JP4881268B2 - Oral preparations with reduced bitterness - Google Patents

Description

  The present invention relates to an oral preparation in which bitterness is remarkably reduced or suppressed, and a bitterness suppressing method (or taste-masking method) even if the preparation contains a medicinal component having a bitter taste.

  Many medicinal components have a bitter taste when taken orally. In order to reduce or enhance the bitterness of such medicinal ingredients and improve patient compliance, compositions using various ingredients along with medicinal ingredients have been proposed.

For example, Japanese Patent Laid-Open No. 8-99904 (Patent Document 1) discloses a bitterness-improving easy-to-take H ₂ blocker to which a sugar alcohol having a heat of dissolution of −60 KJ / kg or less is added. It is also described that it may be added. JP-A-2000-95707 (Patent Document 2) discloses a solid composition for oral administration or a chewable solid preparation containing a drug having a bitter taste and 0.1 to 2.25% by weight of menthol. Is disclosed. Japanese Unexamined Patent Publication No. 2000-159691 (Patent Document 3) discloses an oral solid preparation containing an unpleasant taste component, menthol, and a sweetening agent (aspartame, glycyrrhizic acid, etc.). JP-A-2001-106641 (Patent Document 4) discloses an oral medicine containing an active ingredient having a bitter taste, a sugar alcohol, a refreshing agent, and an oleaginous base. JP-A-11-228450 (Patent Document 5) discloses an oral pharmaceutical composition that conceals an unpleasant taste containing a basic drug having an unpleasant taste and an anionic polymer substance. Japanese Patent Application Laid-Open No. 2-56416 (Patent Document 6) discloses a granule that suppresses bitterness by adding aspartame as a corrigent. JP-A-8-208517 (Patent Document 7) discloses a molded product containing a metal salt of a physiologically active ingredient having bitter taste, aspartame and a water-soluble saccharide. JP 2000-290199 A (Patent Document 8) discloses an orally active pharmaceutical composition containing an active pharmaceutical ingredient having an unpleasant taste, two or more kinds of high sweeteners (sweetness 150 or more) and a substance exhibiting sourness. Is disclosed. JP-A-2002-316923 (Patent Document 9) has a hardness of 20 N or more and a porosity of 25 to 50%, and the following components (1) to (4): (1) neutral or alkaline conditions (2) Water-soluble acidic substances, (3) Water-soluble binders that are soluble in alcohol solvents, and (4) An intraoral quick disintegrating tablet containing a water-soluble saccharide (provided that at least one of the components (1) and (2) is coated with a water-soluble coating agent insoluble in an alcohol-based solvent) is disclosed. Japanese Patent Application Laid-Open No. 2004-339158 (Patent Document 10) contains magnesium sulfate or magnesium chloride in an amount of 0.5 (w / v)% or more of magnesium, and is selected from the group consisting of sugar alcohols and oligosaccharides. An oral preparation containing at least one and at least one organic acid selected from the group consisting of citric acid, malic acid, tartaric acid and adipic acid is disclosed. JP 2005-508364 A (Patent Document 11) discloses a pharmaceutical powder preparation containing an active ingredient based on epinastine and / or an acid addition salt, at least two kinds of sweeteners and / or flavoring agents, A pharmaceutical powder formulation in which at least one of two kinds of sweeteners and / or flavoring agents is for masking the immediate bitterness of the active ingredient and the other is for masking the sustained bitterness of the active ingredient It is disclosed.

However, these conventional preparations have an insufficient bitterness-inhibiting effect, and in particular, it is difficult to suppress unpleasant tastes such as gummy, astringent taste, and numbness. In addition, even when bitterness can be suppressed at the initial stage of administration to the oral cavity, bitterness is felt after a while after administration, or bitterness tends to occur in the aftertaste. For this reason, it is difficult to sufficiently improve patient compliance in preparations that are swallowed after being kept in the mouth for a while, such as orally disintegrating tablets and chewable tablets.
JP-A-8-99904 (Claims 1 and 8) JP 2000-95707 A (Claim 1) JP 2000-159691 A (Claim 1) JP 2001-106641 A (Claim 1) JP-A-11-228450 (Claim 1) JP-A-2-56416 (Claim 1) JP-A-8-208517 (Claim 1) JP 2000-290199 A (Claim 1) JP 2002-316923 A (Claim 1) JP 2004-339158 A (Claim 1) JP 2005-508364 A (Claim 1)

  Accordingly, an object of the present invention is to provide an oral preparation capable of effectively suppressing the bitter taste of a medicinal component and a method for suppressing bitter taste even in a form that remains in the oral cavity for a relatively long time.

  As a result of intensive studies to achieve the above-mentioned problems, the present inventors have found that the bitterness of medicinal ingredients can be effectively masked by a combination with an acidic mucopolysaccharide, a refreshing agent, and a sweetening agent. completed.

  That is, the oral preparation of the present invention contains (i) a medicinal ingredient having a bitter taste, (ii) an acidic mucopolysaccharide, (iii) a refreshing agent and (iv) a sweetening agent, so that the bitter taste is suppressed.

  The acidic mucopolysaccharide (ii) may be at least one selected from carrageenan, glycosaminoglycans, alginic acid or a salt thereof, acidic plant gum, and microbial-produced acidic gum. The acidic mucopolysaccharide (ii) may be a combination of (a) carrageenan ι or (b) carrageenan ι with carrageenan λ and / or carrageenan κ. The refreshing agent (iii) may be at least one terpene compound selected from menthol, camphor and borneol, or an essential oil, essence or powder containing the terpene compound. The sweetener (iv) is a non-sugar sweetener (such as at least one selected from saccharin, aspartame, acesulfame, sucralose, glycyrrhizic acid, stevia and thaumatin or a salt thereof), sugar alcohol (mannitol, sorbitol, erythritol and / or Or xylitol, etc.) and sugars (sucrose, lactose, and / or reduced maltose water candy, etc.) or a salt thereof.

  The oral preparation has an acidic mucopolysaccharide (ii) 1 to 3000 parts by weight, a refreshing agent (iii) 0.1 to 300 parts by weight, and a sweetener for 100 parts by weight of the medicinal component (i) having a bitter taste (iv) About 5 to 10,000 parts by weight may be contained. The oral preparation may contain 0.1 to 400 parts by weight of acidic mucopolysaccharide (ii) and 0.1 to 250 parts by weight of a cooling agent (iii) with respect to 100 parts by weight of the sweetener (iv). The ratio (weight ratio) between the acidic mucopolysaccharide (ii) and the refreshing agent (iii) may be about 0.1 / 1 to 100/1.

  The oral preparation may further contain (v) an organic acid. The organic acid (v) is at least one selected from saturated carboxylic acids, unsaturated carboxylic acids and oxycarboxylic acids (succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid, isoascorbic acid, etc.) or its It may be a salt or the like. The oral preparation may further contain (vi) a savory ingredient, (vii) a surfactant, (viii) a fragrance, and the like. The dosage form of the oral preparation may be, for example, a solid preparation or a liquid preparation. The oral preparation may be an intraoral rapidly disintegrating tablet.

  In the method of the present invention, (i) a medicinal ingredient having a bitter taste, (ii) an acidic mucopolysaccharide, (iii) a cooling agent, and (iv) a sweetening agent are added to the medicinal ingredient (i) having the bitter taste. Suppresses or reduces the bitter taste.

  In the present specification, unpleasant tastes such as bitterness, astringency, gummy, astringent taste, and numbness may be collectively referred to simply as “bitter taste”.

  Since the oral preparation of the present invention contains a medicinal ingredient having a bitter taste, an acidic mucopolysaccharide, a refreshing agent and a sweetener, even if it is a preparation that stays in the oral cavity for a relatively long time, the bitter taste of the medicinal ingredient Can be effectively suppressed.

  The oral preparation of the present invention contains (i) a medicinal ingredient having a bitter taste, (ii) an acidic mucopolysaccharide, (iii) a refreshing agent, and (iv) a sweetener to effectively suppress the bitter taste. Can do.

  The oral preparation of the present invention may further contain (v) an organic acid, (vi) an umami component, (vii) a surfactant, (viii) a fragrance in addition to the above components. These components may be used alone or in combination of two or more. Among these components, in particular, when the organic acid (v) and / or the umami component (vi) are used, the bitterness can be more effectively reduced. Further, among the above components, when the surfactant (vii) is used, not only the bitter taste can be effectively suppressed, but the taste of the preparation can be mellow. Further, when the fragrance (viii) is used, depending on the type of the fragrance, there are some which show the same effect as the cooling agent, and the effect of suppressing bitterness can be further enhanced.

(i) Medicinal component having bitter taste The medicinal component is not particularly limited as long as it has a bitter taste, and various disease therapeutic agents or preventive agents can be used.For example, analgesics, antipyretic analgesics, headache therapeutic agents, antitussives , Expectorant, sedative, antispasmodic, antihistamine, antiallergic, antiplasmin, bronchodilator, asthma, diabetes, liver disease, ulcer, gastritis, gastric digestive , Gastrointestinal motility agent, antihypertensive agent, angina treatment agent, antihypertensive agent, hypotension agent, hyperlipidemia agent, hormone agent, antibiotic, antiviral agent, sulfa agent, anti-inflammatory agent, mental Nervous agents, intraocular pressure-lowering agents, antiemetics, antipruritics, gout treatment agents, arrhythmia treatment agents, vasoconstrictors, digestive agents, sleep or hypnosis induction (induction) agents, sympathetic nerve blockers, anemia treatment agents, antiepileptic agents , Anti-vertigo, parallel injury treatment, tuberculosis treatment It may be a therapeutic agent, a vitamin deficiency therapeutic agent, a dementia therapeutic agent, a urinary incontinence therapeutic agent, an antidepressant, a mouth bactericidal agent, a parasiticide extermination agent, a vitamin agent, amino acids, minerals and the like.

