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WO2005029980A1 - Composition ou l'odeur et le gout desagreable des cysteines sont attenues - Google Patents

Composition ou l'odeur et le gout desagreable des cysteines sont attenues Download PDF

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Publication number
WO2005029980A1
WO2005029980A1 PCT/JP2004/012364 JP2004012364W WO2005029980A1 WO 2005029980 A1 WO2005029980 A1 WO 2005029980A1 JP 2004012364 W JP2004012364 W JP 2004012364W WO 2005029980 A1 WO2005029980 A1 WO 2005029980A1
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Prior art keywords
cysteines
water
composition
weight
cysteine
Prior art date
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Ceased
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PCT/JP2004/012364
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English (en)
Japanese (ja)
Inventor
Shigeki Sawamura
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Kobayashi Pharmaceutical Co Ltd
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Kobayashi Pharmaceutical Co Ltd
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Publication of WO2005029980A1 publication Critical patent/WO2005029980A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes

Definitions

  • composition with reduced unpleasant odor or taste Composition with reduced unpleasant odor or taste
  • the present invention relates to a composition in which the unpleasant odor or taste of cysteines is reduced, and a method of reducing the unpleasant odor or taste of cysteines.
  • cysteines are used as active ingredients in various compositions for external or oral administration.
  • cysteines have an unpleasant odor or taste, which is thought to be due to SH groups in the cysteine molecules.
  • the odor is peculiar to cysteines and its masking is important.
  • Dragees are commonly used as oral medicines containing cysteines. In other dosage forms such as granules and fine granules, it is not enough to reduce the unpleasant odor or taste of cysteines. The development of other internal medicines did not progress.
  • Patent Document 1 a method of applying a film made of a water-soluble polymer to a drug having an unpleasant taste (see Patent Document 1), forming a drug nucleus, A method of forming a film on the outer sheath of the nucleus (see Patent Document 2) and the like are known, and these methods have a problem that the production process is diversified and the production becomes extremely difficult.
  • Patent Document 3 A method of coexisting a sweetener (see Patent Document 3) is known, but there is a problem that its reducing effect is not sufficient.
  • composition prepared by mixing a water-swellable substance with a drug at a ratio of 30% by weight or more is It is known that by wet granulation, an orally-pharmaceutical preparation with a pleasant feeling in which the taste of an unpleasant drug is masked can be obtained (see Patent Document 4).
  • this technique is mainly aimed at masking the bitter taste of drugs, and not only describes cysteines, but also masks odors, especially the unpleasant sulfur odor characteristic of cysteines. No mention of Sking.
  • the amount of the water-swellable substance in the composition is as large as 30% by weight or more, it is difficult to adjust the amount of water to be added in the production process (for example, to increase the viscosity of the composition), and the granulation There were problems such as worsening.
  • Patent Document 1 JP-A-5-201855
  • Patent Document 2 Japanese Patent No. 3317444
  • Patent Document 3 Japanese Patent Publication No. 4-58305
  • Patent Document 4 JP-A-9-1208458
  • the present inventor has conducted intensive studies in view of the above-mentioned problems of the prior art, and as a result, by adding a water-swellable substance to an oral composition containing a cysteine, the cysteine was obtained. It has been found that unpleasant odor or taste, particularly unpleasant odor peculiar to cysteines, can be reduced, and the present invention has been completed.
  • the present invention provides cysteine-containing compositions listed in the following paragraphs 11-11.
  • Item 1 A composition comprising a cysteine and a water-swellable substance, wherein the unpleasant odor or taste of the cysteine is reduced.
  • the water-swellable substance is hydroxypropylcellulose, low-substituted hydroxypropyl senorelose, hydroxypropinolemethinoresenorelose, crystalline senorelose, canolemelose and Item 2.
  • Item 3 The composition according to Item 1 or 2, wherein the amount of the water-swellable substance is at least 0.5 times the amount of the cysteines by weight.
