CN1127141A - Molded articles and method of producing the same - Google Patents

Abstract

A bitter taste of a metal salt of a physiologically active ingredient is mitigated by adding a combination of aspartame and a water-soluble carbohydrate such as a hydrogenated maltose to such metal salt of physiologically active ingredient. The metal salt of physiologically active ingredient includes alkaline earth metal salts of vitamins such as calcium ascorbate and calcium pantothenate. The relative proportions of each ingredients to 100 parts by weight of the metal salt of the physiologically active ingredient are 0.1 to 100 parts by weight for aspartame, and not less than 10 parts by weight for the water-soluble carbohydrate. For further suppressing the peculiar unpleasant taste of aspartame, the water-soluble carbohydrate is used in an amount of 20 to 1,000 times by weight as much as aspartame.

Description

Shaping thing and preparation method thereof

The present invention relates to and contain bright bitterness physiologically active ingredient, can cover or hide a kind of shaping thing of the discomfort of bitterness as leaving in the oral cavity and so on again; The manufacture method of this shaping thing and a kind of method of covering the bitterness of (improvement) physiologically active ingredient.

Be used for pharmaceutical preparation and active ingredient of drugs, a lot of discomforts that are accompanied by when oral such as tart flavour, bitterness, acid are arranged.In order to alleviate these discomforts, in the Japanese Patent Application Publication the 56416/1990th (JP-A-2-56416) number a kind of granule has been proposed, its uses the bitterness that aspartame is covered antipyretic-antalgic agent acetaminophen or other composition.Also mention with lactose and mannitol in the document and make additives.

Propose a kind of ascorbic grit that contains in the Japanese Patent Application Publication the 295425/1992nd (JP-A-4-295425) number, wherein added the binding agent (glue) of the sweeting agent of aspartame and so on and starch and so on.Even this grit is characterised in that when Vitamin C content is very high it also can alleviate or cover the intensive tart flavour of vitamin C.

Opposite with the shaping thing with relative large volume such as tablet or lozenge, these granules are easy to swallow, thereby are easy to administration.Therefore, as long as the bitterness of active component is temporarily corrected, they just can take no any discomfort or uneasiness.Yet the shaping thing relatively large to volume is applied to the special tablet in oral cavity, need stop for a long time in the oral cavity making it as chewable formulation, lozenge and other preparations and dissolve gradually, and along with the dissolving of tablet, the bitterness of active component exists always in the sheet.Therefore, the taste of these tablets just can not be covered or improves with aspartame.In addition, aspartame itself has special mixing taste, astringent taste and acid and bitterness, and above-mentioned granule is difficult to cover or improve these tastes of aspartame.

Japanese Patent Application Publication the 19475/1985th (JP-A-60-19475) number proposes a kind of sweetening agent compositions again, and it comprises a kind of dipeptide sweetener and vitamin C as aspartame, in order to cover residual special sweet taste behind the picked-up sweeting agent.The document is recorded and narrated the sugar that can share such as fructose, glucose, sucrose, lactose and maltose in this compositions.Yet,, do not provide the method for covering the special bitterness of physiologically active ingredient slaine (as the alkali salt of vitamin) though the ascorbic as can be known tart flavour of document can improve the special sweet taste of aspartame thus.

Therefore, even one of purpose of the present invention just provides a kind of production method of also can efficiently and effectively when resembling the oral cavity with the relatively large tablet of volume covering the shaping thing and this shaping thing of physiologically active ingredient slaine bitterness.

It is simple that another object of the present invention provides a kind of composition, can cover the shaping thing and the production method thereof of physiologically active ingredient slaine bitterness again for a long time.

A further object of the invention provides a kind of bitterness that not only can make the physiologically active ingredient metal and reduces to minimumly, and can make the sort of special offending taste of aspartame reduce to minimum shaping thing and production method thereof.

In addition, further aim of the present invention provides a kind of method that can cover or improve physiologically active ingredient slaine bitterness for a long time.

In order to finish foregoing, inventor of the present invention has carried out sufficient investigation research, finds that the selective binding of Ah phase Ba Tian and a kind of water-soluble sugar can significantly alleviate the bitterness of physiologically active ingredient slaine.The present invention just is based on that this discovery finishes.

Therefore, the present invention relates to a kind of shaping thing, this shaping thing contains a kind of bitterness physiologically active ingredient slaine, aspartame and a kind of water-soluble sugar.

The physiologically active ingredient slaine can comprise various compositions, as the alkali metal salt of physiologically active ingredient, the alkali salt of physiologically active ingredient (as calcium salt and so on).And the physiologically active branch can be vitamin or other composition.For example, the physiologically active ingredient slaine can be a kind of alkali salt (as calcium ascorbate, calcium pantothenate etc.) of water soluble vitamins.Can also add a kind of physiologically active ingredient in addition again in this shaping thing as free vitamin.

Water-soluble saccharides (polysaccharide) can be a saccharide (refined sugar for example, sucrose, the wooden sugar of fructose (fructoligosaccharde), para sugar (palatinose), starch sugar is (as glucose, maltose, hydrogenated maltose, dried syrup, starch slurry, isomerized sugar (fructose)), the lactose class is (as lactose, isomerized lactose (lactulose), reduction lactose (lactitd or the like), Mel, sugar alcohol is (as the D-sorbitol, D-mannitol, maltose alcohol (maltitol) and xylitol etc.When sucrose sweetness was defined as 1, the sugariness of this water-soluble sugar should be not less than 0.2 (approximately 0.2-2.5), as typical maltose.