Medicinal ingredients having a bitter taste include, for example, pyrin compounds (aminopyrine, antipyrine, etc.), non-pyrine compounds (non-pyrine antipyretic analgesics such as dimethothiazine mesylate, acetaminophen), caffeine (caffeine, anhydrous caffeine) , Sodium benzoate caffeine, etc.), barbitals (allobarbital, cyclobarbital, barbital, phenobarbital, etc.), phenacetin, choline salicylate, trimethquinol hydrochloride, furopropion, cyclopeptazine hydrochloride, sulfonelurea urea compounds (tolbutamide, chlorpropa Amide, acetohexamide, etc.), grubuzole, hydrazinophthalazine hydrochloride, reserpine, resinamine, polythiazide, dexamethasone (dexamethasone, dexamethasone acetate) Dexamethasone sodium phosphate), betamethasone (betamethasone, betamethasone sodium phosphate, etc.), cephalexin, chloramphenicol compounds (chloramphenicol, chloramphenicol sodium succinate, etc.), sulfisomezole, sulfi Soxazal, hydroxyzimbamoate, primidone, isosorbide, nicotinic acid or its derivative (such as nicotinamide), ascorbic acid or its salt (such as calcium ascorbate), pantothenic acid or its acid (such as calcium pantothenate), thiamine (Thiamine, fursultiamine, or a salt thereof), lysine hydrochloride, allopurinol, atenolol or a salt thereof, ambroxol or a salt thereof (such as ambroxol hydrochloride), zolmitriptan, orchid Prazole or a salt thereof (such as lansoprazole sodium), hexofenazine, scopolamine (such as methyl scopolamine, N-methyl scopolamine / methyl sulfate, scopolamine hydrobromide, butyl scopolamine bromide), oxerazine or a salt thereof (oxalazine citrate) Diphenhydramines (such as diphenhydramine, diphenhydramine hydrochloride, diphenhydramine lauryl sulfate), ephedrines (such as ephedrine hydrochloride, methylephedrine, methylephedrine hydrochloride), metoclopramide or a salt thereof (such as metoclopramide hydrochloride), dextromethorphan hydrobromide, Eprazinone hydrochloride, dibutate, cetirizine hydrochloride, ebastine, pemirolast potassium, epinastine or a salt thereof (such as epinastine hydrochloride), tranet Xamic acid, ozagrel hydrochloride, roxatidine acetate hydrochloride, ranitidine hydrochloride, famotidine, benexate hydrochloride betadex, pirenzepine hydrochloride, rebamipide, acratenium napadisylate, itopride hydrochloride, chirisolol hydrochloride, bepridil hydrochloride, propranolol hydrochloride, todralazine hydrochloride, hydrochloric acid Hydralazine, ethylephrine hydrochloride, pravastatin or its salts (such as pravastatin sodium), aminobenzylpenicillin compounds (ampicillin, aminobenzylpenicillin, ampicillin natrim, bacampicillin hydrochloride, talamvicillin etc.), tetracycline compounds (tetracycline, tetracycline hydrochloride, minocycline hydrochloride, hydrochloric acid) Doxycycline), amantadine hydrochloride, arylacetic acid compounds (diclofenacna) Lithium, indomethacin, ampenac sodium, etc.), butyrophenone compounds (moperone hydrochloride, bromperidol, etc.), hydroxyzine or salts thereof (hydroxyzine hydrochloride, etc.), cetron compounds (granisetron hydrochloride, azasetron hydrochloride, ramosetron hydrochloride, ramosetron hydrochloride, Ondansetron, ondansetron hydrochloride, etc.), berberine compounds (berberine chloride, berberine sulfate, berberine tannate, etc.), mexiletine hydrochloride, benzodiazepine derivatives (triazolam, brotizolam, rilmazaphone hydrochloride, etc.), propylamine compounds (chlor maleate) Phenylamine, triprolidine hydrochloride, etc.), trazoline hydrochloride, iron preparation (iron sulfate, ferrous fumarate, etc.), sodium valproate, isoproterenol hydrochloride, Hisuchin, (such as hydrochloric dicethiamine) Ethambutol Hydrochloride, Pyridoxine Hydrochloride, Vitamin B ₁ derivatives, donepezil hydrochloride, propiverine hydrochloride, xanthine derivatives (theophylline, etc. diprophylline), domiphen bromide, other such as citric acid diethylcarbamazine, herbal having bitterness Ingredients and the like.

  The herbal medicine ingredients having a bitter taste include, for example, icarius, seisei, guarana, kokushi, jiou, touki, euchu, carrot, ogon, oak, ouren, gadju, calocon, kyouko, kihada, kengoshi, gentian, kobushi, koboku, goshitsu, Extracts or pulverized from herbal raw materials such as psycho, saffron, sandscon, buffalo, assembly, senbou, syojutsu, daiou, chimpi, spruce, nigaki, peony, mugwort, sagebrush, hops, wolves, mao, ryutan, gentian, forsythia Examples can be given.

  The medicinal component is not limited to the compounds exemplified above, and among the above compounds, a compound having a salt-forming site is a physiologically or pharmaceutically acceptable salt (especially a pharmaceutically acceptable salt, etc.). ) Etc. are also included. The acid or base that forms a salt with the above compound can be selected according to the type of component, for example, an inorganic acid salt (for example, a salt with hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.); an organic acid Salts (eg, carboxylates (eg, monocarboxylates (eg, salts with acetic acid, trichloroacetic acid, trifluoroacetic acid, etc.)), polyvalent carboxylates (eg, oxalic acid, succinic acid, maleic acid, fumaric acid) ), Oxycarboxylates (for example, salts with tartaric acid, citric acid, lactic acid, gluconic acid, salicylic acid, phenolphthaline, tannic acid, etc.), amino acid salts (salts with aspartic acid, etc.), Organic sulfonates (eg, alkane sulfonates (eg, salts with methane sulfonic acid, ethane sulfonic acid, etc.), arene sulfonates (eg, benzene sulfonic acid, toluene Salts with inorganic bases (eg, salts with alkali metal hydroxides (eg, salts with sodium hydroxide, potassium hydroxide, etc.), alkali metal carbonates, etc.) , Salts with alkaline earth metal hydroxides (for example, salts with calcium hydroxide, magnesium hydroxide, etc.), alkaline earth metal carbonates, aluminum salts, ammonium salts, etc .: salts with organic bases (alkylamines) Salts (for example, trimethylamine salts, triethylamine salts, etc.), alkanolamine salts (for example, monoethanolamine salts, triethanolamine salts, etc.), polyamine salts such as alkylenediamine, tertiary amine salts such as pyridine salts, etc.) It can be illustrated.

  Medicinal ingredients having a bitter taste can be used alone or in combination of two or more. In the present invention, among the medicinal ingredients, ingredients having a strong bitterness, such as analgesics (such as digestive system analgesics such as methyl scopolamine), non-pyrine antipyretic analgesics or migraine treatment (such as dimethothiazine mesylate), antitussives Or airway mucus solubilizers (oxalazine citrate, eprazinone hydrochloride, dibutate, diphenhydramine, methylephedrine, etc.), antiallergic agents (cetirizine hydrochloride, pemirolast potassium, epinastine hydrochloride, etc.), antiplasmin agents (tranexamic acid, etc.), bronchial asthma Therapeutic agents (such as ozagrel hydrochloride), ulcer agents (metoclopramide hydrochloride, roxatidine acetate hydrochloride, ranitidine hydrochloride, benexate hydrochloride betadex, butylscopolamine bromide ulcer or duodenal ulcer therapeutic agents; pirenzepine hydrochloride, rebamipide, Famotisi Such as peptic ulcer treatment), gastritis treatment (pirenzepine hydrochloride, etc.), gastrointestinal motility activators (acratenium napadisylate, itopride hydrochloride, etc.), hypertension treatment or angina treatment (tilisolol hydrochloride, bepridil hydrochloride, Propranolol hydrochloride, todralazine hydrochloride, etc.), antihypertensive agent (eg, hydralazine hydrochloride), hypotension treatment agent (eg, ethylephrine hydrochloride), hyperlipidemic agent (eg, pravastatin sodium), antibiotics (eg, talamicillin hydrochloride, doxycycline hydrochloride), Anti-influenza virus agent (such as amantadine hydrochloride), anti-inflammatory agent (such as amphenac sodium), psychoneurotic agent (such as moperon hydrochloride, amantadine hydrochloride; antiallergic mild tranquilizer such as hydroxyzine hydrochloride), antiemetic (hydrochloric acid) Granisetron), antidiarrheal ( Berberine acid), arrhythmia treatment (eg mexiletine hydrochloride), sleep inducer (eg rilmazafone hydrochloride), sympathetic blocker (eg trazoline hydrochloride), iron deficiency anemia treatment (eg dry iron sulfate), antiepileptic agent (eg Sodium valproate), anti-vertigo or parallel injury treatment (isoproterenol hydrochloride, betahistine mesylate, etc.), tuberculosis treatment (eg ethambutol hydrochloride, etc.), vitamin B6 deficiency treatment (eg pyridoxine hydrochloride), vitamin B1 deficiency treatment (Such as dicetiamine hydrochloride), Alzheimer-type dementia (such as donepezil hydrochloride), urinary incontinence (such as propiverine hydrochloride), antidepressant (such as diprofiline), oral bactericides (such as domifene bromide), filaria control agent (such as Effective use of diethylcarbamazine citrate) Can be suppressed.

