JP2016204353A - Oral agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel technique that suppresses the unpleasant taste of a basic inorganic compound.SOLUTION: An oral agent comprises following components (A), (B) and (C): (A) basic inorganic compound; (B) at least one selected from the group consisting of lactic acid and salt thereof; and (C) sucralose.SELECTED DRAWING: None

Description

  The present invention relates to an oral preparation. More specifically, the present invention relates to an oral preparation in which an unpleasant taste of a basic inorganic compound is suppressed.

Basic inorganic compounds such as sodium bicarbonate are used in the fields of pharmaceuticals, cosmetics, foods and the like. In particular, in the pharmaceutical field, based on the antacid action and the like of basic inorganic compounds, it is widely used as a so-called antacid or gastric mucosa protective ingredient for oral use such as gastrointestinal and cold medicines.
Thus, although a basic inorganic compound is very useful as a component of an oral preparation, it has a disadvantage of having an unpleasant taste (bitter taste, salty taste, etc.) peculiar to inorganic compounds (for example, Non-Patent Document 1). The unpleasant taste of the components in the oral preparation may impair the feeling of taking it and reduce compliance. In particular, in the case of oral dosage forms such as powders, granules and orally disintegrating tablets, contact between the oral dosage form and the tongue is increased, so that the feeling of dosing due to unpleasant taste is significant.

  In order to improve the deterioration of the feeling of administration due to the unpleasant taste of the basic inorganic compound, and to improve the compliance of medication, various methods for suppressing unpleasant taste and masking methods have been proposed. For example, in Patent Document 1, the feeling of intake, flavor and aftertaste are improved by combining stevia with a basic inorganic compound such as synthetic hydrotalcite, magnesium oxide, sodium bicarbonate, precipitated calcium carbonate, magnesium aluminate metasilicate. It is described that an oral composition can be obtained. However, suppression of unpleasant taste by such a method is not necessarily sufficient.

  By the way, as a technique for suppressing unpleasant taste, an orally disintegrating tablet containing a bitter drug and a specific amount of calcium lactate has been reported (Patent Document 2). However, only organic compounds such as anhydrous caffeine, acetaminophen, mosapride citrate, and dl-chlorpheniramine maleate are described as “drugs having a bitter taste” in the literature. No unpleasant taste-inhibiting action on different basic inorganic compounds has been clarified.

JP-A-9-52827 Japanese Patent No. 5097488

The 16th revision Japanese Pharmacopoeia Manual Sasakawa Shoten Co., Ltd., page C-2671

  The subject of this invention is providing the new technique which suppresses the unpleasant taste which a basic inorganic compound has.

The present inventor first tried to suppress an unpleasant taste by combining calcium lactate with a basic inorganic compound with reference to the description in Patent Document 2, and surprisingly, warping by combining calcium lactate. It became clear that the unpleasant taste was enhanced.
Therefore, the present inventor has further studied diligently, and in addition to the basic inorganic compound and calcium lactate, by combining sucralose, the unpleasant taste of the basic inorganic compound is remarkably suppressed, and the oral preparation has a good feeling of taking. Was found and the present invention was completed.

That is, the present invention includes the following components (A), (B) and (C):
(A) a basic inorganic compound;
(B) one or more selected from the group consisting of lactic acid and salts thereof;
(C) sucralose;
It is intended to provide an oral preparation containing

The present invention also relates to a method for suppressing the unpleasant taste of an oral preparation containing a basic inorganic compound, wherein the oral preparation contains one or more selected from the group consisting of lactic acid and a salt thereof and sucralose. It is to provide.
In addition, the present invention provides an unpleasant taste inhibitor that suppresses unpleasant taste derived from a basic inorganic compound, and comprises an unpleasant taste inhibitor containing at least one selected from the group consisting of lactic acid and a salt thereof and sucralose. It is to provide.
Furthermore, the present invention is a method for producing an oral preparation with suppressed unpleasant taste derived from a basic inorganic compound, the oral preparation containing at least one selected from the group consisting of lactic acid and salts thereof and sucralose. A method including a caulking step is provided.

In the oral preparation of the present invention, the unpleasant taste derived from the basic inorganic compound is suppressed and the feeling of taking is good. Therefore, it can be set as the medicine etc. which are excellent in medication compliance.
According to the method of the present invention, it is possible to provide an oral preparation having a good feeling of taking and excellent compliance, in which an unpleasant taste derived from a basic inorganic compound is suppressed.

First, the oral preparation of the present invention will be described in detail below.
<Component (A)>
In the present invention, examples of the “basic inorganic compound” include alkaline earth metals such as magnesium, aluminum and calcium and / or earth metal basic inorganic compounds; alkali metal basic inorganic compounds such as sodium and potassium, etc. Can be mentioned.
Specific examples of the alkaline earth metal and / or earth metal-based basic inorganic compound include, for example, magnesium silicate, magnesium aluminate silicate, magnesium aluminum silicate, magnesium oxide, magnesium hydroxide, magnesium hydroxide, Coprecipitation product of potassium aluminum sulfate, magnesium carbonate, synthetic hydrotalcite, magnesium aluminate metasilicate, dry aluminum hydroxide gel, synthetic aluminum silicate, synthetic aluminum silicate, hydroxypropyl starch, crystalline cellulose, magnesium alumina hydroxide, Aluminum hydroxide gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, Bentonite, calcium silicate, calcium carbonate, precipitated calcium carbonate, calcium hydrogen phosphate, magnesium such as anhydrous calcium hydrogen phosphate, metal inorganic salts selected from aluminum and calcium and the like.
Specific examples of the alkali metal basic inorganic compound include, for example, dry sodium carbonate, sodium hydroxide, sodium hydrogen carbonate, sodium carbonate hydrate, tetrasodium pyrophosphate, trisodium phosphate, sodium hydrogen phosphate. Examples thereof include hydrates, anhydrous sodium pyrophosphate, anhydrous sodium phosphate monohydrate, potassium hydroxide, potassium hydrogen carbonate, potassium metal carbonate and other inorganic salts of metals selected from sodium and potassium.
Furthermore, in the present invention, a crude drug containing a basic inorganic compound as a main component such as bandit bone, stone decision, or volley may be used.
In addition, all of the above-described components are known compounds, and commercially available products may be used, or they can be produced by a known method.

