts by mass, and particularly preferably 0.5 to 1 part by mass of component (B) with respect to 1 part by mass of component (A) from the viewpoint of suppressing solidification of component (A). Further, when the content of component (A) is converted to the crude drug amount, from the same viewpoint, 0.01 to 10 parts by mass of component (B) is preferably used with respect to 1 part by mass of component (A) in terms of crude drug conversion, more preferably 0.05 to 1 part by mass, and particularly preferably 0.1 to 0.5 part by mass.

[0018] In the present invention, the pharmaceutical composition may be in any of solid, semi-solid, and liquid forms, and can be in a form commonly used in pharmaceuticals, quasi-drugs, etc. according to the purpose of use. For example, solid preparations such as tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, soluble tablets, oral tablets (including lozenges, sublingual tablets, buccal tablets, adherent tablets, gums)), capsules, granules (including effervescent granules), powders, pills, etc.; liquid preparations such as oral liquids (including elixirs, suspensions, emulsions, lemonades), syrups, oral liquids, etc.; semi-solid preparations such as oral jellies, oral semi-solid agents, etc., and can be in dosage forms described in the General Rules of Preparations of the 17th Revised Japanese Pharmacopoeia. In the present invention, from the viewpoints of formulation stability, ease of administration, production efficiency, etc., a solid composition is preferable, a dosage form selected from the group consisting of tablets, capsules, granules, powders, and pills is more preferable, and a dosage form selected from the group consisting of tablets and granules is particularly preferable.

[0019] The pharmaceutical composition of the present invention can be produced according to known methods in the pharmaceutical field, quasi-drug field, etc. depending on the above-described shape and dosage form, for example, according to the methods described in the General Rules for Preparations of the 17th Revised Japanese Pharmacopoeia. In addition to the above-described components, the pharmaceutical composition of the present invention may contain one or more carriers (for example, excipients, binders, disintegrants, lubricants, coloring agents, flavoring agents, fragrances, coating agents, etc.) used in the pharmaceutical field, quasi-drug field, etc.

[0020] Examples of excipients include lactose, crystalline cellulose, sucrose, calcium lactate, mannitol, light anhydrous silicic acid, and the like. Examples of binders include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, corn starch, dextrin, povidone, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, and the like. Examples of disintegrants include carmellose, carmellose calcium, croscarmellose sodium, crospovidone, low-substituted hydroxypropylcellulose, and the like. Examples of lubricants include hardened oil, magnesium stearate, talc, and the like. Examples of coloring agents include tar dyes, iron sesquioxide, and the like. Examples of flavoring agents include sorbitol, maltitol, erythritol, xylitol, trehalose, sucralose, saccharin and its salts, stevia, aspartame, acesulfame potassium, and the like. Examples of fragrances include orange fragrance, lemon fragrance, grapefruit fragrance, vanilla fragrance, mint fragrance, apple fragrance, ginger fragrance, honey fragrance, grape fragrance, menthol, peppermint oil, caramel, and the like. Examples of coating agents include film-forming polymers such as carboxymethylethyl cellulose, cellulose acetate phthalate, methacrylic acid copolymer S, methacrylic acid copolymer L, methacrylic acid copolymer LD, hydroxypropylmethylcellulose phthalate, and hydroxypropylmethylcellulose acetate succinate. When forming a film, plasticizers such as triethyl citrate, triacetin, and polyethylene glycol; powders such as talc, titanium oxide, yellow ferric oxide, ferric oxide, legal pigments, light anhydrous silicic acid, and hydrous silicon dioxide can also be blended. In the present invention, one or more of these carriers can be appropriately combined and blended.

[0021] In addition, in the pharmaceutical composition of the present invention, if desired, a medicinal ingredient may be blended in addition to the above-mentioned components within a range that does not impair the effects of the present invention. Such medicinal ingredients are not particularly limited and may be appropriately considered and selected according to the diseases, symptoms, etc. to which the pharmaceutical composition is applied. Examples include local anesthetics, digestive agents (cholagogues), digestive enzymes, gastric mucosa repair agents (mucosal protective components), crude drug components, and antacids.

