WO2006090640A1 - Composition de comprimé contenant un acide aminé et procédé de fabrication du comprimé - Google Patents

Composition de comprimé contenant un acide aminé et procédé de fabrication du comprimé Download PDF

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Publication number
WO2006090640A1
WO2006090640A1 PCT/JP2006/302797 JP2006302797W WO2006090640A1 WO 2006090640 A1 WO2006090640 A1 WO 2006090640A1 JP 2006302797 W JP2006302797 W JP 2006302797W WO 2006090640 A1 WO2006090640 A1 WO 2006090640A1
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Prior art keywords
tablet
tableting
amino acid
theanine
tablets
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PCT/JP2006/302797
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English (en)
Japanese (ja)
Inventor
Makoto Ozeki
Nobuyuki Aoi
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Taiyokagaku Co., Ltd.
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Priority to JP2007504685A priority Critical patent/JPWO2006090640A1/ja
Publication of WO2006090640A1 publication Critical patent/WO2006090640A1/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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars

Definitions

  • the present invention relates to a tablet containing an amino acid, particularly an amino acid that passes through the blood-brain barrier as an active ingredient.
  • the present invention relates to a tablet production method in which tableting characteristics are improved by mixing and granulating an amino acid that passes through the blood-brain barrier with an excipient and coating, and a tablet produced by the production method.
  • Amino acids are constituents of proteins, and after being incorporated as a diet, they are used not only as energy metabolism and body constituent materials but also as synthetic materials for various physiologically active substances.
  • amino acids themselves function as information transmitters, and some amino acid modifications and other modifications may be made by peptide synthesis.
  • the brain has a blood-brain barrier, and nutrients are selectively taken up. Some amino acids pass through the blood-brain barrier and others do not. Among these, some amino acids that pass through the blood-brain barrier exhibit various physiological actions in the brain, as will be described later.
  • theanine that passes through the blood-brain barrier via the L system has been reported to exhibit various actions such as regulating the concentration of physiologically active amines in the brain, stabilizing blood pressure, and stimulating sedation.
  • Permissible literature 1 Theanine has been known as a tea extract and is an amino acid contained in green tea. Among them, it has the highest content!
  • the turntable rotation speed is 25 rpm, and the tableting speed efficiency is poor. Furthermore, only 100 tablets were molded. There was a problem to do.
  • Patent Document 1 Japanese Patent Laid-Open No. 2003-267867
  • Non-patent literature 1 Yokogoshi, H., M. Kobayashi, et ai., Effect of tneanine, r-glutamyleth ylamide, on brain monoamines and striatal dopamine release in conscious rats., Neurochem Res, 23 (5) 667-673 , 1998
  • a first object of the present invention is to provide a tablet free from tableting troubles containing, as an active ingredient, one or more amino acids that pass through the blood-brain barrier.
  • the second object of the present invention is to granulate a particle mixture containing an amino acid that passes through the blood-brain barrier to form granules, coat the condyles, and produce coated granules, and the coated granules
  • An object of the present invention is to provide a tablet containing an amino acid that passes through the blood-brain barrier as an active ingredient, which comprises a step of producing a tablet by tableting.
  • the third object of the present invention is to provide a production method that can reduce the molding time without any tableting trouble and can be continuously molded.
  • the present inventor has passed through a specific blood 'brain barrier. Acquired knowledge that the above problems can be solved by granulating the excess amino acids and excipients, coating the granulated granules with a specific coating solution, and molding into tablets.
  • the present invention has been completed.
  • the present invention is particularly effective for improving the tableting characteristics of amino acids that pass through the brain barrier via the L system, particularly L-theanine.
  • the present invention includes the following (1) to (9).
  • a tablet comprising 10% or less of a particle size having an amino acid particle size of 80 m or more according to (1).
  • a tablet wherein the ratio of amino acids contained in the tablet according to (1) is 1% by mass to 40% by mass.