  • Item 4 The composition according to any one of Items 1 to 3, wherein the amount of the water-swellable substance is at least 1 times the amount of the cysteines by weight.
  • Item 5 The composition according to any one of Items 1 to 4, wherein the amount of the water-swellable substance is at least 1.5 times the amount of the cysteines by weight.
  • Item 6 The composition according to any one of Items 1 to 5, further comprising at least one selected from the group consisting of sour agents and sweeteners.
  • Item 7 The composition according to item 6, wherein the sour agent is at least one selected from the group consisting of ascorbic acid, derivatives thereof, and salts thereof.
  • Item 8 The composition according to Item 6 or 7, wherein the sweetener is at least one selected from the group consisting of aspartame, saccharin, sodium saccharin, erythritol, xylitolone, mannitol, sorbitol, maltitol, trehalose and stevia. object.
  • Item 9 The composition according to any one of Items 1 to 8, which is a solid.
  • Item 10 The composition according to item 9, wherein the composition has a form of a granule, a fine granule or a powder.
  • Item 11 The composition according to any one of Items 1 to 10, wherein the amount of the water-swellable substance is 0.005 to 20% by weight relative to 100% by weight of the total amount of the composition.
  • the present invention provides a method for reducing the unpleasant odor or taste of cysteines listed in the following items 12 and 13.
  • Item 12 A method for reducing an unpleasant odor or taste of cysteines, which comprises using a water-swellable substance in combination with cysteines.
  • a method for reducing unpleasant odor or taste of cysteines which comprises using a water-swellable substance and at least one member selected from the group consisting of a sour agent and a sweetener in combination with the cysteines. how to. [0022]
  • the present invention further includes the following method.
  • the water-swellable substance is hydroxypropylcellulose, low-substituted hydroxypropinolecellulose, hydroxypropinolemethinolecellulose, crystalline cellulose, canolemelose and salts thereof, croscarmellose sodium, copolyvidone, polybulpyrrolidone, Item 14.
  • Item 15 The method according to any one of Items 12 to 14, wherein the water-swellable substance is mixed in a ratio of 0.5 part by weight or more to 1 part by weight of cysteine.
  • Item 16 The method according to any one of Items 13 to 15, wherein the sour agent is at least one selected from the group consisting of ascorbic acid, derivatives thereof, and salts thereof.
  • Item 17 The method according to any one of Items 13 to 16, wherein the sweetener is at least one selected from the group consisting of aspartame, saccharin, saccharin sodium, erythritol, xylitolone, mannitol, sonorebitone, manoletitone, trehalose and stevia.
  • the sweetener is at least one selected from the group consisting of aspartame, saccharin, saccharin sodium, erythritol, xylitolone, mannitol, sonorebitone, manoletitone, trehalose and stevia.
  • the present invention also provides a method for producing a composition in which the unpleasant odor or taste of cysteines listed in the following items 18 to 23 is reduced.
  • Item 18 A method for producing a composition having reduced unpleasant odor or taste of cysteines, comprising mixing the cysteines with a water-swellable compound and wet-granulating the resulting composition.
  • Item 19 A method comprising mixing at least one selected from the group consisting of cysteines, a water-swellable substance, and an acidulant and a sweetener, and wet-granulating the obtained composition, A method for producing a composition in which the unpleasant odor or taste of cysteines is reduced.
  • the water-swellable substance is hydroxypropylcellulose, low-substituted hydroxypropinolesenorelose, hydroxypropinolemethinoresenorelose, crystalline senorellose, canolemelose and salts thereof, croscarmellose sodium, copolyvidone, polybulpyrrolidone, Item 20.
  • Item 21 The method according to any one of Items 18 to 20, wherein the water-swellable substance is mixed in a ratio of 0.5 part by weight or more to 1 part by weight of cysteine.
  • Item 22 The method according to any one of Items 19 to 21, wherein the sour agent is at least one selected from the group consisting of ascorbic acid, derivatives thereof, and salts thereof.
  • Item 23 The production method according to Item 19-22, wherein the sweetener is at least one selected from the group consisting of aspartame, saccharin, sodium saccharin, erythritol, xyrithonole, mannitole, sonorebitone, manoletitone, trehalose and stevia. .