In addition, this shaping thing should be a kind of preparation of the compression molding as chewable formulation.The ratio of various components (composition) can be selected in a very wide scope.For example, this shaping thing can contain the aspartame of 0.1-100 part weight, the water-soluble sugar that is no less than 10 parts of weight (approximately 10-2000 part weight) and the physiologically active ingredient slaine of 100 parts of weight.The weight of water-soluble sugar can be about 20-1000 times of aspartame weight.

For example, this shaping thing comprises (1): the vitamin slaine is a kind of shaping thing of alkali salt of water soluble vitamins.It contains the vitamin alkali salt of 100 parts of weight, the aspartame of 0.1-50 part weight and the sugariness of 25-800 part weight and is not less than 0.2 sugar.This shaping thing also comprises, for example, and (2): the shaping thing that contains a kind of vitamin ingredients, aspartame and water-soluble sugar of forming by vitamin alkali salt and free vitamin.As (3): the shaping thing of the sugariness of contained water-soluble sugar between 1.2 to 2.0.It contains the free vitamin of 10-1000 part weight, the aspartame of 1-10 part weight, the water-soluble sugar of 25-2000 part weight and the vitamin alkali salt of 100 parts of weight.

When free vitamin was acidity, this shaping thing should be divided into two groups with free vitamin and aspartame and be shaped then, to reduce or to avoid the two direct contact.Illustrate, it can be a kind of like this shaping thing, has at least a kind of composition to be mixed in the carrier-containing granule in wherein acid free vitamin and the aspartame; Also can be that acid free vitamin and aspartame are contained in the shaping thing in the variable grain respectively, and the shaping thing of other types.

The mold formed shaping thing that can produce among the present invention of mixture with physiologically active ingredient slaine, aspartame and a kind of water-soluble sugar of tool bitterness.In addition, the method to modify taste in according to the present invention adds the bitterness that the biological active substances slaine could be covered or improve to aspartame and a kind of water-soluble sugar.

Need to prove, in this description bitterness, astringent taste, acid etc. are referred to as " bitterness ".

Shaping thing among the present invention and method to modify taste be applicable to and comprise various physiologically active ingredient slaines pharmacological component, that have bitterness, and especially general prescription is difficult to the bitter principle that alleviates or cover.

The physiologically active ingredient slaine of tool bitterness comprises and can and have the various physiologically active ingredients of bitterness with the metal salify.For not having particular restriction with the salifiable physiologically active ingredient of metal, the example of this composition has vitamins (as ascorbic acid, pantothenic acid, folic acid etc.), Glycodiazine, copper chlorophyllin, sucrose sulfuric ester, solubility pyrophosphate or the like.Comparatively ideal physiologically active ingredient comprises vitamin, especially resembles water soluble vitamins such as ascorbic acid and pantothenic acid.

Slaine comprises alkali metal salt, as lithium salts, potassium salt and sodium salt; Alkali salt is as calcium salt, magnesium salt, strontium salt and barium salt; 3B family slaine in the periodic table of elements is as aluminum salt; The 8th family's slaine in the periodic table of elements is as iron salt or the like.Alkali metal salt wherein (as sodium salt, potassium salt etc.) and alkali salt (as calcium salt, magnesium salt etc.) have special bitterness.Especially the calcium salt in the above-mentioned alkali salt, it has extremely intensive bitterness (palates).The present invention has advantage covering on the composition that this class has special bitterness.

The slaine of physiologically active ingredient can be the slaine of water soluble vitamins, as ascorbic acid (L-ascorbic acid, D-ascorbic acid etc.) alkali metal salt is (as potassium salt, sodium salt etc.) or alkali salt (as calcium salt, magnesium salt), pantothenic acid (L-pantothenic acid, D-pantothenic acid etc.) alkali metal salt is (as potassium salt, sodium salt etc.) or alkali salt (calcium salt, magnesium salt), Riboflavin Sodium Phosphate, two chlorobenzenesulfonic acid sodium (diclofenal sodium), glymidine sodium (glymidinesodium), sodium copper chlorophyllin, calcium p-aminosalicylate salt, magnesium sulfate, sucrose sulfate aluminium salt, soluble ferric pyrophosphate, Bilophtin, sodium cromoglicate, colistimethate sodium, cefazolin sodium, cefadole sodium, cephalothin sodium, cefoperazone sodium, sodium valproate, antibiotic sodium or the like.The physiologically active ingredient slaine of these tool bitterness can be singly with or share.

Comparatively ideal physiologically active ingredient slaine comprises the water soluble vitamins alkali salt in the vitamin alkali salt, especially its calcium salt.In these vitamin alkali salts, the vitamin calcium salt also has astringent taste and acid as calcium ascorbate, calcium pantothenate etc. except that having bitterness, and these senses of taste are difficult to cover or eliminate.These vitamin slaines can be singly with or share.

Metal ingredient content in the shaping produce product among the present invention can be regulated or control by adding with the corresponding free physiologically active ingredient of physiologically active ingredient slaine, to avoid the excessive picked-up or the injection of metal ingredient.Illustrate, when the alkali salt of using a kind of vitamin (as calcium salt etc.), can in alkali salt, add corresponding free vitamin, with the content of adjusting alkaline-earth metal.In this case, whole shaping thing can be alleviated the intensive tart flavour of free vitamin by efficiently and effectively.The relative scale of free physiologically active ingredient (as free vitamin) and physiologically active ingredient slaine (as the vitamin alkali salt) should be selected according to size and other factors of final application need, mouldings.Such as, with respect to the physiologically active ingredient slaine of 100 fens weight, add the physiologically active ingredient of about 10-1000 part weight, add the more satisfactory of 25-700 part weight, add the better of 50-500 part weight.

The physiologically active ingredient slaine can together be used with other any tool bitterness active component (as physiologically active ingredient, pharmacological component, crude drug etc.).Kind for this extra active component does not have particular restriction.