  • a step of producing a coated granule by coating a granule obtained by granulating a particle mixture containing the amino acid described in (1) as an active ingredient with a coating liquid containing a binder component; and A tablet containing an amino acid as an active ingredient, which comprises a step of tableting to produce a tablet.
  • the binder component in the coating solution according to (5) is shellac, mannitol, erythritole, sonorebitonore, xylitonole, trenosylose, ethinoresenorelose, methinoresenorelose, hydroxypropinoresenorelose , Hydroxypropinoremethinorescenellose, strength carboxymethylethyl cellulose, polybulur pyrrolidone, carboxybulu polymer, polybulualcohol, gum arabic, sodium alginate, and gelatin tablet.
  • the amino acid used in the present invention is an amino acid that passes through the blood 'brain barrier.
  • the blood-brain barrier restricts the transfer of blood substances (for example, drugs, toxins, neurotransmitters, etc.) that cause central nervous system function breakdown into the brain, and selectively selects nutrients that serve as energy sources for neural activity. It means a mechanism to transfer to. Just like a barrier between the blood and the brain, it is a mechanism that does not allow the substances in the blood to pass through the brain easily.
  • transport systems for example, L system, A system, and ASC system
  • amino acids transported via the L system include long-chain neutral amino acids such as phalalanin, tyrosine, leucine, isoleucine, norrin, histidine, methionine, threonine, and theanine.
  • amino acids transported via the A system include short-chain neutral amino acids such as alanine, glycine, serine, and thread nin.
  • Amino acids transported via the ASC system include alanine, serine, and cysteine.
  • amino acids transported by other transport systems include taurine, gnoretamic acid, asnoragin, lysine, and anoreginine.
  • Theanine used in the present invention is a glutamic acid derivative contained in tea leaves, which is the main ingredient of the umami of tea and is used as a food additive for the purpose of taste. Specifically, it is also called ⁇ -daltamylethylamide, L-glutamic acid-y-ethylamide and the like.
  • Examples of the production method of theanine used in the present invention include a method of extracting from tea leaves, a method of obtaining theanine by organic synthesis reaction (Chem. Pharm. Bull., 19 (7) 1 301-1307 (1971)) , A method of obtaining theanine by acting glutaminase on a mixture of glutamine and ethylamine (Japanese Patent Publication No.
  • the theanine used in the present invention is a “refined product” having a theanine content of 98% or more, a “crude product” having a theanine content of 50% to 98%, or a “refined product” having a theanine content of 10% to 50%. Misaligned shapes, such as “extraction ex” can also be used.
  • Theanine used in the present invention is highly safe. For example, in an acute toxicity test using mice, no abnormalities are observed in the general state and body weight, etc. in which death occurs after oral administration of 5 gZkg.
  • theanine is known as a umami component of tea, and it is also used as a food additive for flavoring purposes. There is no limit to the amount of addition under the Food Sanitation Law.
  • the particle diameter of amino acids passing through the blood-brain barrier in the present invention is characterized by containing a particle diameter of 80 / zm or more in a ratio of 10% or less, preferably 10 ⁇ m or less.
  • the upper particle size is contained in a proportion of 10% or less of the whole, and more preferably, the particle size of 5 m or more is contained in a proportion of 10% or less of the whole.
  • a particle size distribution measuring device can be used to measure the particle size.
  • a measuring device suitable for the purpose such as a laser diffraction method, a chirality method, a zeta potential method, a particle image analysis method can be used.
  • the measurement range of the particle diameter is that the number of particles is 80 ⁇ m or more (preferably 10 ⁇ m or more, more preferably 5 ⁇ m or more) in all particles as long as the size of 0.5 / ⁇ ⁇ to 500 ⁇ m can be measured. It is sufficient if the ratio can be measured.
  • an appropriate pulverizer such as a hammer mill, a sample mill, a pin mill, or a jet mill can be used.
  • a pulverizer such as a hammer mill, a sample mill, a pin mill, or a jet mill.
  • the proportion of the particle size of 80 m or more is larger than 10%, a cabbage that peels off in a cap shape is observed on the upper side of the tablet when demolding.
