WO2011049093A1 - Comprimé pelliculé dont l'altération de la couleur et l'odeur sont supprimées - Google Patents

Comprimé pelliculé dont l'altération de la couleur et l'odeur sont supprimées Download PDF

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WO2011049093A1
WO2011049093A1 PCT/JP2010/068398 JP2010068398W WO2011049093A1 WO 2011049093 A1 WO2011049093 A1 WO 2011049093A1 JP 2010068398 W JP2010068398 W JP 2010068398W WO 2011049093 A1 WO2011049093 A1 WO 2011049093A1
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film
tablet
discoloration
coating
thickness
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PCT/JP2010/068398
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English (en)
Japanese (ja)
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剛士 松下
裕介 望月
英一 真船
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第一三共ヘルスケア
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Priority to KR1020127006557A priority Critical patent/KR101670693B1/ko
Priority to CN201080047369.8A priority patent/CN102573835B/zh
Priority to JP2011537266A priority patent/JP5694177B2/ja
Publication of WO2011049093A1 publication Critical patent/WO2011049093A1/fr

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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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • 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
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0216—Solid or semisolid forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8129—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers or esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers, e.g. polyvinylmethylether
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to a film-coated tablet containing tranexamic acid, ascorbic acid and L-cysteine, which hardly causes discoloration of the preparation and suppresses the odor generated from the preparation.
  • Tranexamic acid has anti-bleeding, anti-allergy, anti-inflammatory effects, etc. as an antiplasmin agent, is widely used as a medical drug, and is also included in OTC drugs.
  • tranexamic acid was administered to a patient with chronic urticaria, tranexamic acid was prescribed for the treatment of melasma after it was reported that it had disappeared. (For example, see Non-Patent Document 1).
  • Ascorbic acid has long been known to suppress pigmentation by suppressing the production of melanin pigments and by degrading the accumulated melanin pigments.
  • pigmentation due to stains, freckles, sunburns and rashes has been observed (see Non-Patent Document 2).
  • a pigmentation treatment preparation containing tranexamic acid and ascorbic acid has been disclosed, and it has been reported that the improvement degree of pigmentation is superior to the case where tranexamic acid alone or ascorbic acid alone is administered ( Patent Document 1).
  • a whitening composition containing tranexamic acid, ascorbic acid and L-cysteine is disclosed, and it has been found that pigmentation is further suppressed than the combined use of tranexamic acid and ascorbic acid (see Patent Document 2).
  • a solid preparation containing L-cysteine has a strong unpleasant odor of cysteine itself and is difficult to take as it is.
  • a general method for masking an unpleasant odor that is, a method of applying a film coating based on a water-soluble polymer such as hydroxypropylcellulose, hydroxypropylmethylcellulose (hypromellose), or polyvinylpyrrolidone to a solid preparation has a cysteine odor. It could not be prevented, and it was prevented by applying sugar coating.
  • the sugar coating process has drawbacks such as taking a long time, increasing the formulation, and affecting the stability and appearance of the active ingredient (see Patent Document 3 above).
  • the present inventors when actually producing a tablet containing tranexamic acid, ascorbic acid and L-cysteine disclosed in Patent Document 2, for long-term storage (accelerated test at a temperature of 40 ° C. and a relative humidity of 75%). As a result, it was newly found that the color gradually changed (red), and a coating having a problem of generating a cysteine odor was also confirmed.
  • Polyvinyl alcohol copolymer is a copolymer of polyvinyl alcohol and a polymerizable vinyl monomer, but it is used as a de-gelatin capsule material due to the bovine spongiform encephalopathy (BSE) problem.
  • BSE bovine spongiform encephalopathy