  In the present invention, as the basic inorganic compound, dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesium alumina hydroxide, aluminum hydroxide gel, Aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, magnesium hydroxide, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate One or more selected from the group consisting of magnesium aluminate metasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, bandit bone, stone decision and borei, synthetic hydrotalcite, magnesium oxide, Magnesium oxide, sodium bicarbonate, more preferably at least one member selected from the group consisting of precipitated magnesium calcium carbonate and metasilicate, sodium hydrogen carbonate are particularly preferred. Although sodium bicarbonate has a unique salty taste, according to the present invention, such an unpleasant salty taste can be remarkably suppressed.

  Content of the basic inorganic compound in the oral preparation of this invention is not specifically limited, What is necessary is just to set suitably according to the compounding purpose. In the present invention, the basic inorganic compound is preferably contained in an amount of 15 to 85% by mass relative to the total mass of the oral preparation, more preferably 25 to 80% by mass, and further preferably 30 to 70% by mass. Preferably, the content is 32.5 to 60% by mass, more preferably 35 to 55% by mass, still more preferably 35 to 50% by mass, and particularly preferably 35 to 40% by mass. preferable.

<Component (B)>
In the present invention, “lactic acid” is not particularly limited, and any of L-lactic acid and D-lactic acid may be used, and a mixture thereof may be used.
In the present invention, examples of the “lactic acid salt” include alkali metal salts such as sodium salt and potassium salt of the above “lactic acid”; alkaline earth metal salts such as calcium salt and magnesium salt, and the like. Or in combination of two or more.
Furthermore, in the present invention, “one or more selected from the group consisting of lactic acid and salts thereof” may be a hydrate or an anhydride.
In the present invention, “one or more selected from the group consisting of lactic acid and salts thereof” is preferably calcium lactate from the viewpoint of the action of suppressing unpleasant taste. In addition, lactic acid and its salt are well-known compounds, and a commercially available thing may be used and it can also manufacture by a well-known method.

The content of one or more selected from the group consisting of lactic acid and salts thereof in the oral preparation of the present invention is not particularly limited, and may be appropriately set according to the action of suppressing unpleasant taste. In the present invention, from the viewpoint of the effect of suppressing unpleasant taste, it is preferably contained in an amount of 0.05 to 4% by mass, more preferably 0.1 to 3% by mass, based on the total mass of the oral preparation. The content is particularly preferably 5 to 2% by mass.
Further, the content mass ratio [(B) / (A)] of (A) the basic inorganic compound and (B) one or more selected from the group consisting of lactic acid and salts thereof in the oral preparation of the present invention is not particularly limited. However, from the viewpoint of the effect of suppressing unpleasant taste, 0.005 to 7 is preferable, 0.01 to 6 is more preferable, 0.02 to 5 is further preferable, 0.03 to 1 is further preferable, and 0.04 to 0.5 is particularly preferred.

<Ingredient (C)>
“Sucralose” (trichlorogalactosucrose) is a known compound, which may be commercially available or can be produced by a known method.
The content of sucralose in the oral preparation of the present invention is not particularly limited, and may be appropriately set according to the action of suppressing unpleasant taste. In the present invention, from the viewpoint of an unpleasant taste inhibitory effect, it is preferably contained in an amount of 0.005 to 3% by mass, more preferably 0.01 to 2% by mass, based on the total mass of the oral preparation. The content is more preferably from 0.5 to 1.5% by mass, particularly preferably from 0.1 to 1% by mass.
In addition, the content mass ratio [(C) / (A)] of (A) the basic inorganic compound and (C) sucralose in the oral preparation of the present invention is not particularly limited. 0.0001 to 3 is preferable, 0.0005 to 2 is more preferable, 0.001 to 1.5 is more preferable, 0.002 to 1 is still more preferable, and 0.005 to 0.5 is particularly preferable.
Further, the content mass ratio [(C) / (B)] of (C) sucralose to one or more selected from the group consisting of (B) lactic acid and salts thereof in the oral preparation of the present invention is not particularly limited, but is uncomfortable. From the viewpoint of the taste-suppressing action, 0.001 to 10 is preferable, 0.01 to 5 is more preferable, 0.03 to 3 is further preferable, and 0.06 to 1 is particularly preferable.