  • composition of the present invention is characterized by containing a cysteine and a water-swellable substance.
  • reduction of unpleasant odor or taste peculiar to cysteines may be simply referred to as masking.
  • the target cysteines include cysteine, cysteine derivatives and salts thereof.
  • a cysteine L-cystine is preferred.
  • the cysteine derivative include cysteine methyl ester, cysteine ethyl ester, methyl cysteine, L-ethyl cysteine, N-acetyl cysteine and the like.
  • the salt is not particularly limited as long as it is a pharmaceutically or food hygiene acceptable salt that can be administered orally.
  • cysteine or a hydrochloride of the above cysteine derivative examples thereof include cysteine hydrochloride (particularly, L-cysteine hydrochloride), methinoresistine hydrochloride, and L-ethyl cysteine hydrochloride.
  • cysteines are L-cysteine and cysteine hydrochloride, more preferably L-cysteine.
  • cysteines may be previously coated with a coating agent.
  • a coating agent used in a composition used orally for example, a composition for oral administration, a composition for oral cavity, a food composition, etc.
  • a coating agent used in a composition used orally for example, a composition for oral administration, a composition for oral cavity, a food composition, etc.
  • the amount of the cysteines in the composition of the present invention is not particularly limited. Among the amount 0/0, usually 0. 01 66.666 weight 0/0, preferably ⁇ or 0. 1 40 wt 0/0, more preferably (or 0.1 one 30 wt%, even more preferably 0. 3-20% by weight.
  • the water-swellable substance used in combination with cysteines in the present invention is not particularly limited as long as it has a property of absorbing water and swelling.
  • it is a water-swellable substance having a swelling ratio of 25% or more.
  • the swelling ratio refers to a value calculated by the following method.
  • Examples of the water-swellable substance having a swelling ratio of 25% or more according to the above method include hydroxypropylcellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose (2208, 2906, 2910, etc.), crystal Examples thereof include cellulose, carmellose or a salt thereof (carmellose sodium, carmellose calcium, etc.), croscarmellose sodium, copolyvidone, polybulpyrrolidone, crosporylpyrrolidone, methylcellulose and the like.
  • a water-swellable substance having a relatively high swelling ratio such as carmellose calcium, croscarmellose sodium, or low-substituted hydroxypropylcellulose
  • a water-swellable substance having a relatively low swelling rate such as carmellose, carmellose sodium, crospolybulpyrrolidone, crystalline cellulose, copolyvidone, and hydroxypropylcellulose.
  • polyvinylpyrrolidone and methylcellulose are preferred.
  • These water-swellable substances can be used alone or in combination of two or more.
  • Copolyvidone is a copolymer of 1-vinyl-2-piperidone and vinyl acetate (weight ratio 3: 2).
  • the amount of the water-swellable substance in the composition of the present invention is not particularly limited as long as masking of cysteines is achieved. Usually, it can be determined according to the mixing ratio of cysteines contained in the composition of the present invention. Specifically, it is preferable to mix the water-swellable substance at a ratio of 0.5 times or more by weight with respect to the amount of the cysteines contained in the composition of the present invention. More preferably, the ratio by weight is at least 1 times, more preferably at least 1.5 times, the amount of the cysteine compounded.
  • the proportion of the water-swellable substance in 100% by weight of the composition of the present invention is not particularly limited as long as it is as described above.
  • the composition of the present invention is a composition containing cysteines in the minimum amount of 0.01% by weight, which is the minimum amount
  • the water-swellable substance contained in 100% by weight of the composition is used.
  • the lower limit is 0.005% by weight.
  • the lower limit of the water-swellable substance blended in 100% by weight of the composition is preferably 0.05% by weight, more preferably 0.15% by weight.
  • the upper limit of the proportion of the water-swellable substance in 100% by weight of the composition of the present invention is not particularly limited.
  • the mixing ratio of the water-swellable substance is preferably 20% by weight or less in 100% by weight of the composition of the present invention, and more preferably 15% by weight or less. Is more preferable, and 10% by weight or less is still more preferable.
  • a combination of the upper and lower limits of the mixing ratio of these water-swellable substances is preferable.