Other physiology with unhappy sense of taste or pharmacological component have vitamins such as nicotinic acid, nicotiamide, L-ascorbic acid, D-ascorbic acid, L-pantothenic acid, D-pantothenic acid, thiamine, fursultiamine; Salt of these vitamin (as chloride, nitrate, sulfate etc.) and analog thereof; Analgesic such as phenazone, phenacetin, Caffeine Anhydrous etc.; Antipyretic analgesic such as choline salicylate; Analgesia expectorant such as N-cyclohexyl-N-methyl-(2-amino-3,5-dibromobenzene methyl)-amine hydrochlorate, 3-(N methyl piperidine thiazolinyl)-2,2-two thiophene methane citrates, dromethan hydrobromate, trimethoquinol hydrochlorate etc.; Tranquilizer such as phenobarbital; Spasmolytic such as hyoscine-N-n-butyl bromide, N-methyl scopolamine Methylsulfate, flopropione etc.; Cardiac tonic such as digoxin; Antihistaminic such as alimemazine, chlorphenamine, his pyridine of hydrochloric acid ring etc.; Treatment diabetes medicament such as tolbutamide, benzene desaglybuzole, acetophenone sulphur ring ethyl urea, chlorpropamide or the like; The medicine of treatment hepatic disease such as probanthine, digestant such as pancreas digestive enzyme, bile component, the burnt deoxycholic acid of gastric acid etc.; Depressor (antihypertensive) is as hydralazine hydrochlorate, reserpine, many thiazines etc.; Hormone medicine such as dexamethasone and betamethasone; Antibiotic such as stilbene diamidogen two penicillins-G, ampicillin, cephalexin, quadracycline, salt doxycycline, chloromycetin or the like; Sulfa drugs such as sulfamethoxazole, sulfafurazole etc.; Other active component comprise mental illness medicine such as hydroxyzine pamoate, antuepileptic such as P. R. M. Primoline, eye tension force inhibitor such as isosorbide, amino acid whose nutrient example hydrochloric acid lysine, Small Intestine disorder treatment medicine such as paspertin metoclopramide or the like are provided.

Crude drug as extra active component comprises Lu Ling, " engosaku " (Rhizoma Corydalis), rose fruct (Radix Cirsii Japonici), " ougi " (astragalus root), " ousei " (Rhizoma Polygonati), payta, guarana, " Kukoshi " (Fructus Lycii), Radix Rehmanniae, " touki " (Radix Angelicae Sinensis), Chinesegutta percha, Radix Ginseng, amarogentin, Radix Scutellariae, phellodendron bark, the Rhizoma Coptidis rhizome, Zedoary, cascara sagrada, " Kasukaariranoki " (bitter XIANGSHU), Japanesevalerian (Valeriana Fauriei Briq.), " Karoukon " (Fructus Trichosanthis), Radix Platycodonis, immature Fructus Citri tangerinae, Semen Armeniacae Amarum or Japanese Semen Armeniacae Amarum, " Kihada " (yellow tiller), " kuko " (Lycium Zhombifolium), Radix sophorae, " ketsumeishi " (Semen Cassiae), morning glory seed, Radix Gentianae, the Japan Herba Erodii, the dried tuber rhizome, the Cortex Magnoliae Officinalis skin, east gastrolith (bezoar bovis), Radix Achyranthis, " go shuyu " (Fructus Evodiae), Shisandra fruit, Colombo, CondurangoBark, the Radix Bupleuri root, " Sanshishi " (son), Saffron, " Sanzukon " (Vietnam's Radix sophorae), Radix Rehmanniae, Radix Arnebiae (Radix Lithospermi), Peony root, " shajin " (Japanese SANYE Radix Adenophorae (Radix Glehniae)), Herba Plantaginis or Semen Plantaginis, Moschus, black cohsh root or Rhizoma Cimicifugae rhizome, green Citrus pericarp, Japanese sweetflag, " senkyuu " (cnidium rhizome), " senkotsu " (spatterdock rhizome), Centaurea cyanus, " senburi " (Japanese Herba Swertiae bimaculatae), " senbou " (Rhizoma Curculiginis rhizome), bufonin or Bufo siccus cake, kind great leaf, the Atractylodes lancea (Thunb.) DC. rhizome, Cortex Mori, " daiou " (Radix Et Rhizoma Rhei), " chikusetsuninnjin " (Panaeis japonici rhizoma), the Rhizoma Anemarrhenae, Chiretta, living satsuma orange skin early, exsiccant bitter Fructus Citri tangerinae skin, " tounin " (Semen Persicae), ipecac or ipecacuanha, lignum quassiae japonensis (bitter tree), " byakushaku " (Radix Paeoniae root), the Rhizoma Atractylodis rhizome, belladonna root, American Worm Seed oil, bitter cardamon (cardamom), Fel Ursi, " yomogi " (Artemisia princeps Pamp.), " nigayomogi " (Artemisia absinihium L), bitter tincture, " jishuyu ", hop, " homika " (nuxvomia), " boui " (Sinomenium acutum stem and rhizome), Herba Ephedrae, akebia stem, hieracioides root (Costus speciosus root), " ryuutan " (Ben Shi Gentiana lutea), " rindou " (Ben Shi Radix Gentianae), SaintIgnatius beans, " rengyou " (Fructus Forsythiae fruit), scopola extract or the like.