  • Patent Document 6 As pharmaceutical uses other than capsules of PVA copolymer, use as a coating agent for tablets or granules (Patent Document 6) and a binder for pharmaceutical preparations (Patent Document 7) is disclosed.
  • An object of the present invention is to provide a solid preparation for internal use that is superior in stability and has little discoloration (red discoloration) or odor generation in tablets containing tranexamic acid, ascorbic acid, and L-cysteine. is there.
  • a partially saponified polyvinyl alcohol or polyvinyl alcohol copolymer is used for film coating, it adheres between tablets during drying due to the strong adhesion resulting from the physical properties of the partially saponified polyvinyl alcohol and polyvinyl alcohol copolymer. There was a problem that was likely to occur.
  • discoloration red discoloration
  • discoloration of the uncoated tablet internal
  • discoloration of the uncoated tablet internal
  • it is possible to produce a film coating agent in which adhesion between tablets hardly occurs even when the drying time is shortened, and the production process time is short.
  • 1 shows a cross-sectional view of a film-coated tablet of the present invention.
  • 1 diameter (tablet diameter)
  • 2 radius of curvature.
  • the R plane indicates the upper or lower surface of the tablet
  • the O plane indicates the band portion.
  • 1 shows a cross-sectional view of a film-coated tablet of the present invention.
  • 1 diameter (tablet diameter)
  • 3 crown height.
  • the R plane indicates the upper or lower surface of the tablet, and the O plane indicates the band portion.
  • L-cysteine and “polyvinyl alcohol partial saponified product” are listed in, for example, Pharmaceutical Additive Standard 2003.
  • the “polyvinyl alcohol copolymer” can be produced according to the method described in WO2005 / 19286 and WO2002 / 17848, and is a partially saponified polyvinyl alcohol having an average degree of polymerization of 100 to 2000 and at least one polymerizable vinyl monomer. Is a copolymer obtained by copolymerizing the polymer with a weight ratio of 6: 4 to 9: 1, and the viscosity of a 2 wt% solution of the copolymer at 20 ° C. is 10 to 300 mPa ⁇ s. It is an alcohol copolymer.
  • a partially saponified polyvinyl alcohol having an average degree of polymerization of 150 to 1000 and at least one “polymerizable vinyl monomer” are preferably copolymerized in a weight ratio of 6: 4 to 9: 1.
  • acrylic acid methacrylic acid, macrogol and the like are preferable.
  • a copolymer of polyvinyl alcohol and polyethylene glycol (macrogol) is also preferable as the polyvinyl alcohol copolymer used in the present invention.
  • the polyvinyl alcohol copolymer used in the present invention is commercially available, for example, under the trade name Povacoat (Nisshin Kasei), the trade name Kollicoat IR (BASF), etc., and can be easily obtained.
  • the content ratios of tranexamic acid, ascorbic acid, L-cysteine and polyvinyl alcohol copolymer or polyvinyl alcohol partial saponified product used in the present invention are 0.01 to 10 wt.
  • the shape of the tablet of the present invention is not particularly limited. For example, when viewed from above, it is usually a circle, an ellipse, a so-called caplet shape, a rhombus, or the like, and preferably a circle.
  • the cross section of the tablet of the present invention comprises an R surface (upper surface or lower surface) and an O surface (side surface or band portion).
  • the “diameter” is the length from one O plane to the other O plane in the cross-sectional view (1 in FIG. 1).
  • the “curvature radius” is the radius of curvature of the R surface (2 in FIG. 1).
  • an arithmetically averaged radius of curvature can be used.
  • “Spherical crown height” is the maximum value (3) of the length from the top of the O plane in FIG. 2 to the R plane when the line is drawn (1). The same applies when the shape of the tablet is not circular.
  • the “film coating thickness” is the thickness of the O-side film coating.
  • the “thickness / diameter” is the thickness of the uncoated tablet (the longest distance from one R surface to the other R surface in the cross-sectional view) / diameter.
  • “Uncoated tablet” refers to a tablet before film coating.
  • the “spherical crown height / diameter” is a value obtained by dividing the above-mentioned “spherical crown height” by the above-mentioned “diameter”.
