JP6910103B2 - Oral preparation - Google Patents

Description

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

Basic inorganic compounds such as sodium hydrogen carbonate are used in the fields of pharmaceuticals, cosmetics, foods and the like. In particular, in the pharmaceutical field, it is widely used for oral oral medicines such as gastrointestinal medicines and cold medicines as so-called antacids and gastric mucosa protective components based on the antacid action of basic inorganic compounds.
As described above, the basic inorganic compound is extremely useful as a component of an oral preparation, but has a drawback that it has an unpleasant taste (bitter taste, salty taste, etc.) peculiar to the inorganic compound (for example, Non-Patent Document 1). The unpleasant taste of the ingredients in the oral preparation impairs the feeling of taking the medicine and causes the compliance with the medicine to be lowered. In particular, in the case of oral preparations in the form of powders, granules, orally disintegrating tablets, etc., the contact between the components of the oral preparation and the tongue increases, so that the feeling of ingestion due to the unpleasant taste becomes remarkable.

Various methods for suppressing unpleasant taste and masking methods have been proposed in order to improve the deterioration of the feeling of ingestion due to the unpleasant taste of the basic inorganic compound and to improve the compliance with taking the drug. For example, Patent Document 1 states that by combining Stevia with a basic inorganic compound such as synthetic hydrotalcite, magnesium oxide, sodium hydrogen carbonate, precipitated calcium carbonate, and magnesium aluminometasilicate, the feeling of administration, flavor, and aftertaste are improved. It is described that an oral composition can be obtained. However, the suppression of unpleasant taste by such a method is not always sufficient.

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

Japanese Unexamined Patent Publication No. 9-5827 Japanese Patent No. 5097488

16th Amendment Japanese Pharmacy Manual, Hirokawa Bookstore Co., Ltd. C-2671

An object of the present invention is to provide a new technique for suppressing the unpleasant taste of a basic inorganic compound.

First, the present inventor tried to suppress the unpleasant taste by combining calcium lactate with a basic inorganic compound with reference to the description in Patent Document 2, and surprisingly, the combination of calcium lactate warped. It was revealed that the unpleasant taste was enhanced.
Therefore, as a result of further diligent studies, the present inventor has found that by further combining sclarose in addition to the basic inorganic compound and calcium lactate, the unpleasant taste of the basic inorganic compound is remarkably suppressed, and an oral preparation having a good feeling of administration. The present invention was completed by finding that

That is, in the present invention, the following components (A), (B) and (C):
(A) Basic inorganic compound;
(B) One or more selected from the group consisting of lactic acid and its salts;
(C) Sucralose;
To provide an oral preparation containing.

Further, the present invention is a method for suppressing the 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. It is to provide.
Further, the present invention is an unpleasant taste inhibitor that suppresses an unpleasant taste derived from a basic inorganic compound, and contains one or more selected from the group consisting of lactic acid and a salt thereof and sclorose. It is to provide.
Further, the present invention is a method for producing an oral preparation having suppressed unpleasant taste derived from 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 provides a method including a sucralose step.

The oral preparation of the present invention suppresses the unpleasant taste derived from the basic inorganic compound and has a good feeling of ingestion. Therefore, it can be a medicine or the like having excellent medication compliance.
According to the method of the present invention, it is possible to provide an oral preparation in which the unpleasant taste derived from a basic inorganic compound is suppressed, the feeling of ingestion is good, and the compliance with administration is excellent.

First, the oral preparation of the present invention will be described in detail below.
<Ingredient (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-based basic inorganic compounds; alkali metal-based basic inorganic compounds such as sodium and potassium. Can be mentioned.
Specific examples of the alkaline earth metal and / or earth metal-based basic inorganic compound include magnesium silicate, magnesium silicate aluminate, magnesium aluminum silicate, magnesium oxide, magnesium hydroxide, and magnesium hydroxide. Aluminum potassium sulfate co-precipitate product, magnesium carbonate, synthetic hydrotalcite, magnesium aluminometasilicate, dry aluminum hydroxide gel, synthetic aluminum silicate, synthetic aluminum silicate, hydroxypropyl starch, crystalline cellulose, magnesium hydroxide, Aluminum hydroxide gel, aluminum hydroxide / sodium hydrogen carbonate co-precipitated product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitated product, bentonite, calcium silicate, calcium carbonate, Examples thereof include magnesium such as precipitated calcium carbonate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, and inorganic salts of metals selected from aluminum and calcium.
Specific examples of the alkali metal-based basic inorganic compound include dry sodium carbonate, sodium hydroxide, sodium hydrogencarbonate, sodium carbonate hydrate, tetrasodium pyrophosphate, trisodium phosphate, and sodium hydrogenphosphate. Examples thereof include hydrates, anhydrous sodium pyrophosphate, anhydrous sodium monohydrogen phosphate, potassium hydroxide, potassium hydrogen carbonate, potassium carbonate and other sodiums, and inorganic salts of metals selected from potassium.
Further, in the present invention, a crude drug containing a basic inorganic compound such as squid bone, stone determination, and volley as a main component may be used.
All of the above-mentioned components are known compounds, and commercially available ones 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 hydroxide alumina, aluminum hydroxide gel, Aluminum hydroxide / sodium hydrogen carbonate co-precipitated product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitated product, magnesium hydroxide, sodium hydrogen carbonate, magnesium carbonate, precipitated calcium carbonate , Magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, sardine bone, stone determination and volley, preferably one or more selected from the group consisting of synthetic hydrotalcite, magnesium oxide, magnesium hydroxide, One or more selected from the group consisting of sodium hydrogen carbonate, precipitated calcium carbonate and magnesium aluminometasilicate is more preferable, and sodium hydrogen carbonate is particularly preferable. Sodium hydrogen carbonate has a peculiar salty taste, but according to the present invention, such an unpleasant salty taste can be remarkably suppressed.

