CN101574521A - Oral combination shielding indisposed taste - Google Patents
Oral combination shielding indisposed taste Download PDFInfo
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- CN101574521A CN101574521A CNA2009101385068A CN200910138506A CN101574521A CN 101574521 A CN101574521 A CN 101574521A CN A2009101385068 A CNA2009101385068 A CN A2009101385068A CN 200910138506 A CN200910138506 A CN 200910138506A CN 101574521 A CN101574521 A CN 101574521A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/20—Pills, tablets, discs, rods
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Abstract
The present invention provides an oral solid-state combination for shielding indisposed taste (the pharmaceutical bitter). The present invention provides an oral combination shielding indisposed taste containing medicaments, acidic material and alkali earth metal salt and/or earth metal salt presenting indisposed taste, and a method shielding for shielding indisposed taste of acidic material and alkali earth metal salt and/or earth metal salt contained in the medicaments presenting indisposed taste.
Description
Technical field
The Orally administered composition of the taste that convergence, astringent taste, zest, bitterness, pungent that the present invention relates to cover medicine etc. is unhappy and the method for covering unhappy taste.
Background technology
Medicine often presents unhappy tastes such as convergence, zest, bitterness, astringent taste, pungent, can't directly take, and therefore need cover intraoral unhappy taste.The method of covering the unhappy taste of medicine roughly is divided into the control medicine in intraoral dissolved method with cover the method for the taste of medicine itself with odor mask.
As controlling medicine in intraoral dissolved method, can exemplify the method (patent documentation 1～6) that is covered with gastric solubility macromolecule, enteric solubility macromolecule, water-insoluble macromolecule, wax class etc., form the method (patent documentation 7,8) that substrate is carried out taste masking, use the method (patent documentation 9) of inclusion compound enclose etc.Yet in order to control dissolving, small variation takes place in stripping property sometimes, and the performance of the effectiveness of medicine postpones.In addition, when being used for the high medicine of water solublity, a large amount of inadequate situations of covering of using fruit glaze agents or matrix agent or unhappy taste that need are often arranged.On the contrary, when being used for the low medicine of water solublity, also having and utilize biology of medicine the situation that can descend, can't give full play to effectiveness.Also there is following shortcoming: when taking, produce rough sense, if perhaps particle diameter is adjusted into rough sense smaller particle size, then can be and cause after taking, unhappy taste and stimulation can occurring soon because of intraoral particle such as remaining between tooth.In addition, also there is the shortcoming that is difficult to use in semi-solid preparations such as liquid preparation and frozen glue.
On the other hand, as the method for covering the taste of medicine itself with odor mask, can exemplify the method for the sweeting agent that adds acesulfame potassium (patent documentation 10), aspartame (patent documentation 11 and 12), the contour sugariness of Flos Chrysanthemi extract (patent documentation 13), add the method for polyhydric alcohol (patent documentation 19 and 20) such as acid (patent documentation 15～18), glycerol such as Fructus Litchi oil or Fructus Citri Limoniae wet goods quintessence oil (patent documentation 14), ascorbic acid, citric acid, malic acid, fumaric acid, tartaric acid, tannic acid, condensed phosphoric acid, surfactant multiple materials such as (patent documentations 21).These methods are less to the influence of stripping property, but then, the taste masking effect a little less than, only effective to specific medicine, for the taste masking weak effect of the strong medicine of convergence or zest, be not easy-to-use method perhaps, suitable medicine often is subjected to the restriction of odor mask.For improving above-mentioned shortcoming, also attempted combination and added the method with multiple odor mask combination such as the method (patent documentation 22 and 23) of aromatic and sweeting agent, the method (patent documentation 24) that acid and sweeting agent are added in combination, but present situation is can't play sufficient taste masking effect for convergence or strong medicine and the high multiple medicines such as medicine of water solublity of zest.
Patent documentation 1: the Japan Patent spy opens the 2008-37863 communique
Patent documentation 2: the Japan Patent spy opens the 2006-232789 communique
Patent documentation 3: the Japan Patent spy opens the 2006-22039 communique
Patent documentation 4: the Japan Patent spy opens the 2005-343800 communique
Patent documentation 5: Japanese patent laid-open 3-130214 communique
Patent documentation 6: the Japan Patent spy opens clear 57-58631 communique
Patent documentation 7: the Japan Patent spy opens the 2004-189758 communique
Patent documentation 8: Japanese patent laid-open 9-208458 communique
Patent documentation 9: Japanese patent laid-open 3-236316 communique
Patent documentation 10: the Japan Patent spy opens the 2007-269716 communique
Patent documentation 11: the Japan Patent spy opens the 2005-336078 communique
Patent documentation 12: the Japan Patent spy opens the 2002-128705 communique
Patent documentation 13: Japanese patent laid-open 2-56416 communique
Patent documentation 14: the Japan Patent spy opens the 2005-132801 communique
Patent documentation 15: the Japan Patent spy opens the 2007-54001 communique
Patent documentation 16: the Japan Patent spy opens the 2001-213764 communique
Patent documentation 17: Japanese patent laid-open 9-194356 communique
Patent documentation 18: the Japan Patent spy opens the 2000-119175 communique
Patent documentation 19: the Japan Patent spy opens the 2002-363105 communique
Patent documentation 20: the Japan Patent spy opens the 2002-145764 communique
Patent documentation 21: the Japan Patent spy opens the 2004-91408 communique
Patent documentation 22: the Japan Patent spy opens the 2007-217687 communique
Patent documentation 23: the Japan Patent spy opens the 2004-155781 communique
Patent documentation 24: the Japan Patent spy opens the 2000-290199 communique
Summary of the invention
Therefore, the purpose of this invention is to provide a kind of solid preparation that is not limited to, can be used for multiple dosage forms such as liquid preparation, the Orally administered composition and the method for the taste that convergence, zest, bitterness, astringent taste, pungent that can prevent medicine under the situation that does not change stripping property etc. is unhappy.
The inventor in view of the above fact, to not only can be used for solid preparation, the method that also can be used for the unhappy taste that prevents medicine of liquid preparation has been carried out various researchs, found that, if make in the medicine that presents unhappy taste and contain acidic materials as odor mask, then the unhappy taste that is caused by medicine itself significantly reduces, and, if in said composition, add alkali salt and/or earth metal salt, then the unhappy taste that is caused by acidic materials also significantly reduces, the result can not presented the Orally administered composition of unhappy taste, thereby has finished the present invention.
That is, the invention provides a kind of Orally administered composition of having covered unhappy taste, said composition contains medicine, acidic materials and alkali salt and/or the earth metal salt that presents unhappy taste.
