Composition for internal use

Abstract

To provide a composition for internal use, improved in unpleasant feeling of administration such as bitterness, and improved in such a problem that when the composition is contained in a package such as a subdivision bag, the composition sticks to the package and is difficult to take out.SOLUTION: The composition for internal use contains (a) pirenzepine and / or its salt and (b) at least two kinds of digestive enzymes.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an oral composition, and more particularly to an oral composition which has an improved unpleasant feeling when ingested, such as bitterness, and which is easy to take out from a package. [Background technology]

[0002] Conventionally, gastrointestinal drugs containing pirenzepine as an active ingredient have been known (see, for example, Patent Document 1). Pirenzepine is used as a gastric acid secretion inhibitor that is effective in suppressing excessive gastric acid secretion, and also improves blood circulation in the gastric mucosa and can care for a damaged stomach, making it one of the active ingredients that can exert excellent effects as a gastrointestinal drug. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 01-031721 Summary of the Invention [Problem to be solved by the invention]

[0004] However, although pirenzepine exhibits excellent effects as a gastrointestinal drug, it itself has a bitter taste, and various efforts have been made to make it easier to take, but these efforts are still insufficient, and there is a demand for something that is easier to take.

[0005] In other words, to fully utilize the medicinal effects of pirenzepine, it is important to take the entire prescribed dose without leaving any behind. However, if the bitterness or other unpleasant sensations are too strong, there is a risk that the patient will unintentionally choke and not be able to take the entire dose.

[0006] On the other hand, as a method for easily obtaining a prescribed dosage, a single dose is generally packaged in a small package. This is useful in that an accurate amount can be easily obtained, but for example, when an oral composition is processed into a powder or granules, the mass of each tablet is very light, and therefore, when trying to remove it from the package at the time of administration, the tablet adheres to the small package of the package, making it difficult to remove. The problem of the composition adhering to the packaging and being difficult to remove means that the composition may be left behind while adhering to the packaging, and since it is essential to take the prescribed dose of an oral composition, this means that the entire prescribed dose may not be ingested. For this reason, various efforts have been made to date to make it easier to remove oral compositions from packages, such as by improving the materials and processing of packages such as small bags, and by examining the composition and shape of oral compositions, but there is a demand for even easier removal.

[0007] Therefore, under these circumstances, the present invention aims to provide an oral composition that has an improved unpleasant feeling when taken, such as bitterness, and that also overcomes the problem of the composition adhering to the package and making it difficult to remove when packaged. [Means for solving the problem]

[0008] However, in light of these circumstances, the inventors conducted extensive research and discovered that by using pirenzepine as the active ingredient and further containing at least two types of digestive enzymes, an excellent oral composition can be obtained that improves unpleasant intake sensations such as bitterness and is less likely to adhere to packaging such as small bags, thereby completing the present invention.

[0009] That is, the present invention has the following aspects. [1] An oral composition comprising (a) pirenzepine and / or a salt thereof and (b) at least two types of digestive enzymes. [2] The oral composition according to [1], wherein the digestive enzyme (b) is at least two selected from the group consisting of enzymes related to carbohydrates, enzymes related to proteins and / or amino acids, and enzymes related to lipids. [3] The oral composition according to [1] or [2], wherein the digestive enzyme (b) is at least two selected from the group consisting of biodiastase, lipase, and prozyme. [4] The oral composition according to any one of [1] to [3], wherein the mass ratio (b / a) of the digestive enzyme (b) to the pirenzepine and / or its salt (a) is set in the range of 0.1 to 35. [5] The oral composition according to any one of [1] to [4], further comprising menthol (c). [6] The oral composition according to [5], wherein the mass ratio (c / a) of the menthol (c) to the pirenzepine and / or a salt thereof (a) is set in the range of 0.002 to 4. [7] The oral composition according to any one of [1] to [6], further comprising ursodeoxycholic acid. [8] The oral composition according to any one of [1] to [7], which is in the form of granules. [9] The oral composition according to any one of [1] to [8], which is contained in a package having a layer containing aluminum and / or a layer containing polyolefin or polyester as the innermost layer.