The content of the basic inorganic compound in the oral preparation of the present invention is not particularly limited, and may be appropriately set according to the compounding purpose and the like. In the present invention, the basic inorganic compound is preferably contained in an amount of 15 to 85% by mass, more preferably 25 to 80% by mass, and further preferably 30 to 70% by mass with respect to the total mass of the oral preparation. It is preferably contained in an amount of 32.5 to 60% by mass, more preferably 35 to 55% by mass, further preferably 35 to 50% by mass, and particularly preferably 35 to 40% by mass. preferable.

<Ingredient (B)>
In the present invention, the "lactic acid" is not particularly limited, and either L-lactic acid or D-lactic acid may be used, and a mixture thereof may be used.
Further, 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 these are used alone. Or, two or more kinds can be used in combination.
Further, in the present invention, "one or more selected from the group consisting of lactic acid and salts thereof" may be hydrate or anhydride.
In the present invention, calcium lactate is preferable as "one or more selected from the group consisting of lactic acid and salts thereof" from the viewpoint of suppressing unpleasant taste. Lactic acid and its salt are known compounds, and commercially available ones may be used, or they can be produced by a 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 suppressing the unpleasant taste, the content is preferably 0.05 to 4% by mass, more preferably 0.1 to 3% by mass, based on the total mass of the oral preparation. It is particularly preferably contained in an amount of 5 to 2% by mass.
Further, the content mass ratio [(B) / (A)] of (A) a basic inorganic compound and (B) one or more selected from the group consisting of lactic acid and a salt thereof in the oral preparation of the present invention is not particularly limited. However, from the viewpoint of suppressing the 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 0.04 to 1. 0.5 is particularly preferable.

<Component (C)>
"Sucralose" (trichlorogalactosucrose) is a known compound, and a commercially available compound may be used, or it 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 suppressing the unpleasant taste, 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. It is more preferably contained in an amount of 05 to 1.5% by mass, and particularly preferably 0.1 to 1% by mass.
The mass ratio of (A) basic inorganic compound to (C) sucralose [(C) / (A)] in the oral preparation of the present invention is not particularly limited, but is 0 from the viewpoint of suppressing unpleasant taste. .0001 to 3 is preferable, 0.0005 to 2 is more preferable, 0.001 to 1.5 is further preferable, 0.002 to 1 is further preferable, and 0.005 to 0.5 is particularly preferable.
The mass ratio [(C) / (B)] of one or more selected from the group consisting of (B) lactic acid and a salt thereof in the oral preparation of the present invention to (C) sucralose is not particularly limited, but is unpleasant. From the viewpoint of taste suppressing action, 0.001 to 10, 0.01 to 5, more preferably 0.03 to 3, and 0.06 to 1 are particularly preferable.

<Component (D)>
In the oral preparation of the present invention, Swertia japonica may be further blended as the component (D) in addition to the above components (A) to (C). Swertia japonica is a component used as a raw material for a bitter stomachic medicine and as a component of a gastrointestinal drug, 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 a salt thereof and sucralose has a remarkable inhibitory effect on the bitter taste of Swertia japonica. It became clear.
Therefore, the following components (A), (B), (C) and (D):
(A) Basic inorganic compound;
(B) One or more selected from the group consisting of lactic acid and its salts;
(C) Sucralose;
(D) One or more species selected from the group consisting of Swertia japonica and its extracts;
The oral preparation containing the above suppresses not only the basic inorganic compound but also the unpleasant taste derived from Swertia japonica and has a good feeling of ingestion. Therefore, it can be suitably used as a drug (for example, a gastrointestinal drug) that has excellent medication compliance and utilizes the excellent pharmacological action of Swertia japonica.
The oral preparation is an oral preparation obtained by using a granulated product containing the components (A) to (C) and a granulated product containing the component (D) (more specifically, the component (A)). A powder or granule containing a granulated product containing (C) and a granulated product containing the component (D); a granulated product containing the components (A) to (C) and a granulated product containing the component (D). Tablets obtained by using a raw material containing a granulated product) are preferable.