<Component (D)>
In the oral preparation of the present invention, in addition to the components (A) to (C), assembly may be further blended as the component (D). Assembly is a component used as a gastrointestinal component as a bitterness stomachic raw material, but has a drawback of exhibiting an extremely strong bitterness. However, as shown in Test Example 2 below, the combination of one or more selected from the group consisting of lactic acid and its salt and sucralose has a remarkable inhibitory action on the bitter taste of such assembly. It became clear.
Therefore, the following components (A), (B), (C) and (D):
(A) a basic inorganic compound;
(B) one or more selected from the group consisting of lactic acid and salts thereof;
(C) sucralose;
(D) one or more selected from the group consisting of assembly and its extract;
The oral preparation containing, which suppresses not only the basic inorganic compound but also the unpleasant taste derived from the assembly, has a good dosage feeling. Therefore, it can be suitably used as a medicine (for example, a gastrointestinal drug) that is excellent in compliance with medication and uses the excellent pharmacological action of the assembly.
In addition, as the above-mentioned oral preparation, an oral preparation obtained by using a granulated product containing components (A) to (C) and a granulated product containing component (D) (more specifically, component (A) ~ A powder or granule containing a granulated product containing (C) and a granulated product containing component (D); a granulated product containing components (A) to (C) and a component (D) Tablets obtained using a raw material containing a granulated product are preferred.

Further, from another viewpoint, the present invention provides the following components (D), (B) and (C):
(D) one or more selected from the group consisting of assembly and its extract;
(B) one or more selected from the group consisting of lactic acid and salts thereof;
(C) sucralose;
An oral preparation (preferably a gastrointestinal drug) containing Such an oral medicine can be suitably used as a medicine (for example, a gastrointestinal medicine) having good compliance with the use of the pharmacological action of the assembly because the bitterness derived from the assembly is suppressed and easy to take.
Furthermore, from another point of view, the present invention is a method for suppressing an unpleasant taste of an oral preparation containing one or more selected from the group consisting of an assembly and an extract thereof, wherein the oral preparation comprises lactic acid and a salt thereof. The present invention provides a method for containing at least one selected from the group and sucralose. Furthermore, from another viewpoint, an unpleasant taste inhibitor that suppresses an unpleasant taste derived from one or more selected from the group consisting of an assembly and an extract thereof, and one or more selected from the group consisting of lactic acid and a salt thereof And an unpleasant taste inhibitor containing sucralose. Furthermore, from another point of view, the present invention provides a method for producing an oral preparation with reduced unpleasant taste derived from one or more selected from the group consisting of an assembly and an extract thereof. And a method comprising a step of containing sucralose and at least one selected from the group consisting of salts thereof.
According to these methods, it is possible to provide a medicine (for example, a gastrointestinal drug) having good medication compliance in which the pharmacological action of the assembly is used and the bitterness derived from the assembly is suppressed.
In addition, the meaning of each word in such an aspect, the amount of various components, the combination ratio, and the like are the same as in an oral preparation containing a basic inorganic compound as an essential component, unless otherwise specified.

“Assembly” (this drug) means the whole plant in the flowering period of the assembly (Swertia japonica Makino (Gentianaceae)) as described in the 16th revision Japanese Pharmacopoeia. The form of the assembly can be adjusted as needed, and can be cut or crushed into small pieces, small chunks, or pulverized into powder. For example, “assembly powder” in which the assembly is powdered can also be used in the present invention. Can do. In addition, in consideration of the convenience of handling during production of the gastrointestinal composition, a product obtained by subjecting the assembly to some kind of extraction (hereinafter referred to as “assembly extract”) may be used.
The “assembly extract” includes those subjected to processing such as heating, drying, and pulverization in addition to extraction processing. Specifically, after the assembly was appropriately sized as necessary, a liquid leached by adding an appropriate extraction solvent, a liquid (such as a soft extract or tincture) obtained by concentrating the leached liquid, and these were further dried. Things (dry extract etc.) etc. are also included in the “assembly extract” of the present invention.
In the present invention, the assembly powder is preferably used as one or more selected from the group consisting of the assembly and its extract.

  The method for producing the extract of the assembly is not particularly limited.For example, the description of the “Extract”, “Dipping / decoction”, “Tincture”, “Flux Extract” in the 16th revised Japanese Pharmacopoeia General Rules for Preparations, etc. It can manufacture with reference to the manufacturing method of a well-known plant extract. Specifically, for example, the assembly can be produced by cutting, heating, drying, pulverizing, etc., if necessary, and extracting by adding an appropriate extraction solvent. The obtained extract may be further concentrated, dried, etc. as necessary.

Examples of the extraction solvent include lower monohydric alcohols such as methanol, ethanol, isopropanol, and n-butanol; 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; benzene, toluene and the like And 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, water, ethanol, or a mixture of water and ethanol is preferred.
The extraction operation is not particularly limited, and a known method used for the extraction operation from plants can be adopted. Specifically, for example, immersion in extraction solvent (cooling, digestion, percolation, etc.), super For example, extraction using a critical fluid or a subcritical fluid may be mentioned. In addition, in order to raise extraction efficiency, you may homogenize in stirring or an extraction solvent.
Although extraction temperature is not specifically limited, Although it changes with extraction solvents to be used, extraction operation, etc., it is preferable to set it as about 1 hour-14 days.

  In the present invention, a commercially available product can be used as one or more selected from the group consisting of the assembly and the extract thereof. Specific examples of the commercially available product include assembly powder (manufactured by Nippon Powder Chemical Co., Ltd.) and the like. Is mentioned.

