Oral components

Abstract

The present invention provides an oral composition that overcomes the problem of being difficult to remove when enclosed in packaging such as small bags, due to adhesion to the packaging. [Solution] An internal composition containing pirenzepine and / or its salt (a) and a crude drug (b).

Description

Technical Field

[0001] The present invention relates to an oral composition, and more particularly to an oral composition that can be easily taken out from a package.

Background Art

[0002] Conventionally, a gastrointestinal drug containing pirenzepine as an active ingredient has been known (see, for example, Patent Document 1). The pirenzepine is used as an antacid agent having an effect of suppressing excessive gastric acid, and can also care for the damaged stomach by improving blood circulation in the gastric mucosa, so it is one of the active ingredients that can exhibit excellent effects as a gastrointestinal drug. Gastrointestinal drugs containing the pirenzepine as an active ingredient are generally widely used in which the dosage per administration is enclosed in a small package so that a prescribed dosage can be easily obtained.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] However, although the one enclosed in such a small package is useful in that an accurate dosage can be easily obtained, for example, an oral composition processed into a powder, granule, tablet, etc. has a very light mass per grain, so when trying to take it out from the package at the time of taking, there may be a problem that it adheres to a small bag such as the package and is difficult to take out. The problem of being difficult to take out due to adhering to the package means that it may be left behind while adhering to the package, and considering that it is important to take a prescribed dosage in an oral composition, it means that the entire prescribed dosage may not be ingested. Therefore, various measures have been taken to make it easier to remove oral medications from their packaging, such as improving the material and processing of the packaging (e.g., small bags) and examining the composition and shape of the oral medications themselves. However, there is a need for something that makes removal even easier.

[0005] Therefore, against this background, the present invention aims to provide an oral composition that overcomes the problem of being difficult to remove when enclosed in packaging due to adhesion to the packaging. [Means for solving the problem]

[0006] However, in view of these circumstances, the inventors diligently conducted research and, as a result, discovered that by using pirenzepine as the active ingredient and incorporating herbal medicines into it, an excellent oral composition that does not easily adhere to packaging such as small pouches can be obtained, thus completing the present invention.

[0007] In other words, the present invention has the following aspects. [1] An oral composition comprising pirenzepine and / or a salt thereof (a) and a crude drug (b). [2] The oral composition according to [1], wherein the mass ratio (b / a) of the crude drug (b) to the pirenzepine and / or salt thereof (a) is 0.1 to 150. [3] The oral composition according to [1] or [2], further comprising menthol (c). [4] The oral composition according to [3], wherein the mass ratio (c / a) of menthol (c) to pirenzepine and / or its salt (a) is in the range of 0.002 to 4. [5] The oral composition according to any one of [1] to [4], wherein the crude drug (b) is at least one of a crude drug (b1) derived from the roots or rhizomes of a plant and a crude drug (b2) derived from the bark of a plant. [6] The oral composition according to [5], wherein the crude drug (b1) derived from the roots or rhizomes of the plant is at least one selected from the group consisting of Atractylodes macrocephala, Atractylodes lancea, Zingiber officinale, Ginger, Ginseng, Turmeric, Licorice, Belladonna extract, Peony root, and Coptis japonica. [7] The oral composition according to [5] or [6], wherein the crude drug (b2) derived from the bark of the plant is at least one selected from the group consisting of Magnolia bark, Cinnamon bark, and Phellodendron bark. [8] The oral composition according to any one of [1] to [7], wherein the crude drug (b) is at least one selected from the group consisting of saponin glycoside crude drugs, alkaloid crude drugs, essential oil crude drugs, and polyphenol pigment crude drugs. [9] The oral composition according to [8], wherein the saponin glycoside crude drug is at least one selected from the group consisting of ginseng, licorice, and peony; the alkaloid crude drug is at least one selected from the group consisting of Coptis japonica, Phellodendron bark, and belladonna extract; the essential oil crude drug is at least one selected from the group consisting of ginger, cinnamon, Atractylodes macrocephala, and Magnolia bark; and the polyphenol pigment crude drug is turmeric.

[10] An oral composition according to any one of [1] to [9], wherein the oral composition is in the form of granules.

[11] An oral composition according to any one of [1] to

[10] , enclosed in packaging having a polyethylene-containing layer as the innermost layer.

[12] The oral composition according to any one of [3] to

[11] , wherein the mass ratio (b / a) of the crude drug (b) to the pirenzepine and / or salt (a) is 0.1 to 150, the mass ratio (c / a) of the menthol (c) to the pirenzepine and / or salt (a) is 0.002 to 4, and the oral composition is in the form of granules.

[13] A method for inhibiting adhesion of an oral composition to packaging, comprising containing pirenzepine and / or a salt thereof (a) and a crude drug (b). The adhesion suppression method according to

[13] , having any of the configurations of

[14] [2] to

[12] .