In addition, the invention provides a kind of concealing method of unhappy taste, the method is characterized in that, make and contain acidic materials and alkali salt and/or earth metal salt in the medicine that presents unhappy taste.
Utilize the present invention, can under the situation that does not change stripping property, prevent the unhappy taste such as convergence, zest, bitterness, astringent taste, pungent of medicine.
The specific embodiment
Below the present invention is described in detail.
Among the present invention, the medicine that presents unhappy taste is meant when oral can be in the oral cavity or the medicine of the sensation locating to cause that convergence, zest, bitterness, astringent taste, pungent etc. are unhappy such as throat.As said medicine, can exemplify alkalescent medicine, both sexes medicine, acidic drug, also can exemplify Chinese crude drug, medicinal herbs, Chinese medicine etc. and derive from biological extract.Compositions of the present invention any all effective to wherein has the taste masking effect.Among the present invention, alkalescent medicine is meant that episome is the medicine of alkalescence, might not be alkalescence under the salifiable situation of shape.Similarly, acidic drug is meant that episome is tart medicine, might not be acidity under the salifiable situation of shape.In addition, the both sexes medicine is both alkaline soluble also acid-soluble medicine.In addition, alkalescent medicine, the both sexes medicine, acidic drug all can be original form, it also can be its hydrochlorate, nitrate, sulfate, acetate, lactate, citrate, succinate, fumarate, carbonate, teoclate, toluene fulfonate, tartrate, butyrate, hydrobromate, phosphate, hibenzate (hibenzate), benzene sulfonate (besilate), acid-adducting salts such as maleate, it also can be sodium salt, earth metal salt or calcium salts such as potassium salt, magnesium salt, alkali salts such as aluminum salt etc. also can be chlorides, bromide, iodide etc.
As the above-mentioned concrete example that presents the medicine of unhappy taste, can exemplify azelastine, cobamamide, Alimemazine, aldioxa, ambroxol, amlexanox, isothipendyl, ifenprodil, indeloxazine, etilefrine, epinastine, ephedrine, emedastine, oxatomide, octotiamine, olmesartan medoxomil, caffeine, carbinoxamine, candesartan Cilexetil, guaifenesin, clemastine, cloperastine, chlorphenamine, chlorhexidine, codeine, cobalamine, cyanocobalamin, ground match thiamine, paracodin, diphenidol, diphenylpyraline, diphenhydramine, diprophylline, the dibenzoylthiamine element, cimetidine, dimemorfan, diltiazem, sldenafil, scopolamine, sucralfate, department special (Suplatast), cetraxate, cetirizine, tadalafil, thiamine, thiamine disulfide, ticlopidine, it is fixed to propose training, dextromethorphan, telmisartan, doxylamine, donepezil, tranilast, triprolidine, special U.S. quino, nizatidine, narcotine, papaverine, valsartan, Vardenafil, biotin, the gram sodium sulfate, sulbutiamine, bisbentiamine, hydroxocobalamin, Benadon, pyridoxol, pyridoxamine, pyrenzepine, famotidine, Finasteride, pheniramine, phyenlephrinium, Pseudoephedrine, the butyl scopolamine, Flavin Adenin Dinucleotide Sodium, Propranolol, promethazine, bromhexine, Hesperidin, hepronicate, betahistine, berberine, benfotiamine, maprotiline, mequitazine, meclizine, methyl atropine, methylephedrine, methyl cobalamin, the first benactyzine, methoxiphenadrin, riboflavin, riboflavin sodium, ranitidine, lafutidine, the acetic acid roxatidine, Losartan, loperamide, loratadine, aspirin, acetyl aminophenol, isopropylantipyrine, ibuprofen, ethenzamide, diclofenac, salicylamide, mefenamic acid, flufenamic acid, meloxicam, loxoprofen, tranexamic acid, etodolac, celecoxib, rofecoxib, penta ground former times cloth, Parecoxib, rely on former times cloth, Luo Mei former times cloth, theophylline, fexofenadine, cetirizine, isopropamide iodide, berberine, vitamin A palmitate, calcium pantothenate, bromisovalum, chloromycetin, aminophylline, hyoscyamus extract, apronalide etc.In addition, as Chinese crude drug, medicinal herbs, prescriptions etc. derive from biological extract, can exemplify red bud Mongolian oak, catechu, Aloe, wood flesh, Semen Ginkgo, Fructus Foeniculi, Radix Scutellariae, Cortex Phellodendri, Rhizoma Curcumae Longae, Folium Vaccinii vitis-idaeae, the Radix Linderae, Fructus rosae multiflorae, Rhizoma Corydalis, prolong the life grass, Cortex Phellodendri, Rhizoma Coptidis, Radix Polygoni Multiflori, Rhizoma Curcumae, Rhizoma et radix valerianae, Rhizoma Zingiberis, Radix Glycyrrhizae, Radix Platycodonis, Largeleaf Gymnema, chlorella, Cortex cinnamomi japonici (Ramulus Cinnamomi), Radix Gentianae Macrophyllae, yeast, Rhizoma Dioscoreae, Radix Rehmanniae, Rhizoma Zingiberis Recens, Swertia japonica, Radix Sophorae Flavescentis, Flos Carthami, Radix Et Rhizoma Rhei, Fructus Jujubae, Radix Paeoniae, Fructus Corni, Rhizoma Atractylodis, Fructus Jujubae, Rhizoma Alismatis, Flos Caryophylli, Herba Passiflorae Caeruleae, Ramulus Uncariae Cum Uncis, Poria, gun additioner, Cortex Moutan, hops, Aloe, Radix Ginseng, GEGEN TANG, dispeling wind and detoxification soup, sound breaks flute ball material, Herba Sidae Rhombifoliae soup, XIAOQINGLONG TANG, suanzaoren decoction, the relieve internal heat extract of soup etc. of ten flavors.These medicines can use separately, also can be used in combination more than 2 kinds.In these medicines, special preferred diphenhydramine, ambroxol, epinastine, phyenlephrinium, bromhexine, etilefrine, pyrenzepine, pseudoephedrine, methylephedrine, loperamide or their salt.
Among the present invention, be preferably the medicine that in Orally administered composition, contains the unhappy taste of presenting of 0.1～95 quality %, be more preferably the medicine that contains the unhappy taste of presenting of 1～90 quality %.