From another point of view, the present invention describes the following components (D), (B) and (C):
(D) One or more species selected from the group consisting of Swertia japonica and its extracts;
(B) One or more selected from the group consisting of lactic acid and its salts;
(C) Sucralose;
To provide an oral preparation (preferably a gastrointestinal drug) containing the above. Since such an oral drug suppresses the bitterness derived from Swertia japonica and is easy to take, it can be suitably used as a drug having good medication compliance (for example, a gastrointestinal drug) utilizing the pharmacological action of Swertia japonica.
Furthermore, from another point of view, the present invention is a method for suppressing the unpleasant taste of an oral preparation containing at least one selected from the group consisting of Swertia japonica and its extract, which comprises lactic acid and a salt thereof in the oral preparation. It provides a method of containing one or more species selected from the group and sucralose. Further, from another viewpoint, it is an unpleasant taste inhibitor that suppresses an unpleasant taste derived from one or more selected from the group consisting of Swertia japonica and its extract, and one or more selected from the group consisting of lactic acid and a salt thereof. It provides an unpleasant taste inhibitor containing sucralose and sucralose. Furthermore, from another viewpoint, the present invention is a method for producing an oral preparation having suppressed unpleasant taste derived from one or more selected from the group consisting of Swertia japonica and its extract, wherein lactic acid is contained in the oral preparation. The present invention provides a method including a step of incorporating one or more kinds selected from the group consisting of and salts thereof and sucralose.
According to these methods, it is possible to provide a drug having good medication compliance (for example, a gastrointestinal drug) that utilizes the pharmacological action of Swertia japonica and suppresses the bitterness derived from Swertia japonica.
Unless otherwise specified, the meaning of each wording, the amount of various components, the combination ratio, etc. in such an embodiment are the same as in the case of an oral preparation containing a basic inorganic compound as an essential component.

"Swertia japonica" (this drug) means the whole plant of Swertia japonica Makino (Gentianaceae) during the flowering period, as described in the 16th revised Japanese Pharmacy. The form of Swertia japonica can be adjusted as needed, and it can be cut or crushed into small pieces or lumps, or crushed into powder. Can be done. Further, in consideration of convenience of handling at the time of manufacturing the gastrointestinal drug composition, a Swertia japonica subjected to some extraction treatment (hereinafter, referred to as "Swertia japonica extract") may be used.
The above-mentioned "Swertia japonica extract" includes those subjected to processing treatments such as heating, drying, and crushing in addition to the extraction treatment. Specifically, after the assembly was made into an appropriate size as needed, a liquid leached by adding an appropriate extraction solvent, a liquid obtained by concentrating the leaching liquid (soft extract, tincture, etc.), and further dried. Things (dried extract, etc.) are also included in the "assembly extract" of the present invention.
In the present invention, Swertia japonica powder is preferable as one or more selected from the group consisting of Swertia japonica and its extract.

The method for producing Swertia japonica extract is not particularly limited. It can be produced with reference to a known method for producing a plant extract. Specifically, for example, Swertia japonica can be produced by cutting, heating, drying, pulverizing, etc., if necessary, and then adding an appropriate extraction solvent for extraction. The obtained extract may be further concentrated, dried or the like, if 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 Aromatic hydrocarbons; amides such as dimethylformamide; sulfoxides such as dimethylsulfoxide; water (including hot water) and the like. Each of these may be used alone, or two or more thereof may be used in combination. In the present invention, water, ethanol, or a mixed solution of water and ethanol is preferable.
The extraction operation is not particularly limited, and a known method used for the extraction operation from a plant can be adopted. Specifically, for example, immersion in an extraction solvent (cold immersion, warm immersion, percolation, etc.), super Extraction using a critical fluid or a subcritical fluid can be mentioned. In addition, in order to improve the extraction efficiency, it may be homogenized with stirring or in an extraction solvent.
The extraction temperature is not particularly limited and varies depending on the extraction solvent used, the extraction operation and the like, but is preferably about 1 hour to 14 days.

In the present invention, a commercially available product can be used as one or more selected from the group consisting of Swertia japonica and its extract, and specific commercially available products include, for example, Swertia japonica powder (manufactured by Nippon Powder Chemicals Co., Ltd.) and the like. Can be mentioned.