[15] A method for producing an internal medicine composition, comprising the step of mixing pirenzepine and / or a salt thereof (a) with a crude drug (b). A method for producing the oral composition according to

[15] , wherein each component is mixed so as to be one of the compositions of

[16] [2] to

[12] . [Effects of the Invention]

[0008] The present invention relates to an oral composition containing pirenzepine and / or its salt (a) and a crude drug (b). Therefore, when the oral composition is packaged in a dosage form such as powder or granules, it is less likely to adhere to the packaging, allowing for accurate intake of the prescribed dosage and enabling the full efficacy of pirenzepine.

[0009] The reason for the inhibitory effect of herbal medicines on adhesion is not entirely clear, but it is possible that polyphenols in the plants from which the herbal medicines are derived are preventing pirenzepine from adhering. In other words, while adhesion is frequently observed with pirenzepine or menthol alone, in this invention, it is thought that the polyphenols contained in the herbal medicines inhibit the adhesion of pirenzepine through some interaction with pirenzepine. It should be noted that polyphenols are known to be abundant in the flower roots, rhizomes, and bark of plants. [Modes for carrying out the invention]

[0010] The present invention will be described below based on examples of embodiments for carrying out the present invention. However, the present invention is not limited to the embodiments described below.

[0011] In this specification, when "X~Y" (where X and Y are any numbers) is used, unless otherwise specified, it means "greater than or equal to X and less than or equal to Y," and also includes the meanings of "preferably greater than X" or "preferably less than Y." For the numerical ranges described step by step in this specification, the upper limit value or lower limit value of a numerical range at a certain step can be arbitrarily combined with the upper limit value or lower limit value of a numerical range at another step. Also, in the numerical ranges described in this specification, the upper limit value or lower limit value of the numerical range can be replaced with the value shown in the examples.

[0012] <<Oral composition>> The oral composition according to one embodiment of the present invention is an oral composition containing pirenzepine and / or its salt (a) and crude drug (b). Each component will be described below.

[0013] <Pirenzepine and / or its salt (a)> The pirenzepine used in this embodiment is a compound represented by the following formula (1), and its salt is also included. [Chemical formula]

[0014] The pirenzepine and / or its salt (a) may be produced by a known method or may be a commercially available product. The salt of the pirenzepine may be any pharmaceutically acceptable salt, for example, inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, 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, glutamic acid, and acid addition salts thereof, etc. are mentioned, and the hydrochloride is preferably used.

[0015] In the present embodiment, the content of pirenzepine and / or its salt (hereinafter simply referred to as "pirenzepine") (a) is preferably 0.3 to 4% by mass, more preferably 0.5 to 2.5% by mass, and still more preferably 0.75 to 2% by mass with respect to the total mass of the oral composition, from the viewpoint that the adhesiveness can be further improved. Further, it may be 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 2% by mass or more, and may also be 10% by mass or less, 7% by mass or less, 5% by mass or less, 4% by mass or less, 3% by mass or less, 2% by mass or less.

[0016] The daily dosage of pirenzepine (a) is not particularly limited, but as the total amount of pirenzepine (a), it can preferably be 20 to 100 mg, more preferably 30 to 75 mg, and still more preferably 40 to 50 mg.

[0017] <Crude drug (b)> The crude drug (b) used in the present embodiment means those listed in the 18th Revision of the Japanese Pharmacopoeia (implemented on June 7, 2021).

[0018] The crude drug (b) used in the present embodiment may be the various parts of the crude drug (roots, rhizomes, bark, etc.) as they are, or dried, pulverized, or extracted after pulverization, or extracted with an extraction solvent.

[0019] When using the crude drug (b) as an extract, the extraction solvent can be water (including hot water), alcohols such as methanol, ethanol, isopropanol, ethylene glycol, and glycerin, esters such as ethyl acetate, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile, ethers such as diethyl ether and tetrahydrofuran, saturated hydrocarbons such as pentane, hexane, cyclopentane, and cyclohexane, aromatic hydrocarbons such as toluene, halogenated hydrocarbons such as dichloromethane and chloroform, and other organic solvents such as dimethylformamide and dimethyl sulfoxide (all of which may contain water). One or any mixture of two of these solvents may be used. Of these solvents, water, ethanol, or a mixture thereof is preferred from a safety viewpoint.

[0020] The extract of the crude drug (b) may be a crude extract obtained from the necessary parts of the plant, a purified extract, a concentrated extract, a synthetic extract, or a commercially available product. The method for obtaining the extract of the crude drug (b) is not particularly limited, and ordinary extraction methods, purification methods, concentration methods, synthesis methods, drying and powdering methods, etc., can be employed.