  Moreover, even if the medicinal component is water-soluble, bitterness can be efficiently suppressed. Examples of such water-soluble medicinal ingredients include diphenhydramine hydrochloride, pyridoxine hydrochloride, dicetiamine hydrochloride, oxerazine citrate, talamvicillin hydrochloride, trazoline hydrochloride, acratonium napadisylate, metoclopramide hydrochloride, roxatidine acetate, ranitidine hydrochloride, hydrochloric acid Benexate betadex, butylscopolamine bromide, iron sulfate, propiverine hydrochloride, ethylephrine hydrochloride, pravastatin sodium, chlorpheniramine maleate, dimethothiazine mesylate, rilmazaphone hydrochloride, granisetron hydrochloride, hydroxyzine, doxycycline hydrochloride, tranexamic acid, dibunate , Diphenhydramine, methylephedrine, berberine sulfate, sodium valproate, domifene bromide, amantadine hydrochloride, pirenze hydrochloride , Ethambutol hydrochloride, tilisolol hydrochloride, propranolol hydrochloride, todralazine hydrochloride, hydralazine hydrochloride, ampenac sodium, ozagrel hydrochloride, isoproterenol hydrochloride, betahistine mesylate, mexiletine hydrochloride, itopride, cetirizine hydrochloride, pemirolast potassium, epinastine hydrochloride, Examples include donepezil hydrochloride, methyl scopolamine, and diethylcarbamazine citrate. Here, “water-soluble” means “extremely soluble” or “easily soluble” in the “terms indicating solubility” described in the general rules of the 15th revision Japanese Pharmacopoeia (announced on March 31, 2006). And “slightly soluble”.

  Among the above-mentioned medicinal ingredients (i), it was selected from at least one selected from cetirizine, epinastine, ranitidine, pirenzepine, rebamipide, itopride, pravastatin, amantadine, chlorpheniramine maleate, and propiverine (particularly epinastine and rebamipide) At least one kind or a salt thereof (an inorganic acid salt such as hydrochloride; an organic acid salt such as maleate or citrate; an alkali metal or alkaline earth metal salt such as sodium salt) is preferable.

  In addition to the above-mentioned medicinal ingredients, the preparation may contain other physiologically or pharmacologically active ingredients or active ingredients (such as active ingredients with low bitterness) as necessary.

(ii) Acid mucopolysaccharides Acid mucopolysaccharides include carrageenan (carrageenan ι, carrageenan λ, carrageenan κ, etc.), glycosaminoglycans [for example, chondroitin sulfate (chondroitin sulfate, chondroitin sulfate, chondroitin sulfate, etc. Or a salt thereof), hyaluronic acid, keratan sulfate, heparan sulfate, heparin, dermatan sulfate, dextran sulfate, etc.], alginic acid or a salt thereof (eg, sodium alginate), seaweed-derived acidic mucopolysaccharide (eg, fucoidan), acidic plant gum (Tragacanth gum, etc.), microorganism-produced acidic gums (xanthan gum, gellan gum, etc.) and the like.

  These acidic mucopolysaccharides can be used alone or in combination of two or more. Among these acidic mucopolysaccharides, carrageenan, glycosaminoglycans (chondroitin sulfate, dextran sulfate, etc.), alginic acid or salts thereof, acidic plant gum, microbial-produced acidic gum (especially carrageenan, alginate, etc.), etc. Is preferred. Further, among carrageenans, in particular, the use of carrageenan ι can effectively suppress the bitter taste of medicinal ingredients. Carrageenan ι and carrageenan λ and / or carrageenan κ may be used in combination. Further, carrageenan may be used in combination with other acidic mucopolysaccharides.

(iii) Refreshing agent As the refreshing agent, in addition to terpene compounds such as menthol, camphor and borneol (monoterpene alcohol, etc.), essential oils, essences or powders containing the terpene compounds [for example, the terpene series In addition to essential oils, essences or powders (powder) of plants containing compounds (peppermint, spearmint, cool mint, etc.), those obtained by adsorbing essential oils or essences to powdered carriers (eg dextrin), essential oils or essences Etc.] etc.] etc. etc. etc. etc. etc. etc. etc. etc. which were mixed with materials (gum arabic etc.) and liquid bases (water, alcohol, etc.) and granulated. The terpene compound may be any of d-isomer, l-isomer, and dl-isomer. The terpene compounds and / or cooling agents can be used alone or in combination of two or more.

  Among the refreshing agents, menthol, peppermint oil, spearmint oil, cool mint oil, peppermint oil, peppermint powder and the like are preferable.

(iv) Sweetening agent Examples of the sweetening agent include non-sugar sweeteners, sugar alcohols and sugars. As the non-sugar sweetener, both synthetic and naturally-derived sweeteners can be used. The sweetness of the non-sugar sweetener is not particularly limited, but it is preferable to use a sweetener having a sweetness of about 50 times or more compared with sucrose.

  Examples of the synthetic sweetener include saccharin or a salt thereof (such as sodium saccharin), aspartame, sucralose, glycyrrhizic acid or a salt thereof (disodium glycyrrhizinate, trisodium glycyrrhizinate, dipotassium glycyrrhizinate), acesulfame or a salt thereof (acesulfame potassium) Etc.). Natural sweeteners include sugar sweeteners [licorice extract or its salt (such as glycyrrhizin or its salt), stevia extract (such as stevia (such as stevioside, rebaudioside))], protein sweetener [ For example, thaumatin (thaumatin), monelin and the like].

  Examples of the sugar alcohol include mannitol (D-mannitol), sorbitol (D-sorbitol), erythritol, xylitol, reduced palatinose, maltitol, lactitol, and the like.

  Examples of the saccharide include sucrose, glucose, fructose, lactose, brown sugar, honey, trehalose, maltose (maltose), xylose, mannose, raffinose, galactose, fructose, rhamnose, sorbit, isomerized sugar (high fructose syrup) , Palatinose, reducing sugar (reduced maltose water candy etc.).

  These sweeteners can be used alone or in combination of two or more. Of these sweeteners, synthetic sweeteners, sugar sweeteners, protein sweeteners, sugar alcohols and the like are preferred. Moreover, you may combine a saccharide | sugar with a synthetic sweetener, a sugar distribution sweetener, and / or a protein sweetener. Moreover, you may combine sugar alcohol and other saccharides. Among the sweetening agents, at least one selected from saccharin, aspartame, acesulfame, thaumatin, sucralose, glycyrrhizic acid, stevia and thaumatin or a salt thereof (for example, an alkali metal salt such as sodium or potassium) is particularly preferable.

(v) Organic acid The type of organic acid is not particularly limited as long as it exhibits an acidity or a salty taste (savory taste), and various organic acid components can be used, and salts are also included. In the present specification, organic acids including organic acid salts may be simply referred to as organic acids.

  Examples of organic acids include saturated carboxylic acids (saturated monocarboxylic acids such as acetic acid, malonic acid, succinic acid, succinic anhydride, saturated dicarboxylic acids such as glutaric acid), and unsaturated carboxylic acids (maleic acid, fumaric acid, etc.) Unsaturated polycarboxylic acids), oxycarboxylic acids (hydroxymonocarboxylic acids such as lactic acid, hydroxypolycarboxylic acids such as malic acid, tartaric acid and citric acid), ascorbic acid, isoascorbic acid (erythorbic acid), glucone An acid etc. can be illustrated. These organic acids can be used alone or in combination of two or more. Of these organic acids, oxycarboxylic acids (malic acid, tartaric acid, citric acid, etc.), succinic acid, fumaric acid, ascorbic acid, isoascorbic acid and the like are preferable, and at least oxycarboxylic acid is often used. Moreover, as an organic acid salt, the alkali metal salt (sodium salt, potassium salt, etc.) of the organic acid of the said illustration is mentioned, for example.

  When the organic acid is an optically active substance, the optically active substance may be a d, l, dl form, and the organic acid may be a racemate. When a plurality of organic acids are used, it may be effective for bitter taste. The organic acid may have an action as a buffering agent such as pH adjustment.

(vi) Umami component The umami component includes, for example, an amino acid umami component (amino acid or a salt thereof such as glutamic acid, sodium glutamate, potassium glutamate, glutamic acid hydrochloride, sodium guanylate, inosinic acid, sodium inosinate, arginine-glutamic acid. Salt, aspartic acid, sodium aspartate, glycine, alanine, etc.), peptide-based umami components (dipeptides such as L-glutamyl-L-glutamic acid, L-glutamyl-L-serine; tri-L-glutamic acid, L-glutamyl-L) -Tripeptides such as glycyl-L-serine), carboxylic acid-based umami components (carboxylates such as sodium succinate) and the like. These umami components can be used alone or in combination of two or more. As the umami component, an amino acid umami component such as glutamic acid or a salt thereof (sodium glutamate, glutamate hydrochloride, etc.), inosinic acid or a salt thereof (sodium inosinate, etc.) is often used.

(vii) Surfactant As the surfactant (vii), an anionic surfactant, a cationic surfactant, an amphoteric surfactant and the like may be used, but usually a nonionic surfactant. Etc. are often used. Surfactant can be used individually or in combination of 2 or more types.

Nonionic surfactants include poly C _2-3 alkylene glycols such as polyoxyethylene-polyoxypropylene block copolymers (such as homo or copolymers having C _2-3 alkylene oxide as a structural unit), polyoxy (Poly) C _2-3 alkylene glycol C _8-26 fatty acid ester (such as C _10-20 fatty acid ester) such as ethylene hydrogenated castor oil, glycerin C _8-26 fatty acid ester (glycerin C _10-22 such as glyceryl monostearate) Fatty acid esters, etc.) are preferred. In addition, the molecular weight (for example, number average molecular weight) of alkylene glycols may be, for example, about 500 to 10,000, preferably about 1000 to 8000, and more preferably about 3000 to 7000.