In addition, in the compositions of the present invention, except that said medicine, also can mix other medicines.For example, as such medicine, can exemplify at actasal, hypnotic and sedative, inoitantia, the dizzy medicine in town, children's's analgesic, stomachic, antacid, digestant, cardiac tonic, arrhythmia medication, depressor, vasodilator, diuretic, antiulcerative, intestinal and regulate medicine, osteoporosis therapy medicine, antisussive and expectorant agent, antasthmatic, antibacterial, frequent micturition improving agent, nourish the pharmacological component that uses in analeptic, the vitamin agent etc.
Among the present invention, odor mask can be used in combination with acidic materials and alkali salt and/or earth metal salt.The acidic materials here are meant the correctives that is tart pharmaceuticals additive.As its concrete example, can exemplify tannic acid, propyl gallate, citric acid, acetic acid and tartaric acid etc., they can use a kind, also can be used in combination more than 2 kinds.Wherein, from the angle of covering effect of unhappy taste, more preferably tannic acid, propyl gallate, acetic acid.
The addition of acidic materials changes according to the kind that presents the medicine of unhappy taste, the medicine that is preferably the taste unhappy with respect to presenting of 1 mass parts is in the scope of about 0.05～50 mass parts, 0.1～10 mass parts more preferably, further more preferably 0.5～5 mass parts, particularly preferably 0.8～2 mass parts.
Among the present invention, also can add alkali salt and/or earth metal salt as odor mask.As alkali salt and/or earth metal salt, can exemplify and be selected from more than a kind or 2 kinds of magnesium salt, calcium salt and aluminum salt.
Concrete example as alkali salt and/or earth metal salt, can exemplify Magnesiumaluminumsilicate, calcium carbonate, calcium chloride hydrate, magnesium chloride, Aluminium Hydroxide, calcium citrate, calcium glycerophosphate, calcium gluconate, calcium silicates, magnesium silicate, aluminium-magnesium silicate, synthetic aluminium silicate, synthetic hydrotalcite, calcium acetate, magnesium oxide, aluminum magnesium hydroxide, gel aluminum hydroxide, aluminium hydroxide sodium bicarbonate coprecipitate, aluminium hydroxide magnesium carbonate calcium carbonate coprecipitate, magnesium hydroxide, tertiary calcium phosphate, magnesium carbonate, winnofil, natural aluminium silicate, the calcium lactate hydrate, calcium phosphate dibasic anhydrous, calcium phosphate dibasic anhydrous pelletize thing, aluminum sulfate, calcium sulfate, calcium monohydrogenphosphate, the calcium hydrogen phosphate hydrate, calcium hydrogen phosphate pelletize thing, biphosphate hydrate of calcium etc., they can use a kind, also can be used in combination more than 2 kinds.Wherein, from the angle of covering effect of unhappy taste, special preferred Magnesiumaluminumsilicate, calcium carbonate, calcium silicates.
The addition of alkali salt and/or earth metal salt changes according to the kind and the incorporation of the kind of the medicine that presents unhappy taste and incorporation, acidic materials, the acidic materials that are preferably with respect to 1 mass parts are about 0.05～50 mass parts, 0.1～50 mass parts more preferably, further more preferably 0.25～25 mass parts, particularly preferably 0.5～10 mass parts.
For compositions of the present invention, the special good diphenhydramine that is to use, ambroxol, epinastine, phyenlephrinium, bromhexine, etilefrine, pyrenzepine, pseudoephedrine, methylephedrine, loperamide, carbinoxamine maleate, paracodin, isopropamide iodide, Caffeine Anhydrous, theophylline, acetyl aminophenol, ibuprofen, dextromethorphan or their salt, the hops dry extract, the Radix Ginseng dry extract, red bud Mongolian oak dry extract is as the medicine that presents unhappy taste, use tannic acid, propyl gallate or acetic acid use Magnesiumaluminumsilicate as acidic materials, calcium carbonate or calcium silicates are as alkali salt and/or earth metal salt.
Compositions of the present invention provides by mixing in the medicine that presents unhappy taste as the acidic materials of odor mask and alkali salt and/or earth metal salt.When mixing, compositions of the present invention both can be mixed medicine and the odor mask that presents unhappy taste with the form of powder body, also they part or all can be dissolved in suitable solvent, can also remove this solvent by methods such as spray drying, heat drying, lyophilization, air-supply drying, drying under reduced pressure.In addition, the dosage form of compositions of the present invention can be used with the form of various oral Preparations such as tablet, granule, granula subtilis, powder, hard capsule, capsule, soft capsule, pill, mixture for internal use, suspending agent, Emulsion, syrup, dry syrup, masticatory, foaming agent, candy pill, intraoral disintegration agent, membrane, gelatum agent.In addition, also can after making fine particles such as microcapsule, Nano capsule, microsphere, nanosphere, liposome, make above-mentioned preparation again.
Can add generally spendable preparation additive on galenic pharmacy in these preparations as required, stabilization agent for example, stabilizing agent, surfactant, lubricatedization agent, lubricant, solvable (change) agent, buffer agent, sweeting agent, base, adsorbent, correctives, binding agent, (change) agent suspends, sclerosing agent, antioxidant, the gloss agent, spice, coating materials, coating, wetting agent, moistening adjustment agent, filler, defoamer, refrigerant (change) agent, masticatory, antistatic additive, aromatic/spice, coloring agent, the sugar-coat agent, the isotonization agent, softening agent, emulsifying agent, sticker, adhesion enhancing agent, thickening (change) agent, foaming agent, pH adjusts agent, the pH regulator agent, excipient, dispersant, disintegrating agent, help disintegrating agent, aromatic, damp proof compound, antiseptic, preservative agent, lytic agent, cosolvent, solvent, flowing agents etc. are then by the conventional method manufacturing.
Concrete example as the preparation additive can exemplify castor sugar, glucose, trehalose, lactose, maltose, mannitol, Sorbitol, xylitol, erithritol, saccharin sodium, aspartame, acesulfame potassium, sucralose (sucralose), Radix Glycyrrhizae extract, Flos Chrysanthemi extract, Fructus Momordicae extract, corn starch, potato starch, wheaten starch, sodium bicarbonate, sodium chloride, crystalline cellulose, methylcellulose, ethyl cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, carmethose, carboxymethylcellulose calcium, hydroxypropylmethyl cellulose phthalate, the cellulose acetate phthalic acid ester, dextrin, alphalysed starch, arabic gum, gelatin, sodium alginate, polyvinylpyrrolidone, polyvinyl alcohol, CVP Carbopol ETD2050, magnesium stearate, Talcum, hydrogenated vegetable oil, Polyethylene Glycol, silicone oil, agar, lac, glycerol, armaticity quintessence oil class, water solublity food coloring, iron oxide yellow, yellow iron sesquioxide, iron sesquioxide, brown iron oxide, iron oxide black, titanium dioxide, the precipitation pigment, benzoic acid, sodium benzoate, P-hydroxybenzoic acid, polysorbate80, fatty acid glyceride, cera alba, MCT Oil, ascorbic acid, tocopherol, sodium thiosulfate, edetate sodium, citrus such as fragrant citrus and Fructus Citri Limoniae spice and coffee-type spice, chocolate-like spice, Yoghurt class spice, milk spice, Fructus Citri Limoniae oil, Oleum menthae, Oleum Menthae Rotundifoliae, perfumery oil plants essential oils such as (spice oil) etc.The formulation additives that can use in compositions of the present invention is not limited to the above-mentioned additive of enumerating, so long as spendable additive gets final product on the galenic pharmacy, does not have restriction especially.