In the present invention, the content of one or more selected from the group consisting of the assembly and its extract is not particularly limited, but from the viewpoint of pharmacological action, it is 0.05 to 4 in terms of bulk drug based on the total mass of the oral preparation. It is preferably contained in an amount of 0.1% by mass, more preferably 0.1 to 3% by mass, and particularly preferably 0.5 to 2% by mass.
Further, the content mass ratio [(D) / (B) of (B) one or more selected from the group consisting of lactic acid and its salt and one or more selected from the group consisting of (D) assembly and its extract ] Is not particularly limited, but from the viewpoint of the effect of suppressing unpleasant taste, 1 or more selected from the group consisting of lactic acid and its salt is selected from the group consisting of assembly and its extract to 1 part by mass in total 1 The total amount of seeds or more in terms of bulk drug substance is preferably 0.05 to 4 parts by mass, more preferably 0.1 to 3 parts by mass, and particularly preferably 0.5 to 2 parts by mass.
Furthermore, the content mass ratio [(D) / (C)] of (C) sucralose and (D) one or more selected from the group consisting of an assembly and an extract thereof is not particularly limited, but it suppresses unpleasant taste. From the viewpoint of the above, with respect to 1 part by mass of sucralose, a total of 0.1 to 40 parts by mass, preferably 0.5 to 30 parts by mass of one or more selected from the group consisting of the assembly and its extract in terms of the active ingredient is used. More preferred is 1 to 20 parts by mass.

  In the present invention, the “oral preparation” means a preparation to be administered orally, and the specific form (dosage form) is not particularly limited. For example, any form of solid, semi-solid, and liquid may be used, and it can be used in medicines, quasi drugs, and foods. Specifically, solid preparations such as tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, and dissolving tablets), capsules, granules (including effervescent granules), powders, dry syrups, etc. The dosage form described in the 16th revision Japanese Pharmacopoeia, such as liquids (including elixirs, suspensions, emulsions, limonades), semi-solid and liquid preparations such as syrups and oral jellys, etc. it can.

As the dosage form of the oral preparation of the present invention, a solid preparation is preferable from the viewpoint of ease of handling, and powders, granules, and tablets are more preferable.
Among these solid preparations, powders, granules, orally disintegrating tablets are more preferable, and granules are particularly preferable from the viewpoint of the action of suppressing unpleasant taste. These dosage forms, unlike other solid preparations, increase the contact between the oral component and the tongue during administration, and the deterioration of the feeling of administration due to unpleasant taste is significant. According to this, unpleasant taste can be sufficiently suppressed.

  In the oral preparation of the present invention, in addition to the above-described components, a pharmaceutically acceptable carrier (excipient, binder, disintegrant, lubricant, colorant, corrigent, coating, etc., depending on the above-mentioned dosage form. 1 type or 2 types or more of an agent etc. may be mix | blended.

Examples of the excipient include lactose, starches, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid and the like.
In the present invention, the content of the excipient is not particularly limited, but it is preferably 1 to 70% by mass, more preferably 10 to 60% by mass, more preferably 15 to 50% by mass based on the total mass of the oral preparation. % Content is particularly preferable.
Examples of the binder include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan and the like.
In the present invention, the content of the binder is not particularly limited, but it is preferably 1 to 50% by mass, more preferably 2 to 30% by mass, and more preferably 3 to 20% by mass based on the total mass of the oral preparation. It is particularly preferable to contain it.
Examples of the disintegrant include sodium carboxymethyl starch, carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, and low-substituted hydroxypropylcellulose.
In the present invention, the content of the disintegrant is not particularly limited, but it is preferably 0.5 to 30% by mass, more preferably 1 to 20% by mass based on the total mass of the oral preparation, 1.5 It is especially preferable to contain 10 mass%.
Examples of the lubricant include magnesium stearate and talc.
Examples of the colorant include tar pigments and iron sesquioxide.
Examples of the corrigent include stevia and aspartame.
Coating agents include film-forming polymers such as carboxymethyl ethyl cellulose, cellulose acetate phthalate, methacrylic acid copolymer S, methacrylic acid copolymer L, methacrylic acid copolymer LD, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate. Can be mentioned.
When forming a film, a plasticizer such as triethyl citrate, triacetin, or polyethylene glycol; powders such as talc, titanium oxide, yellow ferric oxide, ferric oxide, legal dye, light anhydrous silicic acid, hydrous silicon dioxide, etc. It can also be blended.
In this invention, these 1 type (s) or 2 or more types can be mix | blended combining suitably.

  The use of the oral preparation of the present invention is not particularly limited, and can be used as pharmaceuticals, quasi drugs, foods (particularly foods for specified health use, nutritional functional foods, functional display foods, supplements, etc.) and the like. For example, in the case of use as a pharmaceutical, quasi-drug, etc., depending on the type of basic inorganic compound to be blended, the type of other blending components, etc., specifically, for example, cold medicine, antipyretic analgesic It can be used as an antitussive expectorant, gastrointestinal, laxative, antidepressant, vitamin main ingredient, etc. In the present invention, it is preferably used as a gastrointestinal drug.

  In addition to the above-described components, one or more of other pharmaceutical components may be blended in the oral preparation of the present invention in accordance with the above-described pharmaceutical use.