(viii) Fragrances As fragrances, natural fragrances such as fruit fragrances (for example, strawberry, blueberry, apple, pineapple, banana, ume, lime, vanilla, pepper, etc.), perfumes (for example, orange, grape, white) Grape, grapefruit, lemon, etc.), bark-based fragrances (for example, cinnamon), root-based fragrances (for example, ginger), seed-based fragrances (for example, vanilla beans, coffee, cacao, macadamia nuts, etc.) Mint flavors such as rosemary and tea), flower flavors such as jasmine, lavender, rose, rosemary and hyacinth, brown sugar flavor, milk flavor, drink essence (essence mixed with strawberry and nikki), etc .; Synthetic fragrances such as benzyl acetate Linalyl acetate, citral, citronellal, citronellol, cis jasmine, cis-3-hexenol and the like. These fragrance | flavors can be used individually or in combination of 2 or more types. Of the above fragrances, fruit-based fragrances (such as apples), skin-based fragrances (such as grape, white grape, and grapefruit), seed-based fragrances (such as cacao), and the like are preferable.

  The form of the fragrance can be appropriately selected according to the dosage form of the preparation, the nature of the fragrance (water-soluble, oil-soluble, etc.), and the oil, essence, emulsion, powder (for example, cinnamon powder, ginger powder, cacao) Powder, green tea, etc.). The powdered fragrance is not limited to those obtained by pulverizing natural materials (for example, cinnamon, ginger, cacao, tea, etc.), but fragrances (including fragrances in the form of oils, essences, emulsions, etc.) are also powdered. What is adsorbed on a carrier (for example, dextrin), fragrance is mixed with excipients (such as gum arabic) and liquid base (water, alcohol, etc.), and then granulated (spray drying using a device such as a spray dryer) ) Is also included.

  Among the fragrances, fruit fragrance essence or oil, fruit skin fragrance essence or oil, powdered seed fragrance and the like are particularly preferable. In addition, when cacao powder is used, the taste of the preparation can be mellow.

(Ratio of each component)
The proportion of medicinal ingredients having a bitter taste in the preparation is 0 with respect to a conventional range according to the kind of the medicinal ingredient, the application or administration subject, age and weight, symptoms, frequency of administration, administration method, etc. 0.001 to 50% by weight, preferably 0.01 to 30% by weight, more preferably about 0.1 to 20% by weight.

  The ratio of the acidic mucopolysaccharide (ii) is, for example, 1 to 3000 parts by weight (for example, 1.5 to 2500 parts by weight), preferably 2 to 2000 with respect to 100 parts by weight of the medicinal component (i) having a bitter taste. The amount is about 1 part by weight (for example, 3 to 1500 parts by weight), more preferably about 4 to 1000 parts by weight (for example, 5 to 500 parts by weight), and particularly about 6 to 300 parts by weight (for example, 10 to 100 parts by weight). Moreover, the ratio of acidic mucopolysaccharide (ii) is 0.2-400 weight part with respect to 100 weight part of sweeteners (iv), Preferably it is 1-350 weight part (for example, 1.5-300). Parts by weight), more preferably about 2 to 150 parts by weight (for example, 5 to 100 parts by weight).

  The ratio (weight ratio) between the acidic mucopolysaccharide (ii) and the refreshing agent (iii) is component (ii) / component (iii) = 0.1 / 1 to 100/1, preferably 0.2 / 1. It is about -90/1 (for example, 0.3 / 1-70/1), More preferably, it is about 0.4 / 1-50/1 (for example, 0.5 / 1-30/1).

  The proportion of the refreshing agent (iii) is, for example, 0.1 to 300 parts by weight, preferably 0.2 to 250 parts by weight (for example, 0.3 parts) with respect to 100 parts by weight of the medicinal component (i) having a bitter taste. About 200 parts by weight), more preferably about 0.5 to 150 parts by weight (for example, 1 to 100 parts by weight). Moreover, the ratio of the refreshing agent (iii) is 0.1-250 weight part with respect to 100 weight part of sweeteners (iv), Preferably 0.2-200 weight part (For example, 0.3- 150 parts by weight), more preferably about 0.4 to 100 parts by weight (for example, 0.5 to 80 parts by weight).

  The proportion of the sweetener (iv) is, for example, 5 to 10000 parts by weight, preferably 10 to 8000 parts by weight (for example, 20 to 6000 parts by weight), based on 100 parts by weight of the medicinal component (i) having a bitter taste, The amount is preferably 30 to 3000 parts by weight (for example, 35 to 1000 parts by weight), particularly 40 to 500 parts by weight (for example, 40 to 300 parts by weight).

  The proportion of the organic acid (v) can be selected from the range of, for example, about 1 to 5000 parts by weight, preferably 2 to 3000 parts by weight (for example, 3 to 3 parts by weight) with respect to 100 parts by weight of the medicinal component (i) having a bitter taste. 1000 parts by weight), more preferably 4 to 500 parts by weight (for example, 5 to 200 parts by weight), particularly about 6 to 100 parts by weight. Moreover, the ratio of organic acid (v) is 0.001-1000 weight part with respect to 100 weight part of sweeteners (iv), Preferably it is 0.1-500 weight part (for example, 0.5-100). Parts by weight), more preferably about 1 to 50 parts by weight (for example, 2 to 30 parts by weight).

  The proportion of the umami component (vi) can be selected from the range of, for example, about 1 to 4000 parts by weight, preferably 2 to 1000 parts by weight (for example, 3 to 3 parts by weight) with respect to 100 parts by weight of the medicinal component (i) having a bitter taste. 500 parts by weight), more preferably about 4 to 200 parts by weight (for example, 5 to 150 parts by weight). The proportion of the umami component (vi) is, for example, 0.001 to 100 parts by weight, preferably 0.1 to 50 parts by weight, and more preferably 0.5 to 100 parts by weight with respect to 100 parts by weight of the sweetener (iv). It may be about 30 parts by weight (for example, 1 to 20 parts by weight).

  The proportion of the surfactant (vii) can be selected, for example, from the range of about 0.001 to 200 parts by weight, preferably 0.1 to 100 parts by weight, with respect to 100 parts by weight of the medicinal component (i) having a bitter taste. (For example, 0.5 to 50 parts by weight), more preferably about 1 to 30 parts by weight (for example, 2 to 20 parts by weight). The ratio of the surfactant (vii) is, for example, 0.001 to 30 parts by weight, preferably 0.1 to 15 parts by weight, and more preferably 1 to 10 parts by weight with respect to 100 parts by weight of the sweetener (iv). It may be about parts by weight.

  The ratio of the fragrance (viii) can be selected, for example, from the range of about 0.001 to 100 parts by weight, preferably 0.1 to 50 parts by weight, based on 100 parts by weight of the medicinal component (i) having a bitter taste. Preferably, it may be about 1 to 30 parts by weight (for example, 2 to 15 parts by weight).

  The preparation of the present invention may further contain a sweetness enhancer (or a savory agent) having a savory taste (salt taste). Examples of such sweetness enhancers include sodium chloride, potassium chloride, phosphates (such as potassium hydrogen phosphate and sodium hydrogen phosphate). Sweetness enhancers (or flavoring agents) are often neutral salts, such as salts that dissociate as sodium ions and / or chloride ions (chloride ions). These sweetness enhancers can also be used alone or in combination. A preferred sweetness enhancer is sodium chloride.

  The proportion of the sweetness enhancer can be selected according to, for example, the types and quantitative proportions of the medicinal ingredients and sweeteners, and for example, 1 to 100 parts by weight (for example, 5 to 5 parts by weight based on 100 parts by weight of the sweetener). 80 parts by weight), preferably 10 to 60 parts by weight (for example, 10 to 50 parts by weight), more preferably about 20 to 50 parts by weight (for example, 25 to 50 parts by weight).

  The form of the preparation of the present invention is not particularly limited and may be a capsule or the like. However, since bitterness can be effectively suppressed or reduced, solid preparations other than capsules (powder (powder), granules, rounds) are usually used. Preparations, tablets (bare tablets, etc.), films, etc., liquids (solutions, suspensions, emulsions, gels, gummi, syrups (including dry syrups), etc.), transdermal preparations (oral attachment type) In many cases, it is a preparation). The preparation may be a lyophilized preparation. Among these dosage forms, dosage forms that usually feel bitter, such as solid preparations such as powders, granules, and tablets, and liquid preparations such as syrups are suitable as the dosage forms of the preparation of the present invention. Further, the preparation of the present invention may be an intraoral rapidly disintegrating tablet that rapidly disintegrates in the oral cavity.

  The preparation usually contains a physiologically acceptable carrier, and this carrier depends on the dosage form, dosage form, use, etc., for example, the Pharmacopeia and “Pharmaceutical Additives Dictionary 2000” (Pharmaceutical Daily) Can be selected from the components listed in the second edition issued on March 25, 2002). For example, as a carrier for a solid preparation, at least one carrier selected from excipients, binders and disintegrants is often used, and additives such as lipids may be used.

  Examples of the excipient include sugars such as lactose, sucrose, glucose, sucrose, mannitol, sorbitol, erythritol, or sugar alcohols; starch such as corn starch; polysaccharides such as crystalline cellulose (including microcrystalline cellulose) (for example, , Kimura Sangyo Co., Ltd., Prosolv); Light anhydrous silicic acid, synthetic aluminum silicate, magnesium metasilicate aluminate, synthetic silica and other silicon oxides or silicates (for example, “Neusilin” manufactured by Fuji Chemical Industry Co., Ltd.) Phosphates such as anhydrous calcium hydrogen phosphate (for example, “Fujicalin” manufactured by Fuji Chemical Industry Co., Ltd .; mixtures thereof (for example, “F-melt” manufactured by Fuji Chemical Industry Co., Ltd.), etc.) Examples of the binder include soluble starch such as pregelatinized starch and partially pregelatinized starch; , Polysaccharides such as gum arabic, dextrin, sodium alginate, tragacanth gum, xanthan gum, hyaluronic acid, sodium chondroitin sulfate; synthetic polymers such as polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, polyacrylic acid polymer, polylactic acid, polyethylene glycol And cellulose ethers such as methylcellulose, ethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and the like.