[10] The mass ratio (b / a) of the digestive enzyme (b) to the pirenzepine and / or its salt (a) is set in the range of 0.1 to 35; a mass ratio (c / a) of the menthol (c) to the pirenzepine and / or a salt thereof (a) is set in the range of 0.002 to 4; The formulation is in the form of granules, The oral composition according to [5], which is contained in a package having a layer containing aluminum and / or a layer containing polyolefin or polyester as the innermost layer. [Effects of the Invention]

[0010] The present invention is an oral composition containing pirenzepine and / or its salt (a) and at least two types of digestive enzymes (b), and therefore is an oral composition with improved unpleasant sensations such as bitterness when taken. In addition, when the oral composition is packaged in a dosage form such as powder or granules, it is less likely to adhere to the packaging, which means that the prescribed dosage can be taken accurately and the medicinal effects of pirenzepine can be fully exerted. DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention will be described below based on examples of embodiments for carrying out the present invention, but the present invention is not limited to the embodiments described below.

[0012] In this specification, when the expression "X to Y" (X and Y are any numbers) is used, unless otherwise specified, it means "X or more and Y or less," as well as "preferably larger than X" or "preferably smaller than Y." In the present specification, when numerical ranges are described in stages, the upper or lower limit of a certain numerical range can be arbitrarily combined with the upper or lower limit of another numerical range. In addition, in the numerical ranges described in this specification, the upper or lower limit of the numerical range can also be replaced with the values ​​shown in the examples.

[0013] <<Composition for internal use>> An oral composition according to one embodiment of the present invention is an oral composition containing (a) pirenzepine and / or a salt thereof and (b) at least two kinds of digestive enzymes. Each component will be explained below.

[0014] <Pirenzepine and / or its salt (a)> Pirenzepine used in this embodiment is a compound represented by the following formula (1), and includes salts thereof. [ka]

[0015] The pirenzepine and / or its salt (a) may be produced by a known method or may be a commercially available product. The salt of pirenzepine may be any 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, paratoluenesulfonic acid, and glutamic acid, and hydrochloride salts are preferably used.

[0016] In this embodiment, the content of pirenzepine and / or its salt (hereinafter simply referred to as "pirenzepine") (a) is preferably 0.3 to 3 mass% of the total mass of the oral composition, more preferably 0.5 to 2.5 mass%, and even more preferably 0.75 to 2 mass%, in order to fully exert the inhibitory effect on excessive gastric secretion.

[0017] The daily dose of pirenzepine (a) is not particularly limited, but the total amount of pirenzepine (a) is preferably 20 to 100 mg, more preferably 30 to 75 mg, and even more preferably 40 to 50 mg.

[0018] <Digestive enzymes (b)> In this embodiment, the digestive enzyme (b) refers to an enzyme that promotes the digestion and absorption of food components. Digestive enzymes (b) can be broadly classified according to the target substance they promote digestion. Examples of such classifications include enzymes related to carbohydrates, enzymes related to proteins and amino acids, and enzymes related to lipids. Some enzymes promote digestion of multiple target substances rather than just one. These enzymes can also be used alone or in combination of two or more.

[0019] Examples of the carbohydrate-related enzymes include biodiastase, biotamylase, diastase, diasmene, amylase, glucoamylase, isoamylase, bourlanase, dextranase, cellulosin, pancreatin, glucose isomerase, cellulase, glucanase, xylanase, pectinase, mannanase, hemicellulase, lactase, invertase, alginate lyase, and takadiastase. Of these, biodiastase is preferably used.

[0020] Examples of the enzymes related to proteins and amino acids include neurase, prozyme, protease, peptidase, collagenase, etc., and among these, prozyme is preferably used.

[0021] Examples of the lipid-related enzymes include lipase, phospholipase, esterase, phytase, and nuclease, with lipase being preferred.

[0022] This embodiment contains at least two types of digestive enzymes (b), and may contain three or more types. Furthermore, this embodiment does not limit the combination of types of digestive enzymes (b), but it is preferable to use a combination of digestive enzymes (b) that promote digestion of different target substances. Particularly, at least two enzymes selected from the group consisting of biodiastase, lipase, and prozyme are preferred.

[0023] In this embodiment, the content of the digestive enzyme (b) is preferably 0.04 to 95% by mass, more preferably 0.08 to 85% by mass, even more preferably 0.13 to 80% by mass, even more preferably 0.2 to 60% by mass, particularly preferably 0.27 to 45% by mass, and most preferably 0.5 to 30% by mass, based on the total mass of the oral composition. The content of the digestive enzyme (b) is the total amount (total mass) of at least two types of digestive enzymes (b).

[0024] The daily dose of the digestive enzyme (b) is not particularly limited, but the total amount of the digestive enzyme (b) is preferably 5 to 1500 mg, more preferably 20 to 800 mg, and even more preferably 30 to 500 mg.

