WO2002049638A1 - Medicinal granular preparation containing branched amino acids - Google Patents
Medicinal granular preparation containing branched amino acids Download PDFInfo
- Publication number
- WO2002049638A1 WO2002049638A1 PCT/JP2001/010527 JP0110527W WO0249638A1 WO 2002049638 A1 WO2002049638 A1 WO 2002049638A1 JP 0110527 W JP0110527 W JP 0110527W WO 0249638 A1 WO0249638 A1 WO 0249638A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- pharmaceutical
- amino acids
- leucine
- granulator
- Prior art date
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- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940057106 isoleucine / leucine / valine Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 150000003544 thiamines Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- CCXAYLQLOLXXKE-DWJAGBRCSA-K trisodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4s,5s,6s)-2-[[(3s,4ar,6ar,6bs,8as,11s,12ar,14ar,14bs)-11-carboxylato-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1h-picen-3-yl]oxy]-6-carboxylato-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-t Chemical compound [Na+].[Na+].[Na+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C([O-])=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O CCXAYLQLOLXXKE-DWJAGBRCSA-K 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
Definitions
- the present invention relates to a granular pharmaceutical preparation containing three kinds of branched-chain amino acids consisting of isoleucine, leucine and valine as active ingredients.
- the pharmaceutical granule preparation of the present invention refers to granules and powders described in the Japanese Pharmacopoeia and European Pharmacopoeia, and pills described in the Japanese Pharmacopoeia, and pharmaceutical granules and powders The particle size range of is defined by the Japanese Pharmacopoeia.
- the present invention relates to a pharmaceutical granule containing three types of branched-chain amino acids consisting of isoleucine, leucine, and valine, which has a strong bitterness, as an active ingredient, wherein the pharmaceutical composition eases the bitterness and is easy to take. It is. Background art
- compositions containing three types of branched chain amino acids consisting of isoleucine, leucine and palin as active ingredients are effective therapeutic agents for liver diseases.
- Pharmaceutical granules containing these three types of amino acids have the drawbacks that they are bitter as they are, have poor flavor, and are very difficult to take.
- Japanese Patent No. 29711855 discloses that in foods containing amino acids, acidity is controlled in order to suppress the generation of flavors (generally animal odor) peculiar to amino acids generated by heat sterilization and long-term storage.
- a method has been proposed in which the pH is adjusted to an acidic range with a sweetener and the flavor is further adjusted with a sweetener.
- Japanese Patent Application Laid-Open Publication No. Hei 10-2875751 discloses a method for improving the unpleasant taste of an oral solution containing an amino acid having an unpleasant taste, which has an unpleasant flavor. It has been proposed to incorporate a thiamine derivative, and isoleucine, leucine, valine, etc. are exemplified as amino acids having an unpleasant flavor.However, this method may be effective particularly when methionine is contained as an amino acid. Has been described.
- a sour agent for the purpose of suppressing the bitterness of a pharmaceutical granule formulation containing the highly bitter branched amino acids isoleucine, leucine and palin as active ingredients.
- sucrose, glucose, fructose, etc. which are conventionally used as sweeteners, are blended in the granules, or a flavoring coating layer is provided with these sugars to mask the poor flavor inherent in amino acids.
- the present invention relates to a pharmaceutical granule preparation containing three types of branched-chain amino acids consisting of isoleucine, leucine and valine, which are effective therapeutic agents for liver disease, as an active ingredient, by adding an organic acid as an acidulant, Pharmaceutical granules with less discomfort in taking by improving the bitterness and unpleasant taste peculiar to branched-chain amino acids by further adding flavoring agents and flavoring agents that do not cause coloring due to the Maillard reaction etc. It is intended to provide a formulation.
- the present invention for solving the above-mentioned problem is to provide a pharmaceutical granule manufactured using three kinds of branched-chain amino acids consisting of isoleucine, leucine, and valine as an active ingredient, so as to contain a sour agent as an organic acid.
- the basic means is to add a flavoring agent that does not cause coloring or the like due to the Maillard reaction or the like as necessary, and includes the following inventions.
- the three types of branched-chain amino acids consisting of isoleucine, leucine and pervaline have a particle size of 20 to 700 ⁇ , preferably 50 to 500 ⁇ m Isoloisin, leucine and
- the particle size of the branched-chain amino acid in the pharmaceutical granule is a numerical value measured by the following method.
- 2-propanol 20 Om1 was placed in a circulation tank and stirred and circulated for 5 minutes while irradiating with ultrasonic waves. Then, perform blank measurement (ultrasonic wave is turned off during measurement). Subsequently, 200 ml of 2-propanol is put into the circulation tank, and the amino acid sample to be measured is introduced so that the transmittance becomes about 85%. Circulate for 4 minutes while stirring and irradiating with ultrasonic wave, and measure the particle size 5 minutes after stopping the ultrasonic wave. The median diameter based on volume was used as the average particle diameter.
- sour agent is at least one selected from cunic acid, malic acid, acetic acid, tartaric acid, and ascorbic acid.
- the pharmaceutical granule of the present invention is a pharmaceutical granule produced by granulating particles of three types of branched-chain amino acids consisting of isoleucine, leucine and paparin.
- the sour agent used in the pharmaceutical granule preparation of the present invention is citric anhydride, cunic acid, cU-malic acid, tartaric acid, d-tartaric acid, ascorbic acid, acetic acid, lactic acid, succinic acid, maleic acid, malonic acid, L -Organic acids such as glutamate hydrochloride.
- Particularly preferred are citric anhydride, citric acid, dl-malic acid, tartaric acid, d-tartaric acid, ascorbic acid, and acetic acid. And the like.