[0021] The extract of the crude drug (b) may be used in liquid form, but if necessary, it may be used in concentrated liquid, semi-solid, solid, or powder form by reducing or removing the liquid content by drying treatment such as vacuum drying, freeze-drying, or spray drying, and more preferably in solid or powder form with the liquid content greatly reduced or removed.

[0022] In this embodiment, the amount of crude drug (b), including when used as an extract, is preferably 0.01 to 40% by mass, more preferably 0.05 to 35% by mass, even more preferably 0.1 to 30% by mass, even more preferably 0.5 to 25% by mass, particularly preferably 1 to 20% by mass, and most preferably 3 to 15% by mass, relative to the total mass of the oral composition. It may also be 0.001% or more by mass, 0.005% or more by mass, 0.01% or more by mass, 0.05% or more by mass, 0.1% or more by mass, 0.5% or more by mass, 1% or more by mass, 3% or more by mass, 5% or more by mass, 10% or more by mass, or 70% or less by mass, 50% or less by mass, 40% or less by mass, 30% or less by mass, 20% or less by mass, 10% or less by mass, or 5% or less by mass. When two or more types of crude drug (b) are used, the content of crude drug (b) shall be the total amount (total mass) of crude drug (b).

[0023] The daily dosage of the aforementioned crude drug (b) is set appropriately in consideration of the types and amounts of other components and their interaction with its own medicinal properties. For example, for ginseng, licorice, ginger / dried ginger, atractylodes / atractylodes, cinnamon, and magnolia, the dosage is as follows:

[0024] The daily oral dose of ginseng can be in the range of 0.1 to 6000 mg, more preferably 0.5 to 4000 mg, even more preferably 1 to 3000 mg, particularly preferably 10 to 2000 mg, and most preferably 50 to 1000 mg, when expressed in terms of crude drug equivalent.

[0025] The daily oral dose of licorice can be in the range of 0.1 to 5000 mg, more preferably 0.5 to 4000 mg, even more preferably 1 to 3000 mg, particularly preferably 50 to 2000 mg, and most preferably 100 to 1000 mg.

[0026] The daily oral dose of both ginger and dried ginger can range from 0.1 to 3000 mg, more preferably from 0.5 to 2000 mg, even more preferably from 1 to 1500 mg, particularly preferably from 5 to 1000 mg, and most preferably from 10 to 500 mg, when expressed in terms of crude drug equivalent.

[0027] The daily oral dose of Atractylodes macrocephala and Atractylodes lancea, expressed in terms of crude drug equivalent, can be 0.1 to 5000 mg, more preferably 1 to 4000 mg, even more preferably 5 to 3000 mg, particularly preferably 10 to 2500 mg, and most preferably 20 to 2000 mg.

[0028] The daily oral dose of cinnamon bark, expressed in terms of crude drug equivalent, can be 0.1 to 5000 mg, more preferably 1 to 4000 mg, even more preferably 5 to 3000 mg, particularly preferably 10 to 2500 mg, and most preferably 20 to 2000 mg. Furthermore, the daily oral dose of cinnamon extract can be 10 to 8000 mg, more preferably 30 to 7000 mg, even more preferably 50 to 6000 mg, particularly preferably 80 to 5500 mg, and most preferably 100 to 5000 mg, when expressed in terms of crude drug equivalent.

[0029] The daily oral dose of Magnolia bark, expressed in terms of crude drug equivalent, can be approximately 0.1 to approximately 5000 mg, more preferably approximately 1 to approximately 4000 mg, even more preferably approximately 5 to approximately 3000 mg, particularly preferably approximately 10 to approximately 2500 mg, and most preferably approximately 20 to approximately 2000 mg. Furthermore, the daily oral dose of Magnolia bark extract can be 10 to 8000 mg, more preferably 30 to 7000 mg, even more preferably 50 to 6000 mg, particularly preferably 80 to 5500 mg, and most preferably 100 to 5000 mg, when expressed in terms of crude drug equivalent.

[0030] In this embodiment, the mass ratio (b / a) of the crude drug component (b) to the pirenzepine component (a) is preferably 0.1 to 150, more preferably 0.5 to 50, and even more preferably 1 to 20, from the viewpoint of further improving adhesion. It may also be 0.001 or more, 0.01 or more, 0.05 or more, 0.1 or more, 0.5 or more, 1 or more, 2 or more, 10 or more, and may be 1000 or less, 500 or less, 300 or less, 200 or less, 150 or less, 100 or less, 70 or less, 50 or less, 30 or less, 20 or less, 10 or less, or 5 or less.