[0025] In this embodiment, the mass ratio (b / a) of the component (b) to the component (a) is preferably 0.1-35, more preferably 0.5-20, and even more preferably 1.5-10.

[0026] <Menthol (c)> The oral composition of this embodiment preferably contains menthol (c) as an optional ingredient in addition to the pirenzepine (a) and digestive enzyme (b). Examples of the menthol (c) include l-menthol and dl-menthol, with l-menthol being preferred due to its excellent stability over time. These can be used alone or in combination of two or more.

[0027] When the present embodiment contains menthol (c), in order to improve the feeling of taking it, the content is preferably 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, relative to the total mass of the oral composition.

[0028] When the present embodiment contains menthol (c), the mass ratio (c / a) of the component (c) to the component (a) is preferably 0.002 to 4, more preferably 0.05 to 1, and even more preferably 0.1 to 0.4.

[0029] The oral composition of this embodiment may contain optional ingredients other than those mentioned above. Examples of such optional ingredients include antacids, stomachics, digestive aids, intestinal regulators, antidiarrheals, analgesics and antispasmodics, mucosal repair agents, additives, herbal ingredients, etc. These may be used alone or in combination of two or more.

[0030] Examples of the 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, synthetic hydrotalcite, etc.; squid bone, volcanic ash, boleyn, aminoacetic acid, etc. These can be used alone or in combination of two or more.

[0031] Examples of the stomachic include Mallotus japonicus extract, aniseed, aloe, fennel, turmeric, Uyaku, Enmeisou (long-lived grass), Scutellaria root, Phellodendron bark, Scutellaria root, Wren, processed garlic, Zedoary, Cuckoo, Calamus root, dried ginger, betel husk, Phellodendron sycamore, cinnamon bark, gentian, red ginseng, magnolia bark, Euonymus chinensis, pepper, Colombo, Condurango, Japanese pepper, wild mustard, perilla, celery, ginger, cardamom, green bark, Acorus root, Centaurium grass, Swertia japonica, Perilla herb, Aniseed root, Rhubarb, and Chikusetsuni. Examples include herbal medicines or extracts thereof such as ginseng, clove, tangerine peel, chili pepper, spruce, bittern, nutmeg, carrot, mint (including peppermint), long pepper, Atractylodes rhizome, hops, vomica extract, water cabbage leaf, Saussurea chinensis, Yakuchi, Scutellaria baicalensis, and Rhizome, as well as ginger oil, cardamom oil, clove oil, spruce oil, animal bile (including ginseng), betaine hydrochloride, glutamic acid hydrochloride, carnitine chloride, bethanechol chloride, dry yeast, etc. These can be used alone or in combination of two or more.

[0032] Examples of the digestive aids include ursodeoxycholic acid, oxycholanates, cholic acid, bile powder, bile extract (powder), dehydrocholic acid, animal bile (including gallbladder), etc. These can be used alone or in combination of two or more.

[0033] Examples of the anti-intestinal agent include herbal medicines such as Akasago palm, Acacia japonica, Ubai, Cassia chinensis, and Geranium herb, or extracts thereof, and probiotic components for anti-intestinal bacteria (lactic acid bacteria, butyric acid bacteria, Bacillus subtilis natto, etc.), etc. These can be used alone or in combination of two or more kinds.

[0034] Examples of the antidiarrheal agent include herbal medicines or extracts thereof such as Acacia Root, Ubai, Phellodendron Bark, Coptis Rhizome, Sophora Root, Geranium Herb, Chinese Gallnut, Hawthorn, Swertia japonica, and Umbellifera, acrinol, berberine chloride, guaiacol, creosote, phenyl salicylate, guaiacol carbonate, berberine tannate, bismuth subsalicylate, bismuth subnitrate, bismuth subcarbonate, bismuth subgallate, tannic acid, albumin tannate, methylene thimol tannin, kaolin, natural aluminum silicate, aluminum hydroxynaphthoate, pectin, medicinal charcoal, calcium lactate, etc. These can be used alone or in combination of two or more.

[0035] Examples of the analgesic and antispasmodic agent include herbal medicines or extracts thereof such as Corydalis chinensis, licorice, peony, and belladonna, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, hydrobromic acid, scopolamine, atropine methyl bromide, anisotropine methyl bromide, scopolamine methyl bromide, methyl-l-hyoscyamine bromide, benactidium methyl bromide, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, papaverine hydrochloride, and ethyl aminobenzoate. These can be used alone or in combination of two or more.