[0022] Examples of local anesthetics include ethyl aminobenzoate and oxy sazaine. Examples of digestive agents (cholagogues) include ursodeoxycholic acid and animal bile (bear bile, ox bile). Examples of digestive enzymes include starch digestive enzymes (biodyastase, takadiastase) and fat digestive enzymes (lipase). Examples of gastric mucosa repair agents (mucosal protective components) include sodium copper chlorophyllin, potassium copper chlorophyllin, cetraxate hydrochloride, sophorcarpol, gefarnate, trimebutine maleate, methylmethionine sulfonium chloride, and sodium azulenesulfonate. Examples of crude drug components other than chinpi include crude drugs such as asenyak, anise fruit, aloe, houttuynia, curcuma, eucommia, euonymus, garden burnet, longevity herb, saffron, peony, ginseng, processed garlic, codonopsis, kakko, calamus root, kanshou, licorice, kizitsu, kudzu, cinnamon, ketsumeishi, gentiana, gentian violet, koudin, pepper, gallnut, colombo, condurango, Japanese quince, sansho, kaempferia, perilla, peony, shukusha, ginger, shouzuke, green tangerine peel, red shoot cypress, acorus root, centaury herb, sophora, soyoh, star anise, rhubarb, chikusetsu carrot, clove, capsicum, torreya, bitter orange, nikuzuku, carrot, mint, peppermint, hihatsu, byakujutsu, hops, homika, buckbean leaf, yakuchi, youbaihi, liutan, and ryoukyou, and their extracts. 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 sodium hydrogen carbonate, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, magnesium aluminum silicate, magnesium metasilicate aluminate, magnesium silicate, magnesium hydroxide, magnesium carbonate, aldioxa, synthetic aluminum silicate, and synthetic hydrotalcite; cuttlefish bone, nacre, boleite, and aminoacetic acid. In the present invention, one or more of these medicinal components can be appropriately combined and formulated. The content of such medicinal components can be appropriately set within a range that does not impair the object of the present invention.

[0023] The administration method of the pharmaceutical composition of the present invention is not particularly limited, and includes oral administration and parenteral administration, which can be appropriately selected according to the purpose of use of the composition, etc., but oral administration is preferred. The usage and dosage of the pharmaceutical composition are not particularly limited and may be appropriately selected and determined according to the purpose of use of the composition, the administration method, the dosage form of the composition, etc. For example, the above dosage can be an amount that allows 100 to 5000 mg of component (A) to be taken in terms of crude drug equivalent per day, preferably an amount that allows 200 to 2500 mg to be taken, and more preferably an amount that allows 300 to 1000 mg to be taken. Also, the amount of component (B) can be an amount that allows 10 to 300 mg to be taken, preferably an amount that allows 50 to 200 mg to be taken, and more preferably an amount that allows 100 to 150 mg to be taken.

[0024] Furthermore, in the present invention, the pharmaceutical composition may be contained in an airtight package (hereinafter, in this specification, a pharmaceutical composition contained in an airtight package is referred to as a "pharmaceutical composition in a packaged form"). By containing the pharmaceutical composition of the present invention in an airtight package, the generation of a specific odor derived from itopride can be further suppressed. In this case, the pharmaceutical composition in a packaged form may further include a package other than the airtight package that does not fall under the following "airtight package" (hereinafter, also referred to as "other package"), and the pharmaceutical composition only needs to be directly or indirectly contained in the airtight package. Examples of the mode of being indirectly contained in the airtight package include, for example, a mode in which the pharmaceutical composition is contained in the above "other package" and this is contained in the airtight package.