  • cabbing can be prevented by setting the ratio of particle diameters of 80 m or more to 10% or less.
  • amino acids that pass through the blood-brain barrier commercially available products can be used as they are for tableting.
  • excipients used for tableting when many large particle sizes are included, it is preferable to use them after pulverization using a pulverizer. That's right.
  • the excipient used in the particle mixture in the present invention is not particularly limited, and those exemplified below can be used.
  • the excipient include sugar alcohols such as D-sorbitol, D-mannitol and xylitol, sugars such as glucose, sucrose, lactose and fructose, crystalline cellulose, carmellose sodium, hydrogen phosphate
  • sugar alcohols such as D-sorbitol, D-mannitol and xylitol
  • sugars such as glucose, sucrose, lactose and fructose
  • crystalline cellulose crystalline cellulose
  • carmellose sodium hydrogen phosphate
  • hydrogen phosphate examples include calcium, wheat starch, rice starch, corn starch, potato starch, dextrin, ⁇ -cyclodextrin, light anhydrous carboxylic acid, titanium oxide, magnesium metasilicate aluminate, tanolec, and kaolin.
  • a lubricant may be added to the particle mixture in the present invention in order to improve tableting characteristics.
  • the lubricant used in the present invention is not particularly limited, but those exemplified below can be used.
  • Preferable examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, beeswax, etc. Is mentioned.
  • the blending amount of the lubricant can be appropriately determined from the characteristics of each lubricant.
  • the proportion of theanine in the particle mixture is preferably 1% by mass to 40% by mass, and more preferably 10% by mass to 30% by mass with respect to the excipient blended in the particle mixture. is there.
  • the theanine content is less than 1% by mass, the theanine content per tablet is decreased, and it is necessary to increase the intake of the tablet.
  • the proportion of theanine is more than 40%, tableting troubles such as cabbage are likely to occur, and it is not suitable for continuous tableting in the production process.
  • the granulation method in the present invention is not particularly limited, and there is a method of adding water or hydrous ethanol to a particle mixture containing theanine, mixing, extruding, and drying.
  • the water content of ethanol is preferably 3% to 30%.
  • each step of adding water-containing ethanol to the particle mixture, mixing, extruding, and drying is performed during granulation.
  • the water content of ethanol is less than 3%, the particle mixture has poor binding properties during granulation. And the tablet tends to disintegrate.
  • the water content of ethanol is higher than 30%, kneading becomes difficult.
  • a fluidized bed dryer or a rolling bed dryer can be used so that the granulated granules do not collapse.
  • the extrusion molding in the present invention can be performed using an extrusion granulator.
  • the diameter of the screen used in the extrusion granulator is preferably 0.2 mm to 4 mm, more preferably 0.5 mm to 2 mm. If the aperture of the screen is smaller than 0.2 mm, the kneaded particle mixture does not permeate the screen, which is not preferable. On the other hand, when the caliber force is larger than mm, the flowability of the raw material charged into the die of the tableting machine at the time of tableting is not preferable.
  • the binder component used in the granule coating solution before tableting one or more of the following exemplified components are selected and used. That is, as the binder component, for example, shellac, man-tol, erythritol, sorbitol, xylitolol, trenorose, ethinoresenorelose, methinoresenorelose, hydroxypropinoresenorelose, hydroxypropinoremethinoresenorose Examples thereof include strong levoxino retinoyl cellulose, polyvinyl pyrrolidone, carboxyvinyl polymer, polyvinyl alcohol, gum arabic, sodium alginate, gelatin and the like.
  • the amount of the binder component used is preferably 0.1% to 20%, more preferably 1% to 10%, and most preferably 2% to 5% with respect to the mass of the granulated granule.
  • a sweetener can be used in combination with the coating solution.
  • it is selected from those exemplified below and used.
  • the sweetener component include aspartame, saccharin, sodium saccharin, glycyrrhizic acid, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizate,
  • An example is acesulfame K.
  • the granule coating method in the tablet production process of the present invention is usually a fluidized bed coating, a rolling layer coating, a film coating, or a centrifugal fluidized coating used for the coating of granules.
