KR20090113777A - Oral composition concealing unpleasant taste - Google Patents

Abstract

PURPOSE: An oral solid composition without bitter taste of drug is provided to prevent unpleasant tastes such as strong, bitter, and sour taste without release property of drug. CONSTITUTION: An oral composition without bitter taste contains drug with unpleasant taste, acidic ingredient and alkali earth metal salt and/or earth metal salt. The acidic ingredient is tannic acid, acetic acid, citric acid or tartaric acid. The composition is used in the form of tablet, granule, powder, pill, dry syrup or liquid medicine.

Description

Oral composition concealing unpleasant taste {ORAL FORMULATION CONCEALING UNPLEASANT TASTE}

The present invention relates to an oral composition that hides unpleasant tastes such as astringent, astringent, irritant, bitter, and astringent of a drug, and a method for hiding unpleasant tastes.

The drug often exhibits an unpleasant taste such as astringent, irritant, bitter, astringent, or astringent, and cannot be taken as it is, so it is necessary to conceal the unpleasant taste in the oral cavity. The method of concealing the unpleasant taste of a drug is divided roughly into a method of controlling the dissolution of the drug in the oral cavity and a method of masking the taste of the drug itself with a masking agent.

As a method of controlling the dissolution of a drug in the oral cavity, a method of coating with a gas-soluble polymer, an enteric polymer, a water-insoluble polymer, waxes, and the like (Patent Documents 1 to 6), a method of forming and hiding a matrix (patent Documents 7 and 8) and a method (patent document 9) etc. clapping with a clathrate compound are mentioned. However, in order to control the dissolution, the elution slightly changes, and the expression of the effect of the drug may be delayed in some cases. Moreover, in order to apply to the drug with high water solubility, a coating agent and a matrix agent are needed in large quantities, and the concealment of an unpleasant taste is often inadequate. On the contrary, in some cases, the bioavailability of the drug is lowered and the effect thereof is insufficient for application to a drug having low water solubility. In addition, when the particle size of the tingling feeling or the feeling of tingling occurs at the time of taking it, the remaining particles in the oral cavity, such as interdental, had an unpleasant taste or irritation for a while after taking. Moreover, there existed the fault which is hard to apply to semisolid formulations, such as a liquid formulation and a jelly.

On the other hand, as a method of masking the taste of the drug itself with a concealing agent, a method of adding high-sensitive sweeteners such as acesulfame potassium (Patent Document 10), aspartame (Patent Documents 11 and 12), stevia extract (Patent Document 13) and the like And polyhydric alcohols (Patent Documents 19 and 18) such as essential oils (Patent Document 14), such as leeds oil and lemon oil, ascorbic acid, citric acid, malic acid, fumaric acid, tartaric acid, tannic acid, and condensed phosphoric acid (Patent Documents 15-18). 20) and the method of adding many substances, such as surfactant (patent document 21). While these methods have little effect on elution, they are not easy to use because they have a weak masking effect, are only effective with certain drugs, or have a small masking effect on drugs that have strong astringent or irritant properties. Many drugs can be applied depending on the masking agent. In order to improve such a fault, the method of combining several masking agents, such as the method of adding a flavoring agent and the sweetener in combination (patent documents 22 and 23), and the method of adding the acid and sweetener in combination (patent document 24), is also tried. However, it is a phenomenon that it is not enough to give a sufficient masking effect to many drugs such as astringent and irritant drugs and high water-soluble drugs.

[Patent Document 1] Japanese Patent Laid-Open No. 2008-37863

[Patent Document 2] Japanese Patent Publication No. 2006-232789

[Patent Document 3] Japanese Patent Publication No. 2006-22039

[Patent Document 4] Japanese Patent Laid-Open No. 2005-343800

[Patent Document 5] Japanese Patent Application Laid-Open No. 3-130214

[Patent Document 6] Japanese Patent Application Laid-Open No. 57-58631

[Patent Document 7] Japanese Patent Publication No. 2004-189758

[Patent Document 8] Japanese Patent Application Laid-Open No. 9-208458

[Patent Document 9] Japanese Patent Application Laid-Open No. 3-236316

[Patent Document 10] Japanese Patent Application Laid-Open No. 2007-269716

[Patent Document 11] Japanese Unexamined Patent Publication No. 2005-336078

[Patent Document 12] Japanese Patent Application Laid-Open No. 2002-128705

[Patent Document 13] Japanese Patent Application Laid-Open No. 2-56416

[Patent Document 14] Japanese Unexamined Patent Publication No. 2005-132801

[Patent Document 15] Japanese Patent Publication No. 2007-54001

[Patent Document 16] Japanese Patent Application Laid-Open No. 2001-213764

[Patent Document 17] Japanese Patent Application Laid-Open No. 9-194356

[Patent Document 18] Japanese Unexamined Patent Publication No. 2000-119175

[Patent Document 19] Japanese Unexamined Patent Publication No. 2002-361105

[Patent Document 20] Japanese Patent Application Laid-Open No. 2002-145764

[Patent Document 21] Japanese Unexamined Patent Publication No. 2004-91408

[Patent Document 22] Japanese Unexamined Patent Publication No. 2007-217687

[Patent Document 23] Japanese Unexamined Patent Publication No. 2004-155781

[Patent Document 24] Japanese Patent Application Laid-Open No. 2000-290199

Therefore, the object of the present invention can be applied to many formulations such as liquid formulations, not limited to solid formulations, and to prevent unpleasant tastes such as astringent, irritant, bitter, astringent, and astringent of the drug without changing the dissolution properties. It is to provide an oral composition which can be and a method thereof.

In view of these circumstances, the present inventors have examined various methods of preventing the unpleasant taste of drugs that can be applied not only to solid formulations but also to liquid formulations. It is found that the addition of alkaline earth metal salts and / or earth metal salts to this composition greatly reduces the unpleasant taste, which results in a significantly reduced unpleasant taste due to acidic substances, resulting in an oral composition that does not exhibit an unpleasant taste. The present invention has been completed.