In the present invention, the content of one or more selected from the group consisting of Swertia japonica and its extracts is not particularly limited, but from the viewpoint of pharmacological action, the crude drug equivalent amount is 0.05 to 4 with respect to 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 of one or more selected from the group consisting of (B) lactic acid and its salt and one or more selected from the group consisting of (D) Swertia japonica and its extract [(D) / (B) ] Is not particularly limited, but from the viewpoint of suppressing unpleasant taste, one or more selected from the group consisting of lactic acid and its salt is selected from the group consisting of Swertia japonica and its extract with respect to 1 part by mass in total. A total of 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 of seeds or more in terms of crude drug equivalent.
Further, the content mass ratio [(D) / (C)] of (C) sclarose and one or more selected from the group consisting of (D) Swertia japonica and its extract is not particularly limited, but has an action of suppressing unpleasant taste. From this point of view, it is preferable that one or more kinds selected from the group consisting of Swertia japonica and its extract are added in a total amount of 0.1 to 40 parts by mass, preferably 0.5 to 30 parts by mass, based on 1 part by mass of sclarose. More preferably, 1 to 20 parts by mass is particularly preferable.

In the present invention, the "oral preparation" means a preparation to be orally administered, and the specific form (dosage form) thereof is not particularly limited. For example, it may be in any form of solid, semi-solid or liquid, and may be a form used in pharmaceuticals, quasi-drugs, and foods. Specifically, solid preparations such as tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersed tablets, and dissolving tablets), capsules, granules (including effervescent granules), powders, and dry syrups; oral Dosage forms such as liquid preparations (including elixirs, suspensions, emulsions, limonades), syrups, semi-solid and liquid preparations such as oral jelly, etc., as described in the 16th Amendment of the Japanese Pharmacy, etc. can.

As the dosage form of the oral preparation of the present invention, a solid preparation is preferable, and powders, granules and tablets are more preferable from the viewpoint of ease of handling.
Among these solid formulations, powders, granules, orally disintegrating tablets are more preferable, and granules are particularly preferable, from the viewpoint of suppressing unpleasant taste. Unlike other solid preparations, these dosage forms increase the contact between the components of the oral preparation and the tongue when taken, so that the unpleasant taste causes a remarkable deterioration in the feeling of ingestion. Therefore, the unpleasant taste can be sufficiently suppressed.

In the oral preparation of the present invention, in addition to the above-mentioned components, a pharmaceutically acceptable carrier (excipient, binder, disintegrant, lubricant, colorant, flavoring agent, coating) depending on the above-mentioned dosage form. Agents, etc.) may be blended with one or more.

Examples of the excipient include lactose, starches, crystalline cellulose, sucrose, mannitol, light silicic acid anhydride 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, and 15 to 50% by mass with respect to the total mass of the oral preparation. % Is particularly preferable.
Examples of the binder include hydroxypropyl methylcellulose, hydroxypropyl cellulose, 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 3 to 20% by mass with respect to the total mass of the oral preparation. It is particularly preferable to contain it.
Examples of the disintegrant include carboxymethyl starch sodium, carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, low-degree-of-substitution hydroxypropyl cellulose and the like.
In the present invention, the content of the disintegrant is not particularly limited, but is preferably 0.5 to 30% by mass, more preferably 1 to 20% by mass, 1.5 to 20% by mass, based on the total mass of the oral preparation. It is particularly preferable to contain 10% by mass.
Examples of the lubricant include magnesium stearate and talc.
Examples of the colorant include tar pigments and iron sesquioxides.
Examples of the flavoring agent include stevia and aspartame.
As the coating agent, film-forming polymers such as carboxymethyl ethyl cellulose, cellulose acetate phthalate, methacrylic acid copolymer S, methacrylic acid copolymer L, methacrylic acid copolymer LD, hydroxypropylmethylcellulose phthalate, and hydroxypropylmethylcellulose acetate succinate are used. Can be mentioned.
When forming a film, plasticizers such as triethyl citrate, triacetin, and polyethylene glycol; powders such as talc, titanium oxide, yellow iron sesquioxide, iron sesquioxide, legal pigments, light anhydrous silicic acid, and hydrous silicon dioxide are used. It can also be blended.
In the present invention, one or more of these can be blended as appropriate.

The use of the oral preparation of the present invention is not particularly limited, and it can be used as a pharmaceutical product, a quasi-drug, a food (particularly a food for specified health use, a nutritional functional food, a food with a functional claim, a supplement, etc.). For example, when it is used as a drug, quasi-drug, etc., depending on the type of basic inorganic compound to be blended, the type of other compounding ingredients, etc., specifically, for example, a cold medicine, an antipyretic analgesic, etc. , Antitussive expectorant, gastrointestinal drug, laxative, analgesic, vitamin-based preparation, etc. In the present invention, it is preferably used as a gastrointestinal drug.

In addition to the above-mentioned components, the oral preparation of the present invention may contain one or more of other pharmaceutical components depending on the above-mentioned pharmaceutical uses and the like.