[0031] Examples of crude drugs in the Japanese Pharmacopoeia include crude drugs derived from roots and rhizomes (b1), crude drugs derived from plant bark (b2), crude drugs derived from leaves such as hibiscus, crude drugs derived from flowers such as chamomile, crude drugs derived from fruits such as dried tangerine peel, crude drugs derived from seeds such as Corydalis, and crude drugs derived from the whole plant such as Geranium thunbergii. Among these, crude drugs derived from roots and rhizomes (b1) and crude drugs derived from plant bark (b2) are preferred because they are less likely to adhere to the packaging. These may be used individually or in combination of two or more.

[0032] [Crude drugs derived from plant roots and rhizomes (b1)] While not limited to a wide range of crude drugs (b1) derived from plant roots and rhizomes, examples include Atractylodes macrocephala, Atractylodes lancea, Zingiber officinale, Ginger, Ginseng, Turmeric, Licorice, Belladonna extract, Peony, and Coptis japonica. Ginseng and Licorice are more preferably used due to their improved adhesion properties.

[0033] [Herbal medicine derived from the bark of plants (b2)] The crude drug (b2) derived from the bark of the plant used in this embodiment is not limited, but examples include Magnolia bark, Cinnamon bark, and Phellodendron bark. Cinnamon bark is more preferably used in terms of improving adhesion.

[0034] Furthermore, as crude drugs in the Japanese Pharmacopoeia, from the viewpoint of their constituent components, examples include saponin glycoside crude drugs such as ginseng, licorice, and peony; alkaloid crude drugs such as Coptis japonica, Phellodendron bark, and belladonna extract; essential oil crude drugs such as ginger, cinnamon, Atractylodes macrocephala, and Magnolia bark; and polyphenol pigment crude drugs such as turmeric. Among these, cinnamon, ginseng, licorice, turmeric, Phellodendron bark, Atractylodes macrocephala, Coptis japonica, ginger, Magnolia bark, peony, and belladonna extract are more preferably used from the viewpoint of improving adhesion.

[0035] <Menthol (c)> In this embodiment, the oral composition preferably contains menthol (c) as an optional component in addition to pirenzepine (a) and the herbal medicine (b). Examples of menthol (c) include l-menthol and dl-menthol, but l-menthol is preferred due to its superior stability over time. These can be used individually or in combination of two or more types.

[0036] When this embodiment contains menthol (c), it is preferable to include 0.0005 to 12% by mass, more preferably 0.005 to 10% by mass, even more preferably 0.01 to 5% by mass, and even more preferably 0.03 to 1.5% by mass, based on the total mass of the oral composition, in order to improve the feeling of taking the medicine and to further improve its adhesiveness. 0.00001 mass% or more, 0.00005 mass% or more, 0.0001 mass% or more, 0.0005 mass% or more, 0.001 mass% or more, 0.005 mass% or more, 0.01 mass% or more, 0.05 mass% or more, 0.1 mass% or more, 0.3 mass% or more, 0.5 mass% or more, 1 mass% or more, 5 mass% or more. It may be 30% by mass or less, 20% by mass or less, 15% by mass or less, 12% by mass or less, 10% by mass or less, 7% by mass or less, 5% by mass or less, 3% by mass or less, 2% by mass or less, 1.5% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less, 0.05% by mass or less, 0.01% by mass or less.

[0037] If this embodiment contains menthol (c), the mass ratio (c / a) of component (c) to component (a) is preferably 0.002 to 4, more preferably 0.05 to 1, and even more preferably 0.1 to 0.4, from the viewpoint of further improving adhesion. It may also be 0.0001 or more, 0.0005 or more, 0.001 or more, 0.005 or more, 0.01 or more, 0.05 or more, 0.1 or more, 0.5 or more, 1 or more, 3 or more, 5 or more, 10 or more, or 50 or less, 30 or less, 10 or less, 5 or less, 3 or less, 1 or less, 0.5 or less, or 0.1 or less.

[0038] The oral composition described herein may contain optional components other than those mentioned above. Examples of such optional components include antacids, stomachic agents, digestive agents, intestinal regulators, antidiarrheals, analgesics and antispasmodics, mucosal repair agents, and additives. These may be used individually or in combination of two or more.

[0039] Examples of the aforementioned antacids include inorganic salts such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, magnesium aluminosilicate, magnesium aluminometasilicate, magnesium silicate, magnesium oxide, magnesium hydroxide, magnesium alumina hydroxide, magnesium carbonate, aldioxa, synthetic aluminum silicate, and synthetic hydrotalcite; as well as cuttlefish bone, oyster shell, oyster shell, aminoacetic acid, etc. These can be used individually or in combination of two or more.

[0040] Examples of the aforementioned stomachic agents include ginger oil, cardamom oil, clove oil, spruce oil, animal bile (including bear bile), betaine hydrochloride, glutamate hydrochloride, carnitine chloride, betanethol chloride, and dried yeast. These can be used individually or in combination of two or more.