  Examples of the disintegrant include calcium carbonate, carboxymethylcellulose or a salt thereof (carmellose (for example, “NS-300” manufactured by Gotoku Pharmaceutical Co., Ltd.), carmellose sodium, carmellose calcium (for example, “ECG-manufactured by Gotoku Pharmaceutical Co., Ltd.) 505 ")), polyvinylpyrrolidone (polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone (crospopidone), etc.), low-substituted hydroxypropylcellulose, sodium starch glycolate (for example," Exprotab "manufactured by Kimura Sangyo Co., Ltd.), etc. Can be illustrated. These carriers can be used alone or in combination of two or more.

Among liquid carriers, aqueous carriers (or water-soluble carriers) include water (purified or sterile water, distilled water for injection, etc.), physiological saline, Ringer's solution, glucose solution, water-soluble organic solvents [e.g., lower grades such as ethanol and isopropanol. Aliphatic alcohols; (poly) alkylene glycols (ethylene glycol, polyethylene glycol and the like); glycerin and the like], dimethylisosorbide, dimethylacetamide and the like. Examples of oily carriers include animal and vegetable oils (vegetable oils such as jojoba oil, olive oil, palm oil, and cottonseed oil; animal oils such as squalane) and mineral oils (liquid paraffin, silicone oil, and the like). The semi-solid carrier may be selected from the solid pharmaceutical carrier and / or the liquid carrier. The carrier of the semisolid agent may contain a lipid. Examples of lipids include waxes (honey wax, carnauba wax, lanolin, paraffin, petrolatum, etc.), long chain fatty acid esters (saturated or unsaturated fatty acid alkyl esters, fatty acids and polyhydric alcohols (poly C _2-4 alkylene glycol, glycerin or Polyglycerin, etc.) and esters (such as glycerides), hydrogenated oils, higher alcohols (saturated fatty alcohols such as stearyl alcohol, unsaturated fatty alcohols such as oleyl alcohol), higher fatty acids (stearic acid, oleic acid, etc.) ), Metal soaps (for example, fatty acid metal salts such as coconut oil fatty acid sodium and calcium stearate) and the like.

  Examples of additives include lubricants (eg, talc, magnesium stearate, polyethylene glycol 6000, sodium stearyl fumarate, etc.), disintegration aids, antioxidants or antioxidants, and emulsifiers (eg, nonionic interfaces). Various surfactants such as active agents), dispersants, suspending agents, solubilizers, thickeners (water-soluble polymers such as carboxyvinyl polymer, polyvinyl alcohol, gelatin; cellulose ethers such as carboxymethylcellulose) PH adjusters or buffers (citric acid-sodium citrate buffer, etc.), preservatives or preservatives (parabens such as methylparaben and butylparaben), bactericides or antibacterial agents (benzoic acids such as sodium benzoate, etc.) ), Antistatic agents, taste-masking agents or masking agents (for example, sweeteners), Colorant (such as a dye or pigment such as red iron oxide), (such as fragrances) flavoring or perfume, fresheners, defoamers, isotonic agents, soothing agents. These additives can be used alone or in combination of two or more.

  The preparation of the present invention can be produced by a conventional production method using the constituents of the preparation. For example, the solid preparation contains medicinal ingredients, acidic mucopolysaccharides, cooling agents, sweeteners, organic acids, umami ingredients, surface activity. Agents, fragrances, sweetness enhancers and the like can be appropriately combined as necessary and prepared using a carrier. For example, the granule can be prepared by granulating a carrier component and other components by extrusion granulation, spray granulation, and the like, and adjusting the size if necessary. Tablets can be produced by mixing the granulated product with carriers and / or additives as necessary and compression molding. The liquid preparation is a combination of medicinal ingredients, acidic mucopolysaccharides, cooling agents, sweeteners, organic acids, umami ingredients, surfactants, fragrances, sweetness enhancers, etc., as necessary, and further a liquid carrier (purified water) Aqueous carriers such as oily carriers, etc.) and carriers for solid or semi-solid preparations, additives (emulsifiers, dispersants, suspending agents, isotonic agents, solubilizers, preservatives, flavoring agents, pH, if necessary) Can be prepared by mixing (e.g., dissolving, suspending, emulsifying, etc.) and sterilizing treatment if necessary.

  Thus, the preparation of the present invention contains (ii) an acidic mucopolysaccharide, (iii) a refreshing agent, and (iv) a sweetening agent, together with (i) a medicinal ingredient having a bitter taste, and therefore the bitter taste of the medicinal ingredient. Is effectively suppressed.

  The preparation of the present invention can be applied not only to humans but also to non-human animals, usually mammals (eg, humans, non-human animals (eg, mice, rats, rabbits, dogs, cats, cows, horses, pigs, monkeys, etc.)). You can also use it.

  The dosage and administration schedule of the preparation of the present invention can be selected from conventional ranges according to the type of medicinal ingredients, the degree of disease of the patient, the age, sex and weight of the patient. In addition, in the formulation of this invention, since the bitterness of a medicinal ingredient can be suppressed effectively, taking property can be improved and a patient's compliance can be improved. Therefore, it is easy for a patient to observe the administration, an appropriate dose can be more reliably administered, and the effect of the medicinal component can be surely exhibited.

  For example, epinastine is useful for the treatment of diseases such as bronchial asthma; allergic rhinitis; urticaria, eczema / dermatitis, pruritus, pruritus, psoriasis vulgaris, etc. It can be appropriately determined depending on the symptom, age, weight, etc. of the administration subject. For example, in the case of allergic rhinitis, the dosage is usually converted to the amount of the medicinal component, usually once a day, about 10 to 20 mg once, in the case of other diseases once a day once. About 20 mg. When rebamipide is used, the dosage is usually 100 mg of rebamipide once a day for adults, 3 times a day, in the morning, evening and before going to bed. For improvement of gastric mucosal lesions (erosion, bleeding, redness, edema) of acute gastritis and acute exacerbations of chronic gastritis, 100 mg of rebamipide is orally administered to an adult three times a day.

  The present invention can effectively reduce the bitterness of medicinal ingredients, and is useful for improving the feeling of oral administration or taking, for example, pharmaceuticals, quasi drugs, supplements, foods, health It can be used as food (dietary supplement). In particular, it is effective for improving patient compliance because it is excellent in ingestion in applications such as pharmaceuticals.

  Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

<Epinastine hydrochloride-containing preparation (tablet / film-coated tablet)>
Comparative Example 1 (commercial product)
A commercially available Alesion tablet (Nippon Boehringer Ingelheim Co., Ltd., tablet / film-coated tablet) was used. Table 1 shows the weight of allezion tablets (shown in Table 1 as total amount (mg)) and the proportion of epinastine hydrochloride, and the components contained in the allezion tablets are indicated by “◯”.

  In addition, in the film-coated tablet of Comparative Example 1, in addition to the components indicated by “◯” in the table, corn starch, HPMC 2910, ethyl acrylate-methyl methacrylate copolymer, Macrogol 6000 (manufactured by NOF Corporation), Contains talc, titanium oxide and silicone resin.

<Epinastine hydrochloride-containing orally disintegrating tablets>
Comparative Examples 2-5 and Example 1
Each component shown in Table 1 is weighed and mixed in a mortar, and the mixed powder is tableted by using a rotary tableting machine (manufactured by Hata Iron Works Co., Ltd., p-18) and disintegrated in the oral cavity. A tablet was made.

Examples 2 and 3
Among the components shown in Table 1, components other than sodium saccharin, light anhydrous silicic acid, sodium bicarbonate, PVP-xL (made by ISP JAPAN), carmellose (made by Gotoku Pharmaceutical Co., Ltd., NS-300) are mixed, An appropriate amount of water was added, kneaded, and dried. Saccharin sodium, light anhydrous silicic acid, sodium bicarbonate, PVP-xL, and carmellose are added to and mixed with the resulting dried product, and the mixture is tableted using a rotary tableting machine to produce an orally disintegrating tablet. did.

  In Example 2, a 32-mesh sieve was passed before tableting, and tableting was performed using the remainder on the sieve.

Examples 4 and 5
Among the components shown in Table 1, other than thaumatin (Example 4), Theolas, PVP-xL, D-mannitol, sodium stearyl fumarate (manufactured by Kimura Sangyo Co., Ltd., Prove), peppermint and grape flavor (Example 4) The ingredients were mixed, an appropriate amount of water was added, kneaded, and dried. To the obtained dried product, thaumatin (Example 4), Theolas, PVP-xL, D-mannitol, sodium stearyl phthalate, and peppermint or grape flavor (Example 4) were added and mixed. Tableting was performed using a tablet machine to prepare an orally disintegrating tablet.

Test example 1
Using the preparation of Comparative Example 1 and the orally disintegrating tablets obtained in Comparative Examples 2 to 5 and Examples 1 to 5, the disintegration time in the oral cavity, the sensory function in the oral cavity (particularly, (Bitterness, astringent taste, numbness, etc.) and a rough feeling were evaluated, and pH was measured.

(i) Disintegration time in the oral cavity For three panelists, the preparation of the comparative example and the orally disintegrating tablet of the example were administered to the oral cavity, and the time from the administration to the disintegration (disintegration time) was measured and averaged. The value was calculated. In addition, it was judged that disintegration was particularly effective for a tablet that disintegrates within 25 seconds (").

(ii) Bitterness and roughness in the oral cavity For 3 panelists, the preparation and oral disintegrating tablet were administered into the oral cavity, and the bitterness and roughness associated with administration until disintegration ranged from 1 to 5 points ( The higher the score, the greater the bitterness or roughness, and the average value was calculated. The bitterness of the preparation of Comparative Example 1 was evaluated.

In addition, the bitterness score evaluation is based on the following criteria:
I feel a little: 2
Feel ： 3
Feel strong: 4
Unbearable: 5.