[0036] Examples of the mucosal repair agent include herbal medicines or extracts thereof such as Chinese holly, Corydalis fructus, and Licorice Root, azulene sodium sulfonate, aldioxa, glycyrrhizinic acid and its salts, L-glutamine, potassium copper chlorophyllin, sodium copper chlorophyllin, histidine hydrochloride, pepsin digestion product of porcine stomach wall, acid hydrolyzate of porcine stomach wall, methylmethionine sulfonium chloride, gefarnate, cetraxate hydrochloride, sucralfate hydrate (aluminum salt of sucrose sulfate), sofalcone, etc. These can be used alone or in combination of two or more.

[0037] Examples of the additives include excipients, stabilizers, surfactants, lubricants, solubilizers, buffers, sweeteners, bases, adsorbents, flavorings, binders, suspending agents, hardeners, antioxidants, glossing agents, flavorings, coating agents, shells, humectants, moisturizing agents, fillers, antifoaming agents, refreshing agents, chewing agents, antistatic agents, flavorings, colorants, sugar coating agents, isotonicity agents, softeners, emulsifiers, adhesives, adhesion enhancers, viscosity adjusters, foaming agents, pH adjusters, dispersants, disintegrants, disintegration aids, fragrances, moisture-proofing agents, preservatives, solubilizers, solubilizing aids, solvents, and fluidizing agents. These may be used alone or in combination of two or more.

[0038] Examples of the excipient include preferred sugars such as refined sucrose, glucose, trehalose, lactose, maltose, and cornstarch, with lactose and cornstarch being more preferred. Preferred are sugar alcohols such as sorbitol, xylitol, erythritol, and granutol. These can be used alone or in combination of two or more.

[0039] When this embodiment contains a sugar or sugar alcohol, in order to improve the feeling of taking the oral composition, the sugar or sugar alcohol is preferably contained in an amount of 5 to 90% by mass, more preferably 10 to 80% by mass, and even more preferably 15 to 70% by mass, based on the total mass of the oral composition.

[0040] When this embodiment contains a sugar or sugar alcohol, the mass ratio of the sugar to the component (a) is preferably 1.5-300, more preferably 5-250, and even more preferably 15-200.

[0041] Specific examples of the additives include refined sucrose, glucose, trehalose, lactose, maltose, mannitol, sorbitol, xylitol, erythritol, granitol, saccharin sodium, aspartame, acesulfame potassium, sucralose, licorice extract, stevia extract, Monk fruit extract, corn starch, potato starch, wheat starch, sodium chloride, crystalline cellulose, methylcellulose, ethylcellulose, hypromellose, hydroxypropyl cellulose, carboxymethylcellulose, carboxymethylcellulose sodium, carboxymethylcellulose calcium, carmellose calcium, croscarmellose sodium, hypromellose phthalate, cellulose acetate phthalate, dextrin, pregelatinized starch, gum arabic, gelatin, sodium alginate, polyvinylpyrrolidone, crospovidone, polyvinyl alcohol, polyethylene glycol, and casein. , sodium caseinate, carboxyvinyl polymer, tartaric acid, light anhydrous silicic acid, hydrous silicic acid 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 iron sesquioxide, iron sesquioxide, brown iron oxide, black iron oxide, titanium dioxide, lake color, benzoic acid, sodium benzoate, parahydroxybenzoate Examples include aromatic acid, cyclodextrin, polysorbate 80, glycerin fatty acid ester, propylene glycol fatty acid ester, lecithin, white beeswax, medium-chain fatty acid triglyceride, ascorbic acid, tocopherol, sodium thiosulfate, sodium edetate, plant-derived flavors (fruit flavors such as orange and lemon, coffee flavors, and tea flavors), chocolate flavors, yogurt flavors, milk flavors, and plant essential oils such as peppermint oil, spearmint oil, and spice oils. These can be used alone or in combination of two or more.

[0042] The herbal ingredients include, for example, the herbal medicines themselves (raw herbal medicines), as well as powdered herbal medicines obtained by powdering raw herbal medicines, and extracts obtained by extracting the herbal medicines or powdered herbal medicines with water, organic solvents such as ethanol, or mixtures thereof, and are intended to include any form such as the extract itself, a soft extract obtained by concentrating the extract, a dried extract obtained by drying the extract or soft extract, etc. These can be used alone or in combination of two or more.