[0025] As used herein, the "airtight package" means a package that can suppress the intrusion of solid or liquid foreign substances in the state of normal handling, transportation, or storage, etc., and is a concept that includes the "airtight container" and "sealed container" defined in the General Rules of the 17th Revised Japanese Pharmacopoeia. As the airtight package, either a regular or irregular one can be used. Specifically, for example, bottle packaging, SP (Strip Package) packaging, PTP (Press Through Package) packaging, pillow packaging, stick packaging, etc. can be mentioned. The airtight package may be a combination of a plurality of these, for example, a mode in which the pharmaceutical composition is first packaged in a PTP package and then further packaged in a pillow package.

[0026] The packaging material (material) of the hermetic package is not particularly limited. For example, materials used in the field of pharmaceuticals such as glass, plastics (polyesters such as polyethylene terephthalate and polyethylene naphthalate; polyolefins such as polyethylene (including low density (LDPE), medium density (MDPE), and high density (HDPE)), polypropylene, etc.; polycarbonate; polystyrene, etc.), metals (such as aluminum, etc.) can be appropriately used alone or in combination of two or more.

[0027] For example, the packaging material used for bottle packaging is not particularly limited, and examples include the above-mentioned glass, plastics, metals, etc., and one or more of these can be appropriately combined. As the material for bottle packaging, 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 performing bottle packaging, for example, an appropriate amount of the pharmaceutical composition can be stored in the bottle, and then it can be sealed with an appropriate stopper or lid. The bottle can be appropriately selected according to the amount of the composition to be stored, etc. The capacity of the bottle is, for example, about 10 to 500 mL, preferably 14 to 400 mL, and more preferably 24 to 350 mL.

[0028] In addition, the packaging materials used for SP packaging, PTP packaging, pillow packaging, stick packaging, etc. are not particularly limited. For example, 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), ionomer resin (IO), ethylene-methacrylic acid copolymer (EMAA), polyacrylonitrile (PAN), biaxially oriented polyvinylidene chloride (PVDC), ethylene-vinyl alcohol copolymer resin (EVOH), polyvinyl chloride (PVC), cyclic olefin copolymer (COC), unoriented nylon (CNy), polycarbonate (PC), polystyrene (PS), rigid vinyl chloride (VSC), etc. resins, and metal foils such as aluminum foil (AL), etc. can be mentioned, and one or more of these can be appropriately combined.

[0029] When performing SP packaging, PTP packaging, pillow packaging, stick packaging, etc., it may be manufactured by a known method using a sheet made of one or more of the above-mentioned packaging materials. In this case, it can also be made into a multilayer structure by appropriately combining the packaging materials. As a method of making a multilayer structure using two or more types of packaging materials as the sheet, a method of laminating the packaging materials to manufacture a laminated sheet can be mentioned. The laminated sheet can be manufactured by known methods such as extrusion lamination, dry lamination, co-extrusion lamination, thermal lamination, wet lamination, non-solvent lamination, heat lamination, etc. Also, commercially available products known to the public can be used as the sheets for SP packaging, PTP packaging, pillow packaging, and stick packaging.

[0030] In the above-mentioned sheet, examples of the single-layer sheet using one type of packaging material include PVC sheets and CPP sheets. Examples of the laminated sheet using two or more types of packaging materials include those with a sheet structure such as PVC laminated with PVDC (PVC / PVDC; hereinafter abbreviated in the same manner), 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 left-mentioned sheet uses two or more types as CPP), etc., but are not limited thereto.

[0031] As a form of PTP packaging, the composition is stored one by one or in one dosage unit in pockets formed in a resin sheet or the like by a known method, and then a lid is made using a sheet made of a metal foil such as aluminum foil as a covering material. Note that a so-called double-sided aluminum PTP packaging using a sheet made of aluminum foil as a constituent material for the sheet forming the pocket may also be used. When performing PTP packaging, it is preferable to further package the PTP packaging by pillow packaging (for example, aluminum pillow packaging, etc.). As forms of SP packaging, pillow packaging, and stick packaging, the composition can be packaged one by one or in one dosage unit using a resin sheet or a sheet made of aluminum foil as a constituent material by a known method. When performing SP packaging, pillow packaging, or stick packaging, it is preferable to use a sheet made of aluminum foil as a constituent material.