  When used as a cold medicine, for example, aspirin, aspirin aluminum, acetaminophen, etenzamide, sazapyrine, salicylamide, lactylphenetidine, isothipentyl hydrochloride, diphenylpyralin hydrochloride, diphenhydramine hydrochloride, dipheterol hydrochloride, triprolidine hydrochloride, tripelenamine hydrochloride , Tonsylamine hydrochloride, phenetazine hydrochloride, methodirazine hydrochloride, diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline tecolate, promethazine methylene disalicylate, carbinoxamine maleate Lamin, dipheterol phosphate, aloclamide hydrochloride, Acid cloperastine, Pentoxifylline citrate (Carbetapentane citrate), Tipepidine citrate, Dibutate sodium, Dextromethorphan hydrobromide, Dextromethorphan / phenolphthaline salt, Tipepidine hibenzate , Fendizoic acid cloperastine, phosphate codeine, dihydrocodeine phosphate, noscapine hydrochloride, noscapine, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, potassium guaiacolsulfonate, guaifenesin, sodium benzoate caffeine, anhydrous caffeine, Vitamin B1 and derivatives thereof and salts thereof, vitamin B2 and derivatives thereof and salts thereof, vitamin C and derivatives thereof and salts thereof, hesperidin and derivatives thereof and salts thereof, Acetic acid, Maoh, Nantenjitsu, Spruce, Onji, Licorice, Kyary, Shazenshi, Shazenso, Ishigaki, Senega, Baimo, Fennel, Oats, Auren, Gajutsu, Chamomile, Keihi, Gentian, Gooh, Beast (including Utan), Shajin , Showa, Sojitsu, Clove, Chinpi, Sandalwood, Ground dragon, Chicksetsu carrot, Carrot, Kakkon-yu, Katsue-yu, Koso-san, Saiko-Kei-yu, Sho-saiko-yu, Shosei-yu What is necessary is just to mix | blend semi-summer Kobaku-to, Mao-to, etc. suitably.

  When used as an antipyretic analgesic, for example, acetaminophen, ibuprofen, loxoprofen, lactylphenetidine, aspirin, aspirin aluminum, etenzamide, sazapyrine, salicylamide, sodium salicylate, allylisopropylacetylurea, bromvalerylurea, sodium benzoate Caffeine, anhydrous caffeine, vitamin B1 and derivatives thereof and salts thereof, vitamin B2 and derivatives thereof and salts thereof, vitamin C and derivatives thereof and salts thereof, hesperidin and derivatives thereof and salts thereof, aminoacetic acid , Earth dragons, licorice, kehi, peonies, buttonpi, valerian, salamander, ginger, chimpi and the like may be combined as appropriate.

  When used as an antitussive expectorant, for example, aloclamide hydrochloride, cloperastine hydrochloride, pentoxyberine citrate (carbetapentane citrate), tipepidine citrate, dibutate sodium, dextromethorphan hydrobromide Dextromethorphan phenolphthaline salt, tipepidine hibenzate, cloperastine phendizoate, codeine phosphate, dihydrocodeine phosphate, trimethquinol hydrochloride, methoxyphenamine hydrochloride, dl-methylephedrine hydrochloride, 1-methylephedrine hydrochloride , Noscapine hydrochloride, noscapine, aminophylline, diprofylline, theophylline, proxyphylline, ammonium chloride, l-menthol, ammonia fennel, potassium guaiacol sulfonate, guaifenesin, cresol Potassium sulfonate, lysozyme chloride, ethylcysteine hydrochloride, methylcysteine hydrochloride, isothipentyl hydrochloride, iproheptin hydrochloride, dipheterol hydrochloride, diphenylpyralin hydrochloride, diphenhydramine hydrochloride, triprolidine hydrochloride, tripelenamine hydrochloride, tonsylamine hydrochloride, phenetazine hydrochloride, promethazine hydrochloride, diphenhydramine salicylate, Carbinoxamine diphenyldisulfonate, alimemazine tartrate, diphenhydramine tannate, phenetazine tannate, diphenylpyraline teocrate, promethazine methylene disalicylate, carbinoxamine maleate, dl-chlorpheniramine maleate, chlorpheniramine maleate, dipheterol phosphate , Sodium benzoate caffeine, caffeine, anhydrous cafe , Cetylpyridinium chloride, Decalinium chloride, Chlorhexidine hydrochloride, Aminoacetic acid, Mao, Nantenjitsu, Spruce, Onji, Licorice, Kyoukyo, Kyonin, Shazenshi, Shazenso, Sexane, Senega, Tokon, Baimo, Azalea, Fennel, Ogon, Caronin, Keihi , Goo, trash, saishin, sion, musk, shajin, ginger, sohakuhi, soyo, chikutsujinjin, chimpi, carrot, bacmond, hanger, etc.

  In the case of use as a gastrointestinal agent, for example, aminoacetic acid, funnel extract, aniseed fruit, aloe, fennel, turmeric, yak, life-extending grass, cormorant, duckweed, auren, processed large coral, gadget, cuckoo, columnar root, pheasant, caihi , Gentian, Kojin, Koboku, Goshuyu, Pepper, Colombo, Conzurango, Salamander, Yamana, Shisoshi, Shukusha, Shoyo, Shozuo, Aoshima, Ishizone, Centaurium grass, Sojutsu, Soyo, Daiou, Chikusetsuninjin, Choji, Chimpi , Capsicum, spruce, animal gall (including yutan), oyster, nutmeg, carrot, mint (including mint), baboon, peafowl, hops, honey extract, waterseed, mokko, yakchi, ryutan, ryokyo, fennel Oil, cinnamon oil, ginger oil, ginger oil, clove oil, spruce oil, mint oil, lemon oil, l-menthol, dl-menthol, betaine hydrochloride, glutamate hydrochloride, carnitine chloride, betanecol, dry yeast, starch digestion Enzymes, protein digestive enzymes, fat digestive enzymes, fibrin digestive enzymes, ursodeoxycholic acid, oxycoranoates, cholic acid, bile powder, bile extract (powder), dehydrocholic acid, animal gall (including utan), Red buds, Acacia yam, Ubi, Ketsumeishi, Gennosho, Acrinol, Berberine chloride, Guayacol, Creosote, Phenyl salicylate, Guayacol carbonate, Berberine tannate, Bismuth subsalicylate, Bismuth nitrate, Bismuth subcarbonate, Bismuth gallate, Tannic acid, Albu tannate , Methylene thymol tannin, kaolin, natural aluminum silicate, hydroxy naphthoate aluminum, pectin, medicinal charcoal, kudin, pentaploid, hawthorn, baihi, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, odor Methyl atropine bromide, methyl anisotropin bromide, methyl scopolamine bromide, methyl l-hyostiamine bromide, methylbenactidium bromide, belladonna extract, iodopropamide iodide, diphenylpiperidinomethyldioxolane iodide, funnel extract, Funnel root total alkaloid citrate, papaverine hydrochloride, ethyl aminobenzoate, engosaku, licorice, peony, sodium azulenesulfonate, aldioxa, glycyrrhizic acid and its salts and licorice extraction , L- glutamine, copper chlorophyllin potassium, sodium copper chlorophyllin, histidine hydrochloride, porcine gastric wall pepsin decomposition product, pig stomach acid hydrolyzate may be formulated in combination methylmethionine sulfonium chloride, dimethylpolysiloxane and the like as appropriate.