[0043] The oral composition of this embodiment can be obtained by mixing pirenzepine (a), at least two kinds of digestive enzymes (b), and, if necessary, other ingredients, in a conventional manner. That is, pirenzepine (a) and at least two types of digestive enzymes (b) may be mixed together, and other ingredients may be added to this mixture, or all ingredients including the pirenzepine (a) and at least two types of digestive enzymes (b) may be mixed together at once. Furthermore, these mixed ingredients may be dried, sized, etc. to prepare an oral composition.

[0044] According to the oral composition of this embodiment, unpleasant sensations such as bitterness when taken are alleviated. In addition, since the oral composition is less likely to stick to the packaging, it is easy to take the prescribed dose accurately, and the efficacy of pirenzepine (a) can be fully exerted.

[0045] The oral composition of this embodiment can be formulated to contain other ingredients as needed.

[0046] The oral composition of this embodiment may contain a combination of various ingredients (including pharmacologically active ingredients and physiologically active ingredients) in addition to the above ingredients, as long as the effects of the present invention are not impaired. The types of such ingredients are not particularly limited, but representative examples include ingredients having the effect of treating gastrointestinal diseases, such as gastroenterics, digestive drugs, antacids, astringents, adsorbents, mucosal protective drugs, mucosal repair drugs, and analgesics and antispasmodics. These gastrointestinal drugs, digestive drugs, antacids, astringents, adsorbents, mucosal protecting drugs, mucosal repairing drugs and analgesics and antispasmodics can be used singly or in combination of two or more kinds.

[0047] Furthermore, the oral composition of this embodiment can also contain other physiologically active ingredients or pharmacologically active ingredients as needed, provided that the effects of the present invention are not impaired. Representative examples of such ingredients include antipyretics, analgesics, anti-inflammatory drugs, various herbal ingredients, antiallergic drugs, cold medicines, antitussives, expectorants, analgesics, rhinitis medicines, intestinal regulators, antidiarrheals, laxatives, tonics, antibiotics, etc. These can be used alone or in combination of two or more.

[0048] The oral composition of this embodiment can be formulated by arbitrarily selecting various ingredients and additives used in pharmaceuticals, quasi-drugs, foods, etc. depending on the form of the formulation. For example, solid formulations can use binders (hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose sodium, polyvinylpyrrolidone, polyvinyl alcohol, etc.), excipients (sucrose, lactose, starch, corn starch, crystalline cellulose, light anhydrous silicic acid, etc.), lubricants (sucrose fatty acid esters, magnesium stearate, etc.), disintegrants (methyl cellulose, polysorbate 80, croscarmellose sodium, etc.), etc. Liquid formulations can use solvents or water as bases, oily bases, solubilizers, suspending agents or emulsifiers, isotonicity agents, buffers, etc. These can be used alone or in combination of two or more. Furthermore, if necessary, these preparations may contain preservatives, antioxidants, sweeteners, acidulants, colorants, flavorings, taste-imparting agents, etc. These may be used alone or in combination of two or more.

[0049] The dosage form of the oral composition of this embodiment is not particularly limited, and may be, for example, any of a solid, semi-solid, or liquid form. Specific examples of known forms include tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, lozenges, jelly drops, etc.), granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including drinks, suspensions, and syrups), chewable tablets, gels, liposomes, extracts, tinctures, lemonades, and jellies. Of these, tablets, granules, fine granules, powders, hard capsules, soft capsules (soft capsules, seamless capsules, etc.), dry syrup, liquids, and suspensions are preferred because they are expected to have an immediate effect, and tablets, granules, fine granules, powders, hard capsules, soft capsules, and dry syrup are more preferred, with powders and granules being most preferred because they have an excellent balance with the feeling of taking the drug.

[0050] When the dosage form of the oral composition of this embodiment is granules, the average particle size is preferably 0.01 to 5.0 mm, more preferably 0.02 to 0.75 mm, and even more preferably 0.05 to 0.5 mm. When the oral composition of this embodiment is in the form of a powder, the average particle size is preferably 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 is a value measured using a laser diffraction particle size distribution analyzer, and calculated from the D50 value (particle size at 50% of the cumulative volume) of the obtained cumulative volume distribution.

[0051] These formulations can be prepared by conventional methods depending on the formulation form, and various formulations can be prepared.