Example with active component of bitterness has (1) barbiturates compounds, as allobarbital, cyclobarbitone, barbital, phenobarbital and P. R. M. Primoline; (2) pyrazolone compounds is as aminophenazone, phenazone and Sulpyrine; (3) appropriate compounds of pyrrole Lapie such as pyrrole Lapie are appropriate; (4) phenothiazines chemical compound, example hydrochloric acid chlorpromazine, promethazine hydrochloride; (5) amino benzoic Acid ammonium esters, example hydrochloric acid tetracaine and procaine hydrochloride; (6) dimethylaniline compounds example hydrochloric acid lignocaine; (7) dibucaine compounds example hydrochloric acid dibucaine; (8) mephensine compounds such as mephensine; (9) atropine compounds such as atropine sulfate; (10) papaverine compounds example hydrochloric acid papaverine; (11) chlorphenamine compounds such as chlorphenamine maleate; (12) diphenhydramine compounds example hydrochloric acid diphenhydramine and dimenhydrinate; (13) xanthine derivative such as aminophylline, caffeine, theophylline, brontyl, oxyethyltheophylline (oxyethyltheophylline), caffeine and sodium benzoate, calcium diuretin and other; (14) digitalin compounds such as digitalin, digitophyllin, digoxin; (15) ajmaline compounds such as ajmaline; (16) hydralazine compounds example hydrochloric acid hydralazine; (17) rutin compounds such as rutin; (18) phyenlephrinium compounds example hydrochloric acid phyenlephrinium; (19) dimorpholamine compounds dimorpholamine; (20) ephedrines chemical compound such as dl-mephedrine; (21) narcotine compounds example hydrochloric acid narcotine; (22) cholic acid compounds such as ursodesoxycholic acid, dehydrocholic acid etc.; (23) thiouracil compounds such as methylthiouracil and propylthiouracil; (24) niacin compound serving such as nicotinic acid and nicotiamide; (25) sulfonamides compound such as sulfaphenazole, ayerlucil sulfamethoxazole, sulfafurazole, sulfamethoxypyridazine or sulfametoxydiazine (sulfamethoxypyrimidine) etc.; (26) quinine class example hydrochloric acid quinine, quinine sulfate, quinin(e) acetate, (27) other pharmaceutically active compounds such as Bromovalerylurea (bromvalerylurea), chloral hydrate, acetaminophen, amitriptyline hydrochloride, benzocaine, the G-strophanthin, quinidine sulfate, acetazolamide, spironolactone, hydrogenation thiazine (hydrothiazide), guanethidine monosulphate, naphcon, isoprenaline, berberine hydrochloride, dexamethasone, pyridoxine hydrochloride, ampicillin, kanamycin sulfate, erythromycin, acetylspiramycin, spiramycin, chloromycetin, tetracycline, ethionamide, emetine hydrochloride, Arechin (Polfa), Santonin, diethylcarbamazine citrate, cocaine hydrochloride, the dl-menthol, l-menthol or the like.

Characteristic of the present invention has been use in conjunction, and aspartame and a kind of water-soluble sugar (polysaccharide) improve or cover the bitterness of the slaine of physiologically active ingredient.Water-soluble sugar can be a sucrose, as refined sugar, sucrose, the wooden sugar of fructose, para sugar etc.; Starchy carbohydrate is as glucose, maltose, hydrogenated maltose, dried syrup, starch slurry, isomerized sugar (fructose) etc.; The lactose class is as lactose, isomery lactose (lactulose), reduction lactose (lactitol) etc.; The Mel class; Sugar alcohols is as D-sorbitol, D-mannitol, maltose alcohol, xylitol etc.These water-soluble sugars can be singly with or share.

Be used for the comparatively ideal water-soluble sugar kind of the present invention and comprise sucrose such as sucrose; Starchy carbohydrate is as glucose, maltose, hydrogenated maltose, fructose etc.; Lactose; Sugar alcohols is as D-sorbitol, maltose alcohol, xylitol etc.Wherein maltose, hydrogenated maltose, lactose, D-sorbitol and maltose alcohol, particularly the hydrogenated maltose effect is better.This hydrogenated maltose comprises hydrogenated maltose starch slurry and hydrogenated maltose starch starch.Comparatively ideal sugar should have the sugariness of water-soluble sugar, when sucrose sweetness was defined as 1, it was not less than 0.2 (about 0.2-2.5), between 0.2-2.0 better, better between 0.3-1.7.

In addition, with sugar low in calories, share the low mouldings of composition heat that provides a kind of ratio to make correctives with sucrose etc. as maltose, hydrogenated maltose, D-sorbitol, maltose alcohol, xylitol etc. and aspartame.This mouldings is suitable for the people or the experimenter of caloric restriction picked-up.

Every kind of components in proportions all can be selected in wide range in the mouldings of the present invention, to correct the sense of taste of mouldings.For example, when the physiologically active ingredient slaine was 100 fens weight, aspartame was approximately 0.1-100 part weight, and wherein 0.5-100 part weight is more satisfactory, and is the most desirable during 1-10 part weight.When the physiologically active ingredient slaine is 100 parts of weight, the many 10 parts of weights of the relative quantity of water-soluble sugar (for example, about 10-2000 part is heavy), comparatively desirable between 25-2000 part, better when 50-5000 part weight.Illustrate, when the physiologically active ingredient in the mouldings was a kind of water soluble vitamins, it should contain the about 0.1-50 part of aspartame weight, and is quite a lot of when 0.1-10 part is heavy, better when about 0.2-5 part is heavy; Should contain water-soluble sugar 25-800 part weight that sugariness is not less than 0.2 (0.2-2.5), 50-500 part is better when heavy, and is better when 25-300 part is heavy; The water soluble vitamins alkali salt (as calcium salt) that also contains 100 parts of weights.The mouldings that it is water soluble vitamins that the present invention more is applicable to for this contained physiologically active ingredient.