  • the thickness of the film coating is preferably 60 ⁇ m or more and 400 ⁇ m or less, and more preferably 70 ⁇ m or more and 300 ⁇ m or less.
  • the “thickness / diameter” is large, a thick film coating can be applied with a small film coating amount.
  • the value of “thickness / diameter” is usually 0.5 or more, preferably 0.60 or more and 1. 0 or less, and more preferably 0.70 or more and 0.9 or less.
  • the thickness of the film coating is the same, discoloration inside the tablet can be suppressed as the tablet having a larger value of “crown height / diameter”.
  • the value of “crown height / diameter” is preferably 0.15 or more, and more preferably 0. .18 or more.
  • the film-coated tablet of the present invention is blended with tranexamic acid, ascorbic acid and L-cysteine and other medicinal ingredients as required, and further added with additives as necessary, and granulated by dividing granules as necessary. After performing tableting and manufacturing an uncoated tablet, it can manufacture by performing film coating.
  • Test Example 1 Comparative test of contact surface (interface) between tablet and film coating
  • Preparation of tablet (1) Preparation of plain tablet 1
  • a granules 2403.8 g of tranexamic acid, 769.2 g of L-cysteine, 118.6 g of calcium pantothenate, 19.2 g of pyridoxine hydrochloride, appropriate amount of crystalline cellulose in a fluid bed granulator Were added and mixed, and a hypromellose aqueous solution was sprayed as a binder to prepare a granulated powder to obtain A granules.
  • B granule 961.5 g of ascorbic acid and a suitable amount of crystalline cellulose were charged into a fluid bed granulator and mixed, and a hypromellose aqueous solution was sprayed as a binder to prepare a granulated powder, which was designated as B granule.
  • Uncoated tablet 1 To 3651.3 g of granulated granules in which A granules and B granules are mixed, 205.1 g of crystalline cellulose, 102.6 g of croscarmellose sodium, and 41.0 g of magnesium stearate are added and mixed, and the diameter is 9.5 mm.
  • An uncoated tablet 1 having a mass of 390 mg and a thickness of 5.6 mm was tableted with a two-stage R-face punch having a radius of curvature of 11.0 mm and 3.8 mm.
  • (2) Preparation of uncoated tablet 2 A granules: 2403.8 g of tranexamic acid, 118.6 g of calcium pantothenate, and appropriate amounts of crystalline cellulose are added to and mixed in a fluidized bed granulator, and a hypromellose aqueous solution is sprayed as a binder to form a granulated powder. To prepare A granules.
  • B granule 961.5 g of ascorbic acid, 769.2 g of L-cysteine, 19.2 g of pyridoxine hydrochloride and appropriate amount of crystalline cellulose are added to and mixed in a fluidized bed granulator, and a hypromellose aqueous solution is sprayed as a binder to form a granulated powder.
  • a hypromellose aqueous solution is sprayed as a binder to form a granulated powder.
  • Uncoated tablet 2 To 3651.3 g of granulated granule mixed with A granule and B granule, 205.1 g of crystalline cellulose, 102.6 g of croscarmellose sodium and 41.0 g of magnesium stearate were added and mixed, and the diameter was 9.5 mm An uncoated tablet 2 having a tablet weight of 390 mg and a thickness of 5.6 mm was tableted with a two-stage R-face punch having a radius of curvature of 11.0 mm and 3.8 mm.
  • B granule 255.5 g of ascorbic acid, 204.4 g of L-cysteine, 10.2 g of pyridoxine hydrochloride and a suitable amount of crystalline cellulose are added to and mixed in a fluid bed granulator, and an aqueous hypromellose solution is sprayed to prepare a granulated powder. Granules were used.
  • Uncoated tablet 3 688.0 g of granulated granule mixed with A granule and B granule, 77.7 g of crystalline cellulose, 22.3 g of croscarmellose sodium, 12.0 g of magnesium stearate, 9.5 mm diameter mortar, curvature
  • An uncoated tablet 3 having a tablet weight of 350 mg and a thickness of 5.6 was tableted with an R-faced punch having a radius of 7.6 mm.
  • Comparative Example 19.5 g of hydroxypropylmethylcellulose (hypromellose) and 3.0 g of talc were dispersed and dissolved in 240 g of purified water to obtain a coating solution.
  • Uncoated tablet 1 (250 g, about 640 tablets) was filled in a coating pan (High coater mini, Freund Sangyo), and the coating solution was sprayed to 410 mg per tablet to obtain film-coated tablets.
  • Comparative Example 2 22.5 g of a film coating base (trade name: Opadry II) containing a polyvinyl alcohol part saponified product was dispersed and dissolved in 240 g of purified water to obtain a coating solution.