[0052] The dosage of the oral composition in this embodiment is not fixed and is determined appropriately depending on the form, administration method, purpose of administration, and the age, weight, symptoms, and physical condition of the recipient of the composition. Furthermore, the oral composition of this embodiment may be administered once or in divided doses per day within the desired dosage range, and may be administered before meals, between meals, after meals, or simultaneously with meals. It should be noted that the term "administration" as used herein is intended to encompass "taking the medicine."

[0053] The oral composition of this embodiment is preferably packaged in a single dose individually, more preferably in a sealable package, and examples of such packages include an SP (Strip Package) package and a stick-shaped package. As the packaging material for the stick-shaped package, any known material can be used, taking into consideration moisture permeability, openability (tearability), etc., such as the packaging materials described in JP-A-2006-143276 and JP-A-2003-192023, and the package can be produced by a known method. The stick-shaped package may be a package containing a resin containing polyolefin or a package containing a resin containing polyester.

[0054] [Packaging containing polyolefin-containing resin] The composition of the present invention can be housed in a package comprising a resin containing a polyolefin. The packaging preferably has a layer containing a polyolefin on the surface that comes into contact with the composition. Here, preferred polyolefins include polyethylene (PE) (including high-density polyethylene (HDPE), low-density polyethylene (LDPE), very-low-density polyethylene, linear low-density polyethylene (LLDPE), ultra-high-molecular-weight polyethylene, etc.), polypropylene (PP) (including homopolymer, random copolymer, block copolymer, etc.), ethylene-propylene copolymer, cyclic olefin copolymer, polymethylpentene, and polybutene-1,1,2-polybutadiene, with polyethylene resin or polypropylene resin being more preferred, and resins containing at least polyethylene being particularly preferred.

[0055] The layer containing the polyolefin may be a layer consisting of only polyolefin, but the proportion of polyolefin is not limited as long as it contains polyolefin. The packaging material may also contain aluminum, and for example, a packaging material having a layer with an aluminum content of 3% by mass or more, 5% by mass or more can be used. When the packaging material has an aluminum-containing layer, the thickness thereof is preferably 1 μm or more, 3 μm or more, or 5 μm or more, and is preferably 20 μm or less, 15 μm or less, or 10 μm or less. When the packaging material has an aluminum-containing layer, moisture absorption of the internally administered composition is reduced, which is preferable. The packaging material may be multi-layered or single-layered, and its form does not matter as long as it contains polyolefin. It may also contain polyester. Of the layers, the polyolefin layer in contact with the composition is preferably 5 μm or more, 10 μm or more, 20 μm or more, 30 μm or more, or 40 μm or more, and preferably 100 μm or less, 80 μm or less, 60 μm or less, 50 μm or less, or 40 μm or less.

[0056] [Packaging containing polyester-containing resin] The composition of the present invention may be contained in a package that includes a resin containing a polyester. The packaging preferably has a layer containing polyester on the surface that comes into contact with the composition. Here, examples of polyesters that can be used include polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene naphthalate (PEN), polybutylene naphthalate (PBN), polyethylene isophthalate (PEIT), and polycaprolactone (PCL), and resins containing at least polyethylene terephthalate are more preferred. Furthermore, the polyester may contain aluminum, and for example, a packaging material having a layer with an aluminum content of 3% by mass or more, or 5% by mass or more, can be used. When an aluminum-containing layer is present, its thickness is preferably 1 μm or more, 3 μm or more, or 5 μm or more, and preferably 20 μm or less, 15 μm or less, or 10 μm or less. Having an aluminum-containing layer is preferred because it reduces moisture absorption of the internally contained oral composition. Here, the packaging material may be multi-layered or single-layered, and any form is acceptable as long as it contains polyester. It may also contain polyolefin.

[0057] The oral composition of this embodiment is preferably packaged in an aluminum package in which the surface in contact with the oral composition is formed of a layer containing polyolefin or polyester, since it has high moisture absorption resistance and little residue of the oral composition remains when the oral composition is removed. The aluminum packaging body has the packaging material sealed at its ends and at the top and bottom of the cylinder so that the packaging material is cylindrical, and has a storage section inside that serves as an airtight space.

[0058] According to the oral composition of this embodiment, unpleasant sensations such as bitterness when taken are eliminated, so that unintentional choking is avoided and it becomes easier to take the entire prescribed amount. Furthermore, when the drug is packaged in a powder or granule form, it is less likely to adhere to the packaging, such as a small bag, so that the prescribed dose can be accurately taken, allowing the efficacy of pirenzepine (a) to be fully exerted. [Example]

[0059] 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 as long as it does not depart from the gist of the invention. In the examples, "parts" and "%" are by mass unless otherwise specified.