  In the case of use as a laxative, for example, carboxymethylcellulose calcium, sodium carboxymethylcellulose, prandako obata seed coat (Ispagra seed coat), dioctyl sodium sulfosuccinate, aloin, sulfur, casantranol, sennoside AB, bisacodyl, Aloe, age, cascara sagrada, kengo, kengo fat, senna, senna fruit (senna fruit), diau, frangula peel, yarapa, yarapa fat, malt extract, scented castor oil, castor oil, ursodeoxycholic acid, oxycoranoic acid Salts, dry yeast, cholic acid, dimethylpolysiloxane, live intestinal fungi component, dehydrocholic acid, flaxseed, valerian, licorice, beetle, sankirai, sanshishi, jiou, peony, juyaku, shouma, Nyukyu, Tiso, Bile extract (powder), Toki, Animal gall, Button pi, Macinin, Yokuinin, fennel, Life-saving grass, Ogon, Ouaku, Oren, Gakutsu, Calamus root, Pheasant, Keihi, Gentian, Koboku, Kuzurango, Yamana, Sho Kyou, Sojutsu, Soyo, Chinpi, Spruce, Carrot, Pepper, Pepper Oil, Sandalwood, Homica Extract, dl-Menthol, 1-Menthol, Mokko, Ryutan, Vitamin B1 and its Derivatives, and Their Salts, Vitamin B6 and Derivatives, and Their These salts, nicotinamide, calcium pantothenate and the like may be combined in an appropriate combination.

  When used as an antidepressant, for example, diphenidol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, promethazine hydrochloride, meclizine hydrochloride, diphenhydramine salicylate, dimenhydrinate, diphenhydramine tannate, phenetazine tannate, diphenylpyraline teocrate, fumaric acid Diphenhydramine, promethazine methylene disalicylate, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, pheniramine maleate, scopolamine hydrobromide, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, methyl atropine bromide , Methyl anisotropin bromide, scopolamine bromide, methyl-1-hyostiamine bromide, methylbenactidium bromide, verado Extract, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, funnel extract, papaverine hydrochloride, ethyl aminobenzoate, cerium oxalate, ethyl piperidylacetylaminobenzoate, allylisopropylacetylurea, bromvalerylurea, caffeine, Caffeic acid citrate, anhydrous caffeine, aminophylline, diprofylline, theophylline, mint oil, dl-menthol, l-menthol, vitamin B1 and its derivatives and their salts, vitamin B2 and its derivatives and their salts, vitamin B6 and its Derivatives and salts thereof, nicotinamide, calcium pantothenate and the like may be combined in an appropriate combination.

  When used as a vitamin main drug formulation, for example, retinol acetate, retinol palmitate, vitamin A oil, liver oil, strong liver oil, ergocalciferol, cholecalciferol, d-α-tocopherol succinate, dl-α-succinate Tocopherol, dl-α-tocopherol calcium succinate, d-α-tocopherol acetate, dl-α-tocopherol acetate, d-α-tocopherol, dl-α-tocopherol, thiamine hydrochloride, thiamine nitrate, bistamine nitrate, thiamine disulfide, thiamine Dicetyl sulfate ester salt, dicetiamine hydrochloride, fursultiamine hydrochloride, octothiamine, chicotiamine, bisbutiamine, bisbenchamine, fursultiamine, prosultiamine, benfotiamine, flavin adenine dinuclear Sodium tide, riboflavin, sodium riboflavin, riboflavin butyrate, pyridoxine hydrochloride, pyridoxal phosphate, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, hydroxocobalamin, mecobalamin, ascorbic acid, calcium ascorbate, sodium ascorbate, nicotinic acid, nicotine Acid amide, panthenol, calcium pantothenate, sodium pantothenate, biotin, potassium aspartate / magnesium equivalent mixture, inositol hexanicotinate, ursodeoxycholic acid, L-cysteine hydrochloride, L-cysteine, orotic acid, gamma oryzanol , Calcium glycerophosphate, calcium gluconate, glucuronolactone, glucuronic acid amide, chondro What is necessary is just to mix | blend sodium itine sulfate, processed potato, a carrot, Yokuinin, etc. suitably.