  • composition of the present invention contains cysteines and a water-swellable substance as essential components, but is preferably selected from the group consisting of sour agents and sweeteners as optional components. It can also contain at least one substance.
  • the sour agent used in the present invention is not particularly limited as long as it has a sour taste. acidity By blending the agent, the masking effect on cysteines is further improved.
  • sour agents include darcono delta ratatone, carbon dioxide, organic acids, derivatives thereof, and salts thereof.
  • organic acid for example, ascorbic acid, citric acid and malic acid (dHJ gluconic acid), adipic acid, dalconic acid, glacial acetic acid, tartaric acid (DL-, L-), lactic acid, acetic acid, fumaric acid, etc. Can be mentioned.
  • Examples of the organic acid derivative include an ascorbic acid ester such as L-ascorbic acid stearic acid ester and the like, and an alkyl citrate such as triethyl citrate.
  • Examples of the salt of the organic acid or a derivative thereof include a sodium salt of the above organic acid or a derivative thereof (for example, sodium ascorbate, sodium L-ascorbate, sodium citrate, sodium dihydrogen citrate, disodium citrate, d Alkali metal salts such as sodium or sodium fumarate) and potassium salts; alkaline earth metal salts such as calcium salts of the above organic acids or derivatives thereof (for example, calcium ascorbate or calcium citrate). Can be mentioned.
  • sour agents are ascorbic acid, calcium ascorbate, and sodium ascorbate, and more preferred sour agents are ascorbic acid.
  • an acidulant is used in the composition of the present invention, the amount thereof is not particularly limited, but is 0.001 to 99.985% by weight, preferably 20 to 80% by weight, and more preferably 30 to 70% by weight. .
  • the sweetener used in the present invention can be widely used as long as it has sweetness, and is not particularly limited. By adding a sweetener, the masking effect on cysteines is further improved.
  • the sweetener include aspartame, saccharin, sodium saccharin, erythritol, mannitol, sonorebitonore, xylitole, manolethitole, ratatitol, trehalose, stevia, disodium glitinoleitinate, sucralose, licorice, potassium sesame, sesame thaumatin, and sesame thaumatin And can be used irrespective of synthetic sweetener, sugar alcohol, natural sweetener and the like.
  • sweeteners can be used alone or in any combination of two or more.
  • the group consisting of aspartame, saccharin, erythritol, xylitole nore, mannitol, sorbitol, maltitol, trehalose and stevia Force is at least one selected.
  • the amount thereof is not particularly limited as long as the effect of the present invention is exerted. Since sweeteners are also used as excipients, it is difficult to set an upper limit. Usually, 0.001-99.985% by weight, preferably 10-80% by weight, more preferably 20-70% by weight. Exemplify the scope.
  • a sour agent and a sweetener can further enhance the masking effect on cysteines as compared to the case of using a sour agent alone or a sweetener alone.
  • the ratio of the sour agent and the sweetener to be blended in the composition is not particularly limited, but usually 1 part by weight of the sour agent, 0.00001 to 100000 parts by weight of the sweetener, Preferred ⁇ is 0.0001-10000 parts by weight, and more preferred ⁇ 0.001-1000 parts by weight.
  • the composition of the present invention may contain, if necessary, other active ingredients, vitamins, excipients, lubricants, coloring agents, antioxidants (antioxidants), disintegrants, and bulking agents.
  • Agents fresheners, bases, adsorbents, fragrances, disintegration aids, coatings, wetting agents, defoamers, brighteners, corrigents, suspending agents, moisture inhibitors, preservatives, preservatives, solvents , Dissolving agents, synergists, attractants, solvents, softeners, emulsifiers, adhesives, thickeners, foaming agents, dispersants, sugar coatings, pH regulators, stabilizers, surfactants, plasticizers and buffers
  • Ingredients such as a carrier such as an agent and an additive can be added according to the form and purpose of the composition. The addition amount of these components is not particularly limited as long as the masking effect of the cysteines, which is the object of the present invention, is not impaired.
  • the composition of the present invention is particularly useful for applications ingested orally or used in the oral cavity, since reduction of unpleasant odor or taste of cysteines has been achieved.
  • Oral or oral composition can be used as, for example, foods, food additives, pharmaceuticals, quasi-drugs, supplements, health foods, and the like.