In the time of need adjusting the pelletize end in the preparations such as tablet, granule, granula subtilis, powder, pill, dry syrup for example, can pass through spray granulation, stirring-granulating method, fluidized granulation method, rotate wet granulations such as comminution granulation, rotational flow comminution granulation, comminution granulation commonly used such as dry pelletizing methods such as densification comminution granulation is made preparation.In addition, powder and the pelletize end of containing effective ingredient can be mixed, be packetized into fractional pack then and fill.Tablet can be by with powder, powder agent, granula subtilis, granule or pill and the preparation additives mixed of effective ingredient, compression molding be made then.Coated preparations such as coated tablet, thin membrane coated tablet, coated granule can pass through the pan coating method, flow coating method, rotation coating method and their conventional method manufacturings such as combination.
Mixture for internal use such as drink agent, syrup, elixir, limonada, extractant and be filled with liquid state or the soft capsule of semisolid, hard capsule etc. are made usually by the following method: the part of preparation additives such as each composition and Purified Water equal solvent is mixed, dissolving, disperseed, add preparation additive such as remaining solvent then to adjust liquid measure.Also can carry out the adjustment of pH with acid or alkali as required.In addition, but also can preparation additives such as surfactant solvation, emulsifying agent, suspending agent make that preparation can dissolve by using, emulsifying, suspensionization.Also can heat as required during adjustment, cooling, nitrogen replacement, filtration, sterilization treatment etc.
Also can utilize as required the preparation additive wait to add active ingredient stabilisation, slow releaseization, ensured sustained development, disintegrateization, instantizing fast, improve dissolubility, improve functions such as taking sense.The method of additional these functions can be undertaken by common method, can exemplify and for example active ingredient be mixed a plurality of granules, make multiwalled granule, make multilayer tablet or the nuclear sheet is arranged, make a plurality of granules tabletting then, make microcapsule, make coated tablet, thin membrane coated tablet, coated preparations such as coated granule, make the foaming preparation, make chewable formulation, make the intraoral disintegration agent, make matrix formulations, pulverize altogether, make solid solution, add sweeting agent and refrigerantization agent, add antioxidant and stable (change) agent, be adjusted to specific pH, viscosity, osmotic pressure, methods such as salinity also can be with these method combinations.
Embodiment
Disclose embodiment and comparative example below the present invention is carried out more specific description, but the present invention is not limited to this.
Embodiment 1
Weighing 1g diphenhydramine hydrochloride (Buddha's warrior attendant KCC system), 1g tannic acid (Dainippon Sumitomo Pharma Co., Ltd's system) and 4g Magnesiumaluminumsilicate (Fuji Chemical Industry Co., Ltd's system), dissolve, be scattered in Purified Water, total amount is adjusted into 100mL, obtains the mixture for internal use of embodiment 1.
Comparative example 1
Operate similarly to Example 1, from embodiment 1, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 1a, from embodiment 1, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 1b, from embodiment 1, remove tannic acid, obtain the mixture for internal use of comparative example 1c.
Embodiment 2
Change the diphenhydramine hydrochloride of embodiment 1 into 1g ambroxol salt hydrochlorate (positive Shindo Co. system), in addition similarly operate, obtain the mixture for internal use of embodiment 2.
Comparative example 2
Operate similarly to Example 2, from embodiment 2, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 2a, from embodiment 2, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 2b, from embodiment 2, remove tannic acid, obtain the mixture for internal use of comparative example 2c.
Embodiment 3
Change the diphenhydramine hydrochloride of embodiment 1 into 1g epinastine hydrochlorate (Boehringer Ingelheim (boehringer-ingelheim) Co., Ltd. system), in addition similarly operate, obtain the mixture for internal use of embodiment 3.
Comparative example 3
Operate similarly to Example 3, from embodiment 3, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 3a, from embodiment 3, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 3b, from embodiment 3, remove tannic acid, obtain the mixture for internal use of comparative example 3c.
Embodiment 4
Change the diphenhydramine hydrochloride of embodiment 1 into 1g phenylephrine hydrochloride (Boehringer Ingelheim Co., Ltd. system), in addition similarly operate, obtain the mixture for internal use of embodiment 4.
Comparative example 4
Operate similarly to Example 4, from embodiment 4, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 4a, from embodiment 4, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 4b, from embodiment 4, remove tannic acid, obtain the mixture for internal use of comparative example 4c.
Embodiment 5
Change the diphenhydramine hydrochloride of embodiment 1 into 1g bromhexine salt hydrochlorate (rock city Pharmaceutical Co., Ltd system), in addition similarly operate, obtain the mixture for internal use of embodiment 5.
Comparative example 5
Operate similarly to Example 5, from embodiment 5, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 5a, from embodiment 5, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 5b, from embodiment 5, remove tannic acid, obtain the mixture for internal use of comparative example 5c.
Embodiment 6
Change the diphenhydramine hydrochloride of embodiment 1 into 1g etilefrine hydrochlorate (Boehringer Ingelheim Co., Ltd. system), in addition similarly operate, obtain the mixture for internal use of embodiment 6.
Comparative example 6
Operate similarly to Example 6, from embodiment 6, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 6a, from embodiment 6, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 6b, from embodiment 6, remove tannic acid, obtain the mixture for internal use of comparative example 6c.
Embodiment 7
Change the diphenhydramine hydrochloride of embodiment 1 into 1g pyrenzepine hydrochlorate (Boehringer Ingelheim Co., Ltd. system), in addition similarly operate, obtain the mixture for internal use of embodiment 7.
Comparative example 7
Operate similarly to Example 7, from embodiment 7, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 7a, from embodiment 7, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 7b, from embodiment 7, remove tannic acid, obtain the mixture for internal use of comparative example 7c.