  • Various methods such as grains can be applied.
  • Tableting is performed by a method known to those skilled in the art. There is no particular limitation as long as it is a method of making the shape of the tablet above the minimum pressure necessary to maintain the shape of the tablet. Such tableting involves the addition of a lubricant such as magnesium stearate to the above composition, as well as the necessary additional calorie. After blending the agent, it can be carried out using a generally used tableting machine such as a single tableting machine or a rotary tableting machine. The composition can also be made into tablets using an external lubricant tableting machine.
  • the tableting pressure is usually preferably about 25 kgZ ⁇ to about 800 kgZ ⁇ , and most preferably about 50 kgZ ⁇ to about 300 kgZ ⁇ , more preferably about 50 kgZ ⁇ to about 500 kgZ ⁇ .
  • the tablet of the present invention can generally contain a taste-masking agent used in foods and pharmaceuticals.
  • a taste-masking agent used in foods and pharmaceuticals.
  • various flavors can be used. Although not particularly limited, for example, lemon flavor, orange flavor, grapefruit flavor, chocolate flavor, dl-menthol, and 1 menthol.
  • the tablet of the present invention can be used in combination with crude drugs, herbs, amino acids, vitamins, minerals, other foods and pharmaceutical acceptable materials.
  • the herbal medicine is not particularly limited, and examples thereof include power rooster, toki, glaze, peony, and ginseng.
  • the herbs are not particularly limited, but examples include anise, carrot seed, clove, coriander, cypress, cinnamon, juniper, ginger, sweet orange, pine-one dollar, nozinole, notch lily, Bitter Orange, Fennel, Black Pepper, Bay, Peno Mint, Bergamot, Mandarin, Minorella, Lemongrass, Rosemary, Grapefruit, Cedarwood, Citronella, Sage, Thyme, Tea Toe Lee, Violet Leaf, Vanilla, Hyssop, Eucalyptus, Lime, Lemon, Ylang Ylang, Cardamom, Clari Sage, Jasmine, Zeraum, Chamomile, Benoregalia Rose, Rose, Orinokunam, Lavender, Power Mitsuru, Zeranium, Sandalwood Neroli, Verbena, Puchida Down, downy Chi Bar, marjoram, melissa, rosewood, Otogirisou, Saint di Yohn's wort, such as force Wakawa and the like.
  • the vitamin is not particularly limited, but for example, vitamin A, vitamin B, and vitamin
  • Examples include cotinic acid, lipoic acid, pantothenic acid, biotin, ubiquinone, and prostaglandins.
  • derivatives of these vitamins are also included.
  • a mineral For example, calcium, iron, magnesium, copper, zinc, selenium, potassium etc. are mentioned.
  • the tablets exemplified below can be used in combination with those exemplified below.
  • the tableting failure means various failures that occur during tableting, such as cabbing, laminating, stateking, and nodding.
  • “Cabbing” means an obstacle in which a part of the tablet adheres to the upper heel side and the convex part of the tablet peels off in a cap shape during demolding.
  • Laminating means an obstacle that the tablet breaks into layers.
  • “Staging” means an obstacle in which the powder adheres to the wrinkles during tableting, the wrinkles become worse, the surface of the tablets become cloudy or flutters.
  • binding means that the friction between the tablet and the mortar is large, so that the dischargeability of the tablet after tableting deteriorates and a part of the tablet surface adheres to the mortar or roll. Yes. When these tableting obstacles become severe, smooth punching operations cannot be performed.
  • the isolated substance was subjected to an amino acid analyzer (manufactured by Hitachi, Ltd.) and paper chromatography, and compared with a standard substance to confirm that it was L-theanine.
  • hydrolysis of the isolated material with hydrochloric acid or dartaminase produced glutamic acid and ethylamine in a ratio of 1: 1.
  • the isolated substance was hydrolyzed by dartaminase, it was shown that ethylamine was bound to the ⁇ -position of glutamic acid.
  • glutamate dehydrogenase that the glutamate was produced by hydrolysis. As a result, 8.5 g of L-theanine was obtained.