[0041] Examples of the aforementioned digestive agents include ursodeoxycholic acid, oxycorana salts, cholic acid, bile powder, bile extract (powder), and dehydrocholic acid. These can be used individually or in combination of two or more.

[0042] Examples of the aforementioned intestinal regulators include intestinal probiotic components (lactic acid bacteria, butyric acid bacteria, natto bacteria, etc.). These can be used individually or in combination of two or more.

[0043] Examples of the antidiarrheal agents include acrinol, berberine chloride, guaiacol, creosote, phenyl salicylate, guaiacol carbonate, berberine tannate, bismuth subsalicylate, bismuth subnitrate, bismuth subcarbonate, bismuth subgallate, tannic acid, albumin tannate, methylenethimole tannin, kaolin, natural aluminum silicate, aluminum hydroxynaphthoate, pectin, medicinal charcoal, calcium lactate, etc. These can be used individually or in combination of two or more.

[0044] Examples of the aforementioned analgesic and antispasmodic agents include oxyfencycline hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, hydrobromic acid, scopolamine, methylatropine bromide, methylanisotropine bromide, methylscopolamine bromide, methyl-l-hyoscyamine bromide, methylbenactidium bromide, isopropamide iodide, dihunylpiperidinomethyldioxolane iodide, papaverine hydrochloride, and ethyl aminobenzoate. These can be used individually or in combination of two or more.

[0045] Examples of the aforementioned mucosal repair agents include sodium azulene sulfonate, aldioxa, glycyrrhizic acid and its salts, L-glutamine, potassium copper chlorophyllin, sodium copper chlorophyllin, histidine hydrochloride, porcine gastric wall pepsin hydrolysate, porcine gastric wall acid hydrolysate, methylmethionine sulfonium chloride, gefarnate, cetraxate hydrochloride, sucralfate hydrate (aluminum sucrose sulfate salt), and sofalcone. These can be used individually or in combination of two or more.

[0046] Examples of the aforementioned additives include excipients, stabilizers, surfactants, lubricants, solubilizers, buffers, sweeteners, bases, adsorbents, flavoring agents, binders, suspending agents, curing agents, antioxidants, glossing agents, fragrances, coating agents, coating agents, wetting agents, wetting modifiers, fillers, defoaming agents, cooling agents, chewing agents, antistatic agents, flavoring agents, colorants, sugar coating agents, isotonic agents, softeners, emulsifiers, adhesives, tack enhancers, viscosity modifiers, foaming agents, pH adjusters, dispersants, disintegrants, disintegration aids, fragrances, moisture-proofing agents, preservatives, preservatives, solvents, solubilizers, solvents, and fluidizers. These can be used individually or in combination of two or more.

[0047] The excipients are preferably sugars such as refined sucrose, glucose, trehalose, lactose, maltose, cellulose, and corn starch, with lactose, cellulose, and corn starch being more preferred. In particular, sugar alcohols such as mannitol, sorbitol, xylitol, erythritol, and granitol are preferred, with mannitol being more preferred, from the viewpoint of further enhancing the effects of the invention. These can be used individually or in combination of two or more.

[0048] Specific examples of the aforementioned additives include, for example, refined sucrose, glucose, trehalose, lactose, maltose, mannitol, sorbitol, xylitol, erythritol, granitol, sodium saccharin, aspartame, acesulfame potassium, sucralose, licorice extract, stevia extract, monk fruit extract, corn starch, potato starch, wheat starch, sodium chloride, crystalline cellulose, methylcellulose, ethylcellulose, hypromellose, hydroxypropylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, calcium carboxymethylcellulose, calcium carmellose, croscarmellose sodium, hypromellose phthalate, cellulose acetate phthalate, dextrin, pregelatinized starch, acacia gum, gelatin, sodium alginate, polyvinylpyrrolidone, crospovidone, polyvinyl alcohol, polyethylene glycol, and casein. Sodium caseinate, carboxyvinyl polymer, tartaric acid, light anhydrous silicic acid, hydrated silica dioxide, magnesium stearate, calcium stearate, sodium stearate, sodium lauryl sulfate, talc, hydrogenated vegetable oil, macrogol, silicone oil, agar, shellac, glycerin, aromatic essential oils, water-soluble food coloring, yellow iron oxide, yellow ferric oxide, ferric oxide, brown iron oxide, black iron oxide, titanium dioxide, lake coloring, benzoic acid, sodium benzoate, parahydroxybenzoic acid Examples include aromatic acids, cyclodextrin, polysorbate 80, glycerin fatty acid esters, propylene glycol fatty acid esters, lecithin, bleached beeswax, medium-chain triglyceride, ascorbic acid, tocopherol, sodium thiosulfate, sodium edetate, plant-derived fragrances (fruit fragrances such as orange and lemon, coffee fragrances, and tea fragrances), chocolate fragrances, yogurt fragrances, milk fragrances, and plant essential oils such as peppermint oil, spearmint oil, and spice oils. These can be used individually or in combination of two or more.