  • the composition of the present invention can be used at a ratio such that the daily intake of cysteines is in the range of 0.13000 mg.
  • the preferred dose (dose) is such that the daily intake of cysteines is in the range of 10-200 mg.
  • the composition of the present invention can be in the form of a liquid preparation such as a suspension, and the like. Tablets, dragees, pills, granules, powders, fine granules are available. , Coatings, capsules, etc. Is a solid dosage form.
  • granules, fine granules, and powders dissolve the unpleasant odor and unpleasant odor of cysteines as compared with sugar-coated tablets and tablets because the components contained in the preparation dissolve quickly in the mouth. The taste is easy to spread in the mouth. This makes masking cysteines even more important and valuable in granules, fine granules or powders.
  • composition of the present invention even when it is prepared in the form of granules, fine granules or powder, the unpleasant odor or taste of cysteines can be significantly masked, and as a result, Can reduce discomfort caused by oral administration or intraoral application of.
  • the application of the composition of the present invention to the form of granules, fine granules or powders has a high practical value. In this sense, the composition of the present invention is used in the form of granules, fine granules or powders. Can be suitably used.
  • the production method of the composition of the present invention is not particularly limited.
  • cysteines, a water-swellable substance, and if necessary, a powdery mixture of an acidulant and / or a sweetener may be used, and a binder may be used as another component to form a solid. It may be solid by pressurization, or it may be produced by a usual method for producing a solid preparation.
  • the preferred production method is production by granulation. Therefore, the present invention includes a method for producing a composition having reduced unpleasant odor or taste of cysteines, which comprises mixing cysteines and a water-swellable compound and subjecting the mixture to wet granulation.
  • a method of granulation a general granulation method of a solid preparation can be used, and for example, wet granulation, dry granulation and the like can be used.
  • wet granulation methods such as extrusion, flow, tumbling, crushing, spraying, and stirring can be used.
  • dry granulation in addition to melting, there can be used a method of molding with a roller or a tableting machine, and then molding and granulating with a variety of crushing machines. In either case, after granulation, light pulverization or sieving (granulation, granulation) can be performed to keep the particle diameter range constant.
  • a preferred granulation method is wet granulation.
  • the following method can be exemplified. That is, first, the cysteine, the water-swellable substance, and, if necessary, the sour agent and / or sweetener and other components are mixed with a stirring mixer, and then about 315% by weight of water is added to the mixture. Calorie and mix further. This mixture is granulated by an extrusion granulator, and the granulated product is dried by a fluidized bed dryer. Dry with. Also, if necessary, after drying the granulated material, disperse or disperse a fragrance or the like in a volatile solvent such as ethanol, spray this solvent on the granulated material, and further dry the granulated material. , Fragrance and the like can be provided. In the above granulation process, powders, fine granules, and granules can be produced by changing the amount of water added and the screen diameter of an extrusion granulator.
  • the method for reducing the unpleasant odor or taste of cysteines of the present invention can be carried out by using cysteines in combination with a water-swellable substance.
  • a cysteine By combining a cysteine with a water-swellable substance, an unpleasant odor or taste peculiar to the cysteine, particularly an unpleasant odor peculiar to the cysteine can be reduced.
  • the cysteines of interest here include cysteine, cysteine derivatives and their salts described above in (1), and their salts.
  • it is L-cysteine or hydrochloric cysteine, and more preferably, it is L-cysteine.
  • the water-swellable substance used in the method of the present invention is not particularly limited as long as it has a property of absorbing water and swelling as described above in (1).
  • it is a water-swellable substance having a swelling ratio of 25% or more.