That is, the present invention provides an oral composition which hides an unpleasant taste containing a drug, an acidic substance and an alkaline earth metal salt and / or an earth metal salt, which exhibit an unpleasant taste.

The present invention also provides a method for concealing an unpleasant taste, characterized by containing an acidic substance and an alkaline earth metal salt and / or a earth metal salt in a drug having an unpleasant taste.

According to the present invention, unpleasant tastes such as astringents, irritants, bitterness, astringent taste, and astringency of the drug can be prevented without changing the elution property.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

In the present invention, a drug having an unpleasant taste is a drug which, when taken orally, causes an unpleasant sensation such as astringent, irritant, bitter, astringent or astringent taste in the oral cavity and throat. As such a drug, an alkaline drug, a positive drug, an acidic drug is mentioned, The extract derived from living organisms, such as a herbal medicine, an herb, or a herbal, is also mentioned. In the composition of the present invention, all of these are effective, and there is a masking effect. In the present invention, an alkaline drug means that the vitreous is a drug that shows alkalinity, and when a salt is formed, it is not necessarily alkaline. Likewise, an acidic drug means that the vitreous is an acidic drug, and when a salt is formed, it is not necessarily acidic. A positive drug is a drug that dissolves even when used as a base or as an acid. In addition, the alkaline drug, the positive drug, and the acidic drug may be used as it is, and its hydrochloride, nitrate, sulfate, acetate, lactate, citrate, succinate, fumarate, carbonate, teoclate, tosylate, Even acid addition salts such as tartaric acid, butyrate, hydrobromide, phosphate, bibenzate, besylate and maleate, alkali metal salts such as sodium salts and potassium salts, and alkaline earth metal salts such as calcium salts, magnesium salts and aluminum salts This may be followed by chloride, bromide, iodide or the like.

Specific examples of the drug having such an unpleasant taste include azelastine, adenosyl cobalamin, alimethazine, ardioxa, ambroxol, anlexanox, isotifenzyl, fenprozil, indoroxazine, ethylephrine, epi Nastin, Ephedrine, Emedastine, Oxatomid, Octotamine, Ormesaltan Medoxomil, Caffeine, Carbinoxamine, Candesaltanylcexetyl, Guapenesine, Clemastine, Cloperastine, Chlorphenylamine , Chlorhexidine, codeine, cobalamin, cyanocobalamin, dicetiamine, dihydrocodeine, diphenidol, diphenylpyraline, diphenhydramine, dibrophylline, dibenzoisothiamine, cimetidine, dimemomorphane, diltia Gem, Sildenafil, Scopolamine, Scuralphite, Supradust, Setlacsite, Cetiridin, Tadalafil, Thiamine, Thiaminedisulfide, Ticlopidine, Thifepidine, Dextromethorphan, Termisaltan, Doxyramine, Do Nefedil, Trianist, Triplerrolidine, Trimethokinol, Nizatidine, Noscapine, Papaverine, Versaltan, Valdenafil, Biotin, Picosulphide Sodium, Bisibtiamine, Hydroxocobalamin, Pyridoxine, Pyridine Doxosol, pyridoxamine, pyrenzepine, pamotidine, finasterite, peniramine, phenylephrine, pseudoephedrine, butylscopolamine, flavinadenindinucleotide sodium, hepronicate, bepotastine, berberine, benfotiamine , Maprotimin, mequitazine, meclazine, methylatropine, methylhydroxycobalamin, methylbenatizium, methoxyphenamine, fiboflavin, riboflavin sodium, ranitidine, raftidine, roxatidine acetate, Loxaltan, loperamide, rotadine, aspirin, acetaminophen, isopropyl ampicillin, ibuprofen, ethenamide, diclofenac, salicyamide, mefenamic acid, flufenamic acid, methoxycamp, loxoprofen, Ranexamic acid, etodorak, celecoxib rofecoxib, valdecoxib, palecoxib, erythroxib, lumiracoxib, theophylline, fexofanadine, isoprodamide, berberine, palmidine retinol, calcium pantothenate, Brom valeryl urea, chloramphenicol, aminophylline, veradon, total alkaloids, allyl isopropylacetylurea and the like. In addition, extracts derived from living organisms such as herbal medicines, herbs and herbal medicines can be used as virtuous trees, subtropical medicines, aloe, yellow wall, ginkgo, fennel, golden yellow, yellow white, turmeric, ubaursi, oak, youngsil, Hyunho color, yeonmyeongcho, yellow wall. , Yellow lotus, sewage, azu, gileuncho, health, licorice, gilyeong, kimnema, chlorella, cinnamon, gentian, yeast, medicine, yeast, ginger, early spring, red ginseng, yellow flower, rhubarb, jujube , Peony, Cornus, Creation, Taxi, Cloves, Clockwork, Jodeung-gu, Bokryeong, Houbushi, Bark skin, Hope, Rohoe, Ginseng, Gal Geun-tang, Gupoong Hae-deok-tang, Hyangseongdeokhwan, Soshiho-tang And extracts such as acid rate intang and ten mil paddock tang. These drugs may be used alone or in combination of two or more thereof. Of these drugs, diphenhydrazine, ambroxol, epinastine, phenylephrine, brohexine, ethylephrine, pyrenzepine, pseudoephedrine, methylephedrine, loperamide, or these salts are preferred.

It is preferable to contain 0.1-95 mass% in the oral composition, and, as for the drug which shows unpleasant taste in this invention, it is more preferable to contain 1-90 mass%.

Moreover, you may mix | blend another drug with the said composition in addition to the said drug. For example, such drugs include antipyretic analgesic drugs, hypnotic sedation drugs, anti-drowsiness drugs, smoky drugs, pediatric pain medications, psoriasis drugs, antacid drugs, digestive drugs, cardiovascular drugs, arrhythmic drugs, hypertensive drugs, vasodilators, Pharmacologically active ingredients used in diuretics, anti-ulcer drugs, formal drugs, osteoporosis treatment drugs, antitussive expectorants, anti-asthmatic drugs, antibacterial agents, urinary medications, nutrient tonics, vitamins and the like.