[0049] The oral composition of this embodiment can be obtained by mixing pirenzepine (a) and a crude drug (b), and other components if necessary, in a conventional manner. That is, pirenzepine (a) and the crude drug (b) may be mixed together, and other ingredients may be added to this mixture, or all the ingredients, including the pirenzepine (a) and the crude drug (b), may be mixed together at once. Furthermore, these mixed ingredients may be dried, granulated, or otherwise processed to form an oral composition.

[0050] According to the oral composition of this embodiment, since it is less likely to adhere to the packaging, it is easy to accurately take the prescribed amount, and the medicinal effects of pirenzepine (a) can be fully exerted.

[0051] The oral composition of this embodiment may contain various components (including pharmacologically active components and physiologically active components) in combination with the above-mentioned components, to the extent that they do not interfere with the effects of the present invention. While there are no particular restrictions on the types of such ingredients, typical examples include ingredients that have an effect in treating gastrointestinal disorders, such as stomach tonics, digestive aids, antacids, astringents, adsorbents, mucosal protective agents, mucosal repair agents, and analgesics / antispasmodics. These gastrointestinal drugs, digestive drugs, antacids, astringents, adsorbents, mucosal protective agents, mucosal repair agents, and analgesic and antispasmodic agents can be used individually or in combination of two or more types.

[0052] Furthermore, the oral composition of this embodiment may contain other physiologically active ingredients or pharmacologically active ingredients as needed, to the extent that they do not interfere with the effects of the present invention. Typical examples of such ingredients include antipyretics, analgesics, anti-inflammatory drugs, various herbal ingredients, anti-allergic drugs, cold medicines, cough suppressants, expectorants, pain relievers, rhinitis medicines, intestinal regulators, antidiarrheals, laxatives, tonics, or antibiotics. These can be used individually or in combination of two or more.

[0053] The oral composition of this embodiment can be formulated by arbitrarily selecting various components and additives used in pharmaceuticals, quasi-drugs, foods, etc., depending on the form of the formulation. For example, in solid formulations, binders (hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, etc.), excipients (sucrose, lactose, starch, corn starch, crystalline cellulose, light anhydrous silicic acid, etc.), lubricants (sucrose fatty acid ester, magnesium stearate, etc.), disintegrants (methylcellulose, polysorbate 80, croscarmellose sodium, etc.) can be used. In liquid formulations, solvents or water as a base, oily bases, solubilizers, suspending agents or emulsifiers, isotonic agents, buffers, etc. can be used. These can be used individually or in combination of two or more. Furthermore, preservatives, antioxidants, sweeteners, acidulants, colorants, fragrances, flavoring agents, etc., may be added to these formulations as needed. These can be used individually or in combination of two or more.

[0054] The shape of the oral composition in this embodiment is not particularly limited, but it may be in the form of a solid, semi-solid, or liquid preparation, for example. Specifically, known forms such as tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, lozenges, jelly-like drops, etc.), granules, fine granules, powders, dry syrups, chewable tablets, liposomes, extracts, tinctures, and lemonades can be cited as examples. Among these, tablets, granules, fine granules, powders, and dry syrups are preferred because they offer improved adhesion, and tablets, granules, fine granules, powders, and dry syrups are even more preferred, while powders and granules are most preferred because they offer excellent protection against adhesion to packaging.

[0055] When the dosage form of the oral composition of this embodiment is granules, the preferred average particle size is 0.01 to 5.0 mm, more preferably 0.02 to 0.75 mm, and even more preferably 0.05 to 0.5 mm. Furthermore, when the dosage form of the oral composition of this embodiment is a powder, the preferred average particle size is 0.01 to 5 mm, more preferably 0.02 to 0.75 mm, and even more preferably 0.05 to 0.5 mm. The average particle size of the oral composition was measured using a laser diffraction particle size distribution analyzer and was calculated from the D50 value (particle size at 50% cumulative volume) of the obtained cumulative volume distribution.

[0056] Formulation into these dosage forms can be carried out by conventional methods, depending on the formulation form, and various forms of formulations can be prepared.

[0057] The dosage of the oral composition in this embodiment is not fixed and is determined appropriately depending on its form, method of administration, purpose of administration, and the age, weight, symptoms, and physical condition of the recipient of the oral composition. Furthermore, the oral composition in this embodiment may be administered as a single dose or in several divided doses per day, within the desired dosage range, and may be administered before meals, between meals, after meals, or at the same time as meals. Furthermore, the term "administration" in this specification is intended to include "taking" or "taking."