  • Uncoated tablet 1 (250 g, about 640 tablets) was filled in the coating pan, and the coating solution was sprayed to 410 mg per tablet to obtain film-coated tablets.
  • a film coating base (trade name: Opadry AMB) 22.5 g containing a saponified product of polyvinyl alcohol was dispersed and dissolved in 240 g of purified water to obtain a coating solution.
  • Uncoated tablet 1 (250 g, about 640 tablets) was filled in the coating pan, and the coating solution was sprayed to 410 mg per tablet to obtain film-coated tablets.
  • Comparative Example 4 19.5 g of hydroxypropylmethylcellulose (hypromellose), 1.0 g of carmellose sodium and 2.0 g of talc were dispersed and dissolved in 240 g of purified water to obtain a coating solution.
  • Uncoated tablet 1 (250 g, about 640 tablets) was filled in a coating pan, and the coating solution was sprayed to 410 mg per tablet to obtain film-coated tablets.
  • Comparative Example 5 Using the uncoated tablet 2, a film-coated tablet was obtained in the same manner as in Comparative Example 1.
  • Comparative Example 6 Using the uncoated tablet 2, a film-coated tablet was obtained in the same manner as in Comparative Example 2.
  • Comparative Example 7 Using the uncoated tablet 2, a film-coated tablet was obtained in the same manner as in Comparative Example 3.
  • Example 9 Using the uncoated tablet 3, a film-coated tablet was obtained in the same manner as in Comparative Example 1. (Comparative Example 10) Using the uncoated tablet 3, a film-coated tablet was obtained in the same manner as in Comparative Example 2.
  • Example 1 19.5 g of polyvinyl alcohol copolymer (trade name Povacoat) and 3.0 g of talc were dispersed and dissolved in 240 g of purified water to obtain a coating solution. Uncoated tablet 1 (250 g, about 640 tablets) was filled in the coating pan, and the coating solution was sprayed to 408 mg per tablet to obtain film-coated tablets.
  • Example 2 Using the uncoated tablet 2, a film-coated tablet was obtained in the same manner as in Example 1. (Example 3) Using the uncoated tablet 3, a film-coated tablet was obtained in the same manner as in Example 1. 2.
  • Test Method 60 samples of Comparative Example 1-10 and Example 1-3 were filled and sealed in a glass bottle (6k standard bottle). Tablets were divided after storage at 50 ° C. for 2 days, and the discoloration (red discoloration) at the interface of the tablets and the odor immediately after opening were evaluated.
  • (1) Evaluation criteria [Visual evaluation (coloring)] Evaluation was made in four stages: A: no discoloration, B: slight discoloration, C: discoloration, D: significant discoloration.
  • B granule 961.5 g of ascorbic acid and a suitable amount of crystalline cellulose were charged into a fluid bed granulator and mixed, and a hypromellose aqueous solution was sprayed as a binder to prepare a granulated powder, which was designated as B granule.
  • Tableting powder a Into a granulated granule 3651.3 g in which A granule and B granule are mixed, 205.1 g of crystalline cellulose, 102.6 g of croscarmellose sodium and 41.0 g of magnesium stearate are added and mixed to form a tableting powder. a was obtained.
  • B granule 961.5 g of ascorbic acid, 769.2 g of L-cysteine, 19.2 g of pyridoxine hydrochloride and appropriate amount of crystalline cellulose are added to and mixed in a fluidized bed granulator, and a hypromellose aqueous solution is sprayed as a binder to form a granulated powder.
  • Tableting powder b To 3651.3 g of granulated granule mixed with A granule and B granule, 205.1 g of crystalline cellulose, 102.6 g of croscarmellose sodium and 41.0 g of magnesium stearate were added and mixed, and tableting powder b Got.
  • (C) Tableting powder c A granule: 432.5 g of tranexamic acid, 16.0 g of calcium pantothenate, 17.3 g of nicotinic acid amide and appropriate amounts of crystalline cellulose are added to and mixed in a fluidized bed granulator, and an aqueous hypromellose solution is sprayed to prepare a granulated powder. Granules were used.
  • B granule 255.5 g of ascorbic acid, 204.4 g of L-cysteine, 10.2 g of pyridoxine hydrochloride and a suitable amount of crystalline cellulose are added to and mixed in a fluid bed granulator, and an aqueous hypromellose solution is sprayed to prepare a granulated powder. Granules were used.