In the present invention, the concealing agent is used in combination with an acidic substance and alkaline earth metal salt and / or earth metal salt. An acidic substance here is a mating agent of a pharmaceutical additive which shows acidicity. Specific examples thereof include tannic acid, acetic acid propyl, citric acid, acetic acid and tartaric acid, and these can be used alone or in combination of two or more thereof. Among these, tannic acid, a glutamic acid profile, and acetic acid are more preferable at the point of the concealment effect of an unpleasant taste.

Although the addition amount of an acidic substance changes also with the kind of drug which shows an unpleasant taste, 0.05-50 mass parts is preferable with respect to 1 mass part of drugs which show an unpleasant taste, It is more preferable that it is 0.1-10 mass parts, 0.5-5 mass parts is more preferable, and 0.8-2 mass parts is especially preferable.

In the present invention, alkaline earth metal salts and / or earth metal salts are further added as the concealment agent. As alkaline earth metal salt and / or earth metal salt, 1 type (s) or 2 or more types chosen from a magnesium salt, a calcium salt, and an aluminum salt is mentioned.

Specific examples of alkaline earth metal salts and / or earth metal salts include magnesium metasilicate aluminate, calcium carbonate, calcium chloride hydrate, magnesium chloride, dry aluminum hydroxide gel, calcium citrate, glycerin phosphate, calcium gluconate hydrate, calcium silicate, magnesium silicate, Magnesium aluminum silicate, synthetic aluminum silicate, synthetic hydrotalcite, calcium acetate, magnesium oxide, alumina hydroxide magnesium hydroxide, aluminum hydroxide gel, aluminum hydroxide, sodium hydrogen carbonate co-precipitate, aluminum hydroxide, magnesium carbonate, calcium carbonate co-precipitate, magnesium hydroxide, Tricalcium phosphate, magnesium carbonate, impregnated calcium carbonate, natural aluminum silicate, calcium lactate hydrate, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate granulated product, aluminum sulfate, calcium sulfate, calcium monohydrogen phosphate, calcium hydrogen phosphate hydrate, hydrogen phosphate Calcium granules, calcium dihydrogen phosphate hydrate, and the like. It can be used 1 type or in combination of 2 or more types. Among these, magnesium metasilicate aluminate, calcium carbonate, and calcium silicate are especially preferable at the point of the concealment effect of an unpleasant taste.

The amount of the alkaline earth metal salt and / or the earth metal salt added varies depending on the kind or compounding amount of the drug having an unpleasant taste, the type or amount of the acidic substance, but is generally 0.05 to 50 parts by mass, and preferably 0.1 part by mass based on 0.1 mass of the acidic substance. 50 mass parts is more preferable, Furthermore, it is preferable that it is 0.25-25 mass parts, and 0.5-10 mass parts is especially preferable.

The composition of the present invention is a drug having an unpleasant taste, diphenhydramine, ambroxol, epinastine, phenylephrine, brohexine, ethyllepurin, pyrenzepine, pseudoephedrine, methylphedrine, loperamide, carbinoxamine Maleic acid dihydrocodeine, isopropidemide, caffeine anhydrous, theophylline, acetaminophen, ibuprofen, dextromethorphan or salts thereof, hop dry extract, ginseng dry extract, cedar dry extract, as acidic substance Particular preference is given to using tannic acid, molar acid profile or acetic acid, and using magnesium metasilicate, calcium carbonate or calcium silicate as alkaline earth metal salts and / or earth metal salts.

The composition of the present invention is provided by combining an acidic substance with an alkaline earth metal salt and / or an earth metal salt as a concealing agent to a drug having an unpleasant taste. When blending, the composition of the present invention may be mixed with a powder and a masking agent having an unpleasant taste as a powder, may be dissolved some or all of them in a suitable solvent, and furthermore, the solvent is spray-dried, heated and dried, You may remove by freeze drying, ventilation drying, reduced pressure drying, etc. In addition, the formulation of the composition of the present invention tablets, granules, granules, powders, hard capsules, caplets, soft capsules, pills, oral solution, suspensions, emulsions, syrups, dry syrups, chewables, foams, drops , Oral disintegrating tablets, films, and jelly can be used as various oral dosage preparations. Moreover, you may make it a microparticle, such as a microcapsule, a nanocapsule, a microspi, a nanospi, and a liposome, and to make it the above-mentioned formulation.

These formulations are generally pharmaceutically acceptable additives, such as stabilizers, stabilizers, surfactants, glidants, lubricants, solubilizers, buffers, sweeteners, bases, adsorbents, copulating agents, binders. , Suspending agents, curing agents, antioxidants, brightening agents, flavoring agents, coating agents, coatings, wetting agents, wetting agents, fillers, antifoaming agents, refreshing agents, chewing agents, antistatic agents, flavoring agents, flavoring agents, coloring agents, sugar Agent, tonicity agent, emollient, emulsifier, pressure-sensitive adhesive, adhesion enhancer, consistency agent, blowing agent, pH adjuster, pH adjuster, excipient, dispersant, disintegrant, disintegration aid, fragrance, desiccant, preservative, preservative, dissolving agent, dissolution aid , A solvent, a fluidizing agent, and the like can be added as needed and produced by a conventional method.

Specific examples of the formulation additives include purified white sugar, glucose, trehalose, lactose, maltose, mannitol, sorbitol, xylitol, erythritol, sodium saccharin, aspartame, acesulfame potassium, sucrose, licorice extract, stevia extract, lacan Ka extract, corn starch, potato starch, wheat starch, sodium bicarbonate, sodium chloride, crystalline cellulose, methyl cellulose, ethyl cellulose, hypromerose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxymethyl cellulose Calcium, Hypromerophthalate, cellulose acetate phthalate, dextrin, alpha starch, gum arabic, gelatin, sodium alginate, polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, magnesium stearate, talc, hydrogenated vegetable oil, macro Goal, silicone oil, agar, shellac, text Serine, aromatic essential oils, water soluble pigments, iron sulfate, iron trioxide, iron trioxide, brown iron oxide, black iron oxide, titanium dioxide, lake pigments, benzoic acid, sodium benzoate, paraoxybenzoic acid, polysorbate 80, glycerin fatty acid esters, Citrus flavors, coffee flavors, chocolate flavors, yogurt flavors, milk flavors, lemon oil, peppermint oil, such as pewter, medium chain triglycerides, ascorbic acid, tocopherol, sodium thiosulfate, sodium edetate, orange or lemon And plant essential oils such as sparemint oil and spice oil. The formulation additive which can be used for the composition of the present invention is not limited to those described above, and is not particularly limited as long as the formulation additive is usable in formulation.