[0058] The oral composition of this embodiment is preferably packaged in individual doses, and more preferably in a resealable packaging. Examples of such packaging include strip packaging (SP) and stick-shaped packaging. As the packaging material for the stick-shaped packaging body, for example, known materials such as the packaging materials described in Japanese Patent Publication No. 2006-143276 and Japanese Patent Publication No. 2003-192023 can be used as appropriate, taking into consideration moisture permeability, ease of opening (tearability), etc., and can be manufactured by known methods. The stick-shaped packaging may be a packaging containing a resin containing polyolefin or a packaging containing a resin containing polyester.

[0059] [Packaging containing polyolefin-based resin] The oral composition of this embodiment can be contained in packaging containing a resin that includes polyolefin. Preferably, the packaging has a layer containing polyolefin on the surface that comes into contact with the oral composition. Here, as the polyolefin, polyethylene (PE) (including high-density polyethylene (HDPE), low-density polyethylene (LDPE), ultra-low-density polyethylene, linear low-density polyethylene (LLDPE), ultra-high molecular weight polyethylene, etc.) and polypropylene (PP) are preferred. Among these, resins containing at least polyethylene are particularly preferred.

[0060] The layer containing the polyolefin may consist solely of polyolefin, but it is sufficient that it contains polyolefin, and the proportion is not limited. Furthermore, the composition may also contain an aluminum layer, which is preferable because it reduces the moisture absorption of the internally encapsulated oral composition.

[0061] The oral composition of this embodiment is preferably enclosed in an aluminum package in which the surface in contact with the oral composition is formed of a layer containing polyolefin, as it has high moisture-resistant properties and leaves little residue when removed. The aluminum packaging body has at least one layer containing an aluminum layer. This refers to a material that consists of a single layer or a multi-layer structure. In the case of a multi-layer structure, each layer is integrated via a laminate or adhesive layer as needed. The aluminum packaging is sealed at its ends and the upper and lower ends of the cylindrical shape so that the packaging material becomes cylindrical, and has a sealed storage compartment inside.

[0062] According to the oral composition of this embodiment, when packaged in a dosage form such as powder or granules, the oral composition has the property of not easily adhering to the packaging, so that the prescribed dosage can be accurately taken and the pharmacological effects of pirenzepine (a) can be fully exerted.

[0063] <<Method for inhibiting adhesion>> Another embodiment of the present invention is a method for suppressing adhesion of an oral composition to a packaging body, characterized in that when an oral composition containing pirenzepine and / or a salt thereof (a) is enclosed in a packaging body, the oral composition contains a crude drug (b). From another viewpoint, a method can be provided to impart an adhesion-suppressing effect to an oral composition to a packaging body, comprising blending the oral composition with pirenzepine and / or a salt thereof (a) and a crude drug (b). In the method of this embodiment, the type and amount of component (a) and the type and amount of component (b) used are the same as described in the above-mentioned <<Oral Composition>>. The same also applies to the blending of optional component (c), the mass ratio of each component, the material of the packaging, and other preferred embodiments.

[0064] <<Method for manufacturing oral compositions>> Another embodiment of the present invention is a method for producing an oral composition that has reduced adhesion to packaging, characterized by comprising the step of mixing pirenzepine and / or a salt thereof (a) with a crude drug (b). In the method of this embodiment, the type and amount of component (a) and the type and amount of component (b) used are the same as described in the <<Oral Composition>> above. The same also applies to preferred embodiments such as the mixing of optional component (c), the mass ratio of each component, the shape of the oral composition, and filling into the packaging. The specific manufacturing procedure in this embodiment can be obtained, for example, by adding component (c) and other optional components (such as excipients) to component (a) and component (b) as needed, and mixing them in a conventional manner. The mixed components may also include steps of drying, sizing, molding, and filling into packaging as needed. [Examples]

[0065] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples unless it exceeds the gist of the invention. In the examples, "parts" and "%" refer to mass unless otherwise specified.

[0066] First, the following components (materials) were prepared to create examples, comparative examples, and reference examples. • Pirenzepine and / or its salts (a): Pirenzepine hydrochloride hydrate • Crude drugs (b) Herbal medicines derived from the roots and rhizomes of plants (b1) Carrot (extract powder): Carrot powder (Nippon Powder Pharmaceutical Co., Ltd.) Licorice (extract powder): Licorice powder (Nippon Funka Yakuhin Co., Ltd.) Turmeric (extract powder): Turmeric powder (Nippon Funka Yakuhin Co., Ltd.) Coptis japonica (extract powder): Coptis japonica powder (Tochimoto Tenkaido Co., Ltd.) Kankyo (extract powder): Kankyo powder (Tochimoto Tenkaido Co., Ltd.) Atractylodes macrocephala (extract powder): Atractylodes macrocephala powder (Tochimoto Tenkaido Co., Ltd.) Peony (extract powder): Peony powder (Tochimoto Tenkaido Co., Ltd.) Belladonna extract (extract powder): Belladonna extract powder (Alps Pharmaceutical Co., Ltd.) Herbal medicine derived from the bark of plants (b2) Cinnamon (extract powder): Cinnamon powder (Nippon Funka Yakuhin Co., Ltd.) Phellodendron bark extract powder: Phellodendron bark powder (Tochimoto Tenkaido Co., Ltd.) Magnolia bark extract powder: Magnolia bark powder (Nippon Funka Yakuhin Co., Ltd.) • Menthol (c): L-Menthol JP (Takasago International Corporation) • Excipient: A mixture of lactose and corn starch in a 7:3 (mass ratio) mixture. Lactose: Lactose Pharmatose 100M (DFEpharma) Corn starch: Matsutani Corn Starch (Matsutani Chemical Industry Co., Ltd.)