In order to cushion or reduce the bitterness and the special unpleasant taste of aspartame of physiologically active ingredient slaine, be necessary the relative scale of aspartame and water-soluble sugar is regulated or controlled, to water down or to alleviate this bitterness and unhappy sense of taste.The relative scale of water-soluble sugar and aspartame can be selected not sacrificing under its situation to composition bitterness masking ability (flavoring performance), in fact should not be less than the consumption of aspartame.For example, for the aspartame of 1 part of weight, water-soluble sugar can be used 1-2000 part weight, and is more satisfactory when wherein 10-1500 part is heavy, and 20-1000 part is better when heavy, and is the most desirable during 50-500 part.

If desired, shaping thing of the present invention also can contain other physiologically active ingredient except that the bitterness physiologically active ingredient.The physiologically active ingredient of this additional code comprises: other pharmacological components; Chinese medicine extract; Antacid and mucosa protective agent, as magnesium hydroxide, aluminium hydroxide, aluminum sulfate, aluminosilicate magnesium (as, " Neusilin " (trade name)), Magnesiumaluminumsilicate, a kind of synthetic hydrogenation talcite (hydrotalcite) (as " Alcamac " (trade name)), the coprecipitate of aluminium hydroxide and sodium bicarbonate is (as " Kumulite " ((trade name)) and sucralfate; Mineral; Aminoacid or the like.

This shaping thing also can contain a kind of carrier and/or various other additives in addition except that containing aspartame, water-soluble sugar and physiologically active ingredient slaine.As carrier can be to the not reactive various compositions of the rectification of physiologically active ingredient slaine bitterness.For example, this carrier comprises: excipient, as corn starch, Pulvis Talci, crystalline cellulose (as Aricel (trade name) etc.), magnesium stearate, light silicon anhydride, magnesium carbonate, calcium carbonate, L-cysteine etc.; Binding agent is as starch, gelatinized starch (a-starch), gelatin, gummi arabicum pulveratum, methylcellulose, carboxymethyl cellulose, Sodium Tvlose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, polyethylene pyrrole such as alkane ketone, Pullulan, dextrin etc.; Disintegrating agent such as carboxymethyl cellulose (calcium is as " ECG 505 " (trade name)), low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose (as " Acdisol " (trade name)) or the like.Additives then comprise surfactant, as anion surfactant alkyl sodium sulfate, non-ionic surfactant polyoxyethylene fatty acid esters of sorbitan, polyoxyethylene fatty acid ester and castor oil derivatives etc.; Coloring agent (pigment); Absorbent; Antiseptic; Wetting agent; Antistatic additive; Delay disintegration agent and other.Water-soluble sugar such as lactose, sucrose, mannitol etc. also can be used as excipient.At least excipient and binding agent can act on the carrier of this shaping thing, and also will use disintegrating agent under a lot of situation.

According to the present invention, the bitterness of physiologically active ingredient slaine can be covered the long period.Therefore the present invention can be effectively used to various bigger shaping things, particularly need stop for a long time in the oral cavity and dissolved gradually shaping thing.These shaping things comprise that special snack food (table head food) are as oral preparations such as confection and tablet, lozenge and Sublingual tablets.Typical shaping thing comprises molded product (for example pharmaceutical preparation) as tablet, lozenge and chewable formulation, particularly can stop long period and dissolved gradually chewable formulation in the oral cavity.According to method to modify taste of the present invention,, thereby avoid making bulky shaping thing as long as use a spot of correctives just can cover the bitterness of molded product (as tablet and chewable formulation) fully, effectively.

The preparation of shaping thing of the present invention is the kind according to shaping produce product, and the mixture press forming of physiologically active ingredient slaine, aspartame and oozing property of the water sugar of bitterness will be arranged according to suitable method.The bitterness that contains physiologically active ingredient slaine shaping thing can be covered and improve by the combined effect of aspartame and water-soluble sugar wherein.

Mold formed technology comprises dissolves or finely dispersed various technology contained each composition of shaping thing therein.For example, for exquisiteness and tasty food can adopt hot melt to make, the molten mixture that also is about to aspartame, water-soluble sugar and physiologically active ingredient slaine in the composition is made shape and is got in mould; And for mold pressing preparation such as oral cavity tablet, can get according to the mixture die forming of tablet manufacturing technology with each component.If needing the shaping thing of preparation is mould compacting preparation, physiologically active ingredient slaine, aspartame and water-soluble sugar can be mixed, if desired, also can add adjuvant or carrier, mixed pelletization is then with made granule (as particle powder) compression molding.Granulation can be undertaken by traditional granulation technique, as the direct blended dry granulation of each component or use the wet granulation of solvent (for example: organic solvent, as ethanol, solvent particularly safe in utilization is as water.)

What particularly point out is to be generally will use adjuvant or carrier in granulation.System material process can be finished by wet method classer and non-slurry pelletizing machine.Wet granulator such as cylinder comminutor, stirring granulating machine, suspension comminutor, sponging granulator, centrifugal rolling comminutor, rolling suspension comminutor etc.; The non-slurry pelletizing machine is as using the Squeezinggranulator of binding agent.

Sometimes because the existence of acid ingredient can be decomposed aspartame, its stability is reduced.Illustrate, when vitamin component by having tart free type vitamin (as ascorbic acid, pantothenic acid etc.) and slaine thereof (for example alkali salt such as calcium salt etc.) when forming, have of the coexistence of tart free vitamin, will reduce the stability of aspartame with aspartame; Otherwise, when coexisting with the vitamin slaine, aspartame stable unaffected.Therefore, in order to strengthen or improve the stability of aspartame, mouldings best (1) does not contain acid ingredient, as free vitamin, or (2) are when containing acid ingredient in the shaping thing, acid ingredient such as free vitamin and aspartame split in the variable grain (promptly make variable grain), reducing or to avoid being in contact with one another between two components, even reach the purpose of isolating two components.