[0032] In this specification, for the pharmaceutical composition in the packaged pharmaceutical composition, the occupancy rate (volume ratio) inside the package of the pharmaceutical composition is usually 25 to 90% when the package is a bottle package, preferably 28 to 75%, and more preferably 30 to 50%. When the package is an SP package, a PTP package, a pillow package, or a stick package, it is usually 30 to 98%, preferably 40 to 95%, more preferably 45 to 93%, and particularly preferably 50 to 90%. In this case, the occupancy rate means the occupancy rate of the composition with respect to the total volume inside the package, and fillers, inner stoppers, etc. for preventing damage to the composition stored inside the package are not considered when calculating the space occupancy rate.

[0033] As the airtight package, a commercially available package may be used as it is, or a commercially available packaging material may be processed and used. Examples of the commercially available bottle package include glass bottles (manufactured by Isuya Glass Industry Co., Ltd.), tablet bottles (manufactured by Tokyo Glass Co., Ltd.), Z-series (manufactured by Hanshin Kasei Kogyo Co., Ltd.), etc. Examples of the commercially available pillow package include Lamidip (registered trademark) (manufactured by Seisan Nippon Co., Ltd.). Furthermore, as packaging materials for SP packages, PTP packages, pillow packages, and stick packages, Sumilite VSS, Sumilite VSL, Sumilite NS, Sumilite FCL (all manufactured by Sumitomo Bakelite Co., Ltd.), TAS series (manufactured by Daisheng Chemical Industry Co., Ltd.), PTP vinyl foil, PTP super foil (both manufactured by Mitsubishi Resin Co., Ltd.), Nippaku aluminum foil (manufactured by Nippon Foil Mfg. Co., Ltd.), aluminum foil plain silver (manufactured by Yamato Chemical Industry Co., Ltd.), etc.

[0034] The method of accommodating the pharmaceutical composition in the airtight package is not particularly limited and can be achieved by arranging the composition in the package by appropriate means such as introducing the composition into the package. In this case, a means of introducing a desiccant (for example, a cylindrical (tablet type) or sheet-like one) together with the composition into the package may be used.

[0035] The pharmaceutical composition and the packaged pharmaceutical composition of the present invention can be used as pharmaceuticals, quasi-drugs, etc., and their usage purposes are not particularly limited. However, since they contain (A) Tinpin or its extract and (B) Itopride or its salt, they are preferably used as pharmaceuticals for improving digestive symptoms (such as gastric fullness, abdominal distension, upper abdominal pain, loss of appetite, heartburn, nausea, vomiting) in stomachic, antitussive, expectorant, and chronic gastritis.

[0036] The present invention also relates to a method for stabilizing the component (A) in a pharmaceutical composition (preferably a method for suppressing solidification of the component (A) in the pharmaceutical composition due to high-temperature storage), which includes a step of containing (A) Tinpin or its extract and (B) Itopride or its salt in the same pharmaceutical composition. In the invention of such an aspect, the order of the step of containing the component (A) and the step of containing the component (B) is not particularly limited, and it is only necessary that a composition containing the component (A) and the component (B) is directly or indirectly produced. In the invention of such an aspect, the meanings of various expressions, the blending amounts of each component, etc. are all the same as those described for the above-mentioned pharmaceutical composition.

Examples

[0037] Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

[0038] [Sample 1] 0.5 g of Tinpin (manufactured by Alps Pharmaceutical Industry Co., Ltd.: dried extract of Tinpin) (2500 mg in terms of crude drug equivalent) was placed in a glass bottle (3K standard bottle) to obtain Sample 1.

[0039] [Sample 2] A mixture obtained by mixing 0.5 g of Itopride (manufactured by Zhuhai Rundu Pharmaceutical Co., Ltd.: Itopride Hydrochloride) with Sample 1 was designated as Sample 2.