  • hydroxypropylcellulose low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose (2208, 2906, 2910), crystalline cellulose, carmellose or a salt thereof (carmellose sodium, carmellose potion concentrate, etc.), croscarmellose Examples thereof include sodium, copolyvidone, polyvinylpyrrolidone, crospolyvininolepyrrolidone, and methylcellulose, and these can be used alone or in combination of two or more.
  • the water-swellable substance in a proportion of 0.5 part by weight or more based on 1 part by weight of cysteines. More preferably, the ratio is at least 1 part by weight, more preferably at least 1.5 parts by weight, per 1 part by weight of the cysteines.
  • the method of the present invention can be achieved by combining a cysteine with a water-swellable substance, and as described above, by adding at least one of a sour agent and a sweetener, the cysteine is added.
  • a sour agent and a sweetener to improve the masking effect of the water-swellable substance on As a component other than the water-swellable substance, at least one substance selected from the group consisting of sour agents and sweeteners can be used in combination with cysteines.
  • the sour agent used in the present invention is not particularly limited as long as it is a substance having a sour taste, and any of the above-mentioned sour agents can be used without limitation.
  • a sour agent is used in combination with the method of the present invention, the amount of the sour agent used is not particularly limited, but preferably the sour agent is added to 1 part by weight of the total amount of the cysteines and the water-swellable substance.
  • 0001-6666.667 parts by weight more preferably 0.25-5333.333 parts by weight, even more preferably 0.429 4666.667 parts by weight, most preferably 0.510 parts by weight. Ratio.
  • the sweetener used in the method of the present invention is not particularly limited as long as it is a substance having a sweet taste, and those listed above can be used without limitation. Is at least one selected from the group consisting of aspartame, saccharin, erythritol, xylitole, mannitol, sorbitol, maltitol, trehalose and stevia.
  • the amount thereof is not particularly limited as long as the effects of the present invention are exhibited, but is preferably based on 1 part by weight of the total of the cysteines and the water-swellable substance. 0.0001-6666.667 parts by weight, more preferably 0.111-5333.333 parts by weight, even more preferably 0.25-4666.667 parts by weight, and most preferably 0.5-5-5 parts by weight.
  • the ratio is such that
  • the combined use of a sour agent and a sweetener can further improve the masking effect of the water-swellable substance on cysteines as compared with the case of using the sour agent alone or the sweetener alone. it can.
  • the ratio of the acidulant to the sweetener to be mixed in the composition is not particularly limited, but is usually 0.000001 100000 parts by weight of the sweetener per 1 part by weight of the acidulant. More preferably, the ratio is 0.0001 to 10,000 parts by weight, and more preferably, the ratio is 0.001 to 1000 parts by weight.
  • cysteines are combined with a water-swellable substance, and if necessary, an acidulant or Z and a sweetener are combined therewith to form tablets, sugar coatings, pills, and the like.
  • solid dosage forms such as granules, powders, fine granules, coated tablets, capsules, etc. It is preferable to manufacture them. Further preferred formulations are in the form of granules, fine granules or powders.
  • Example 1 Masking action of hydroxypropylcellulose
  • Hydroxypropylcellulose which has the lowest swelling property (hereinafter sometimes referred to as HPC), is mixed with L-cysteine in the amount shown in Table 2, added with an appropriate amount of water, and kneaded in a mortar.
  • Granules were produced by passing through a mesh of 560 ⁇ m and openings of 1000 ⁇ m.
  • the “HPC addition ratio” in Table 2 is a value that shows the mixing ratio of HPC to the mixing amount of L-cystine (1 part by weight) as a weight ratio.
  • the granules were placed on the tongue of the test subjects (10), and the immediate odor and taste were evaluated on a 5-point scale. The amount of granules used for the subjects was such that L-cystine would be 50 mg per person.
  • Table 3 The results are shown in Table 3
  • Example 2 Masking action of low-substituted hydroxypropylcellulose
  • a low-substituted hydroxypropylcellulose having a relatively high swelling ratio (hereinafter referred to as LHPC having a power S) 7.5 g was mixed with 5 g of L-cysteine (the proportion of HPC added to 1 part by weight of cysteine (weight ratio); 1.5), A granulated product was produced and evaluated in the same manner as in Example 1. The results are shown in Table 4.