(iii) pH
Two tablets each of the preparation of Comparative Example 1 and Comparative Examples 2 to 5 and the orally disintegrating tablets of Examples were dissolved in 10 mL of water, and the pH was measured.

  The results are shown in Table 2.

  The preparation of Comparative Example 1 dissolved rapidly after administration in the oral cavity, but a strong bitter taste was felt. Although the orally disintegrating tablet of Comparative Example 2 had a low roughness, it felt bitter and took a long time to disintegrate. Although the orally disintegrating tablet of Comparative Example 3 had a little rough feeling and bitterness was reduced to some extent, the sweet taste was insufficient, the taste was insufficiently improved, and it took a long time to disintegrate. The orally disintegrating tablet of Comparative Example 4 has a bitter taste reduced to some extent and the disintegration time is 90 seconds, which is shorter than those of Comparative Examples 2 and 3, but has a strong feeling of roughness, lack of sweetness, and poor taste improvement. It was enough. The orally disintegrating tablet of Comparative Example 5 had a short disintegration time and reduced bitterness to some extent, but had a rough feeling at the initial stage of disintegration. In addition, stickiness was also felt in the oral cavity, sweetness was insufficient, and bitterness was felt.

  The orally disintegrating tablet of Example 1 had a short disintegration time, a reduced feeling of roughness, a refreshing feeling of menthol, and an improved taste. The orally disintegrating tablets of Examples 2 and 4 disintegrated rapidly in the oral cavity, almost no rough feeling was felt, and the taste was also excellent. The orally disintegrating tablets of Examples 3 and 5 were excellent in disintegration, almost free of roughness, and excellent in taste. In addition, the elution curve of Example 5 was equivalent to the preparation of Comparative Example 1. That is, in the elution curve, the 5-minute value is Comparative Example 1: 86% and Example 5: 93%, and the 10-minute value is Comparative Example 1: 92% and Example 5: 94%, 15 minutes. The value was 95% for both Comparative Example 1 and Example 5.

  In addition, the detail of the used component is as follows.

Prosolv 90: excipient (manufactured by Kimura Sangyo Co., Ltd.)
L-HPC LH-11: excipient (manufactured by Shin-Etsu Chemical Co., Ltd., low-substituted hydroxypropylcellulose)
L-HPC LH-12: disintegrant (manufactured by Shin-Etsu Chemical Co., Ltd., low-substituted hydroxypropylcellulose)
HPMC 2910: binder (hydroxypropylmethylcellulose)
PVPk25: binder (polyvinylpyrrolidone)
Theolas: Excipient (Asahi Kasei Chemicals Corporation, crystalline cellulose)
Carmellose: disintegrant (NS-300, manufactured by Gotoku Pharmaceutical Co., Ltd.)
Carmellose calcium: disintegrant (Gogaku Pharmaceutical Co., Ltd., ECG-505)
Sodium stearyl fumarate: lubricant (manufactured by Kimura Sangyo Co., Ltd., Prove)
Mg-St: Lubricant (manufactured by Taihei Chemical Industry Co., Ltd., magnesium stearate).

<Rebamipide-containing film-coated tablets>
Comparative Example 6 (commercially available product)
Commercially available Mucosta Tablets 100 (manufactured by Otsuka Pharmaceutical Co., Ltd., film-coated tablets) was used. Table 3 shows the weight of Mucosta tablets (shown in Table 3 as total amount (mg)) and the ratio of rebamipide, and the components contained in Mucosta tablets are indicated by “◯”.

<Rebamipide-containing tablets>
Comparative Example 7 and Example 6
Each component shown in Table 3 was weighed and mixed in a mortar, and the mixed powder was tableted with a tableting pressure shown in Table 4 using a rotary tableting machine to produce a tablet having a diameter of 8 mm.

<Rebamipide-containing orally disintegrating tablets>
Comparative Example 8
It was obtained after mixing rebamipide, saccharin sodium and dipotassium glycyrrhizinate in the proportions shown in Table 3, and adding the aqueous solution containing the carrageenan ι and HPC-H in the proportions shown in Table 3 to the mixed powder and kneading. The jelly-like product was dried.

  The dried product is sieved, and a 32 mesh pass product is recovered. Carmellose (NS-300, manufactured by Gotoku Pharmaceutical Co., Ltd.), F-melt (F-melt M, manufactured by Fuji Chemical Industry Co., Ltd.) and Mg-St And tableted with the tableting pressure shown in Table 4 using a rotary tableting machine to produce an orally disintegrating tablet with a diameter of 8 mm.

Example 7
Rebamipide, sodium saccharin, tartaric acid, sodium glutamate, l-menthol and glyceryl monostearate shown in Table 3 were mixed, and 50 mg (concentration 6% by weight) of an aqueous solution containing carrageenan i in the ratio shown in Table 3 was mixed. Added, kneaded and dried.

  The dried product is sieved, and a 32 mesh pass product is collected. Crystalline cellulose, crosslinked polyvinylpyrrolidone (PVP-cl), carmellose (manufactured by Gotoku Pharmaceutical Co., Ltd., NS-300), synthetic silica (Fuji Silysia Chemical Co., Ltd.) , Silysia (pH 7.6)), carmellose calcium (manufactured by Gotoku Yakuhin Co., Ltd., ECG-505) and Prosolv 90, and tableting with the tableting pressure shown in Table 4 using a rotary tableting machine. Thus, an orally disintegrating tablet having a diameter of 8 mm was prepared.

Example 8
Rebamipide, sodium saccharin, tartaric acid, sodium glutamate, and glyceryl monostearate shown in Table 3 were mixed, and 50 mg (concentration 6% by weight) of an aqueous solution containing carrageenan i in the ratio shown in Table 3 was added to the mixed powder. , Kneaded and dried.

  The dried product is sieved, and a 32 mesh pass product is collected. L-menthol, crystalline cellulose, crosslinked polyvinylpyrrolidone (PVP-cl), carmellose (NS-300, manufactured by Gotoku Pharmaceutical Co., Ltd.), synthetic silica (Fuji Silysia) Manufactured by Chemical Co., Ltd., Cylysia (pH 7.6)), carmellose calcium and prosolv 90, and tableted with a tableting pressure shown in Table 4 using a rotary tableting machine. Disintegrating tablets were prepared.

Example 9
Rebamipide in the proportion shown in Table 3, sodium saccharin, tartaric acid, sodium glutamate, and D-mannitol were mixed, and 50 mg (concentration 6% by weight) of an aqueous solution containing carrageenan ι in the proportion shown in Table 3 was added to the mixed powder. Kneaded and dried.

  Sieve the dried product, collect 32 mesh pass product, l-menthol, crystalline cellulose, crosslinked polyvinylpyrrolidone (PVP-cl), carmellose (NS-300, manufactured by Gotoku Pharmaceutical Co., Ltd.), cacao powder, synthetic silica (Fuji Silysia Chemical Co., Ltd., Silysia (pH 7.6)), carmellose calcium (Gotoku Pharmaceutical Co., Ltd., ECG-505) and sodium stearyl fumarate (manufactured by Kimura Sangyo Co., Ltd., Prob) Using a rotary tableting machine, the tablets were tableted with the tableting pressure shown in Table 4 to produce tablet orally disintegrating tablets with a diameter of 8 mm.

Example 10
Rebamipide, sodium saccharin, saccharin, sucralose, dipotassium glycyrrhizinate, sodium glutamate, and D-mannitol in the ratio shown in Table 3 were mixed, and 50 mg of an aqueous solution containing carrageenan iota in the ratio shown in Table 3 (concentration 6 weight) %) Was added, kneaded and dried.

  The dried product is sieved, and a 32 mesh pass product is collected. L-menthol, crystalline cellulose, crosslinked polyvinylpyrrolidone (PVP-cl), cacao powder, PEG6000 and sodium stearyl fumarate (manufactured by Kimura Sangyo Co., Ltd., Prove) And tableting with a tableting pressure shown in Table 4 using a rotary tableting machine to produce an orally disintegrating tablet with a diameter of 8 mm.

Test example 2
Using the film-coated tablets of Comparative Example 6 and the tableted tablets obtained in Comparative Examples 7 to 8 and Examples 6 to 10, dissolution, disintegration time in the oral cavity, bitterness in the oral cavity were as follows. In addition, the rough feeling and the sensory evaluation were evaluated, and the pH was measured.

(i) Dissolution The dissolution rate (%) was measured under the condition of pH 6.0 based on the dissolution test method of the 14th revised Japanese Pharmacopoeia (JP XI XIV).

  Namely, 900 ml of McI1vaine buffer (pH 6.0) diluted with 0.05 mol / l concentration of disodium hydrogen phosphate at pH 6.0 and 0.025 mol / l concentration of citric acid aqueous solution was used as a test solution. About the tablet (one piece) of a comparative example or an Example, the test was done on the conditions of 50 rotations per minute by the dissolution test method 2nd method.

  After elapse of the time shown in Table 4 from the start of the dissolution test, 20 ml of the eluate was collected and filtered through a membrane filter having a pore size of 0.45 μm or less. After removing 2 ml of the filtrate at the initial stage of filtration, 5 ml of the filtrate was accurately weighed, A sample solution was prepared by adding the same buffer as above and adjusting to exactly 25 ml.

  About 0.05 g of a rebamipide standard product whose dry weight loss (1 g, 105 ° C., 2 hours) was measured in advance was accurately weighed, dissolved in dimethylformamide, and accurately adjusted to 25 ml. 2 ml of this solution was accurately weighed, a buffer solution similar to the above was added, and adjusted to 200 ml accurately to prepare a standard solution.

The sample solution and the standard solution were tested by an absorbance measurement method, and the absorbance at a wavelength of 326 nm (sample solution: A _T , standard solution: A _S ) was measured. And the elution rate (%) with respect to the display amount of rebamipide was computed based on the following formula.