When used as a cold medicine, for example, aspirin, aspirin aluminum, acetaminophen, ethenzamid, sazapyrin, salicylamide, lactylphenetidine, isotipendyl hydrochloride, diphenylpyrrine hydrochloride, diphenhydramine hydrochloride, dipheterol hydrochloride, triprolysine hydrochloride, triperenamine hydrochloride , Tondylamine hydrochloride, phenetazine hydrochloride, metodilazine hydrochloride, diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline theocrate, mebuhydroline napadisylate, promethazine methylene disalicylate, carbinoxamine maleate Lamine, dipheterol phosphate, allocramide hydrochloride, cloperastine hydrochloride, pentoxyphyllin citrate (carbetapentane citrate), tipepidin citrate, sodium dibunato, dextrometholphan hydrobromide, dextrometholphan phenol Phtalin salt, tipepidin hibenzate, cloperastine fendyzoate, codeine phosphate, dihydrocodein phosphate, noscapine hydrochloride, noscapin, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, potassium guaiacol sulfonate, guayphenesin, benzo Sodium acid caffeine, anhydrous caffeine, vitamin B1 and its derivatives and their salts, vitamin B2 and its derivatives and their salts, vitamin C and its derivatives and their salts, hesperidin and its derivatives and their salts, Aminoacetic acid, Maou, Nantenjitsu, Ohi, Onji, Kanzo, Kikyo, Shazenshi, Shazensou, Ishibuki, Senega, Baimo, Uiko, Oubaku, Ouren, Gajutsu, Kamitsure, Keihi, Gentiana, Goou, Beast (including Yutan), Shajin, Shokyo, Soujutsu, Chouji, Chinpi, Byakujutsu, Jiryu, Chikusetsu carrot, Carrot, Katsune-to, Keishi-to, Kaso-san, Saiko-Keishi-to, Koshiba-ko-to, Kosei-ryu-to, Mugimon-fuyu-yu , Half-summer Koboku-to, Mao-to, etc. may be combined and blended as appropriate.

When used as an antipyretic analgesic, for example, acetaminophen, ibuprofen, loxoprofen, lactylphenetidine, aspirin, aspirin aluminum, etenzamid, sazapyrin, salicylamide, sodium salicylate, allylisopropylacetylurea, bromvalerylurea, sodium benzoate. Caffeine, anhydrous caffeine, vitamin B1 and its derivatives and their salts, vitamin B2 and its derivatives and their salts, vitamin C and its derivatives and their salts, hesperidin and its derivatives and their salts, aminoacetic acid , Earth dragon, Kanzo, Keihi, Shakuyaku, Buttonpi, Kanokosou, Sansho, Shokyo, Chimpi, etc. may be combined and blended as appropriate.

When used as an antitussive and sputum, for example, allocramide hydrochloride, cloperastine hydrochloride, pentoxiberin citrate (carbetapentane citrate), tipepidin citrate, dibunato sodium, dextrometholphan hydrobromide. , Dextrometorphanphenol phthaline salt, tipepidin hibenzate, cloperastine fendyzoate, codeine phosphate, dihydrocodein phosphate, trimetokinol hydrochloride, methoxyphenamine hydrochloride, dl-methylephedrine hydrochloride, l-methylephedrine hydrochloride , Noscapine Hydrochloride, Noscapine, Aminophyllin, Diprofyrin, Theophylline, Proxyphyllin, Ammonium Chloride, l-Mentor, Ammonia Wikyosei, Potassium Guayacol Sulfonate, Guayphenesin, Potassium Cresole Sulfonate, Resoteam Chloride, Ethylcysteine Hydrochloride, Methylcysteine Hydrochloride, Isotipendyl hydrochloride, iproheptin hydrochloride, dipheterol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, triprolysine hydrochloride, tryperenamine hydrochloride, tonzilamine hydrochloride, phenetazine hydrochloride, promethazine hydrochloride, diphenhydramine salicylate, diphenyldisulfonate carbinoxamine, diphenyl disulfonate carbinoxamine, diphenyltanide tannate diphenate. , Diphenylpyraline theocrate, promethazine methylene disalicylate, carbinoxamine maleate, dl-chlorpheniramine maleate, chlorpheniramine d-maleate, diferrol phosphate, sodium benzoate caffeine, caffeine, anhydrous caffeine, chloride Cetylpyridinium, decalinium chloride, chlorhexidine hydrochloride, aminoacetic acid, maou, nantenjitsu, ouhi, onji, kanzo, kikyo, kyonin, shazenshi, shazensou, sexan, senega, tokon, baimo, asenyaku, uikyo, ougon, karonin, keihi Gomishi, Saishin, Zion, Jakou, Shajin, Shokyo, Sohakuhi, Soyo, Chikusetsu carrot, Chinpi, Carrot, Bakumondou, Hange and the like may be blended in an appropriate combination.