Embodiment 8
Change the diphenhydramine hydrochloride of embodiment 1 into 1g pseudoephedrine hydrochlorate (Alps (alps) pharmaceutical industries Co., Ltd. system), in addition similarly operate, obtain the mixture for internal use of embodiment 8.
Comparative example 8
Operate similarly to Example 8, from embodiment 8, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 8a, from embodiment 8, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 8b, from embodiment 8, remove tannic acid, obtain the mixture for internal use of comparative example 8c.
Embodiment 9
Change the diphenhydramine hydrochloride of embodiment 1 into 1gdl-methylephedrine hydrochlorate (Alps pharmaceutical industries Co., Ltd. system), in addition similarly operate, obtain the mixture for internal use of embodiment 9.
Comparative example 9
Operate similarly to Example 9, from embodiment 9, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 9a, from embodiment 9, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 9b, from embodiment 9, remove tannic acid, obtain the mixture for internal use of comparative example 9c.
Embodiment 10
Change the diphenhydramine hydrochloride of embodiment 1 into 1g loperamide hydrochloride (ICFI corporate system), in addition similarly operate, obtain the mixture for internal use of embodiment 10.
Comparative example 10
Operate similarly to Example 10, from embodiment 10, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 10a, from embodiment 10, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 10b, from embodiment 10, remove tannic acid, obtain the mixture for internal use of comparative example 10c.
Test example 1
Perfect the mixture for internal use of the embodiment 1～10 that the experimenter will about 0.5ml and the mixture for internal use of comparative example 1～10 keeps in the mouth by 5, make mixture for internal use be dispersed throughout tongue, spue after about 15 seconds while note not swallowing.Estimate the degree of unhappy taste such as convergence at this moment, zest, bitterness, astringent taste, pungent with 5 following grades.
1: feel very strong unhappy taste
2: the taste of feeling bad
3: feel the taste that a little is unhappy
4: the taste of as if feeling bad
5: what is all imperceptible
The meansigma methods of the score of this moment is shown in table 1.The compositions of the present invention of embodiment is as shown in table 1, particularly covered as the unhappy taste of each medicine of very strong basic salt hydrochlorate such as bitterness, astringent taste, convergence, relative therewith, the unhappy taste of compositions that does not contain side in acidic materials and alkali salt and/or the earth metal salt or two sides' comparative example is not covered.
[table 1]
| Embodiment 1 | Comparative example 1a | Comparative example 1b | Comparative example 1c | Medicine |
| 4.8 | 1.0 | 1.6 | 1.0 | Diphenhydramine hydrochloride |
| Embodiment 2 | Comparative example 2a | Comparative example 2b | Comparative example 2c | |
| 5.0 | 1.8 | 2.6 | 1.8 | The ambroxol salt hydrochlorate |
| Embodiment 3 | Comparative example 3a | Comparative example 3b | Comparative example 3c | |
| 4.8 | 1.4 | 2.3 | 1.4 | The epinastine hydrochlorate |
| Embodiment 4 | Comparative example 4a | Comparative example 4b | Comparative example 4c | |
| 4.8 | 1.6 | 2.4 | 1.6 | Phenylephrine hydrochloride |
| Embodiment 5 | Comparative example 5a | Comparative example 5b | Comparative example 5c | |
| 5.0 | 2.2 | 2.8 | 2.0 | The bromhexine salt hydrochlorate |
| Embodiment 6 | Comparative example 6a | Comparative example 6b | Comparative example 6c | |
| 4.6 | 1.4 | 2.2 | 1.6 | The etilefrine hydrochlorate |
| Embodiment 7 | Comparative example 7a | Comparative example 7b | Comparative example 7c | |
| 4.8 | 1.2 | 2.4 | 1.4 | The pyrenzepine hydrochlorate |
| Embodiment 8 | Comparative example 8a | Comparative example 8b | Comparative example 8c | |
| 4.6 | 1.6 | 2.6 | 1.6 | Pseudoephedrine hydrochlorate |
| Embodiment 9 | Comparative example 9a | Comparative example 9b | Comparative example 9c | |
| 4.8 | 2.0 | 2.8 | 2.0 | Dl-methylephedrine hydrochlorate |
| Embodiment 10 | Comparative example 10a | Comparative example 10b | Comparative example 10c | |
| 4.6 | 2.0 | 2.6 | 2.2 | Loperamide hydrochloride |
Embodiment 11
Weighing 1g carbinoxamine maleate (Buddha's warrior attendant KCC system), 1g tannic acid (Dainippon Sumitomo Pharma Co., Ltd's system) and 4g Magnesiumaluminumsilicate (Fuji Chemical Industry Co., Ltd's system), dissolve, be scattered in Purified Water, total amount is adjusted into 100mL, obtains the mixture for internal use of embodiment 11.
Comparative example 11
Operate similarly to Example 11, from embodiment 11, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 11a, from embodiment 11, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 11b, from embodiment 11, remove tannic acid, obtain the mixture for internal use of comparative example 11c.
Embodiment 12
Change the carbinoxamine maleate of embodiment 11 into 1g paracodin phosphate (Sankyo Co.'s system), in addition similarly operate, obtain the mixture for internal use of embodiment 12.
Comparative example 12
Operate similarly to Example 12, from embodiment 12, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 12a, from embodiment 12, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 12b, from embodiment 12, remove tannic acid, obtain the mixture for internal use of comparative example 12c.
Embodiment 13
Change the carbinoxamine maleate of embodiment 11 into 1g isopropamide iodide (Japanese Ba Erke (Nippon-Bulk) medicine Co., Ltd. system), in addition similarly operate, obtain the mixture for internal use of embodiment 13.
Comparative example 13
Operate similarly to Example 13, from embodiment 13, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 13a, from embodiment 13, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 13b, from embodiment 13, remove tannic acid, obtain the mixture for internal use of comparative example 13c.
Embodiment 14
Change the carbinoxamine maleate of embodiment 11 into 1g Caffeine Anhydrous (Co., Ltd. of Shizuoka caffeine industry institute system), in addition similarly operate, obtain the mixture for internal use of embodiment 14.
Comparative example 14
Operate similarly to Example 14, from embodiment 14, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 14a, from embodiment 14, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 14b, from embodiment 14, remove tannic acid, obtain the mixture for internal use of comparative example 14c.
Embodiment 15
Change the carbinoxamine maleate of embodiment 11 into 1g theophylline (Shiratori Pharm's system), in addition similarly operate, obtain the mixture for internal use of embodiment 15.
Comparative example 15
Operate similarly to Example 15, from embodiment 15, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 15a, from embodiment 15, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 15b, from embodiment 15, remove tannic acid, obtain the mixture for internal use of comparative example 15c.