For example, when the formulation needs to adjust the granulation powder with tablets, granules, fine granules, powders, pills, dry syrups, etc., wet granulation methods such as spray granulation method, stirring granulation method, flow granulation method, electric granulation method, and electric flow granulation method, consolidation It is manufactured by generally used granulation methods, such as dry granulation methods, such as an granulation method. In addition, the powder or granulated powder containing the active ingredient can be mixed and subdivided into distribution to fill. Tablets are prepared by mixing the active ingredient powder, powder, fine granules, granules or pills with the additives of the preparation and compression molding. Coating preparations such as dragees, film coated tablets and coated granules are produced by conventional methods such as pan coating, flow coating, rolling coating and combinations thereof.

Oral liquid preparations such as drinks, syrups, ericsils, limonades, extracts, soft capsules filled with liquids or semi-solids, hard capsules, etc., are usually mixed with a part of the preparation additives such as solvents such as tablets and the like. It melt | dissolves, and disperse | distributes, it adds formulation additives, such as a remaining solvent, and adjusts a liquid amount, and is manufactured. As needed, you may adjust pH using an acid or an alkali. Moreover, you may solubilize, emulsify, and suspend by using preparation additives, such as surfactant, a solubilizer, an emulsifier, and a suspending agent. As needed at the time of adjustment, heating, cooling, nitrogen substitution, filtration, sterilization treatment, etc. may be performed.

Moreover, you may add functions, such as stabilization, sustained-release, sustaining, quick disintegration, quick dissolution, improvement of solubility, improvement of a feeling of dose, etc., using a drug additive as needed. The method of adding these functions can be performed by the method generally used, For example, it is set as the other granule which uses a multilayered tablet or nucleated tablet which mix | blends an active ingredient with another granule, and makes it into other granules, Solid solution to be co-pulverized as a matrix preparation, which is an intraorally disintegrating preparation, which is a chewable formulation, which is a foaming formulation, which is a coating formulation such as dragee, film coated tablet, coated granules, etc. The method of adjusting to specific pH, a viscosity, a penetration pressure, salt concentration which adds an antioxidant and a stabilizer which adds a sweetening agent and a refreshing agent to these, etc. can be mentioned, You may combine these methods.

EXAMPLE

Hereinafter, although an Example and a comparative example are given and this invention is demonstrated further more concretely, this invention is not limited to these.

Example 1

1 g of diphenhydramine hydrochloride, 1 g of tannic acid, and 4 g of magnesium metasilicate were weighed, dissolved and dispersed in purified water, and the total amount was 100 mL. The internal liquid solution of 1 was obtained.

Comparative Example 1

In the same manner as in Example 1, except for tannic acid and magnesium metasilicate in Example 1, the internal liquid solution of Comparative Example 1a except for magnesium metasilicate aluminum silicate in Example 1, the internal liquid solution of Comparative Example 1b, In Example 1, the internal liquid solution of Comparative Example 1c was obtained except for tannic acid.

Example 2

The diphenhydramine hydrochloride of Example 1 was changed to 1 g of ambroxole hydrochloride (manufactured by Yangsei Co., Ltd.), and in the same manner as in the above, the internal liquid solution of Example 2 was obtained.

Comparative Example 2

In the same manner as in Example 2, except for the tannic acid and magnesium metasilicate in Example 2, except for the internal liquid solution of Comparative Example 2a, except for magnesium metasilicate in Example 2, the internal liquid solution of Comparative Example 2b, In Example 2, the internal liquid solution of Comparative Example 2c was obtained except for tannic acid.

Example 3

The diphenhydramine hydrochloride of Example 1 was changed to 1 g of epinastine hydrochloride (Beringer Ingelheim), and the internal liquid solution of Example 3 was similarly obtained.

Comparative Example 3

In the same manner as in Example 3, except for the tannic acid and magnesium metasilicate in Example 3, the internal liquid solution of Comparative Example 3a except for magnesium metasilicate in Example 3, the internal liquid solution of Comparative Example 3b, In Example 3, the internal liquid solution of Comparative Example 3c was obtained except for tannic acid.

Example 4

The diphenhydramine hydrochloride of Example 1 was changed to 1 g of phenylephrine hydrochloride (Boehringer Ingelheim), and the internal liquid solution of Example 4 was similarly obtained.

Comparative Example 4

In the same manner as in Example 4, except for the tannic acid and magnesium metasilicate in Example 4, except for the internal liquid solution of Comparative Example 4a, except for magnesium metasilicate in Example 4, the internal liquid solution of Comparative Example 4b, In Example 4, the internal liquid solution of Comparative Example 4c was obtained except for tannic acid.

Example 5

The diphenhydramine hydrochloride of Example 1 was changed to 1 g of brohexine hydrochloride (manufactured by Shokai Co., Ltd.), and the same procedure was followed to obtain the internal liquid solution of Example 5.

Comparative Example 5

In the same manner as in Example 5, except for tannin acid and magnesium metasilicate in Example 5, the internal liquid solution of Comparative Example 5a was removed, and the internal liquid solution of Comparative Example 5b was removed except for magnesium metasilicate in Example 5 In Example 5, the internal liquid solution of Comparative Example 5c was obtained except for tannic acid.

Example 6

The diphenhydramine hydrochloride of Example 1 was changed to 1 g of ethylepurine hydrochloride (Beringer Ingelheim agent), and it carried out similarly to obtain the internal liquid solution of Example 6.