[0040] [Test Example 1] Storage Stability Test After preparing each of the samples shown below, they were placed in glass bottles and stored at 80°C for 3 days. The appearance changes (presence or absence of solidification) before the start of storage and after 3 days of storage were visually evaluated. The results are shown in Table 1.

[0041]

Table 1

[0042] As shown in Table 1, solidification was confirmed in Sample 1 after storage at 80°C for 3 days. In contrast, in Sample 2 where itopride was added to Sample 1, solidification was not confirmed after storage at 80°C for 3 days.

[0043] From the above test results, it became clear that solidification during high-temperature storage of chinpi, typified by chinpi dry extract, can be suppressed by co-existing itopride or its salt with chinpi.

[0044] [Production Example 1] A 3900 mg granule containing the following components in one daily dose (in 3 packets) was prepared according to a conventional method and SP-packaged with aluminum foil for strip packaging (manufactured by Nissan Chemical Industries, Ltd.). Sodium bicarbonate 240 mg Precipitated calcium carbonate 710 mg Magnesium aluminometasilicate 900 mg Magnesium hydroxide 550 mg Methylmethioninium chloride 30 mg Itopride hydrochloride 150 mg Soyou dry extract 30 mg (equivalent amount of crude drug: 270 mg) Cinnamon powder 100 mg Chinpi powder 300 mg Hardened oil, hydroxypropylcellulose, D-mannitol, calcium carmellose, calcium lactate, sucralose, l-menthol, silicon dioxide, fragrance, corn starch, dextrin

[0045] [Production Example 2] A 3900 mg granule containing the following components in a daily dose (in 3 sachets) was prepared according to a conventional method and SP-packaged with aluminum foil for strip packaging (manufactured by Nissan Chemical Industries, Ltd.). Precipitated calcium carbonate 1000 mg Synthetic hydrotalcite 780 mg Magnesium hydroxide 300 mg Aldioxa 150 mg Itopride hydrochloride 150 mg Zingiber officinale powder 300 mg Dried carrot extract 20 mg (equivalent amount of crude drug: 290 mg) Zingiber powder 100 mg Hardened oil, hydroxypropyl cellulose, D-mannitol, calcium carmellose, calcium lactate, sucralose, l-menthol, silicon dioxide, fragrance, corn starch, dextrin

[0046] [Production Example 3] A 3900 mg granule containing the following components in a daily dose (in 3 sachets) was prepared according to a conventional method and SP-packaged with aluminum foil for strip packaging (manufactured by Nissan Chemical Industries, Ltd.). Precipitated calcium carbonate 1000 mg Synthetic hydrotalcite 780 mg Magnesium hydroxide 300 mg Methylmethionine sulfonium chloride 30 mg Itopride hydrochloride 150 mg Zingiber officinale powder 300 mg Aldioxa 150 mg Cinnamon powder 100 mg Zingiber powder 100 mg Hardened oil, hydroxypropyl cellulose, D-mannitol, calcium carmellose, calcium lactate, sucralose, l-menthol, silicon dioxide, fragrance, corn starch, dextrin

[0047] [Production Example 4] A 4800 mg granule containing the following components in a daily dose (in 3 packets) was prepared according to a conventional method and SP-packaged with aluminum foil for strip packaging. Precipitated calcium carbonate 900 mg Synthetic hydrotalcite 780 mg Magnesium carbonate 675 mg Methylmethionium sulfonium chloride 50 mg Corn starch, low-substituted hydroxypropyl cellulose, povidone, sucralose, hardened oil, calcium carboxymethyl cellulose, hydroxypropyl cellulose, acesulfame potassium, l-menthol, hydrated silicon dioxide, fragrance