Under (2) kind situation, at least a cooperation adjuvant or the carrier that have in two kinds of components of tart free vitamin and aspartame should be made granule (as granule, particle powder), to reduce or to avoid being in contact with one another of two components.In this case, not making particulate component just can make particulate component with adjuvant or carrier with another kind and mix mutually.Better method is that aspartame is made different granules respectively with acid ingredient.That is to say that the preparation of shaping thing is preferably made granule respectively with acid ingredient such as free vitamin (acid ingredient group) and other group (aspartame group) of containing aspartame, then these two kinds of granule mixing press formings is got.

In the process of preparation variable grain, be with acid composition, the active component that need add and the mixture that comprises the adjuvant of binding agent and excipient at least for the granule that contains acidic components, granulate by traditional mode.And the granule method for making that contains aspartame is identical, just acid ingredient is replaced with aspartame.

In order further to avoid being in contact with one another of acid ingredient and aspartame, mouldings can be made the multilayer film tabletting (as double-layer tablet, three-layer tablet etc.) that contains acid ingredient group layer and aspartame group layer, or to make coated tablet be that the sheet heart contains a kind of component in two groups of acid ingredient and the aspartames, and the another kind of component of reuse packs and forms.

According to the kind and the purposes of physiologically active ingredient slaine, its content generally accounts for the 0.001-70% of shaping thing gross weight, and suitable scope is at 0.01-60%, and better scope is 0.1-50%.

Shaping thing among the present invention can adopt coating, and its clothing film is formed the correcting that should not disturb physiologically active ingredient slaine bitterness.For the composition of clothing film, can adopt with sugar to be the sugar-coat film of main component or to be the film-coat of main component with the cellulose family.

Material as coating material comprises saccharide (as particulate sugar and mannitol), arabic gum, Pulvis Talci, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, ethyl cellulose, hydroxy methocel, cellulose acetate-phthalate, hydroxypropyl methyl cellulose phthalate, succinic acid acetic acid hydroxy methocel, acrylic copolymer, carboxymethylethylcellulose, polyethylene acetal diethylin acetate, Lac, wax etc.These components can be singly with or share.Also often contain traditional clothing film adjuvant in the coating material as sugar (as lactose, mannitol etc.), Polyethylene Glycol, Tweens (as tween 80 etc.) and coloring agent, as titanium oxide, ferrum oxide etc.

The consumption of coating material is decided according to shaping kind and other factor of need preparation.For example, to mould compacting solid preparation such as tablet, the consumption of its coating material accounts for the heavy 0.1-30% of total sheet.

To sum up, in the shaping thing among the present invention use in conjunction aspartame and water-soluble sugar, it can reduce or the unhappy sense of taste of elimination activity composition slaine in the oral cavity by efficiently and effectively, as bitterness, even in the shaping thing of oral cavity, also be the same, thereby the finished product quality improved greatly with the big shape of sheet.In addition, although this shaping thing is formed simply, can cover the bitterness of physiologically active ingredient slaine for a long time.Also have, this mouldings has the inhibition except that the bitterness to the physiologically active ingredient slaine, even that special unwelcome sense of taste of aspartame also can be weakened or eliminate.

The method according to this invention, the mixture that the above-mentioned mouldings that can alleviate bitterness can be about to aspartame, water-soluble sugar and physiologically active ingredient metallic salt according to simple and easy to do method is mold formed and get.In addition,, in the physiologically active ingredient slaine, add aspartame and water-soluble sugar, can reduce or eliminate the bitterness of slaine for a long time effectively according to method to modify taste of the present invention.

Following example mainly is to be used for further setting forth the present invention, but can not be considered to define scope of the present invention.

Example 1

According to following prescription 1 preparation planar chip.Prescription 1 is made up of to composition (8) composition (1).Adhesive therefor is a starch slurry, and 1 part of (38.2g) corn starch (6) is added in the 318ml purified water, and heating for dissolving promptly.On the other hand, in fluidized granulation machine (Japanese Pownex company produces, FD-5S), pack ascorbic acid (1) into to aspartame (5) and these 6 kinds of compositions of remaining corn starch (6).Use the top-spray method, control supply hot air temperature is 70 ℃, sprays into binder solution, and the production temperature is controlled at 30 ℃, makes granule.

The granule that makes is pulverized, used pulverizer (Power Mill.P3S, the sieve plate of joining a Ф 1.5mm the production of Japan Showakagakukikai Kousakusho company limited), powder behind the crushing screening and magnesium stearate (7) and calcium pantothenate are at rolling type mixer (Tumbler Mixer, TM-15, Japan's Showa kagakakikaiKousakkusho company limited is produced) the middle mixing 1 minute, at last with blended powder in tablet machine (Correct 12HUK, Japan Kikusui Seisakasho production) drift of going up with Ф 15mm is pressed into planar chip under the pressure of 2.0 tons/drift, the heavy 1.150mg of sheet, the thick 5.0mm of sheet.

(prescription 1) (1) ascorbic acid 1400.0g (Takeda CHemical Industries.Ltd) (2) Calcium Ascorbate 726.0g (Takeda CHemical Industries.Ltd) (3) Riboflavin Tetrabutyrate .0g (Tokyo Tanabe Co.Ltd.) (4) hydrogenated maltose starch slurry powder 2089.6g (Towa kasei Co.Ltd.) (5) Aspartame 23.0g (Ajinomoto Corporation) (6) cornstarch 297.2g (Nippon Shokuhin Co.; Ltd) (7) calcium pantothenate 32.2g (Fuji.Yakahin Co.; Ltd.) (8) dolomol 30.3g (Sakai Kagaku Co., Ltd.)

Amount to 4600.0g

Example 2

The planar chip preparation method is with example 1, but with the hydrogenated maltose starch slurry powder in lactose (Meggle Co.Ltd. production) alternate example 1 prescription.