When used as a gastrointestinal drug, for example, aminoacetic acid, scopolia extract, anis fruit, aloe, uikyo, kon, oyaku, prolongation grass, sardine, sardine, sardine, processed sardine, scopolia japonica, sardine root, scopolia japonica, keihi , Gentiana, Kojin, Koboku, Goshuyu, Kosho, Colombo, Konzlango, Sansho, Yamana, Shisoshi, Shuksha, Shokyo, Shozuku, Aohide, Stone iris, Centaurium grass, Sojutsu, Soyo, Daiou, Chikusetsu carrot , Togarashi, Tohi, Animal Bold (including Yutan), Nigaki, Nikuzuku, Carrot, Scopolia (including Scopolia japonica), Hihatsu, Byakujutsu, Hop, Homika Extract, Scopolia japonica, Mokko, Yakuchi, Ryutan, Ryokyo, Yakuchi, Ryutan, Ryokyo Oil, ginger oil, ginger oil, chow oil, peppermint oil, scopolia oil, lemon oil, l-menthol, dl-menthol, betaine hydrochloride, glutamate salt, carnitine chloride, betanecol chloride, dried yeast, starch digestive enzyme, tan Scopolia digestive enzyme, fat digestive enzyme, fibrin digestive enzyme, ursodeoxycholic acid, oxycholates, cholic acid, bile powder, bile extract (powder), dehydrocholic acid, animal bile (including yutan), red bud Kashiwa, Asenyaku , Ubai, Ketsumeishi, Gennoshoco, Aclinol, Berberin Chloride, Guayacol, Cleosoto, phenyl salicylate, Guayacol Carbonate, Berberin Tannate, Bismus subsalicylate, Bismus hyponitrate, Bismus hypocarbonate, Bismas hypodigestive acid, Tannic acid, Albumin tannate , Methylenetimoltannin, Kaolin, Natural aluminum silicate, Aluminum silicate, Pectin, Medicinal charcoal, Kujin, Scopolia japonica, Scopolia japonicum, Youbaihi, Oxyphencyclimine hydrochloride, Dicyclomine hydrochloride, Methixene hydrochloride, Scopolamine hydrobromide, Bromide Methylatropin, methylanisotropin bromide, methylscopolamine bromide, methyl-l-hyostiamine bromide, methylbenactidium bromide, veradonna extract, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, funnel extract, scopolia Root total alkaloid citrate, papaverin hydrochloride, ethyl aminobenzoate, engosaku, kanzo, scopolia japonica, sodium azulene sulfonate, aldioxa, glycyrrhizinic acid and its salts, and licorice extract A product, L-glutamine, copper chlorophyllin potassium, copper chlorophyllin sodium, histidine hydrochloride, porcine stomach wall pepsin decomposition product, porcine stomach wall acid hydrolyzate, methylmethionine sulfonium chloride, dimethylpolysiloxane, and the like may be blended in an appropriate combination.

When used as a laxative, for example, carboxymethyl cellulose calcium, sodium carboxymethyl cellulose, plandaco obata seed coat (ispagra seed coat), dioctylsodium sulfosuccinate, aloin, sulfur, casantranol, sennoside AB, bisacodyl, Aloe, Agetsu, Cascara Sagrada, Kengoshi, Kengoshi Fat, Senna, Senna Fruit (Senna Fruit), Daiou, Frangula Skin, Yarappa, Yarappa Fat, Marutsu Extract, Scented Castor Oil, Castor Oil, Ursodeoxycholic Acid, Oxycoranic Acid Salts, dried yeast, cholic acid, dimethylpolysiloxane, live intestinal components, dehydrocoric acid, flaxseed, kanokosou, kanzo, ketsumeishi, sankirai, sanshishi, jiou, sennaku, juyaku, ginger, senna, taiso, bile extract (powder) ), Touki, Animal Bold, Buttonpi, Mashinin, Yokuinin, Uikyo, Enmeisou, Ogon, Oubaku, Ouren, Gajutsu, Karamus Root, Kijitsu, Keihi, Gentiana, Koboku, Konzurango, Yamana, Shokyo, Sojutsu, Soyo, Chimpi, Castor oil, carrots, peppermint oil, buckthorn oil, beakjutsu, homica extract, dl-menthol, l-menthol, mokko, ryutan, vitamin B1 and its derivatives and their salts, vitamin B6 and its derivatives and their salts, nicotinic acid amide, pantoten Calcium acid and the like may be appropriately combined and blended.