[0048] [Production Example 5] A 4800 mg granule containing the following components in a daily dose (in 3 packets) was prepared according to a conventional method and SP-packaged with aluminum foil for strip packaging. Precipitated calcium carbonate 900 mg Magnesium aluminometasilicate 1800 mg Magnesium carbonate 675 mg Methylmethionium sulfonium chloride 225 mg Corn starch, low-substituted hydroxypropyl cellulose, povidone, sucralose, hardened oil, calcium carboxymethyl cellulose, hydroxypropyl cellulose, acesulfame potassium, l-menthol, hydrated silicon dioxide, fragrance

[0049] [Production Example 6] A 4800 mg granule containing the following components in a daily dose (in 3 packets) was prepared according to a conventional method and SP-packaged with aluminum foil for strip packaging. Sodium hydrogen carbonate 700 mg Magnesium aluminometasilicate 1800 mg Magnesium hydroxide 300 mg Methylmethionium sulfonium chloride 150 mg Corn starch, low-substituted hydroxypropyl cellulose, povidone, sucralose, hardened oil, calcium carboxymethyl cellulose, hydroxypropyl cellulose, acesulfame potassium, l-menthol, hydrated silicon dioxide, fragrance

[0050] [Production Example 7] A 4800 mg granule containing the following components in a daily dose (in 3 sachets) was prepared according to a conventional method and SP-packaged with an aluminum foil for strip packaging. Precipitated calcium carbonate 900 mg Synthetic hydrotalcite 780 mg Magnesium hydroxide 300 mg Methylmethionine sulfonium chloride 225 mg Corn starch, low-substituted hydroxypropyl cellulose, povidone, sucralose, hardened oil, calcium carboxymethyl cellulose, hydroxypropyl cellulose, acesulfame potassium, l-menthol, hydrated silicon dioxide, fragrance

[0051] [Production Example 8] A 3600 mg tablet containing the following components in a daily dose (in 6 tablets) was manufactured according to a conventional method and contained in a bottle made of low-density polyethylene. Precipitated calcium carbonate 1000 mg Synthetic hydrotalcite 780 mg Magnesium hydroxide 300 mg Methylmethionine sulfonium chloride 30 mg Aldioxa 150 mg Itopride hydrochloride 150 mg Ginger powder 300 mg Cinnamon powder 100 mg Ginger powder 100 mg Cellulose, D-mannitol, hydroxypropyl cellulose, magnesium aluminometasilicate, calcium hydrogen phosphate, silicon dioxide, l-menthol, magnesium stearate

[0052] [Production Example 9] A 3600 mg tablet containing the following ingredients in a daily dose (in 6 tablets) was manufactured according to a conventional method and contained in a bottle made of low-density polyethylene. Sodium hydrogen carbonate 240 mg Precipitated calcium carbonate 710 mg Magnesium aluminometasilicate 900 mg Magnesium hydroxide 550 mg Itopride hydrochloride 150 mg Ginger powder 300 mg Dried soy extract 30 mg (equivalent amount of crude drug: 270 mg) Cinnamon powder 100 mg Cellulose, D-mannitol, hydroxypropylcellulose, calcium hydrogen phosphate, silicon dioxide, l-menthol, magnesium stearate

[0053] [Production Example 10] A 3600 mg tablet containing the following ingredients in a daily dose (in 6 tablets) was manufactured according to a conventional method and contained in a glass bottle. Precipitated calcium carbonate 1000 mg Synthetic hydrotalcite 780 mg Magnesium hydroxide 300 mg Methylmethioninesulfonium chloride 30 mg Aldioxa 150 mg Itopride hydrochloride 150 mg Dried carrot extract 20 mg (equivalent amount of crude drug: 290 mg) Ginger powder 100 mg Ginger powder 300 mg Cellulose, D-mannitol, hydroxypropylcellulose, magnesium aluminometasilicate, calcium hydrogen phosphate, silicon dioxide, l-menthol, magnesium stearate

Claims

1. The following components (A) and (B): (A) Chinpi or its extract (B) Itopride or its salt A pharmaceutical composition containing the same.

2. The pharmaceutical composition according to Claim 1, wherein the dosage form is selected from the group consisting of tablets, capsules, granules, powders and pills.

Images