Embodiment 16
Change the carbinoxamine maleate of embodiment 11 into 1g acetyl aminophenol (Yamamoto chemical industry Co., Ltd. system), in addition similarly operate, obtain the mixture for internal use of embodiment 16.
Comparative example 16
Operate similarly to Example 16, from embodiment 16, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 16a, from embodiment 16, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 16b, from embodiment 16, remove tannic acid, obtain the mixture for internal use of comparative example 16c.
Embodiment 17
Change the carbinoxamine maleate of embodiment 11 into 1g ibuprofen (BASF (BASF) corporate system), in addition similarly operate, obtain the mixture for internal use of embodiment 17.
Comparative example 17
Operate similarly to Example 17, from embodiment 17, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 17a, from embodiment 17, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 17b, from embodiment 17, remove tannic acid, obtain the mixture for internal use of comparative example 17c.
Embodiment 18
Change the carbinoxamine maleate of embodiment 11 into 1g dextromethmorphan hydrobromide hydrate (Japanese DSM nutrition (DSM Nutrition Japan) Co., Ltd.'s system), in addition similarly operate, obtain the mixture for internal use of embodiment 18.
Comparative example 18
Operate similarly to Example 18, from embodiment 18, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 18a, from embodiment 18, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 18b, from embodiment 18, remove tannic acid, obtain the mixture for internal use of comparative example 18c.
Embodiment 19
Change the carbinoxamine maleate of embodiment 11 into 1g hops dry extract (Alps pharmaceutical industries Co., Ltd. system), in addition similarly operate, obtain the mixture for internal use of embodiment 19.
Comparative example 19
Operate similarly to Example 19, from embodiment 19, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 19a, from embodiment 19, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 19b, from embodiment 19, remove tannic acid, obtain the mixture for internal use of comparative example 19c.
Embodiment 20
Change the carbinoxamine maleate of embodiment 11 into the red bud Mongolian oak of 1g dry extract (Japanese powder pharmaceutical Industrial Co., Ltd system), in addition similarly operate, obtain the mixture for internal use of embodiment 20.
Comparative example 20
Operate similarly to Example 20, from embodiment 20, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 20a, from embodiment 20, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 20b, from embodiment 20, remove tannic acid, obtain the mixture for internal use of comparative example 20c.
Embodiment 21
Change the carbinoxamine maleate of embodiment 11 into 1g Radix Ginseng dry extract (Japanese powder pharmaceutical Industrial Co., Ltd system), in addition similarly operate, obtain the mixture for internal use of embodiment 21.
Comparative example 21
Operate similarly to Example 21, from embodiment 21, remove tannic acid and Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 21a, from embodiment 21, remove Magnesiumaluminumsilicate, obtain the mixture for internal use of comparative example 21b, from embodiment 21, remove tannic acid, obtain the mixture for internal use of comparative example 21c.
Test example 2
Perfect the experimenter by 5 and use the mixture for internal use of embodiment 11～21 and the mixture for internal use of comparative example 11～21, similarly estimate the degree of unhappy taste with 5 grades with test example 1.
The meansigma methods of the score of this moment is shown in table 2.In the compositions of the present invention of embodiment, the unhappy taste of the medicine of the various character shown in the table 2 is covered, relative therewith, the unhappy taste of compositions that does not contain side in acidic materials and alkali salt and/or the earth metal salt or two sides' comparative example is not covered.
[table 2]
| Embodiment 11 | Comparative example 11a | Comparative example 11b | Comparative example 11c | Medicine |
| 5.0 | 1.4 | 2.2 | 1.4 | Carbinoxamine maleate |
| Embodiment 12 | Comparative example 12a | Comparative example 12b | Comparative example 12c | |
| 4.8 | 1.6 | 1.8 | 1.6 | Paracodin phosphate |
| Embodiment 13 | Comparative example 13a | Comparative example 13b | Comparative example 13c | |
| 4.6 | 1.2 | 1.6 | 1.2 | Isopropamide iodide |
| Embodiment 14 | Comparative example 14a | Comparative example 14b | Comparative example 14c | |
| 5.0 | 2.0 | 2.8 | 2.0 | Caffeine Anhydrous |
| Embodiment 15 | Comparative example 15a | Comparative example 15b | Comparative example 15c | |
| 5.0 | 1.4 | 3.2 | 1.6 | Theophylline |
| Embodiment 16 | Comparative example 16a | Comparative example 16b | Comparative example 16c | |
| 4.8 | 1.8 | 2.4 | 2.0 | Acetyl aminophenol |
| Embodiment 17 | Comparative example 17a | Comparative example 17b | Comparative example 17c | |
| 4.4 | 1.0 | 2.2 | 1.0 | Ibuprofen |
| Embodiment 18 | Comparative example 18a | Comparative example 18b | Comparative example 18c | |
| 4.4 | 1.2 | 1.8 | 1.4 | The dextromethmorphan hydrobromide hydrate |
| Embodiment 19 | Comparative example 19a | Comparative example 19b | Comparative example 19c | |
| 5.0 | 1.4 | 2.6 | 1.6 | The hops dry extract |
| Embodiment 20 | Comparative example 20a | Comparative example 20b | Comparative example 20c | |
| 5.0 | 1.6 | 2.8 | 1.8 | Red bud Mongolian oak dry extract |
| Embodiment 21 | Comparative example 21a | Comparative example 21b | Comparative example 21c | |
| 5.0 | 1.4 | 2.4 | 1.4 | The Radix Ginseng dry extract |
Embodiment 22
Embodiment 22a: weighing 1g diphenhydramine hydrochloride (Buddha's warrior attendant KCC system), 0.05g tannic acid (Dainippon Sumitomo Pharma Co., Ltd's system) and 40g Magnesiumaluminumsilicate (Fuji Chemical Industry Co., Ltd's system), after the Purified Water kneading, heat drying is removed moisture.With the subpackage of gained dried powder, making diphenhydramine hydrochloride is every bag 50mg, obtains the subpackage agent of embodiment 22.
Embodiment 22b: change the tannic acid of embodiment 22a into 0.1g, in addition similarly operate, obtain the subpackage agent of embodiment 22b.
Embodiment 22c: change the tannic acid of embodiment 22a into 0.5g, in addition similarly operate, obtain the subpackage agent of embodiment 22c.
Embodiment 22d: change the tannic acid of embodiment 22a into 0.8g, in addition similarly operate, obtain the subpackage agent of embodiment 22d.
Embodiment 22e: change the tannic acid of embodiment 22a into 1g, in addition similarly operate, obtain the subpackage agent of embodiment 22e.