  The dosage of the oral preparation of the present invention for humans may be appropriately adjusted according to the dosage form, pharmaceutical use, degree of disease, age of patient, etc., but generally based on basic inorganic compounds for adults, What is necessary is just to administer about 100-5000 mg / day, especially about 500-3000 mg / day, and the dosage of another component can also be determined with reference to said content mass ratio according to such dosage. In the case of an oral preparation that does not contain a basic inorganic compound as an essential component, it is usually 1 or more in terms of bulk drug substance based on at least one selected from the group consisting of assembly and its extract for adults. About 5,000 mg / day, in particular, about 5-1500 mg / day may be administered, and the dosage of other components can also be determined according to such dosage, with reference to the above-mentioned content mass ratio.

Next, the method of the present invention (a method for suppressing unpleasant taste, a method for producing an oral preparation, etc.) will be described.
The method of the present invention is characterized in that a combination of sucralose and one or more selected from the group consisting of lactic acid and salts thereof is further contained in an oral preparation. In the method of the present invention, the meaning of each word, the amount of each component used, and the like are the same as in the case of the oral preparation of the present invention.

  EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[Test Example 1] Evaluation of inhibitory effect of basic inorganic compound on unpleasant taste In order to evaluate the inhibitory action of sodium bicarbonate on unpleasant taste (salt taste), the granules of Examples 1 to 4 below were produced and subjected to the following method. Sensory evaluation (evaluation of salty taste) was performed.

[Example 1]
700 g of sodium hydrogen carbonate, 600 g of mannitol, 120 g of carmellose calcium, 180 g of hydroxypropyl cellulose, 10 g of sucralose and 30 g of calcium lactate were put into a universal mixing stirrer (manufactured by Dalton: 5DML type) and mixed and kneaded. The obtained kneaded product is extruded and granulated with a dome gran (made by Fuji Powder Co., Ltd .: DG-L11 type) equipped with a die of φ8 mm, and put into a fluidized bed dryer (Freund Sangyo Co., Ltd .: FLO-5 type). After drying, the particles were sized using a sizing machine (manufactured by Okada Seiko: ND-10 type). The sized product was classified using a 50 mesh sieve to obtain the granule of Example 1.

[Example 2]
The granule of Example 2 was obtained in the same manner as in Example 1 except that both sucralose and calcium lactate were not added.
[Example 3]
The granule of Example 3 was obtained in the same manner as in Example 1 except that sucralose was not added.
[Example 4]
The granule of Example 4 was obtained in the same manner as in Example 1 except that calcium lactate was not added.

[Evaluation of salty taste]
The feeling of taking (salty taste) when 3 g of each granule of Examples 1 to 4 was placed on the tongue for 30 seconds was evaluated by seven panelists with sufficient time.
The feeling of taking (salty taste) was evaluated by scoring according to the following evaluation criteria.
<Evaluation criteria>
Feel extremely salty 4 Feel strong salt 3 Feel salty 2 Feel slightly salty 1 Feel almost salty 0

  The sensory evaluation results (breakdown of evaluation of each panel and total score) are shown in Table 1 together with the blending amount (g) of each component.

From Table 1, the result was that the granule of Example 3 containing sodium hydrogen carbonate and calcium lactate had a stronger unpleasant taste (salt taste) than the granule of Example 2 containing only sodium hydrogen carbonate. Moreover, the unpleasant taste of the granule of Example 4 containing sodium hydrogen carbonate and sucralose was the same as the unpleasant taste of the granule of Example 2 containing only sodium hydrogen carbonate.
On the other hand, in addition to sodium hydrogen carbonate and calcium lactate, the granule of Example 1 further containing sucralose has markedly suppressed unpleasant saltiness derived from sodium hydrogen carbonate, and has a good feeling of administration. .
From the above test results, it is clear that by combining sucralose in addition to calcium lactate, an unpleasant taste of basic inorganic compounds such as sodium hydrogen carbonate is remarkably suppressed, and an oral preparation with a good feeling of administration can be obtained. It became.

[Test Example 2] Evaluation of inhibitory action of unpleasant taste of assembly In order to evaluate the inhibitory action of unpleasant taste (bitter taste) of assembly, granules of Examples 5 to 8 below were produced, and sensory evaluation was performed by the following method ( (Evaluation of bitterness).

[Example 5]
30 g of assembly powder, 195 g of hardened oil, and 35 g of hydroxypropyl cellulose were put into a universal mixing stirrer (manufactured by Dalton: 5DML type) and mixed and kneaded. The obtained kneaded product is extruded and granulated with a dome gran (made by Fuji Powder Co., Ltd .: DG-L11 type) equipped with a die of φ8 mm, and put into a fluidized bed dryer (Freund Sangyo Co., Ltd .: FLO-5 type). After drying, the particles were sized using a sizing machine (manufactured by Okada Seiko: ND-10 type). This sized product was classified using a 50 mesh sieve.
The obtained granule was mixed with the granule of Example 1 to obtain the granule of Example 5.

[Example 6]
The granule of Example 6 was obtained in the same manner as in Example 5 except that the granule of Example 2 was used instead of the granule of Example 1.
[Example 7]
The granule of Example 7 was obtained in the same manner as in Example 5 except that the granule of Example 3 was used instead of the granule of Example 1.
[Example 8]
A granule of Example 8 was obtained in the same manner as in Example 5 except that the granule of Example 4 was used instead of the granule of Example 1.