  • L-theanine manufactured by Taiyo Gakken Co., Ltd., trade name: Santheanine
  • Palin manufactured by Ajinomoto Co., Inc.
  • Example 5 Dry flow granulation of a theanine-containing compounding agent
  • Suntheanine 400g Lactose (Megrene Soil) 870g, Guagam Enzyme Decomposition (Sunfiber; Taiyogaku Co., Ltd.) 200g, Crystalline Cellulose (Asahi Kasei Co., Ltd.) 60g, Reduced Maltose Minamata Powder (Towa Kasei Kogyo Co., Ltd.) 400 g, silicon dioxide (manufactured by Shionogi & Co., Ltd.) lg, 400 g of 5% water-containing ethanol are mixed, kneaded and granulated with an extrusion granulator (Daltron) with a screen diameter of 1 mm, and fluidized bed granulation The product was dried at 60 ° C.
  • Daltron extrusion granulator
  • Example 7 Dry flow granulation of pulverized theanine-containing compounding agent
  • the particle size of the commercially available valine was measured with a laser diffraction particle size distribution analyzer (Accumizer 780 series, manufactured by Matec Applied Science). The average particle size was 11.9 ⁇ m, and the particle size was 5 ⁇ m or more. The percentage was 54%.
  • Example 13 Dry flow granulation of pulverized parin-containing compounding agent
  • Example 10 400 g of the ground product of Example 10 and 870 g of lactose (Megretene) are mixed and fluidized-bed granulator (Freund Sangyo Co., Ltd.) is used for fluidized bed granulation and drying while spraying water! ⁇ After sizing with 9 mesh (aperture 1.98 lmm), 1009 g of Norin granulated product was obtained.
  • lactose Meltose
  • the tableting method for preparing the tablets was as follows. Using a rotary tableting machine (CLEANPRESS CORRECT 12HUK, manufactured by Kikusui Seisakusho Co., Ltd.), the tablet was tableted with 9 mm ⁇ , 12R at a turntable rotation speed of 30 rpm to obtain a tablet having a weight of 200 mg.
  • a rotary tableting machine (CLEANPRESS CORRECT 12HUK, manufactured by Kikusui Seisakusho Co., Ltd.)
  • the tablet was tableted with 9 mm ⁇ , 12R at a turntable rotation speed of 30 rpm to obtain a tablet having a weight of 200 mg.
  • the tableting property was evaluated by visual inspection, which is a sensory evaluation for each of the following problems: tableting, laminating, binding, and sticking after molding the tablet by the method described in “1. Tableting Method” above. After observing and expressing the number of corresponding tablets in numbers according to “1. Tableting method” described above, 100 tablets were molded, and the finished tablets were evaluated according to the above “2. Evaluation method”. Table 1 shows the number of tablets where cabbing, laminating, binding, and stateking occurred when 100 tablets were formed.
  • Example 5 dry fluid granulation of santheanine
  • Example 7 pulverized theanine dry fluid granulation
  • Example 6 extruded granulation of santheanine
  • Example Compared with 8 extruded granulated pulverized theanine
  • the tableting characteristics were improved by using pulverized theanine.
  • comparing dry fluid granulation with extruded granulation by comparing Example 5 with Example 6 and comparing Example 7 with Example 8 extrusion granulation is compared with dry fluid granulation.
  • Example 11 (Palin with dry fluidized granulation) and Example 13 (pulverized Parin with dry fluidized granulation), and Example 1 2 (Palin with extruded granulation) and Example 14
  • tableting characteristics were improved by using pulverized norrin.
  • the granulation characteristics according to the water content of ethanol when the granulated theanine was extruded and granulated were compared.