Comparative Example 6

In the same manner as in Example 6, except for the tannic acid and magnesium metasilicate in Example 6, except for the internal liquid solution of Comparative Example 6a, except for magnesium metasilicate in Example 6, the internal liquid solution of Comparative Example 6b, In Example 6, the internal liquid solution of Comparative Example 6c was obtained except for tannic acid.

Example 7

The diphenhydramine hydrochloride of Example 1 was changed to 1 g of pyrenezepine hydrochloride (Boehringer Ingelheim), and the internal liquid solution of Example 7 was similarly obtained.

Comparative Example 7

In the same manner as in Example 7, except for tannic acid and magnesium metasilicate in Example 7, the internal liquid solution of Comparative Example 7a was removed, and the internal liquid solution of Comparative Example 7b was removed in Example 7, except for magnesium metasilicate. In Example 7, the internal liquid solution of Comparative Example 7c was obtained except for tannic acid.

Example 8

The diphenhydramine hydrochloride of Example 1 was changed to 1 g of pseudoephedrine hydrochloride (manufactured by Alps Co., Ltd.), and the same procedure was followed to obtain the internal liquid solution of Example 8.

Comparative Example 8

In the same manner as in Example 8, except for the tannic acid and magnesium metasilicate in Example 8, except for the internal liquid solution of Comparative Example 8a, except for the magnesium metasilicate in Example 8, the internal liquid solution of Comparative Example 8b, In Example 8, the internal liquid solution of Comparative Example 8c was obtained except for tannic acid.

Example 9

The diphenhydramine hydrochloride of Example 1 was changed to 1 g of dl-methylephedrine hydrochloride (made by Alps Co., Ltd.), and it carried out similarly to obtain the internal liquid solution of Example 9.

Comparative Example 9

In the same manner as in Example 9, except for tannic acid and magnesium metasilicate in Example 9, the internal liquid solution of Comparative Example 9a except for magnesium metasilicate in Example 9, and the internal liquid solution of Comparative Example 9b In Example 9, the internal liquid solution of Comparative Example 9c was obtained except for tannic acid.

Example 10

The diphenhydramine hydrochloride of Example 1 was changed to 1 g of loperamide hydrochloride (manufactured by ICFI), and the same procedure was followed to obtain the internal liquid solution of Example 9.

Comparative Example 10

In the same manner as in Example 10, except for tannic acid and magnesium metasilicate in Example 10, except for the internal liquid solution of Comparative Example 10a, except for magnesium metasilicate in Example 10, the internal liquid solution of Comparative Example 10b In Example 10, the internal liquid solution of Comparative Example 10c was obtained except for tannic acid.

Test Example 1

Five normal subjects put about 0.5 ml of the oral solution of Examples 1 to 10 and the oral solution of Comparative Examples 1 to 10 into the mouth, spread it widely on the tongue while being careful not to swallow, and spit out after about 15 seconds. At this time, the degree of unpleasant taste such as convergence, irritation, bitterness, astringent taste, and astringency was evaluated in five steps shown below.

1: I feel very unpleasant taste

2: I have an unpleasant taste

3: I feel a little unpleasant taste

4: I feel like I'm feeling unpleasant

5: feel nothing

The average value of the score at this time is shown in Table 1. As shown in Table 1, the composition of the present invention, in particular, has an unpleasant taste of each drug, which is a base hydrochloride, which is considered to be very strong in bitterness, astringent taste, astringent, etc., whereas an acidic substance and an alkaline earth metal salt are concealed. And / or the composition of the comparative example which does not include any or both of the earth metal salts did not conceal the unpleasant taste.

TABLE 1

 Example 1  Comparative Example 1a  Comparative Example 1b  Comparative Example 1c         drug    4.8    1.0    1.6    1.0    Diphenhydramine hydrochloride  Example 2  Comparative Example 2a  Comparative Example 2b  Comparative Example 2c    5.0    1.8    2.6    1.8    Ambroxol Hydrochloride  Example 3  Comparative Example 3a  Comparative Example 3b  Comparative Example 3c    4.8    1.4    2.3    1.4    Efinastin hydrochloride  Example 4  Comparative Example 4a  Comparative Example 4b  Comparative Example 4c    4.8    1.6    2.4    1.6    Phenylephrine Hydrochloride  Example 5  Comparative Example 5a  Comparative Example 5b  Comparative Example 5c    5.0    2.2    2.8    2.0    Brohexine hydrochloride  Example 6  Comparative Example 6a  Comparative Example 6b  Comparative Example 6c    4.6    1.4    2.2    1.6    Ethylephrine hydrochloride  Example 7  Comparative Example 7a  Comparative Example 7b  Comparative Example 7c    4.8    1.2    2.4    1.4    Pyrenzepine hydrochloride  Example 8  Comparative Example 8a  Comparative Example 8b  Comparative Example 8c    4.6    1.6    2.6    1.6    Pseudoephedrine hydrochloride  Example 9  Comparative Example 9a  Comparative Example 9b  Comparative Example 9c    4.8    2.0    2.8    2.0    dl-methylephedrine hydrochloride  Example 10  Comparative Example 10a  Comparative Example 10b  Comparative Example 10c    4.6    2.0    2.6    2.2    Loperamide Hydrochloride

Example 11

Weigh 1 g of carbinoxamine maleate, 1 g of tannin acid, and 4 g of magnesium metasilicate, and dissolve and disperse in purified water to make 100 ml. The internal liquid solution of Example 11 was obtained.

Comparative Example 11

In the same manner as in Example 11, except for the tannic acid and magnesium metasilicate in Example 11, except for the internal liquid solution of Comparative Example 11a, except for the magnesium metasilicate aluminum silicate in Example 11, the internal liquid solution of Comparative Example 11b In Example 11, the internal liquid solution of Comparative Example 11c was obtained except for tannic acid.

Example 12

The carbinoxamine maleate of Example 11 was changed to 1 g of dihydrocodein phosphate (manufactured by Mitsubishi Co., Ltd.).