Example 3

The planar chip preparation method is with example 1, but with the hydrogenated maltose starch slurry powder in sucrose (Osaka Seito Co.Ltd.Japan production) alternate example 1 prescription.

Example 4

The planar chip preparation method is with example 1, but with the hydrogenated maltose starch slurry powder in xylitol (Towa Kasei Co.Ltd.Japan) alternate example 1 prescription.

Example 5

The planar chip preparation method is with example 1, but hydrogenated maltose starch slurry powder consumption is reduced to 1489.6g by 2089.6g.

Example 6

The planar chip preparation method is with example 1, but the aspartame of 23g is reduced to 5g, adds the corn starch of 18g again.

Case of comparative examples 1

The planar chip preparation method is with example 1, except that (MaruzenKasei Co.Ltd. Japan) substitutes outside the aspartame, and other compositions are identical with example 1 prescription with glycyrrhizic acid dipotassium salt.

Case of comparative examples 2

The planar chip preparation method is with example 1, except that (Dainippon InkCorporation Japan) substitutes outside the aspartame, and other compositions are identical with example 1 prescription with stevioside.

Case of comparative examples 3

The planar chip preparation method is with example 1, except that (DainipponInk Corpioration Japan) substitutes outside the aspartame, and other compositions are identical with example 1 prescription with Rebandioside A.

Case of comparative examples 4

The planar chip preparation method is with example 1, and except that substituting the aspartame with Thaumatin (San-eigin F, F, I Co.Ltd.), other compositions are identical with example 1 prescription.

Example 7

Divide two groups to prepare powder, one group is the ascorbic acid powder, and another group is calcium salt group powder, wherein contain calcium ascorbate and calcium pantothenate powder by prescription 2 form use with example 1 in identical method preparation.Aspartame only is added in the calcium salt group, and does not add in the ascorbic acid group, two groups make granule respectively after, mix, by being pressed into planar chip with example 1 similar methods.Aspartame is with in ascorbic acid lays respectively at different groups in this planar chip.

(prescription 2)

Ascorbic acid group calcium salt group

(1) ascorbic acid 1400.0g-

(2) calcium ascorbate-726.0g

(3) riboflavin 1.0g 1.0g

(4) hydrogenated maltose 734.3g 1355.3g

The starch starch

(5) aspartame-23.0g

(6) corn starch 148.6g 148.6g

(7) calcium pantothenate-30.0g

(8) magnesium stearate 16.1g 16.1g

Amount to 2300.0g 2300.0g

Above-mentioned example 7 and example 1 make in the tablet stability of aspartame and estimate in the following method.Make from example 7 and example 1 and respectively to get 100 the tablet, place polyethylene bottle, sealing respectively, under 40 ℃ of temperature, relative humidity 75% condition, placed for 4 weeks, detect with the content of high-efficient liquid phase technique then aspartame.Original content in aspartame is 100%, and example 1 and example 7 make that the content of aspartame is respectively 90.7% and 97.7% in the tablet as a result.The result shows, according to example 7, divides the mouldings of making on the same group not with component, and wherein aspartame stability is higher.

Example 8

Make planar chip with composition (1) to the composition (7) in the prescription 3, the Riboflavin butyrate (3) that also is about to 40g is dissolved in 296ml 99% ethanol, and the solution that makes is scattered in the 1180ml purified water, makes the crystalline dispersion liquid of Riboflavin butyrate.In addition, 1 part of (154g) corn starch (6) is placed the 2400ml purified water, after the heating for dissolving as binding agent.

With these 5 kinds of compositions of ascorbic acid (1), calcium ascorbate (2), hydrogenated maltose starch starch (4), aspartame (5) and remaining corn starch (6) fluidized granulation machine (Japanese Powrex company of packing into; FD-2S); control moving air temperature (intake air temperature) is 70 ℃; the production temperature is at 35 ℃; successively spray into above-mentioned dispersion liquid and binding agent with the top-spray method, make coloured particle.

The granule that makes is pulverized, be furnished with the sieve plate of a Ф 1.5mm in the pulverizer (Power Mill P-3S Japan Showa Kagakukikai Kousakusho company limited).Pulverize back gained powder and magnesium stearate (7) at rolling type mixer (Tumbler Mixer, TM-15, Japanese Showa Kagakukikai Kousakuso company limited) mixed 1 minute, last mixed powder is at tablet machine (Correct12HUK, Japan Kikusui Seisakusho) goes up under the pressure with the drift of Ф 15mm and 2.0 tons/drift and be pressed into planar chip, the heavy 1150mg of sheet, the thick 5.0mm of sheet.

(prescription 3)

(1) ascorbic acid 5600.0g (Takeda Chemical Industries, Ltd.) (2) calcium ascorbate 2904.0g (Takeda CHemical Industries, Ltd.) (3) Riboflavin butyrate 40.0g (Tokyo Tanabe Co., Ltd.) (4) hydrogenated maltose starch slurry 8438.4g (Towa Kasei Co., Ltd.) (5) aspartame 92.0g (Ajinomoto Corporation) (6) corn starch 1196.8g (Nippon Shokuhin Co., Ltd.) (Sakai Kaagaku Co., Ltd.) (Sakai Kagaku Co.Ltd) amounts to 18400.0g example 9 to (7) magnesium stearate 128.8g

Prepare planar chip with composition (1) in the prescription (3) to composition (7).Portion (154g) corn starch (6) is scattered in the 2400ml pure water, and heating for dissolving is made binding agent.In addition, ascorbic acid (1) to aspartame (5) and residue corn starch (6) these 6 kinds of compositions pack into the fluidized granulation machine (Powrex company produces, FD-2S) in; use the top-spray method, setting the moving air temperature is 70 ℃, and the production temperature is 35 ℃; spray into binder solution, make granule.