Dissolution rate (%) = W _S × (A _T / A _S ) × (1 / C) × 180
(In the formula, W _S represents the weight (mg) of the rebamipide standard product converted to a dry product, and C represents the displayed amount (mg) of rebamipide in one tablet).

(ii) Disintegration time in the oral cavity, bitterness and sensuality in the oral cavity, and pH
Each item was evaluated in the same manner as in Test Example 1.

  The results are shown in Table 4.

  As is apparent from Table 4, the tablets of the examples and the orally disintegrating tablets were highly disintegratable and suppressed bitterness despite their high dissolution properties from the initial stage, and were excellent in taste. Although the tablet of the comparative example and the orally disintegrating tablet had low dissolution property and bitterness was suppressed in the initial stage, bitterness was felt in the aftertaste.

  The film-coated tablet of Comparative Example 6 dissolved rapidly after administration into the oral cavity, and a strong bitter taste was felt. In Comparative Examples 7 and 8, it takes time to disintegrate and the initial bitterness is reduced, but the aftertaste is bitter. In the tablet of Example 6, almost no bitterness was felt, and the taste was also excellent. Moreover, the orally disintegrating tablet of Example 7 had high disintegration, almost no roughness, and the bitterness was remarkably reduced. Although the orally disintegrating tablet of Example 8 had a slight bitter taste in the aftertaste, it was highly disintegratable and excellent in taste. The orally disintegrating tablets of Examples 9 and 10 were highly disintegratable, hardly felt bitter, easy to take with a cacao flavor, and had a mild taste.

<Rebamipide-containing granules>
Comparative Example 9 (commercially available product)
Commercially available Mucosta granules 20% (manufactured by Otsuka Pharmaceutical Co., Ltd., film-coated granules) were used. In Table 5, while showing the ratio of the rebamipide contained in 1000 mg of mucosta granule, the other component contained is shown by "(circle)".

  The Mucosta granule is a cylindrical granule having a size of φ0.6 mm × 1.276 mm (major axis numeric width: 0.614 to 2.294 mm).

Comparative Example 10 and Examples 11 to 14 (Rebamipide-containing preparation (granule))
The components shown in Table 5 were mixed on a scale such that the total amount was 8 g, then kneaded with the kneading medium shown in Table 6, further dried, and rectified to a size of 16 to 42 mesh to obtain granules. In addition, drying was performed at the temperature of 65 degreeC in the comparative example 10, and 35 degreeC in Examples 11-14.

Test example 3
Using the film-coated granules of Comparative Example 9 and the granules obtained in Comparative Example 10 and Examples 11-14, the dissolution properties were evaluated in the same manner as in Test Example 2 and the same as in Test Example 1 by the following method. In addition, the pH was measured and the sensory function in the oral cavity was evaluated.

  The results are shown in Table 6.

  As can be seen from Table 6, the granules of the examples were suppressed in bitterness and excellent in taste even though the dissolution properties were high from the initial stage. In contrast, the granules of the comparative example felt a strong bitter taste from the initial stage.

  Moreover, in Comparative Example 9, the coating film dissolved immediately after administration in the oral cavity, and a strong bitter taste was felt. Moreover, in the comparative example 10, the bitterness inhibitory effect was low and bitterness was felt from the initial stage administered to the oral cavity.

  In the granule of Example 12, the menthol taste was refreshing, the bitterness was remarkably suppressed, the granule was soft, and rapidly disintegrated after administration in the oral cavity. In the granules of Example 13, the bitterness was remarkably suppressed, and the granules were moderately hard. In addition, the granule of Example 14 had a mild taste, a bitter taste significantly improved, and a moderate hardness.

(Amantadine hydrochloride fine granules)
Comparative Example 11
Commercially available Symmetrel fine granules (manufactured by Novartis Co., Ltd.) were used. Table 7 shows the ratio of amantadine hydrochloride contained in 1000 mg of simmetrel fine granules, and the other components contained are indicated by “◯”.

Example 15
Among the components shown in Table 7, components other than sodium stearyl fumarate were mixed in a mortar, added with an appropriate amount of purified water, kneaded and dried at 40 ° C. The dried product was passed through a 32 mesh sieve, sodium stearyl fumarate was further added, the 200 mesh sieve was passed through, and the remainder on the sieve was made fine.

Test example 4
The sensory evaluation was conducted in the same manner as in Test Example 1 using the fine particles of Comparative Example 11 and Example 15. The fine granules of Example 15 had almost no bitter taste, had a refreshing acidity, and were excellent in taste.

<Chlorpheniramine maleate-containing powder>
Comparative Example 12 (commercially available product)
Commercially available Allergin San (manufactured by Sankyo Co., Ltd.) was used. Table 8 shows the ratio of chlorpheniramine maleate contained in 1000 mg of Allergin powder and the other components contained are indicated by “◯”.

Examples 16 and 17
All components shown in Table 8 were mixed in a mortar, added with an appropriate amount of purified water, kneaded and dried at 40 ° C. The dried product was passed through a 32 mesh sieve, Mg-St was further added, the 200 mesh sieve was passed through, and the remainder on the sieve was used as a powder.

Test Example 5
Using the powders of Comparative Example 12 and Examples 16 and 17, sensory evaluation was performed in the same manner as in Test Example 1. In the powder of Comparative Example 12, the astringent taste of chlorpheniramine maleate was felt, whereas in the powder of Example 16, the astringent taste was reduced, and the sweetness and sourness of the moderate sweetness was excellent. . Further, the powder of Example 17 had a milder taste than the powder of Example 16.

<Plavastatin sodium-containing tablets>
Comparative Example 13 (commercial product)
Commercially available mevalotin 10 tablets (manufactured by Sankyo Co., Ltd.) were used. Table 9 shows the proportion of pravastatin sodium contained in 140 mg of a tablet, and other components contained are indicated by “◯”.

Example 18
Among the components shown in Table 9, components other than Mg-St were mixed in a mortar, then Mg-St was added, mixed gently, and directly tableted to obtain 140 mg tablet (plain tablet).

Test Example 6
Using the tablets of Comparative Example 13 and Example 18, sensory evaluation was performed in the same manner as in Test Example 1. In the tablet of Example 18, the bitter taste of pravastatin sodium was reduced, and it had a refreshing acidity and excellent taste.

<Internal liquid containing epinastine hydrochloride>
Comparative Example 14 (commercially available product)
A commercially available Alezion oral solution (manufactured by Boehringer Ingelheim Co., Ltd.) was used. In Table 10, the components contained in 100 ml of the oral solution are indicated by “◯”.

Comparative Examples 15-16 and Examples 19-20 (Liquid containing epinastine hydrochloride (internal liquid))
The components shown in Table 10 were added to purified water at 40 ° C. and stirred to dissolve. Next, the mixture was cooled and filtered using a 0.45 μ membrane filter to obtain an internal solution (solution).

Test Example 7
Using the solutions of Comparative Examples 14 to 16 and Examples 19 to 20, the sensory evaluation was conducted in the same manner as in Test Example 1, and the solution was stored in a glass bottle and cooled to a temperature of 4 ° C (storage state). ) Was evaluated.

  The sensory evaluation results are shown in Table 10.

  In the solutions of Comparative Examples 14 and 15, although sweetness was felt, the bitterness was not masked, and both sweetness and bitterness were felt. The liquid agent of Comparative Example 14 was a colorless to slightly yellow clear liquid and did not change even when cooled. In the liquid preparation of Comparative Example 16, although bitterness was reduced to some extent, precipitation occurred at 4 ° C. by cooling.

  In addition, the liquid preparations of Examples 19 and 20 hardly felt bitterness, and were excellent in terms of aroma and taste. Moreover, the liquid agent of an Example is a colorless or slightly yellowish clear liquid, and the change was not seen even if it cooled.

<Epinastine hydrochloride-containing dry syrup>
Example 21
The following ingredients were mixed in a mortar, added with 15 ml of purified water, kneaded, and extruded and granulated. After granulation, it was dried at 40 ° C. and subjected to a 16-mesh sieving process to obtain clear dissolution type dry syrup granules.

  Further, 0.3 g of the obtained granule was dissolved in 20 ml of purified water, and the obtained syrup was evaluated for sensuality in the same manner as in Test Example 1. As a result, the evaluation was “1”, and almost no bitterness was felt. The sweetness was strong.

Formula:
Epinastine hydrochloride 2.0
Peppermint powder 0.5
Carrageenan ι 0.2
Aspartame 1.1
Erythritol 32.0
D-mannitol 50.0
Na citrate 4.8
Malic acid 1.4
Glutamate Na 4.0
Polyethylene glycol 6000 3.0
HPC-L 1.0
Total 100 mg.

<Tablets containing itopride hydrochloride>
Example 22
Of the following ingredients, all ingredients other than sodium stearyl fumarate (manufactured by Kimura Sangyo Co., Ltd., Prove) are all mixed in a mortar, further mixed with sodium stearyl fumarate and mixed lightly, and the mixture is directly compressed into tablets. To get an uncoated tablet.

  Moreover, when sensory evaluation was carried out using the obtained uncoated tablet in the same manner as in Test Example 1, the evaluation was “2”, the bitterness was reduced, and the taste was excellent.

Formula:
Itopride hydrochloride 50
(Astellas Pharma Inc., Ganaton Tablets 50mg)
l-Menthol 4
Carrageenan λ 5
Aspartame 15
Xylitol 10
Fumarate Na 8
L-glutamic acid 5
NS-300 15
Crospovidone INF10 15
Carmellose calcium 5
(ECG-505, manufactured by Gotoku Pharmaceutical Co., Ltd.)
End of Kenten 5
Sodium stearyl fumarate 2
(Probes made by Kimura Sangyo Co., Ltd.)
Apple flavor 0.2
Total 139.2 mg.