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  • Pulmonology (AREA)
  • Obesity (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Mycology (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Epidemiology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention concerne une composition dans laquelle on a atténué l'odeur ou le goût désagréable caractéristique des cystéines en associant aux cystéines une substance gonflant dans l'eau. L'invention concerne également un procédé permettant d'atténuer les l'odeur et le goût désagréable des cystéines en associant aux cystéines une substance gonflant dans l'eau. L'effet d'atténuation peut être encore renforcé en ajoutant un acidifiant ou un édulcorant.
PCT/JP2004/012364 2003-09-26 2004-08-27 Composition ou l'odeur et le gout desagreable des cysteines sont attenues Ceased WO2005029980A1 (fr)

Applications Claiming Priority (2)

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JP2003336369A JP3774814B2 (ja) 2003-09-26 2003-09-26 システイン類の不快な臭気又は味が軽減された組成物
JP2003-336369 2003-09-26

Publications (1)

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WO2005029980A1 true WO2005029980A1 (fr) 2005-04-07

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PCT/JP2004/012364 Ceased WO2005029980A1 (fr) 2003-09-26 2004-08-27 Composition ou l'odeur et le gout desagreable des cysteines sont attenues

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JP (1) JP3774814B2 (fr)
WO (1) WO2005029980A1 (fr)

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JP4766941B2 (ja) * 2005-07-14 2011-09-07 小林製薬株式会社 システイン類の不快な臭気又は味が軽減された組成物
JP2007031285A (ja) * 2005-07-22 2007-02-08 Aska Pharmaceutical Co Ltd 苦味が軽減したエピナスチン含有安定化製剤
JP2008127350A (ja) * 2006-11-22 2008-06-05 Ss Pharmaceut Co Ltd 臭いを防止した固形組成物
JP5676834B2 (ja) * 2006-11-29 2015-02-25 エスエス製薬株式会社 消化管への刺激性を減少した経口固形組成物
JP5605805B2 (ja) * 2008-12-25 2014-10-15 共和薬品工業株式会社 ドネペジル経口製剤
JP2012207038A (ja) * 2012-07-20 2012-10-25 Ssp Co Ltd 消化管への刺激性を減少した経口固形組成物
JP2014055187A (ja) * 2013-12-25 2014-03-27 Ss Pharmaceut Co Ltd 消化管への刺激性を減少した経口固形組成物
JP2015199720A (ja) * 2014-03-31 2015-11-12 富山化学工業株式会社 セフテラムピボキシルを含む粒状固形製剤
JP6799795B2 (ja) * 2015-08-21 2020-12-16 大正製薬株式会社 経口組成物
AU2020224843B2 (en) * 2019-02-20 2025-11-13 Suntory Holdings Limited Protein-containing oral composition and method for improving flavor of protein-containing oral composition

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010154769A (ja) * 2008-12-26 2010-07-15 Asahi Breweries Ltd ポリフェノール含有顆粒またはポリフェノール含有チュアブル錠剤およびその製造方法

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