Comparative Example 12

In the same manner as in Example 12, except for the tannic acid and magnesium metasilicate, in Example 12, except for the internal liquid solution of Comparative Example 12a, except for magnesium metasilicate in Example 12, the internal liquid solution of Comparative Example 12b, In Example 12, the internal liquid solution of Comparative Example 12c was obtained except for tannic acid.

Example 13

The carbinoxamine maleate of Example 11 was changed to 1 g of isopropride iodide (made by Japan Bulk Co., Ltd.), and it carried out similarly to obtain the internal liquid solution of Example 13.

Comparative Example 13

In the same manner as in Example 13, except for the tannic acid and magnesium metasilicate in Example 13, except for the internal liquid solution of Comparative Example 13a, except for magnesium metasilicate in Example 13, the internal liquid solution of Comparative Example 13b, In Example 13, the internal liquid solution of Comparative Example 13c was obtained except for tannic acid.

Example 14

The carbinoxamine maleate of Example 11 was changed to 1 g of anhydrous caffeine (made by Shizuoka Caffeine Industrial Co., Ltd.), and it carried out similarly to obtain the internal liquid solution of Example 14.

Comparative Example 14

In the same manner as in Example 14, except for the tannic acid and magnesium metasilicate in Example 14, except for the internal liquid solution of Comparative Example 14a, except for magnesium metasilicate in Example 14, the internal liquid solution of Comparative Example 14b, In Example 14, the internal liquid solution of Comparative Example 14c was obtained except for tannic acid.

Example 15

The carbinoxamine maleate of Example 11 was changed to 1 g of theophylline, and it carried out similarly to obtain the internal liquid preparation of Example 15.

Comparative Example 15

In the same manner as in Example 15, except for the tannic acid and magnesium metasilicate in Example 15, except for the internal liquid solution of Comparative Example 15a, except for magnesium metasilicate in Example 15, the internal liquid solution of Comparative Example 15b In Example 15, the internal liquid solution of Comparative Example 15c was obtained except for tannic acid.

Example 16

The carbinoxamine maleate of Example 11 was changed to 1 g of acetaminophen (manufactured by Yamamoto Chemical Co., Ltd.), and the same procedure was followed to obtain the internal liquid solution of Example 16.

Comparative Example 16

In the same manner as in Example 16, except for the tannic acid and magnesium metasilicate in Example 16, except for the internal liquid solution of Comparative Example 16a, except for the magnesium metasilicate aluminum silicate in Example 16, the internal liquid solution of Comparative Example 16b In Example 16, the internal liquid solution of Comparative Example 16c was obtained except for tannic acid.

Example 17

The carbinoxamine maleate of Example 11 was changed to 1 g of ibuprofen (made by BASF), and it carried out similarly to obtain the internal liquid preparation of Example 17.

Comparative Example 17

In the same manner as in Example 17, except for the tannic acid and magnesium metasilicate in Example 17, the internal liquid solution of Comparative Example 17a except for the magnesium metasilicate aluminum silicate in Example 17, the internal liquid solution of Comparative Example 17b In Example 17, the internal liquid solution of Comparative Example 17c was obtained except for tannic acid.

Example 18

The carbinoxamine maleate of Example 11 was changed to 1 g of dextromethorphan hydrobromide hydrochloride (manufactured by DSM Neutral Jaffen), and the internal liquid solution of Example 18 was similarly obtained.

Comparative Example 18

In the same manner as in Example 18, except for the tannic acid and magnesium metasilicate in Example 18, except for the internal liquid solution of Comparative Example 18a, except for magnesium metasilicate in Example 18, the internal liquid solution of Comparative Example 18b, In Example 18, the internal liquid solution of Comparative Example 18c was obtained except for tannic acid.

Example 19

The carbinoxamine maleate of Example 11 was changed to 1 g of hop dry extract (made by Alps Co., Ltd.), and it carried out similarly to obtain the internal liquid solution of Example 19.

Comparative Example 19

In the same manner as in Example 19, except for the tannic acid and magnesium metasilicate in Example 19, except for the internal liquid solution of Comparative Example 19a, except for magnesium metasilicate in Example 19, the internal liquid solution of Comparative Example 19b In Example 19, the internal liquid solution of Comparative Example 19c was obtained except for tannic acid.

Example 20

The carbinoxamine maleate of Example 11 was changed to 1 g of akamegashi and a dry extract (made by Nippon Kogyo Co., Ltd.), and it carried out similarly to obtain the internal liquid solution of Example 20.

Comparative Example 20

In the same manner as in Example 20, except for the tannic acid and magnesium metasilicate in Example 20, except for the internal liquid solution of Comparative Example 20a, except for the magnesium metasilicate silicate in Example 20, the internal liquid solution of Comparative Example 20b, In Example 20, the internal liquid solution of Comparative Example 20c was obtained except for tannic acid.

Example 21

The carbinoxamine maleate of Example 11 was changed to 1 g of carrot dry extracts, and it carried out similarly to obtain the internal liquid solution of Example 21.

Comparative Example 21

In the same manner as in Example 21, except for the tannic acid and magnesium metasilicate in Example 21, the internal liquid solution of Comparative Example 21a except for magnesium metasilicate in Example 21, the internal liquid solution of Comparative Example 21b, In Example 21, the internal liquid solution of Comparative Example 21c was obtained except for tannic acid.

Test Example 2

Five normal subjects evaluated the degree of unpleasant taste in five steps like the test example 1 using the oral solution preparation of Examples 11-21 and the oral solution preparation of Comparative Examples 11-21.

The average value of the score at this time is shown in Table 2. The composition of the present invention of the Examples was compared to hide the unpleasant taste of the drugs of the various properties shown in Table 2, the comparison does not include any one or both of the acidic substance and alkaline earth metal salts and / or earth metal salts The example composition did not conceal the unpleasant taste.