Embodiment 22f: change the tannic acid of embodiment 22a into 1.5g, in addition similarly operate, obtain the subpackage agent of embodiment 22f.
Embodiment 22g: change the tannic acid of embodiment 22a into 2g, in addition similarly operate, obtain the subpackage agent of embodiment 22g.
Embodiment 22h: change the tannic acid of embodiment 22a into 5g, in addition similarly operate, obtain the subpackage agent of embodiment 22h.
Embodiment 22i: change the tannic acid of embodiment 22a into 10g, in addition similarly operate, obtain the subpackage agent of embodiment 22i.
Comparative example 22
Remove the tannic acid of embodiment 22a, in addition similarly operate, obtain the subpackage agent of comparative example 22.
Test example 3
Perfect the experimenter by 5 the subpackage agent of embodiment 22a～i and the subpackage agent of comparative example 22 are kept in the mouth, be placed on the tongue, spue after about 15 seconds while note not swallowing.Estimate the degree of unhappy taste such as convergence at this moment, zest, bitterness, astringent taste, pungent with 5 following grades.
1: feel very strong unhappy taste
2: the taste of feeling bad
3: feel the taste that a little is unhappy
4: the taste of as if feeling bad
5: what is all imperceptible
The meansigma methods of the score of this moment is shown in table 3.The compositions of the present invention of embodiment is as shown in table 3, with respect to the medicine of 1 mass parts, correctives reaches 0.05 mass parts when above, and the unhappy taste of medicine begins to be covered, acidic materials reach 0.08 mass parts when above, and unhappy taste is almost completely covered.
[table 3]
| Score | The ratio of acidic materials and medicine 1 | |
| Embodiment 22a | 1.8 | 0.05 |
| Embodiment 22b | 2.6 | 0.1 |
| Embodiment 22c | 3.8 | 0.5 |
| Embodiment 22d | 4.8 | 0.8 |
| Embodiment 22e | 5.0 | 1.0 |
| Embodiment 22f | 5.0 | 1.5 |
| Embodiment 22g | 5.0 | 2.0 |
| Embodiment 22h | 5.0 | 5.0 |
| Embodiment 22i | 5.0 | 10.0 |
| Comparative example 22 | 1.0 | 0 |
Embodiment 23a: weighing 1g diphenhydramine hydrochloride (Buddha's warrior attendant KCC system), 1g tannic acid (Dainippon Sumitomo Pharma Co., Ltd's system) and 0.05g Magnesiumaluminumsilicate (Fuji Chemical Industry Co., Ltd's system), dissolve, be scattered in Purified Water, total amount is adjusted into 500mL, obtains the mixture for internal use of embodiment 23a.
Embodiment 23b: change the Magnesiumaluminumsilicate of embodiment 23a into 0.25g, in addition similarly operate, obtain the mixture for internal use of embodiment 23b.
Embodiment 23c: change the Magnesiumaluminumsilicate of embodiment 23a into 0.5g, in addition similarly operate, obtain the mixture for internal use of embodiment 23c.
Embodiment 23d: change the Magnesiumaluminumsilicate of embodiment 23a into 1g, in addition similarly operate, obtain the mixture for internal use of embodiment 23d.
Embodiment 23e: change the Magnesiumaluminumsilicate of embodiment 23a into 2g, in addition similarly operate, obtain the mixture for internal use of embodiment 23e.
Embodiment 23f: change the Magnesiumaluminumsilicate of embodiment 23a into 5g, in addition similarly operate, obtain the mixture for internal use of embodiment 23f.
Embodiment 23g: change the Magnesiumaluminumsilicate of embodiment 23a into 10g, in addition similarly operate, obtain the mixture for internal use of embodiment 23g.
Embodiment 23h: change the Magnesiumaluminumsilicate of embodiment 23a into 25g, in addition similarly operate, obtain the mixture for internal use of embodiment 23h.
Embodiment 23i: change the Magnesiumaluminumsilicate of embodiment 23a into 50g, in addition similarly operate, obtain the mixture for internal use of embodiment 23i.
Test example 4
Perfect the mixture for internal use that the experimenter uses embodiment 23a～i by 5, similarly estimate the degree of unhappy taste with 5 grades with test example 1.
The meansigma methods of the score of this moment is shown in table 4.The compositions of the present invention of embodiment is as shown in table 4, and with respect to the acidic materials of 1 mass parts, alkali salt and/or earth metal salt are 0.1 mass parts when above, and unhappy taste is covered.
[table 4]
| Score | The ratio of alkali salt and/or earth metal salt and acidic materials | |
| Embodiment 23a | 3.2 | 0.1 |
| Embodiment 23b | 3.8 | 0.25 |
| Embodiment 23c | 4.0 | 0.5 |
| Embodiment 23d | 4.4 | 1.0 |
| Embodiment 23e | 4.8 | 2.0 |
| Embodiment 23f | 5.0 | 5.0 |
| Embodiment 23g | 5.0 | 10.0 |
| Embodiment 23h | 5.0 | 25.0 |
| Embodiment 23i | 5.0 | 50.0 |
Embodiment 24
Weighing 1g diphenhydramine hydrochloride (Buddha's warrior attendant KCC system), 1g propyl gallate (Dainippon Sumitomo Pharma Co., Ltd's system) and 3g Magnesiumaluminumsilicate (Fuji Chemical Industry Co., Ltd's system), dissolve, be scattered in Purified Water, total amount is adjusted into 100mL, obtains the mixture for internal use of embodiment 24.
Embodiment 25
Change the propyl gallate of embodiment 24 into 1g acetic acid (Japanese synthetic chemistry Co., Ltd. system), in addition operate similarly to Example 24, obtain the mixture for internal use of embodiment 25.
Embodiment 26
Change the propyl gallate of embodiment 24 into 1g tartaric acid (clear and Chemical Co., Ltd's system), in addition operate similarly to Example 24, obtain the mixture for internal use of embodiment 26.
Embodiment 27
Change the propyl gallate of embodiment 24 into 1g citric acid (clear and Chemical Co., Ltd's system), in addition operate similarly to Example 24, obtain the mixture for internal use of embodiment 27.
Embodiment 28
Change the propyl gallate of embodiment 24 into 1g tannic acid (Dainippon Sumitomo Pharma Co., Ltd's system), in addition operate similarly to Example 24, obtain the mixture for internal use of embodiment 28.
Test example 5
Perfect the mixture for internal use that the experimenter uses embodiment 24～28 by 5, similarly estimate the degree of unhappy taste with 5 grades with test example 1.