[0060] First, the following components (materials) were prepared to prepare Examples, Comparative Examples, and Reference Examples. Pirenzepine and / or its salts (a): Pirenzepine hydrochloride (hydrate) ·Digestive enzymes (b) Biodiastase: Biodiastase 2000 (Amano Enzyme Co., Ltd.) Lipase: Lipase AP6 (Amano Enzyme Co., Ltd.) Prozyme: Prozyme 6 (Amano Enzyme Co., Ltd.) Menthol (c): L-Menthol JP (Takasago International Corporation) Excipient: A 7:3 mixture of lactose and cornstarch. Lactose:Lactose Pharmatose 100M (DFE pharma) Cornstarch: Pharmacopoeia Matsutani Cornstarch (Matsutani Chemical Industry Co., Ltd.)

[0061] (feeling when taking) [Examples 1 to 6, Comparative Examples 1 to 4] The components (materials) shown in Tables 1 to 6 were mixed in the amounts shown in Tables 1 to 6 to prepare powdered oral compositions (powder formulations). The oral sensation of the resulting oral compositions was measured and evaluated as described below. The values ​​in the tables are in parts by mass unless otherwise specified, and for pirenzepine hydrochloride, the values ​​are calculated on an anhydrous basis.

[0062] Four panelists were selected through a prescribed sensory evaluation panelist selection screening for the obtained oral compositions, and randomly selected in order, they placed 100 mg of the oral composition of the Example or Comparative Example in their mouths, measured the time (seconds) it took before they needed water and the amount of water (g) they needed to take the composition, and calculated the average values ​​to evaluate the improvement in the feeling of taking the composition. Here, the shorter the time it took to require water, the more bitter the oral composition was, and the greater the amount of water required for administration, the more unpleasant the administration experience. Therefore, in order to show the degree of improvement compared to an oral composition containing only pirenzepine hydrochloride (a), Reference Example 1 containing only pirenzepine hydrochloride (a) is used as the standard, and the degree of improvement compared to this standard is shown as a ratio. The results obtained are shown in Tables 1 to 3 below.

[0063] [Table 1]

[0064] [Table 2]

[0065] [Table 3]

[0066] As shown in Tables 1 to 3 above, it was found that Examples 1 to 6 all had an improved feeling when taken. In particular, the product containing menthol, which is the c-component, along with two types of the b-component, showed an improved feeling when taken. In contrast to these, the improvement in the feeling of taking the medicine was not noticeable in the medicine containing only one kind of component b or the medicine containing only menthol, which is component c. The same evaluation was also carried out on granules (granular oral composition), and the granules showed the same tendency as the powders, with a greater degree of improvement.

[0067] (Adhesion 1) [Examples 7 to 12, Comparative Examples 5 to 8] The powdered oral compositions of the Examples and Comparative Examples were subjected to a conventional method of reducing the particle size and making the particle size uniform to obtain powdered oral compositions. The obtained oral composition was placed in a glass bottle and mixed for 20 seconds using a stainless steel spoon. Thereafter, the mass of the spoon was measured, and the difference between the mass of the spoon before mixing and the mass of the spoon before mixing was calculated to calculate the amount of the oral composition adhering to the spoon. In reality, the medicine spoons are placed on a plastic tray and the total mass of these is measured, but since there is no change in the mass of the plastic tray before and after mixing, the mass of the plastic tray is omitted from the formula below. Amount of oral composition attached to spoon (g) = BA A: Mass of spoon before mixing (g) B: Mass of spoon after mixing (g)

[0068] Here, the larger the adhesion amount (g), the stronger the adhesion to the contact object. Therefore, in order to show the degree of improvement compared to an oral composition containing only pirenzepine hydrochloride (a), Reference Example 1 containing only pirenzepine hydrochloride (a) is used as the standard, and the degree of improvement compared to this standard is shown as a ratio. The results obtained are shown in Tables 4 to 6 below.

[0069] [Table 4]

[0070] [Table 5]

[0071] [Table 6]

[0072] As shown in Tables 4 to 6, it was found that Examples 7 to 12 all had improved adhesion to stainless steel. In particular, the product containing menthol, which is the component c, together with two types of the component b, showed further improved adhesion. In contrast to these, the improvement in adhesion was not noticeable in the case of the product containing only one kind of component b or the product containing only menthol, which is component c. The same evaluation was also carried out on granulated oral compositions (granules), and the results showed the same tendency as the powdered oral compositions, with a greater degree of improvement.