TABLE 2

 Example 11  Comparative Example 11a  Comparative Example 11b  Comparative Example 11c        drug    5.0    1.4    2.2    1.4    Carrubinoxamine maleate  Example 12  Comparative Example 12a  Comparative Example 12b  Comparative Example 12c    4.8    1.6    1.8    1.6    Dihydrocodeine Phosphate  Example 13  Comparative Example 13a  Comparative Example 13b  Comparative Example 13c    4.6    1.2    1.6    1.2    Isopropylpropamide  Example 14  Comparative Example 14a  Comparative Example 14b  Comparative Example 14c    5.0    2.0    2.8    2.0    Caffeine Anhydrous  Example 15  Comparative Example 15a  Comparative Example 15b  Comparative Example 15c    5.0    1.4    3.2    1.6    Theophylline  Example 16  Comparative Example 16a  Comparative Example 16b  Comparative Example 16c    4.8    1.8    2.4    2.0    Acetaminophen  Example 17  Comparative Example 17a  Comparative Example 17b  Comparative Example 17c    4.4    1.0    2.2    1.0    Ibuprofen  Example 18  Comparative Example 18a  Comparative Example 18b  Comparative Example 18c    4.4    1.2    1.8    1.4   Dextrometolfan Hydrobromide Hydrate  Example 19  Comparative Example 19a  Comparative Example 19 b  Comparative Example 19c    5.0    1.4    2.6    1.6    Hope Dry Extract  Example 20  Comparative Example 20a  Comparative Example 20b  Comparative Example 20c    5.0    1.6    2.8    1.8    Yeok Tree Extract  Example 21  Comparative Example 21a  Comparative Example 21a  Comparative Example 21a    5.0    1.4    2.4    1.4    Ginseng Dry Extract

Example 22

Example 22a: 1 g of diphenhydramine hydrochloride (manufactured by Gold Chemical Co., Ltd.), 0.05 g of tannic acid (manufactured by Daito Chemical Co., Ltd.), and 40 g of magnesium metasilicate (manufactured by Toyo Chemical Co., Ltd.) were weighed, kneaded with purified water, and heated and dried. By removing moisture. The obtained dry powder was distributed so that diphenhydramine hydrochloride might be 50 mg per packet, and the distribution agent of Example 22a was obtained.

Example 22b: The tannin acid of Example 22a was changed to 0.1 g, except that the dispersing agent of Example 22b was obtained.

Example 22c: The tannin acid of Example 22a was changed to 0.5 g, except that the dispersing agent of Example 22c was obtained.

Example 22d: The tannin acid of Example 22a was changed to 0.8 g, except that the dispersing agent of Example 22d was obtained.

Example 22e: The tannin acid of Example 22a was changed to 1 g, except that the dispersant of Example 22e was obtained.

Example 22f: The tannin acid of Example 22a was changed to 1.5 g, except that the dispersing agent of Example 22f was obtained.

Example 22g: The tannin acid of Example 22a was changed to 2 g, except that the dispersant of Example 22 g was obtained in the same manner.

Example 22h: The tannin acid of Example 22a was changed to 5 g, except that the dispersing agent of Example 22h was obtained in the same manner.

Example 22i: The tannin acid of Example 22a was changed to 10 g, except that the dispersing agent of Example 22i was obtained in the same manner.

Comparative Example 22

The dispersing agent of Comparative Example 22 was obtained in the same manner except for the tannic acid of Example 22a.

Test Example 3

Five normal subjects put the dispersants of Examples 22a-i and Comparative Example 22 into their mouths, spit it out after about 15 seconds after placing them on their tongues, taking care not to swallow them. At this time, it evaluated in 5 steps which show the degree of unpleasant taste, such as astringent, irritation, bitterness, astringent taste, and astringency.

1: I feel very unpleasant taste

2: I have an unpleasant taste

3: I feel a little unpleasant taste

4: I feel like I'm feeling unpleasant

5: feel nothing

The average value of the score at this time is shown in Table 3. In the composition of the present invention, as shown in Table 3, the unpleasant taste of the drug began to be concealed with 0.05 parts by mass or more of the lipoic agent with respect to 1 part by mass of the drug, and almost completely the unpleasant taste was concealed with 0.8 parts by mass or more of the acidic substance. .

TABLE 3

     Score     Ratio of Acidic Substances to Drug 1    Example 22a       1.8               0.05    Example 22b       2.6               0.1    Example 22c       3.8               0.5    Example 22d       4.8               0.8    Example 22e       5.0               1.0    Example 22f       5.0               1.5    Example 22g       5.0               2.0    Example 22h       5.0               5.0    Example 22i       5.0               10.0    Comparative Example 22       1.0               0

Example 23a: 1 g of diphenhydramine hydrochloride (manufactured by Gold Chemical Co., Ltd.), 1 g of tannic acid (manufactured by Daito Chemical Co., Ltd.), and 0.05 g of magnesium metasilicate (manufactured by Toyo Chemical Co., Ltd.) were weighed, dissolved and dispersed in purified water, Was made into 500 mL, and the internal liquid solution of Example 23a was obtained.

Example 23b: The magnesium metasilicate of Example 23a was changed to 0.25 g, except that the internal liquid solution of Example 23b was obtained.

Example 23c: The magnesium metasilicate aluminum silicate of Example 23a was changed to 0.5 g, except that the internal liquid solution of Example 23c was obtained.

Example 23d: The magnesium metasilicate of Example 23a was changed to 1 g, except that the internal liquid solution of Example 23d was obtained.

Example 23e: The magnesium metasilicate of Example 23a was changed to 2 g, except that the internal liquid solution of Example 23e was obtained in the same manner.

Example 23f: The magnesium metasilicate of Example 23a was changed to 5 g, except that the internal liquid solution of Example 23f was obtained.

Example 23g: The magnesium metasilicate of Example 23a was changed to 10 g, except that the internal liquid solution of Example 23 g was obtained in the same manner.

Example 23h The magnesium metasilicate of Example 23a was changed to 25 g, except that the internal liquid solution of Example 23h was obtained.

Example 23i: The magnesium metasilicate of Example 23a was changed to 50 g, except that the internal liquid solution of Example 23i was obtained.

Test Example 4

Five normal subjects evaluated the degree of unpleasant taste in five steps similarly to Test Example 1 using the oral solution of Examples 23a-i.