This granule that makes is pulverized, be furnished with the sieve plate of a Ф 1.5mm in the pulverizer (Powermill P-3S. Japan Showa Kagakukikai Kousakusho company limited is produced), (Japanese Suehiro Kakoki Seisakusho company limited is produced at the rolling type mixer for powder after the pulverizing and magnesium stearate; TM-20) mixed 1 minute in.The powder of mixing is pressed into planar chip with tablet agent (Japanese Kikusui Seisakusho produces, Correct12HUK Ф 1.5mm drift, 2.0 tons/drift of pressure), and sheet heavily is 1150mg, the thick 5.0mm of sheet.

Example is estimated

By 4 male subject (evaluation person) the flavoring effect of above-mentioned each example and the obtained tablet of case of comparative examples is carried out sensory evaluation.Gained the results are shown in Table 1.Flavoring recruitment evaluation standard is as follows:

Fabulous: extraordinary sense of taste

Good: good sense of taste

Generally: unhappy sense of taste, as bitterness

Bad: significant unhappy sense of taste, as bitterness

Table 1

Sensory evaluation

Example 1 is fabulous

Example 2 is fabulous

Example 3 is fabulous

Example 4 is fabulous

Example 5 is good

Example 6 is good

Example 7 is fabulous

Example 8 is fabulous

Example 9 is fabulous

Case of comparative examples 1 is bad

Case of comparative examples 2 is general

Case of comparative examples 3 is general

Case of comparative examples 4 is bad

As can be seen from Table 1, in substitute aspartame or single case of comparative examples with the aspartame flavoring with other sweeting agents, its bitterness can not reduce or cover effectively.In contrast, the tablet that makes by the example that share aspartame and water-soluble sugar, but its bitterness efficiently and effectively be lowered or cover, thereby make tablet that good sense of taste (tasty) be arranged.

Claims (24)

1. shaping thing, it contains a kind of physiologically active ingredient slaine, aspartame and a kind of water-soluble sugar of tool bitterness.

2. the shaping thing in the claim 1, its contained physiologically active ingredient slaine is a kind of alkali metal salt of physiologically active ingredient.

3. the shaping thing in the claim 1, its contained physiologically active ingredient slaine is a kind of alkali salt of physiologically active ingredient

4. the shaping thing in the claim 1, its contained physiologically active ingredient is a kind of vitamin.

5. the shaping thing in the claim 1, its contained physiologically active ingredient slaine is a kind of alkali salt of water soluble vitamins.

6. the shaping thing in the claim 3, its contained alkali salt is a kind of calcium salt.

7. the shaping thing in the claim 3, its contained physiologically active ingredient slaine is calcium ascorbate or calcium pantothenate.

8. the shaping thing in the claim 1 wherein contains a kind of free physiologically active ingredient in addition.

9. the shaping thing in the claim 8, contained free physiologically active ingredient is a kind of free vitamin.

10. the shaping thing in the claim 1, its contained water-soluble sugar is meant at least a following sugar: refined sugar, sucrose, the wooden sugar of fructose, para sugar, glucose, maltose, hydrogenated maltose, dried syrup, starch slurry, isomerized sugar or fructose, lactose, isomery lactose or Lactulose, reduction lactose or lactitol, Mel, D-sorbitol, D-mannitol, maltose alcohol and xylitol.

11. the shaping thing in the claim 1, when sucrose sweetness was defined as 1, the sugariness of the water-soluble sugar that it is contained was not less than 0.2.

12. the shaping thing in the claim 1, its contained water-soluble sugar is a kind of hydrogenated maltose.

13. the shaping thing of claim 1, this shaping thing are a kind of mold pressing preparation.

14. the shaping thing in the claim 13, this mold pressing preparation is a kind of chewable formulation.

15. the shaping thing in the claim 1, it contain 0.1-100 part weight aspartame, be no less than the water-soluble sugar of 10 parts of weight and the physiologically active ingredient slaine of 100 parts of weights.

16. the shaping thing in the claim 1, the 20-1000 of the weight aspartame of the water-soluble sugar that it is contained are doubly.

17. the shaping thing in the claim 4, its contained vitamin slaine is a kind of alkali salt of water soluble vitamins, this shaping thing contains the water soluble vitamins alkali salt of 100 parts of weight, 0.1-50 the aspartame of part weight and the sugar of 25-800 part weight, when sucrose sweetness was defined as 1, this sugared sugariness was not less than 0.2.

18. the shaping thing in the claim 1, it contains a kind of vitamins composition, and this vitamin ingredients is by its alkali salt and a kind of free vitamin, aspartame and water-soluble sugar.

19. the shaping thing in the claim 18, when sucrose sweetness was defined as 1, the sugariness of the water-soluble sugar in this shaping thing was 0.2-2.This shaping thing contains the free vitamin of 10-1000 part weight, the aspartame of 1-10 part weight, the water-soluble sugar of 25-2000 part weight and the vitamin alkali salt of 100 parts of weight.

20. the shaping thing in the claim 18, it comprises a free vitamin and another aspartame group, and is mold formed again, to avoid the contact of two kinds of compositions.Wherein contained free vitamin is tart.

21. the shaping thing in the claim 20, having a composition in this shaping thing in acid free vitamin and the aspartame at least is together to make granule with carrier.

22. the shaping thing in the claim 20, wherein acid vitamin and aspartame are made variable grain respectively.

23. prepare a kind of method of the thing that is shaped, contain a kind of physiologically active ingredient slaine, aspartame and a kind of water-soluble sugar of tool bitterness in this shaping thing.

24. cover the method for physiologically active ingredient slaine bitterness, be in the physiologically active ingredient slaine, to add aspartame and a kind of water-soluble sugar.