[0073] (Adhesion 2) [Examples 13 to 18, Comparative Examples 9 to 12] The amount of oral composition adhered to the following (aluminum pouch + medicine spoon) was calculated in the same manner as in Adhesion 1, except that the following (aluminum pouch + medicine spoon) was used instead of the medicine spoon used in Adhesion 1. That is, in this test system, the oral composition comes into contact only with the aluminum pouch, so that adhesion to the aluminum pouch can be evaluated. A medicine spoon with an aluminum pouch attached to the spoon part so that the layer containing polyethylene is on the surface (the surface that comes into contact with the oral composition). (Aluminum pouch: a multilayer structure with an innermost layer containing polyethylene and an inner layer containing aluminum)

[0074] Here, the larger the adhesion amount (g), the stronger the adhesion to the contact object. Therefore, in order to show the degree of improvement, Comparative Example 9 containing pirenzepine hydrochloride (a) and menthol (c) was used as the standard, and the degree of improvement relative to this standard was shown as a ratio. The results obtained are shown in Tables 7 to 9 below.

[0075] [Table 7]

[0076] [Table 8]

[0077] [Table 9]

[0078] As shown in Tables 7 to 9, it was found that in all of Examples 13 to 18, the adhesion to the aluminum pouch was improved. In particular, the product containing menthol, which is the component c, together with two types of the component b, showed further improved adhesion. In contrast to these, the improvement in adhesion was not noticeable in the case of the product containing only one kind of component b or the product containing only menthol, which is component c. The same evaluation was also carried out on granulated oral compositions (granules), and the results showed the same tendency as the powdered oral compositions, with a greater degree of improvement.

[0079] [Formulation example] Oral compositions of the present invention (Formulation Examples 1 to 15) were prepared by conventional methods using the materials shown in Tables 10 to 12 below. The pirenzepine hydrochloride, biodiastase, lipase, and prozyme used were the same as those used in Examples 1 to 18, and the other materials used were food ingredients or food additive-compliant products. In the tables, the values ​​for pirenzepine hydrochloride are shown converted to anhydrous values. The dosage forms of Formulation Examples 1 to 15 are as shown in Tables 10 to 12, respectively. In the tables, "granules / powder" means that the same tendency is observed in both the granule and powder dosage forms. These oral compositions all had an improved unpleasant feeling when taken, such as bitterness, and also had improved difficulty in removing the composition from the package.

[0080] [Table 10]

[0081] [Table 11]

[0082] [Table 12] [Industrial Applicability]

[0083] The oral composition of the present invention has an improved feeling of administration and allows the prescribed dose to be accurately taken, and is therefore expected to be an oral composition that can fully exert the medicinal effects of pirenzepine and / or its salt (a).

Claims

1. An oral composition comprising (a) pirenzepine and / or a salt thereof and (b) at least two kinds of digestive enzymes.

2. 2. The oral composition according to claim 1, wherein the digestive enzyme (b) is at least two selected from the group consisting of enzymes related to carbohydrates, enzymes related to proteins and / or amino acids, and enzymes related to lipids.

3. 3. The oral composition according to claim 1, wherein the digestive enzyme (b) is at least two selected from the group consisting of biodiastase, lipase, and prozyme.

4. 3. The oral composition according to claim 1, wherein the mass ratio (b / a) of the digestive enzyme (b) to the pirenzepine and / or its salt (a) is set in the range of 0.1 to 35.

5. 3. The oral composition according to claim 1, further comprising menthol (c).

6. 6. The oral composition according to claim 5, wherein the mass ratio (c / a) of the menthol (c) to the pirenzepine and / or its salt (a) is set in the range of 0.002 to 4.

7. 3. The oral composition according to claim 1, further comprising ursodeoxycholic acid.

8. 3. The oral composition according to claim 1, wherein the formulation is in the form of granules.

9. 3. The oral composition according to claim 1, which is enclosed in a package having a layer containing aluminum and / or an innermost layer containing polyolefin or polyester.

10. a mass ratio (b / a) of the pirenzepine and / or its salt (a) to the digestive enzyme (b) is set in the range of 0.1 to 35; a mass ratio (c / a) of the menthol (c) to the pirenzepine and / or a salt thereof (a) is set in the range of 0.002 to 4; The formulation is in the form of granules, 6. The oral composition according to claim 5, which is contained in a package having a layer containing aluminum and / or a layer containing polyolefin or polyester as the innermost layer.

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