<Oral disintegrating tablets containing pirenzepine hydrochloride>
Example 23
Except having used the following component, operation was performed like Example 22 and the OD tablet was obtained. Using the obtained OD tablet, disintegration and sensory evaluation were conducted in the same manner as in Test Example 1. As a result, the disintegration time was 25 seconds and the sensory evaluation was “1”. Also, almost no bitterness was felt, a mild sweetness was felt, and the taste was excellent.

Formula:
Pirenzepine hydrochloride 26
(Boehringer Ingelheim, Gastrozepine Tablets)
Peppermint powder 6
Carrageenan λ 5
Aspartame 25
Saccharin Na 10
Citric acid 12
Glutamate hydrochloride 15
Carmellose 29
(NS-300)
Crospovidone INF10 35
Carmellose calcium 15
(ECG-505, manufactured by Gotoku Pharmaceutical Co., Ltd.)
End of the end 15
Sodium stearyl fumarate 2
(Probes made by Kimura Sangyo Co., Ltd.)
Grape flavor 0.2
Total 195.2 mg.

<Tablets containing ranitidine hydrochloride>
Example 24
Among the following ingredients, ranitidine hydrochloride, carrageenan λ, aspartame, saccharin Na, and 1/3 amount of crospovidone were added with an appropriate amount of purified water, kneaded and dried, and then the remaining components were mixed. Then, tableting was performed to obtain 280 mg tablets.

  Using the obtained tablet, the sensory evaluation was conducted in the same manner as in Test Example 1. As a result, the evaluation was “2.5”, the bitterness was reduced, and the taste was easy to take.

Formula:
Ranitidine hydrochloride 150
(Glaxo SmithKline Co., Ltd., Zantac Tablets 150)
Peppermint powder 3
Carrageenan λ 3
Aspartame 15
Saccharin Na 5
Citric acid 10
Glutamate hydrochloride 9
Carmellose 25
(NS-300, manufactured by Gotoku Pharmaceutical Co., Ltd.)
Crospovidone INF10 30
Carmellose calcium 5
(ECG505, manufactured by Gotoku Pharmaceutical Co., Ltd.)
Sodium bicarbonate 8
End of the end 15
Sodium stearyl fumarate 2
(Probes made by Kimura Sangyo Co., Ltd.)
Total 280 mg.

<Medical solution containing sodium valproate>
Example 25
Of the following components, methylparaben and propylparaben were dissolved in propylene glycol to prepare a paraben solution, and this paraben solution and menthol were added to purified water (warmed to 50 ° C.) and stirred. While the resulting mixture was allowed to cool, the remaining components were sequentially added and dissolved. Purified water was further added to the resulting solution to adjust to 100 ml, and the solution was filtered through a 0.45 μ membrane filter. The obtained liquid agent was a clear liquid and pH was 7.3.

  When the sensory evaluation was performed using the obtained liquid agent in the same manner as in Test Example 1, the evaluation was “1”, the bitterness was hardly felt, and the taste was easy to take with moderate sweetness.

Formula:
Sodium valproate 5
l-Menthol 0.05
Carrageenan λ 1
Aspartame 0.065
Erythritol 3.5
Saccharin Na 0.05
Glutamate Na 0.15
Na citrate 0.8
Propylene glycol 2
Methylparaben 0.028
Propylparaben 0.02
Polyoxyethylene hydrogenated castor oil 60 1
White grape essence 0.1
Purified water
(G / 100 ml) 100 ml.

<Cetirizine hydrochloride-containing orally disintegrating tablets>
Comparative Examples 17-21 and Examples 26-27
The components shown in Table 11 were mixed in a mortar, kneaded with an appropriate amount of water, dried at 40 ° C. for 5 to 6 hours, and after 32 mesh passes, cetirizine hydrochloride granules were obtained. Then, the tablet orally disintegrating tablet was produced using the rotary tableting machine.

  About the obtained lump, the bitterness was evaluated similarly to Test Example 1. The results are shown in Table 11.

  As is clear from Table 11, the preparations of Comparative Examples 17 to 21 do not contain (ii) to (iv), which are essential components of the present invention, and therefore the effect of suppressing the bitter taste of cetirizine hydrochloride is low. On the other hand, in Example 26 containing (ii) to (iv), bitterness was effectively suppressed. In addition, in the preparation of Example 27, bitterness was further suppressed by adding the sour agent (v).

<Film coated tablets containing propiverine hydrochloride>
Comparative Example 22 (commercial product)
A commercially available BAPFOR tablet (manufactured by Taiho Pharmaceutical Co., Ltd., film-coated tablet) was used. Table 12 shows the weight of one tablet and the proportion of propiverine hydrochloride contained in one tablet, and other components contained in the tablet are indicated by “◯”.

<Oral disintegrating tablet containing propiverine hydrochloride>
Comparative Examples 23-24 and Examples 28-31
The components shown in Table 12 were mixed in a mortar, and the mixture was directly compressed to prepare tablets (circular tablets (R-tab)).

Test Example 8
Using the film-coated tablet of Comparative Example 22 and the tableted tablets of Comparative Examples 23-24 and Examples 28-31, similarly to Test Example 1, pH, disintegration time in the oral cavity, unpleasant taste (bitterness, numbness) Evaluated. The results are shown in Table 12.

  The film-coated tablet of Comparative Example 22 dissolved immediately after administration in the oral cavity and felt strong bitterness and astringent taste. In the tablet of Comparative Example 23, there was no numbness and the bitterness was slightly reduced, but the aftertaste was bitter, the disintegration time was long, and the core remained. In the tablet of Comparative Example 24, both bitterness and numbness were strongly felt. In Example 28, although the acidity at the beginning of administration was strong, bitterness and numbness were hardly felt. In the tablet of Example 29, bitterness and numbness were hardly felt, the sweetness was moderate, and the taste was excellent. Moreover, in Example 30, the gummy remained much, but bitterness and numbness were hardly felt, the sweetness was moderate, and the taste was excellent. In Example 31, although a rubber-like lump was felt, it dissolved immediately and there was no roughness. Also, there was no bitterness, no numbness was felt, sweetness lasted for a long time, and the taste was excellent.

Claims (17)

(i) a medicinal ingredient having a bitter taste, and (ii) acidic mucopolysaccharides, and (iii) fresheners, and (iv) a sweetening agent, (v) organic acids, (vi) umami component and (vii) the interface An oral preparation containing at least one selected from active agents and suppressed bitterness ,
The acidic mucopolysaccharide (ii) is carrageenan ι,
An oral preparation wherein the refreshing agent (iii) is at least one terpene compound selected from menthol, camphor and borneol, or an essential oil, essence or powder containing the terpene compound . Sweetening agent (iv) is a non-saccharide sweeteners, the oral formulation of claim 1, wherein at least one or a salt thereof selected from sugar alcohols and saccharides. The oral preparation according to claim 2, wherein the non-sugar sweetener is at least one selected from saccharin, aspartame, acesulfame, sucralose, glycyrrhizic acid, stevia and thaumatin, or a salt thereof. The oral preparation according to claim 2 , wherein the sugar alcohol is at least one selected from mannitol, sorbitol, erythritol and xylitol. The oral preparation according to claim 2 , wherein the saccharide is at least one selected from sucrose, lactose and reduced maltose water candy. Acidic mucopolysaccharide (ii) 1 to 3000 parts by weight, refresher (iii) 0.1 to 300 parts by weight and sweetener (iv) 5 to 10,000 parts per 100 parts by weight of the medicinal component (i) having a bitter taste The oral preparation according to any one of claims 1 to 5 , which contains parts by weight. It contains 0.1 to 400 parts by weight of acidic mucopolysaccharide (ii) and 0.1 to 250 parts by weight of a cooling agent (iii) with respect to 100 parts by weight of sweetener (iv). ) and the ratio of cooling agent and (iii) (weight ratio), according to any one of claims 1 to 6 as the component (ii) / the component (iii) = 0.1 / 1~100 / 1 Oral formulation. The oral preparation according to any one of claims 1 to 7, wherein the organic acid (v) is at least one selected from a saturated carboxylic acid, an unsaturated carboxylic acid and an oxycarboxylic acid, or a salt thereof. The organic acid (v) is at least one selected from succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid and isoascorbic acid, or a salt thereof, according to any one of claims 1 to 7. Oral formulation. The oral preparation according to any one of claims 1 to 9, wherein the umami component (vi) is at least one selected from glutamic acid and inosinic acid or a salt thereof. The surfactant (vii) is at least one selected from poly C _2-3 alkylene glycols, (poly) C _2-3 alkylene glycol C _8-26 fatty acid esters and glycerin C _8-26 fatty acid esters. The oral preparation according to any one of 1 to 10 . The oral preparation according to any one of claims 1 to 11 , further comprising (viii) a fragrance. The oral preparation according to claim 12 , wherein the flavor (viii) is at least one selected from apple, grape, white grape, grapefruit and cacao. The oral preparation according to any one of claims 1 to 13 , which is a solid preparation. The oral preparation according to any one of claims 1 to 13 , which is a liquid preparation. The oral preparation according to any one of claims 1 to 14 , which is an intraoral rapidly disintegrating tablet. (i) a medicinal ingredient having a bitter taste, (ii) an acidic mucopolysaccharide, and (iii) fresheners, and (iv) a sweetening agent, (v) organic acids, (vi) umami component and (vii) the interface A method of adding at least one selected from active agents to suppress or reduce the bitter taste of the medicinal component (i) ,
As the acidic mucopolysaccharide (ii), using carrageenan ι,
As the refreshing agent (iii), at least one terpene compound selected from menthol, camphor and borneol, or an essential oil, essence or powder containing this terpene compound is used, and the bitter taste of the medicinal component (i) is used. How to suppress or reduce .