The meansigma methods of the score of this moment is shown in table 5.The unhappy taste of the compositions of the present invention of embodiment is covered by the various acidic materials shown in the table 5.
[table 5]
| Score | Acidic materials | |
| Embodiment 24 | 4.6 | Propyl gallate |
| Embodiment 25 | 4.8 | Acetic acid |
| Embodiment 26 | 4.2 | Tartaric acid |
| Embodiment 27 | 4.2 | Citric acid |
| Embodiment 28 | 4.8 | Tannic acid |
Embodiment 29
Weighing 1g diphenhydramine hydrochloride (Buddha's warrior attendant KCC system), 1g tannic acid (Dainippon Sumitomo Pharma Co., Ltd's system) and 5g calcium carbonate (eastern efflorescence worker of day Co., Ltd. system), after the Purified Water kneading, heat drying is removed moisture, add 33g D-mannitol (Mitsubishi's food technology (Foodtech) Co., Ltd. system) and 10g corn starch (Japan Food Chemical Co., Ltd's system) then, with the subpackage of gained powder, making diphenhydramine hydrochloride is every bag 50mg, obtains the subpackage agent of embodiment 29.
Embodiment 30
Change the calcium carbonate of embodiment 29 into 5g calcium silicates (moral mountain (Tokuyama) Co., Ltd. system), in addition operate similarly to Example 29, obtain the subpackage agent of embodiment 30.
Embodiment 31
Change the calcium carbonate of embodiment 29 into 5g Aluminium Hydroxide (Kyowa Chemical Industry Co., Ltd's system), in addition operate similarly to Example 29, obtain the subpackage agent of embodiment 31.
Embodiment 32
Change the calcium carbonate of embodiment 29 into 5g Magnesiumaluminumsilicate (Fuji Chemical Industry Co., Ltd's system), in addition operate similarly to Example 29, obtain the subpackage agent of embodiment 32.
Test example 6
Perfect the subpackage agent that the experimenter uses embodiment 29～32 by 5, similarly estimate the degree of unhappy taste with 5 grades with test example 3.
The meansigma methods of the score of this moment is shown in table 6.The unhappy taste of the compositions of the present invention of embodiment is covered by various alkali salts and/or earth metal salt shown in the table 6.
[table 6]
| Score | Alkali salt and/or earth metal salt | |
| Embodiment 29 | 4.8 | Calcium carbonate |
| Embodiment 30 | 4.6 | Calcium silicates |
| Embodiment 31 | 4.4 | Aluminium Hydroxide |
| Embodiment 32 | 5.0 | Magnesiumaluminumsilicate |
The possibility of utilizing on the industry
For the multi-medicament that presents unhappy taste, Orally administered composition of the present invention can be covered the distinctive convergence of this medicine, excitant, bitter taste. The taste that astringent taste, pungent etc. are unhappy. This Orally administered composition also can be widely used in any formulation in solid pharmaceutical preparation, liquid preparation, the semisolid preparation. Orally administered composition of the present invention also can make when covering unhappy taste in lag time (lag time) after medicine is being taken and discharge immediately, therefore can be used for multiple immediate release preparation. And oral solid composition of the present invention is not only taken easily, but and the most of patients long-term taking, positively bring into play the effect of various medicines. In addition, its taking is good, can expect the raising of patient's compliance, also can improve QOL.
Claims (7)
1. an Orally administered composition of having covered unhappy taste is characterized in that, contains medicine, acidic materials and the alkali salt and/or the earth metal salt that present unhappy taste.
2. the Orally administered composition of having covered unhappy taste as claimed in claim 1 is characterized in that, acidic materials are to be selected from tannic acid, propyl gallate, acetic acid, citric acid and tartaric more than a kind or 2 kinds.
3. the Orally administered composition of having covered unhappy taste as claimed in claim 1 is characterized in that, alkali salt and/or earth metal salt are to be selected from more than a kind or 2 kinds of magnesium salt, calcium salt and aluminum salt.
4. the Orally administered composition of having covered unhappy taste as claimed in claim 1 is characterized in that, the medicine of the taste unhappy with respect to presenting of 1 mass parts contains the acidic materials of 0.05～50 mass parts.
5. the Orally administered composition of having covered unhappy taste as claimed in claim 1 is characterized in that, with respect to the acidic materials of 1 mass parts, contains the alkali salt and/or the earth metal salt of 0.05～50 mass parts.
6. as each described Orally administered composition of having covered unhappy taste in the claim 1～5, it is characterized in that dosage form is tablet, granule, granula subtilis, powder, pill, dry syrup or mixture for internal use.
7. the concealing method of a unhappy taste is characterized in that, makes to contain acidic materials and alkali salt and/or earth metal salt in the medicine that presents unhappy taste.
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| JP2008116743A JP2009263298A (en) | 2008-04-28 | 2008-04-28 | Oral composition having masked disagreeable taste |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6869618B2 (en) * | 2001-04-10 | 2005-03-22 | Kiel Laboratories, Inc. | Process for preparing tannate liquid and semi-solid dosage forms |
| JP4348139B2 (en) * | 2003-08-06 | 2009-10-21 | 花王株式会社 | Solid composition |
| JP2005179311A (en) * | 2003-12-24 | 2005-07-07 | Lion Corp | Jelly state sleeping medicine preparation |
-
2008
- 2008-04-28 JP JP2008116743A patent/JP2009263298A/en active Pending
-
2009
- 2009-04-17 TW TW098112881A patent/TW201000133A/en unknown
- 2009-04-27 CN CNA2009101385068A patent/CN101574521A/en active Pending
- 2009-04-27 KR KR1020090036500A patent/KR20090113777A/en not_active Application Discontinuation
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102309442A (en) * | 2010-07-07 | 2012-01-11 | 澳美制药厂 | Ambroxol hydrochloride oral aqueous composition and preparation method thereof |
| CN103327832A (en) * | 2011-01-24 | 2013-09-25 | 富士胶片株式会社 | Composition for oral administration |
| CN103327832B (en) * | 2011-01-24 | 2016-08-10 | 富士胶片株式会社 | Composition for oral administration |
| CN105580899A (en) * | 2014-11-15 | 2016-05-18 | 柳易程 | Alcoholism-relieving traditional Chinese medicine yogurt and preparation method thereof |
| CN106727272A (en) * | 2016-12-08 | 2017-05-31 | 星康桥医药科技（南京）有限公司 | A kind of mouthwash formulation and method of gargling |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201000133A (en) | 2010-01-01 |
| KR20090113777A (en) | 2009-11-02 |
| JP2009263298A (en) | 2009-11-12 |
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