  • 1,500 g of the granulated granulated product is put into a film coating device (Freund Sangyo Co., Ltd.), and the coating agent shellac (manufactured by Gifu Shellac Co., Ltd.), man-tor (manufactured by Kao Co., Ltd.), erythritol (Niken Iseisei) Co., Ltd.), sorbitol (Towa Kasei Kogyo Co., Ltd.), xylitol (Towa Kasei Kogyo Co., Ltd.), trehalose (Hayashibara Shoji Co., Ltd.), ethyl cellulose (Shin-Etsu Chemical Co., Ltd.), methylcellulose (Shin-Etsu Chemical Co., Ltd.) Ltd.), hydroxypropylcellulose (Shin-Etsu Chemical Co., Ltd.), hydroxypropylmethylcellulose (Shin-Etsu Chemical Co., Ltd
  • This coating solution was spray coated so as to be 3% of the granulated product. Even when any coating agent was used, it was possible to produce coated granules by coating the tear granulated product. 970 g of the coated granule was weighed, and 30 g of sucrose fatty acid ester (Mitsubishi Chemical Co., Ltd.) was mixed.
  • Example 15 200 tablets of the coated granule of Example 15 were molded according to “1. Table 4 shows the number of tablets in which tableting, laminating, binding, and stateking occurred. For comparison, the uncoated granulated product was similarly subjected to tableting to produce and evaluate tablets.
  • Example 10 Using the coated tear granulated product described in Example 10, 1000 tablets were molded according to “1. Tableting method” in Comparative Example 1. The completed tablets were evaluated according to “2. Evaluation method” in Comparative Example 1. Table 5 shows the results of counting the total number of tablets that resulted in cabbing, laminating, binding, and stateking when 1000 tablets were formed.
  • Example 10 Using the 2% coated-tea granulated product described in Example 10, the turntable was molded at 10 rpm, 30 rpm and 50 rpm in Comparative Example 1 according to “1. Tableting method”. The completed tablets were evaluated according to “2. Evaluation method” in Comparative Example 1. Table 6 shows the total number of tablets where cabbing, laminating, nodding, and stateking occurred when 500 tablets were formed. For comparison, tablets that were not coated were similarly molded and evaluated.
  • the number of defective tablets accounted for 376, more than 70%, and the number of defective tablets increased as the rotation speed increased. To do it. In particular, at 50 rpm, the number of defective tablets was 77, accounting for over 90%.
  • the number of defective tablets was 34 at 10 rpm, which was 10% or less.
  • the rotational speed was increased to 50 rpm, 84 tablets, or 20% or less, caused tableting failure.
  • a tablet wherein the mean particle size of theanine according to (1) is 50 ⁇ m to 400 ⁇ m.
  • a tablet wherein the theanine content in the tablet according to (1) is 10% by mass to 30% by mass.
  • the binder component in the coating solution described in (1) is shellac, mannitol, erythritole, sonorebitonore, xylitolenole, trenorose, ethinoresenorelose, methinoresenololose, hydroxypropinoresenorelose, hydroxypropiol
  • a tablet comprising at least one selected from normetinorescenellose, strength noroxylmethylethyl cellulose, polybulur pyrrolidone, carboxybull polymer, polybulal alcohol, gum arabic, sodium alginate and gelatin strength.

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne un comprimé qui comprend comme ingrédient actif un acide aminé qui passe au travers d'une barrière hématoencéphalique et qui est peu endommagé par la mise en comprimé. Le comprimé comprend de préférence un acide aminé en une proportion de 1 % en masse à 40 % en masse. Dans ce comprimé, 10 % ou moins de l’acide aminé présente une dimension de particules de 80 µm ou plus. Dans ce cas, on préfère que le comprimé soit produit en enduisant des granules obtenus par granulation d’un mélange de particules qui comprend l’acide aminé avec un revêtement liquide contenant un liant pour produire des granules enduits, et par la mise en comprimé des granules enduits.