When used as an antispasmodic agent, for example, diphenidol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, promethazine hydrochloride, mecrydin hydrochloride, diphenhydramine salicylate, dimenehydrinate, diphenhydramine tannate, phenetazine tannate, diphenylpyraline theocrate, fumaric acid. Diphenhydramine, promethazine methylene disalicylate, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, phenylamine maleate, scopolamine hydrobromide, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, methylatropin bromide , Methylanisotropin bromide, Methylscopolamine bromide, Methyl-l-hyostiamine bromide, Methylbenactidium bromide, Veradonna extract, Isopropamide iodide, Diphenylpiperidinomethyldioxolane iodide, Rohto extract, Papaverin hydrochloride, Ethyl aminobenzoate, cerium oxalate, ethyl piperidylacetylaminobenzoate, allylisopropylacetylurea, bromvalerylurea, caffeine, caffeine citrate, anhydrous caffeine, aminophyllin, diprophylline, theophylline, peppermint 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 their salts, nicotinic acid amide, calcium pantothenate and the like. good.

When used as a vitamin-based preparation, 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, bistiamine nitrate, thiamine disulfide, thiamine Disetyl sulfate ester salt, disetiamine hydrochloride, flusultiamine hydrochloride, octothiamine, sicothiamine, bisibuchiamine, bisbenchamine, flusultiamine, prosultiamine, benfothiamine, flavin adenine dinucleotide sodium, riboflavin, riboflavin phosphate Sodium, riboflavin butyrate, pyridoxin hydrochloride, pyridoxal phosphate, hydroxocobalamine hydrochloride, hydroxocobalamine acetate, cyanocobalamine, hydroxocobalamine, mecobalamine, ascorbic acid, calcium ascorbic acid, sodium ascorbic acid, nicotinic acid, nicotinic acid amide, pantenol, pantothenic acid Calcium, sodium pantothenate, biotin, potassium-magnesium ascorbic acid equal amount mixture, inositol hexanicotinate, ursodesoxycholic acid, cysteine L-hydrochloride, L-cysteine, orotic acid, gamma oryzanol, calcium glycerophosphate, calcium gluconate, Glucronolactone, glucuronic acid amide, sodium chondroitin sulfate, processed sardine, carrot, yoquinin and the like may be appropriately combined and blended.

The dose of the oral preparation of the present invention to humans may be appropriately adjusted according to the dosage form, pharmaceutical use, degree of disease, age of the patient, etc., but is usually based on a basic inorganic compound for adults. About 100 to 5000 mg / day, particularly about 500 to 3000 mg / day may be administered, and the doses of other components can be determined with reference to the above-mentioned content mass ratio according to such doses. Further, in the case of an oral preparation in a mode in which a basic inorganic compound is not an essential component, one or more selected from the group consisting of Swertia japonica and its extract is usually used for adults, and the amount in terms of crude drug is 1 It suffices to administer about 5000 mg / day, particularly about 5 to 1500 mg / day, and the doses of other components can be determined with reference to the above-mentioned content mass ratio according to such doses.

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

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited to these Examples.

[Test Example 1] Evaluation of the unpleasant taste-suppressing action of a basic inorganic compound In order to evaluate the unpleasant taste (salt taste) suppressing action of sodium hydrogen carbonate, the following granules of Examples 1 to 4 were produced and subjected to the following method. The sensory evaluation (evaluation of saltiness) 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), mixed and kneaded. The obtained kneaded product is extruded and granulated by a dome gran (manufactured by Fuji Paudal: DG-L11 type) equipped with a die of φ8 mm, and put into a fluidized bed dryer (manufactured by Freund Sangyo: FLO-5 type). After drying, the granules were sized using a granulator (manufactured by Okada Seiko: ND-10 type). This sized product was classified using a 50-mesh sieve to obtain the granules of Example 1.

[Example 2]
In Example 1, the granules of Example 2 were obtained by the same method except that both sucralose and calcium lactate were not blended.
[Example 3]
In Example 1, the granules of Example 3 were obtained by the same method except that sucralose was not added.
[Example 4]
In Example 1, the granules of Example 4 were obtained by the same method except that calcium lactate was not added.

[Evaluation of saltiness]
Seven panelists evaluated the feeling of administration (salt taste) when 3 g of each of the granules of Examples 1 to 4 was placed on the tip of the tongue for 30 seconds with sufficient time.
The feeling of taking (salt taste) was evaluated by scoring according to the following evaluation criteria.
<Evaluation criteria>
Extremely strong saltiness 4 points Strong saltiness 3 points Saltiness 2 points Slightly salty 1 point Almost no saltiness 0 points

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

From Table 1, the results showed that the granules of Example 3 containing sodium hydrogen carbonate and calcium lactate exhibited a stronger unpleasant taste (salt taste) than the granules of Example 2 containing only sodium hydrogen carbonate. In addition, the unpleasant taste of the granules of Example 4 containing sodium hydrogen carbonate and sucralose was not different from the unpleasant taste of the granules of Example 2 containing only sodium hydrogen carbonate.
On the other hand, the granules of Example 1 containing sucralose in addition to sodium hydrogen carbonate and calcium lactate remarkably suppressed the unpleasant salty taste derived from sodium hydrogen carbonate, resulting in a good feeling of administration. ..
From the above test results, it is clear that by further combining sucralose in addition to calcium lactate, the unpleasant taste of basic inorganic compounds such as sodium hydrogen carbonate is remarkably suppressed, and an oral preparation having a good feeling of administration can be obtained. It became.