[Evaluation of bitterness]
The feeling of taking (bitter taste) when 3 g of each of the granules of Examples 5 to 8 was placed on the tip of the tongue for 30 seconds was evaluated by seven panelists with sufficient time.
Evaluation of the feeling of taking (bitter taste) was performed by scoring according to the following evaluation criteria.
<Evaluation criteria>
I feel extremely strong bitterness 4 I feel strong bitterness 3 I feel bitterness 2 I feel some bitterness 1 I almost feel no bitterness 0

  The sensory evaluation results (breakdown of evaluation of each panel and total score) are shown in Table 2 together with the blending amount (g) of each component.

From Table 2, the granule of Example 5 containing assembly, calcium lactate, and sucralose has a significantly reduced unpleasant bitterness derived from the assembly, resulting in a good feeling of dosing.
From the above test results, it has been clarified that the combination of calcium lactate and sucralose has an effect of significantly suppressing not only the basic inorganic compound but also the unpleasant taste of the assembly.

[Production example]
Granules of Examples 9 to 13 were obtained in the same manner as in Example 1 except that other basic inorganic compounds were used in place of sodium hydrogen carbonate.
Table 3 shows the blending components and blending amount (g). In all of these, the unpleasant taste was suppressed and the feeling of taking was good.

[Production Example 1]
Granules (mixture of granules 1 and 2 and 75 mg of menthol powder) containing the following components in 3 capsules were produced by a conventional method.
<Granule 1>
Assembly powder 30mg
Roto extract triple powder 90mg
Biodiastase 2000 24mg
Methylmethioninesulfonium chloride 150mg
Lipase AP12 15mg
Soyo Dry Extract 30mg (Drug equivalent)
Hardened oil 195mg
Hydroxypropylcellulose 36mg
<Granule 2>
Sodium bicarbonate 700mg
Precipitated calcium carbonate 1200mg
Magnesium carbonate 250mg
Calcium lactate 30mg
Sucralose 2mg
Mannitol 683mg
Carmellose calcium 120mg
Hydroxypropylcellulose 180mg

[Production Example 2]
Tablets containing the following components in 6 tablets were produced by a conventional method.
Sodium bicarbonate 700mg
Precipitated calcium carbonate 1200mg
Magnesium carbonate 250mg
Calcium lactate 20mg
Sucralose 5mg
Methylmethioninesulfonium chloride 150mg
Soyo Dry Extract 270mg (Drug equivalent)
Rohto extract 90mg
Assembly powder 30mg
Keihi powder 20.5mg
Biodiastase 2000 24mg
Lipase AP12 15mg
Hydroxypropylcellulose 24mg
Hardened oil 206mg
Polyvinyl alcohol 106mg
Carmellose calcium 142.5mg
Corn starch 24mg
Crystalline cellulose 274mg
Low-substituted hydroxypropylcellulose 133mg
Hydrous silicon dioxide 29.5mg
10 mg glyceryl monostearate
Polyoxyl stearate 3mg
Purified shellac 4mg
Talc 26.5mg
l-Menthol 4mg
Magnesium stearate 14.5mg

  ADVANTAGE OF THE INVENTION According to this invention, the oral agent with a favorable feeling of administration containing a basic inorganic compound and the unpleasant taste was suppressed can be provided, and it can utilize in pharmaceutical industry, quasi-drug industry, etc.

Claims (11)

The following components (A), (B) and (C):
(A) a basic inorganic compound;
(B) one or more selected from the group consisting of lactic acid and salts thereof;
(C) sucralose;
An oral preparation containing   Basic inorganic compound is dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesium alumina hydroxide, aluminum hydroxide gel, aluminum hydroxide / carbonic acid Sodium hydrogen coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, magnesium hydroxide, sodium hydrogen carbonate, magnesium carbonate, precipitated calcium carbonate, metasilicate aluminate The oral preparation according to claim 1, wherein the oral preparation is one or more selected from the group consisting of magnesium, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, bandit bones, stone decision and borei.   The oral preparation according to claim 1, wherein the basic inorganic compound is at least one selected from the group consisting of synthetic hydrotalcite, magnesium oxide, magnesium hydroxide, sodium hydrogen carbonate, precipitated calcium carbonate, and magnesium aluminate metasilicate. .   The oral preparation according to any one of claims 1 to 3, wherein at least one selected from the group consisting of lactic acid and a salt thereof is calcium lactate.   The oral preparation according to any one of claims 1 to 4, which is a powder, a granule, or an orally disintegrating tablet.   The oral preparation according to any one of claims 1 to 5, which is used as a gastrointestinal drug.   Furthermore, the oral preparation of any one of Claims 1-6 containing 1 or more types chosen from the group which consists of (D) assembly and its extract.   A method for suppressing an unpleasant taste of an oral preparation containing a basic inorganic compound, wherein the oral preparation contains at least one selected from the group consisting of lactic acid and a salt thereof and sucralose.   Basic inorganic compound is dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesium alumina hydroxide, aluminum hydroxide gel, aluminum hydroxide / carbonic acid Sodium hydrogen coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, magnesium hydroxide, sodium hydrogen carbonate, magnesium carbonate, precipitated calcium carbonate, metasilicate aluminate The method according to claim 8, which is at least one selected from the group consisting of magnesium, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, bandit bones, stone decision and borei.   The method according to claim 8, wherein the basic inorganic compound is at least one selected from the group consisting of synthetic hydrotalcite, magnesium oxide, magnesium hydroxide, sodium hydrogen carbonate, precipitated calcium carbonate, and magnesium aluminate metasilicate.   The method according to any one of claims 8 to 10, wherein at least one selected from the group consisting of lactic acid and a salt thereof is calcium lactate.