PCT/JP2006/302797 2005-02-23 2006-02-17 Composition de comprimé contenant un acide aminé et procédé de fabrication du comprimé WO2006090640A1 (fr)

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JP2012510956A (ja) * 2008-12-05 2012-05-17 バイエル・アニマル・ヘルス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 針状の活性物質を含む押出物
JP2015528487A (ja) * 2012-09-18 2015-09-28 ノヴァルドメディカル リミテッド オサケユキテュアＮｏｖａｌｄＭｅｄｉｃａｌ Ｌｔｄ Ｏｙ 医薬品基材のコーティング方法
JP2015218158A (ja) * 2014-05-21 2015-12-07 協和発酵バイオ株式会社 ３−ヒドロキシ−３−メチル酪酸カルシウム含有錠剤およびその製造方法
WO2021203106A1 (fr) * 2020-04-03 2021-10-07 Nutrition 21, Llc Procédé et composition pour améliorer la qualité et les bénéfices du sommeil
US11311491B2 (en) 2018-01-16 2022-04-26 Applied Materials, Inc. Metal oxide encapsulated drug compositions and methods of preparing the same
US12064522B2 (en) 2020-10-02 2024-08-20 Applied Materials, Inc. Low temperature process for preparing silicon oxide coated pharmaceuticals

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JPS5879917A (ja) * 1981-11-09 1983-05-13 Showa Denko Kk グリシン錠剤の成形方法
JP2003221326A (ja) * 2002-01-25 2003-08-05 Ajinomoto Co Inc 分岐鎖アミノ酸を含有するチュアブル剤
WO2004016262A1 (fr) * 2002-08-12 2004-02-26 Kyowa Hakko Kogyo Co., Ltd. Produit a macher contenant un acide amine

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JPS5879917A (ja) * 1981-11-09 1983-05-13 Showa Denko Kk グリシン錠剤の成形方法
JP2003221326A (ja) * 2002-01-25 2003-08-05 Ajinomoto Co Inc 分岐鎖アミノ酸を含有するチュアブル剤
WO2004016262A1 (fr) * 2002-08-12 2004-02-26 Kyowa Hakko Kogyo Co., Ltd. Produit a macher contenant un acide amine

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015134812A (ja) * 2008-12-05 2015-07-27 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ 針状の活性物質を含む押出物
JP2012510956A (ja) * 2008-12-05 2012-05-17 バイエル・アニマル・ヘルス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 針状の活性物質を含む押出物
JP7171494B2 (ja) 2012-09-18 2022-11-15 アプライド マテリアルズ インコーポレイテッド 医薬品基材のコーティング方法
JP2015528487A (ja) * 2012-09-18 2015-09-28 ノヴァルドメディカル リミテッド オサケユキテュアＮｏｖａｌｄＭｅｄｉｃａｌ Ｌｔｄ Ｏｙ 医薬品基材のコーティング方法
JP2019104763A (ja) * 2012-09-18 2019-06-27 ノヴァルドメディカル リミテッド オサケユキテュアＮｏｖａｌｄＭｅｄｉｃａｌ Ｌｔｄ Ｏｙ 医薬品基材のコーティング方法
US10603284B2 (en) 2012-09-18 2020-03-31 Applied Materials, Inc. Method for coating pharmaceutical substrates
US11986559B2 (en) 2012-09-18 2024-05-21 Applied Materials, Inc. Method for coating pharmaceutical substrates
US11672764B2 (en) 2012-09-18 2023-06-13 Applied Materials, Inc. Method for coating pharmaceutical substrates
JP2015218158A (ja) * 2014-05-21 2015-12-07 協和発酵バイオ株式会社 ３−ヒドロキシ−３−メチル酪酸カルシウム含有錠剤およびその製造方法
US11311491B2 (en) 2018-01-16 2022-04-26 Applied Materials, Inc. Metal oxide encapsulated drug compositions and methods of preparing the same
US12005145B2 (en) 2018-01-16 2024-06-11 Applied Materials, Inc. Metal oxide encapsulated drug compositions and methods of preparing the same
WO2021203106A1 (fr) * 2020-04-03 2021-10-07 Nutrition 21, Llc Procédé et composition pour améliorer la qualité et les bénéfices du sommeil
US12064522B2 (en) 2020-10-02 2024-08-20 Applied Materials, Inc. Low temperature process for preparing silicon oxide coated pharmaceuticals

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TW200642680A (en) 2006-12-16

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