The average value of the score at this time is shown in Table 4. As shown in Table 4, the composition of the present invention concealed the unpleasant taste of the drug at 0.1 part by mass or more of alkaline earth metal salt and / or earth metal salt with respect to 1 part by mass of acidic substance.

TABLE 4

   Score     Ratio of alkaline earth metal salts and / or earth metal salts to acidic substances   Example 23a     3.2                 0.1   Example 23b     3.8                 0.25   Example 23c     4.0                 0.5   Example 23d     4.4                 1.0   Example 23e     4.8                 2.0   Example 23f     5.0                 5.0   Example 23g     5.0                 10.0   Example 23h     5.0                 25.0   Example 23i     5.0                 50.0

Example 24

1 g of diphenhydramine hydrochloride (manufactured by Gold Chemicals Co., Ltd.), 1 g of a mol-alcohol propyl (manufactured by Daito Chemical Co., Ltd.), and 3 g of magnesium metasilicate (manufactured by Toyo Chemical Co., Ltd.) were weighed, dissolved, and dispersed in purified water. 24 underwear liquids were obtained.

Example 25

The molar asset profile of Example 24 was changed to 1 g of acetic acid (manufactured by Nippon Kasei Chemical Co., Ltd.), and the same as in Example 24 except for the internal liquid solution of Example 25.

Example 26

The oral solution profile of Example 24 was changed to 1 g of tartaric acid, and it carried out similarly to Example 24, and obtained the internal liquid solution of Example 26.

Example 27

The internal liquid profile of Example 24 was changed to 1 g of citric acid profiles of Example 24, and it carried out similarly to Example 24 except having obtained the internal preparation liquid of Example 27.

Example 28

The internal liquid solution of Example 28 was obtained like Example 24 except having changed the molten-proprietary profile of Example 24 into tannin acid (made by Daito Chemical Co., Ltd.).

Test Example 5

Five normal subjects evaluated the degree of unpleasant taste in five steps similarly to Test Example 1 using the internal medicine liquid of Examples 24-28.

The average value of the score at this time is shown in Table 5. The composition of this invention of the Example was concealed of the unpleasant taste with the various acidic substances shown in Table 5.

TABLE 5

       Score       Acid      Example 24         4.6     Informal Asset Profile      Example 25         4.8     Acetic acid      Example 26         4.2     Tartaric acid      Example 27         4.2     Citric acid      Example 28         4.8     Tannic acid

Example 29

Weigh 1 g of diphenhydramine hydrochloride, 1 g of tannic acid, and 5 g of calcium carbonate, kneaded in purified water, heat-dry to remove moisture, and again D. -The powder obtained by adding 33 g of mannitol (manufactured by Sanitai Techtec) and 10 g of corn starch (manufactured by Nippon Co., Ltd.) was distributed so that diphenhydramine hydrochloride was 50 mg per packet, thereby obtaining the distribution agent of Example 29.

Example 30

The calcium carbonate of Example 29 was changed to 5 g of calcium silicate (manufactured by Tokuyama), except that the dispersing agent of Example 30 was obtained in the same manner as in Example 29.

Example 31

The calcium carbonate of Example 29 was changed to 5 g of dry aluminum hydroxide gel (manufactured by Japan Chemical Industries, Ltd.), and the same as in Example 29, except that the distribution agent of Example 31 was obtained.

Example 32

The calcium carbonate of Example 29 was changed to 5 g of magnesium aluminum silicate (manufactured by Tokyo Chemical Industry Co., Ltd.), except that the distribution agent of Example 32 was obtained in the same manner as in Example 29.

Test Example 6

Five normal subjects evaluated the degree of unpleasant taste in five steps similarly to Test Example 3 using the distribution agent of Examples 29-32.

The average value of the score at this time is shown in Table 6. The unpleasant taste was concealed by the various alkaline earth metal salts and / or earth metal salts shown in Table 6 of the composition of the present invention.

TABLE 6

   Score    Alkaline earth metal salts and / or earth metal salts    Example 29     4.8               Calcium carbonate    Example 30     4.6               Calcium silicate    Example 31     4.4           Dry aluminum hydroxide gel    Example 32     5.0          Magnesium metasilicate

The oral composition of this invention can conceal unpleasant tastes, such as astringent, irritation, bitterness, astringent taste, and astringency, peculiar to the drug with respect to many drugs which show an unpleasant taste. This oral composition can be widely applied to any formulation of solid preparations, liquid preparations, and semisolid preparations. Furthermore, the oral compositions of the present invention can be applied to many immediate-release preparations because they hide the unpleasant taste and immediately release the drug at lag time after taking. In addition, the oral solid composition of the present invention is not only easy to take, but also can be taken by many patients over a long period of time, and is an agent capable of steadily exerting the effects of various drugs.

Due to its high dose, the patient's compliance can be expected and QOL is also improved.

Claims (7)

An oral composition concealing an unpleasant taste containing drugs, acidic substances and alkaline earth metal salts and / or earth metal salts which exhibit an unpleasant taste. The oral composition according to claim 1, wherein the acidic substance is one or two or more selected from tannic acid, acetic acid profile, acetic acid, citric acid, and tartaric acid. The oral composition according to claim 1, wherein the alkaline earth metal salt and / or earth metal salt is one or two or more selected from magnesium salts, calcium salts and aluminum salts. The oral composition according to claim 1, which hides an unpleasant taste containing 0.05 to 50 parts by mass of an acidic substance with respect to 1 part by mass of the drug having a taste. The oral composition according to claim 1, which hides an unpleasant taste containing 0.05 to 50 parts by mass of an alkaline earth metal salt and / or an earth metal salt with respect to 1 part by mass of an acidic substance. The oral composition according to any one of claims 1 to 5, which hides an unpleasant taste, which is a tablet, granule, fine granule, powder, pill, dry syrup, or an oral solution. A method for concealing an unpleasant taste, characterized by containing an acidic substance and an alkaline earth metal salt and / or a earth metal salt in a drug having an unpleasant taste.