  • Tableting powder c Blended granule granule (744.9 g) with A granule and B granule mixed with 12.8 g of tocopherol succinate, 202.1 g of crystalline cellulose, 25.0 g of croscarmellose sodium, and 15.2 g of magnesium stearate Tableting powder c was obtained.
  • B granule 255.5 g of ascorbic acid, 204.4 g of L-cysteine, 10.2 g of pyridoxine hydrochloride and a suitable amount of crystalline cellulose are added to and mixed in a fluid bed granulator, and an aqueous hypromellose solution is sprayed to prepare a granulated powder. Granules were used.
  • Tableting powder c Tableting powder d was obtained by mixing 243.9 g of crystalline cellulose, 32.5 g of croscarmellose sodium, and 19.7 g of magnesium stearate with 1003.9 g of granulated granules in which A granules and B granules were mixed. .
  • (2) Preparation of uncoated tablet Using the tableting powder ad, tableting was performed with a rotary tableting machine to prepare an uncoated tablet area of the following standards.
  • Uncoated tablet uncoated tablet having a diameter of 9.5 mm, a radius of curvature of 11.4 mm, and a mass of 390 mg (at
  • Polyvinyl alcohol part saponified film coating solution 1 100 g of a film coating base (trade name Opadry II) containing polyvinyl alcohol partly saponified product was dispersed and dissolved in 750 g of purified water to obtain a coating solution (hereinafter sometimes abbreviated as “partial suspension 1”).
  • the thickness (O surface) of the film coating was 45.1 ⁇ m.
  • the uncoated tablet i prepared using the tableting powder b was filled in the above-mentioned coating pan, and coated with polyvinyl alcohol partially saponified film coating solution 1 (partial suspension 1) to 416 mg per tablet. At this time, the thickness (O surface) of the film coating was 75.1 ⁇ m.
  • the uncoated tablet i prepared using the tableting powder b was filled in the coating pan, and coated with polyvinyl alcohol partly saponified film coating solution 2 (partial suspension 2) to 416 mg per tablet. At this time, the thickness (O surface) of the film coating was 72.2 ⁇ m.
  • Example 2-6 An uncoated tablet a was prepared using the tableting powder c.
  • Comparative Example 2-7 An uncoated tablet was prepared using the tableting powder d.
  • Example 2-1 The uncoated tablet prepared using the tableting powder b was filled in the coating pan and sprayed and coated with a copolymer up to 416 mg per tablet. At this time, the thickness (O surface) of the film coating was 64.7 ⁇ m.
  • Example 2-2 The uncoated tablet prepared using the tableting powder b was filled in the coating pan and sprayed and coated with a copolymer up to 427 mg per tablet. At this time, the thickness (O surface) of the film coating was 96.4 ⁇ m.
  • Example 2-3 The uncoated tablet i prepared using the tableting powder b was filled in the coating pan, and sprayed and coated with a copolymer up to 405 mg per tablet. At this time, the thickness (O surface) of the film coating was 61.6 ⁇ m.
  • Example 2-4 The uncoated tablet i prepared using the tableting powder b was filled in the coating pan and sprayed and coated with a copolymer up to 416 mg per tablet. At this time, the thickness (O surface) of the film coating was 71.4 ⁇ m.
  • Example 2-5) The uncoated tablet i prepared using the tableting powder b was filled in the coating pan and sprayed and coated with a copolymer up to 427 mg per tablet.
  • the thickness (O surface) of the film coating was 119.5 ⁇ m.
  • Example 2-6 The uncoated tablet prepared using the tableting powder b was filled in the coating pan, and sprayed and coated with a copolymer up to 413 mg per tablet. The thickness of the film coating at this time was 90.0 ⁇ m.
  • Example 2-7 The uncoated tablet prepared using the tableting powder b was filled in the coating pan and sprayed and coated with a copolymer up to 427 mg per tablet. At this time, the thickness of the film coating was 86.1 ⁇ m.
  • Example 2-8 The uncoated tablet prepared using the tableting powder c was filled in the coating pan, and sprayed and coated with a copolymer up to 425 mg per tablet. At this time, the thickness of the film coating was 94.1 ⁇ m.
  • Example 2-9 The uncoated tablet prepared using the tableting powder d was filled in the coating pan, and sprayed and coated with a copolymer up to 425 mg per tablet. The thickness of the film coating at this time was 94.4 ⁇ m. 3. Test Methods 120 samples of Comparative Examples 2-1 to 2-7 and Examples 2-1 to 2-9 were filled into a glass bottle (6k standard bottle) and sealed. After storage at 60 ° C. for 1 week and at 50 ° C.