[0067] Next, the ingredients (materials) in the quantities shown in Tables 1 to 15 were mixed to prepare powdered oral compositions (powdered preparations). Unless otherwise specified, the values ​​in the tables are expressed in parts by mass.

[0068] [Examples 1-27, Comparative Examples 1-30] The powdered oral compositions of the examples and comparative examples were refined by conventional methods to obtain powdered oral compositions. The obtained oral composition was placed in a glass bottle and mixed for 20 seconds using the spatula shown below (a stainless steel spatula with an aluminum pouch attached to the spoon portion). The aforementioned spatula is a spatula in which an aluminum pouch is attached to the spoon portion such that the surface (the surface that comes into contact with the oral medication composition) has a polyethylene-containing layer. The aforementioned aluminum pouch is a multilayer structure having a polyethylene-containing layer as the outermost layer (innermost layer) and an aluminum-containing layer as the innermost layer (intermediate layer).

[0069] Subsequently, the mass of the aforementioned spatula was measured, and the amount of the oral composition adhering to the spatula was calculated by determining the difference between the mass of the spatula and the mass of the spatula before mixing. In practice, the total mass of the spatulas is measured by placing them on a plastic tray, but since the mass of the plastic tray does not change before and after mixing, the mass of the plastic tray is omitted from the formula below. Amount of oral composition adhering to the spatula (g) = BA A: Weight of the spatula before mixing (g) B: Weight of the spatula after mixing (g) In other words, in this test system, the oral medication composition comes into contact only with the aluminum pouch, allowing for the evaluation of its adhesion to the aluminum pouch. Furthermore, to indicate the degree of improvement compared to oral compositions containing only pirenzepine (a), the amount of adhesion (g) of Comparative Example 1 or Comparative Example 26, which contained only pirenzepine (a), was used as a baseline, and the degree of improvement compared to this baseline was shown as a "ratio to baseline." A smaller value for this "ratio to baseline" indicates a higher degree of improvement.

[0070] Table 1

[0071] Table 2

[0072] Table 3

[0073] Table 4

[0074] Table 5

[0075] Table 6

[0076] Table 7

[0077] Table 8

[0078] Table 9

[0079] Table 10

[0080] [Table 11]

[0081] [Table 12]

[0082] [Table 13]

[0083] [Table 14]

[0084] [Table 15]

[0085] As shown in Tables 1 to 15 above, it was found that the adhesion to the aluminum pouch was improved in all of Examples 1 to 27. In particular, those containing menthol (component c) in addition to components a and b showed improved adhesion. Similar evaluations were also conducted on granular oral compositions (granules), and the same trends were observed as with the powdered oral compositions. Furthermore, similar trends were observed when the excipient was changed to mannitol or cellulose. [Industrial applicability]

[0086] The oral composition of the present invention is expected to be an oral composition that can fully exert the pharmacological effects of pirenzepine (a) because it allows for accurate intake of the prescribed dosage.

Claims

1. An oral composition containing pirenzepine and / or its salt (a) and a crude drug (b).

2. The oral composition according to claim 1, wherein the mass ratio (b / a) of the crude drug (b) to the pirenzepine and / or salt thereof (a) is 0.1 to 150.

3. Furthermore, the oral composition according to claim 1 or 2 further contains menthol (c).

4. The oral composition according to claim 3, wherein the mass ratio (c / a) of menthol (c) to pirenzepine and / or its salt (a) is 0.002 to 4.

5. The oral composition according to claim 1 or 2, wherein the crude drug (b) is at least one selected from the group consisting of Atractylodes macrocephala, Atractylodes lancea, Zingiber officinale, Ginger, Ginseng, Turmeric, Licorice, Belladonna extract, Peony root, Coptis japonica, Magnolia bark, Cinnamon bark, and Phellodendron bark.

6. The oral composition according to claim 1 or 2, wherein the oral composition is in the form of granules and is enclosed in a package having a polyethylene-containing layer as the innermost layer.

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