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

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

[Example 6]
The granules of Example 6 were obtained by the same method as in Example 5 except that the granules of Example 2 were used instead of the granules of Example 1.
[Example 7]
The granules of Example 7 were obtained by the same method as in Example 5 except that the granules of Example 3 were used instead of the granules of Example 1.
[Example 8]
The granules of Example 8 were obtained by the same method as in Example 5 except that the granules of Example 4 were used instead of the granules of Example 1.

[Evaluation of bitterness]
Seven panelists evaluated the feeling of administration (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 with sufficient time.
The feeling of taking (bitter taste) was evaluated by scoring according to the following evaluation criteria.
<Evaluation criteria>
Extremely strong bitterness 4 points Strong bitterness 3 points Bitterness 2 points Slight bitterness 1 point Almost no bitterness 0 points

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

From Table 2, the granules of Example 5 containing Swertia japonica, calcium lactate and sucralose remarkably suppressed the unpleasant bitterness derived from Swertia japonica, resulting in a good feeling of administration.
From the above test results, it was clarified that the combination of calcium lactate and sucralose has an effect of remarkably suppressing not only the basic inorganic compound but also the unpleasant taste of Swertia japonica.

[Manufacturing example]
Granules of Examples 9 to 13 were obtained by the same method as in Example 1 except that another basic inorganic compound was used instead of sodium hydrogen carbonate.
Table 3 shows the compounding ingredients and the compounding amount (g). In addition, the unpleasant taste was suppressed in all of these, and the feeling of taking was good.

[Manufacturing Example 1]
Granules containing the following components in 3 packets (a mixture of granules 1 and 2 and 75 mg of menthol powder) were produced by a conventional method.
<Granule 1>
Swertia japonica powder 30 mg
Scopolia extract triple powder 90mg
Biodiastase 2000 24 mg
Methylmethionine sulfonium chloride 150 mg
Lipase AP12 15 mg
Perilla dried extract 30 mg (equivalent amount of crude drug)
Hydrogenated oil 195 mg
Hydroxypropyl cellulose 36 mg
<Granule 2>
Sodium bicarbonate 700 mg
Precipitated calcium carbonate 1200 mg
Magnesium carbonate 250mg
Calcium lactate 30 mg
Sucralose 2 mg
Mannitol 683 mg
Carmellose Calcium 120mg
Hydroxypropyl cellulose 180 mg

[Manufacturing Example 2]
Tablets containing the following components in 6 tablets were produced by a conventional method.
Sodium bicarbonate 700 mg
Precipitated calcium carbonate 1200 mg
Magnesium carbonate 250mg
Calcium lactate 20 mg
Sucralose 5 mg
Methylmethionine sulfonium chloride 150 mg
Perilla dried extract 270 mg (equivalent amount of crude drug)
Scopolia extract 90 mg
Swertia japonica powder 30 mg
Cinnamon powder 20.5 mg
Biodiastase 2000 24 mg
Lipase AP12 15 mg
Hydroxypropyl cellulose 24 mg
Hydrogenated oil 206mg
Polyvinyl alcohol 106 mg
Carmellose calcium 142.5 mg
Corn starch 24 mg
Crystalline cellulose 274 mg
Low degree of substitution hydroxypropyl cellulose 133 mg
Hydrous silicon dioxide 29.5 mg
Glycerin monostearate 10 mg
Polyoxyl stearate 3 mg
Purified shellac 4 mg
Talc 26.5 mg
l-menthol 4 mg
Magnesium stearate 14.5 mg

According to the present invention, it is possible to provide an oral preparation containing a basic inorganic compound and having a good feeling of ingestion with suppressed unpleasant taste, and can be used in the pharmaceutical industry, quasi-drug industry and the like.

Claims (4)

The following components (A), (B) and (C):
(A) coal oxyhydrogen sodium;
(B) One or more selected from the group consisting of lactic acid and its calcium salt;
(C) Sucralose;
An oral preparation used as a gastrointestinal drug, which contains glycyrrhizic acid and salts thereof. One or more selected from lactic acid and the group consisting of the calcium salt is calcium lactate, oral agent according to claim 1. The oral preparation according to claim 1 or 2 , which is a powder, a granule, an orally disintegrating tablet or an oral liquid preparation. The oral preparation according to any one of claims 1 to 3 , further comprising (D) one or more selected from the group consisting of Swertia japonica and an extract thereof.