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Abstract

L'invention concerne un comprimé contenant de l'acide tranexamique, de l'acide ascorbique et de la L-cystéine, qui a une excellente stabilité et dont l'altération de la couleur et l'odeur désagréable ont été supprimées. De façon spécifique, l'invention porte sur un comprimé pelliculé que l'on a obtenu en dotant un comprimé, qui contient de l'acide tranexamique, de l'acide ascorbique et de la L-cystéine, d'une pellicule d'enrobage qui contient un copolymère d'alcool polyvinylique.
PCT/JP2010/068398 2009-10-20 2010-10-19 Comprimé pelliculé dont l'altération de la couleur et l'odeur sont supprimées WO2011049093A1 (fr)

Priority Applications (3)

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KR1020127006557A KR101670693B1 (ko) 2009-10-20 2010-10-19 변색 및 냄새가 억제된 필름 코팅정
CN201080047369.8A CN102573835B (zh) 2009-10-20 2010-10-19 变色和气味得到抑制的膜包衣片
JP2011537266A JP5694177B2 (ja) 2009-10-20 2010-10-19 変色及び臭いが抑制されたフィルムコーティング錠

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JP2009-241276 2009-10-20
JP2009241276 2009-10-20

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WO2011049093A1 true WO2011049093A1 (fr) 2011-04-28

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PCT/JP2010/068398 WO2011049093A1 (fr) 2009-10-20 2010-10-19 Comprimé pelliculé dont l'altération de la couleur et l'odeur sont supprimées

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JP (1) JP5694177B2 (fr)
KR (1) KR101670693B1 (fr)
CN (1) CN102573835B (fr)
TW (1) TWI488622B (fr)
WO (1) WO2011049093A1 (fr)

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JP2013049671A (ja) * 2011-08-04 2013-03-14 Fancl Corp アスコルビン酸製剤
WO2022196818A1 (fr) 2021-03-19 2022-09-22 Ssp Co., Ltd. Préparation pharmaceutique solide revêtue
WO2023176783A1 (fr) * 2022-03-14 2023-09-21 第一三共ヘルスケア株式会社 Composition solide

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RU2542280C1 (ru) * 2013-11-19 2015-02-20 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Тверской государственный университет" Способ получения пленок с наноструктурированным серебром

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JP2005314403A (ja) * 2004-03-31 2005-11-10 Dai Ichi Seiyaku Co Ltd 新規美白用組成物
JP2007022938A (ja) * 2005-07-13 2007-02-01 Shionogi & Co Ltd 退色を抑制した製剤
WO2007145191A1 (fr) * 2006-06-13 2007-12-21 Nippon Shinyaku Co., Ltd. Comprimé enrobé
WO2010029930A1 (fr) * 2008-09-12 2010-03-18 第一三共ヘルスケア株式会社 Préparation médicinale stable dont la modification de couleur est supprimée.

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JP2004217655A (ja) * 2002-12-27 2004-08-05 Dai Ichi Seiyaku Co Ltd 美白用組成物
MXPA05006924A (es) * 2002-12-27 2005-12-12 Daiichi Seiyaku Co Composicion para blanquear la piel.
JP4680061B2 (ja) * 2003-08-20 2011-05-11 塩野義製薬株式会社 新規コーティング組成物
JP4521454B2 (ja) * 2008-06-06 2010-08-11 京都薬品工業株式会社 フィルムコーティング錠剤

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JP2005314403A (ja) * 2004-03-31 2005-11-10 Dai Ichi Seiyaku Co Ltd 新規美白用組成物
JP2007022938A (ja) * 2005-07-13 2007-02-01 Shionogi & Co Ltd 退色を抑制した製剤
WO2007145191A1 (fr) * 2006-06-13 2007-12-21 Nippon Shinyaku Co., Ltd. Comprimé enrobé
WO2010029930A1 (fr) * 2008-09-12 2010-03-18 第一三共ヘルスケア株式会社 Préparation médicinale stable dont la modification de couleur est supprimée.

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013049671A (ja) * 2011-08-04 2013-03-14 Fancl Corp アスコルビン酸製剤
WO2022196818A1 (fr) 2021-03-19 2022-09-22 Ssp Co., Ltd. Préparation pharmaceutique solide revêtue
WO2023176783A1 (fr) * 2022-03-14 2023-09-21 第一三共ヘルスケア株式会社 Composition solide

Also Published As

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KR101670693B1 (ko) 2016-10-31
TW201119639A (en) 2011-06-16
JPWO2011049093A1 (ja) 2013-03-14
CN102573835B (zh) 2017-04-05
CN102573835A (zh) 2012-07-11
JP5694177B2 (ja) 2015-04-01
TWI488622B (zh) 2015-06-21
KR20120086689A (ko) 2012-08-03

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