- Flavoring agents used in the pharmaceutical granule preparation of the present invention include aspartame, saccharin, saccharin sodium, glycyrrhizic acid, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, Acesulfame K, mannitol, erythritol, sorbitol, xylitol, Torehachirose, cocoa powder, etc. .
- flavors can be used as the flavoring agent used in the pharmaceutical granule preparation of the present invention, and examples thereof include lemon flavor, orange flavor, grapefruit flavor, chocolate flavor, and ( ⁇ -). Menthol, menthol and the like.
- isoleucine one of the active ingredients, generally has a particle size produced by a fermentation method of 1 mm or less, preferably 20 to 700 m, more preferably These particles are 50 to 500 particles and meet any of the standards of the Japanese Pharmacopoeia, the European Pharmacopoeia, and the United States Pharmacopeia.
- leucine is a particle generally produced by a fermentation method or an extraction method and having a particle size of 1 mm or less, preferably 20 to 700 m, more preferably 50 to 500 im. There is no particular limitation as long as it can produce a pharmaceutical granule that meets any of the standards of the Japanese Pharmacopoeia, the European Pharmacopoeia, and the United States Pharmacopeia.
- valine is generally a particle manufactured by fermentation or synthesis and having a particle size of 1 mm or less, and meets any of the standards of the Japanese Pharmacopoeia, European Pharmacopoeia, and the United States Pharmacopeia. There is no particular limitation as long as a granular preparation can be produced.
- a binder can be used to granulate the particles constituting the pharmaceutical granule preparation of the present invention.
- the binder include cellulose derivatives such as methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and hydroxypropylmethylcellulose, starches such as corn starch and wheat starch, polyvinylpyrrolidone, polypinyl alcohol, and acrylic acid.
- Po Synthetic polymers such as lima, agar, gelatin, xanthan gum, gum arabic and the like can be used without particular limitation as long as they can be used for medicine. Also, the amount used is arbitrary as long as normal granulation is possible.
- the granule preparation containing the three types of branched-chain amino acids in the pharmaceutical granule preparation of the present invention may be a high-speed stirring granulator, a fluidized bed granulator, a planetary mixer, a dry press granulator, a crush granulator, or an extruder. It can also be produced using equipment such as a granulator, a tumbling granulator, a spray-drying granulator, and a coating granulator. However, a high-speed stirring granulator or an extrusion granulator is preferable.
- Extrusion granulation is a method in which plasticized powder is extruded from a screen with many holes to granulate it.Pre-extrusion granulator, disc pellet pelletizer, ring die granulator Granulator, basket granulator, oscillating granulator, cylinder granulator, etc. are used.
- the high-speed stirring granulation method is a method in which water or a binder solution is charged or sprayed into powder, and the powder is subjected to shearing, rolling, and consolidation by rotation of a stirring blade, and granulation is performed. A granulator is used.
- the fluidized-bed granulation method is a granulation method performed by spraying water or a binder liquid while flowing the powder to agglomerate the powder.
- the fluidized-bed granulator, the stirred fluidized-bed granulator, A tumbling fluidized bed type granulator and a stirring tumbling fluidized bed type granulator are used.
- Dry compression granulation is a method of compacting powder without using water or a binder solution, and is used for roll pressing, pre-ketting machines, single-shot tablet presses, and single-table tablet presses. Machine is used.
- the tumbling granulation method is a method of rolling and granulating powder, and a drum-type granulator, a dish-type granulator, a vibrating granulator, and a disk-type granulator are used.
- Example 1 Example 1
- High-speed stirring granulator High-speed mixer, Fukae Bautech
- Average particle size 28 urn 47.60 g
- leucine average particle size 23 im
- Example 2 After sieving with a 1400 / im sieve, the sieved product was forcibly sieved using a 1400 sieve and thoroughly mixed with the sieved product to obtain a pharmaceutical granule formulation.
- Example 2 After sieving with a 1400 / im sieve, the sieved product was forcibly sieved using a 1400 sieve and thoroughly mixed with the sieved product to obtain a pharmaceutical granule formulation.
- the granulated product was dried at 60 ° C for 2 hours using a tray dryer to obtain granules. After sieving with a 1400 im sieve, the sieved product was forcibly sieved using a 1400 ⁇ sieve, and sufficiently mixed with the sieved product to obtain a pharmaceutical granule preparation.
- Example 3
- High-speed agitation granulator (high-speed mixer, Fukae Patetech Co., Ltd.) 28.56 g of isoguchiin (average particle size 28 m), leucine (average particle size 23 m) 57.1
- the granulated product was dried at 60 using a tray dryer for 2 hours to obtain granules. After sieving with a 1400 sieve, the sieved product was forcibly sieved using a 1400 m sieve, and thoroughly mixed with the sieved product to obtain a pharmaceutical granule preparation.
- High-speed agitation granulator (8-speed mixer, manufactured by Fukae Patetech Co., Ltd.), 38.08 g of isoguchiine (average particle size 28 m), leucine (average particle size 23 im) 76.16 g, valine (average (Particle size 22 / m) 45.76 g and hydroxypropyl cellulose 4.00 g were weighed out and mixed uniformly.
- a solution obtained by dissolving a trace amount of lemon flavor in 40.00 g of distilled water was used as a binding solution, and this was added to perform granulation.
- Shelves with granules The granules were dried at 60 ° C for 2 hours using a stage dryer. After sieving with a 1400 / xm sieve, the sieved product was forcibly sieved using a 1400 sieve, and thoroughly mixed with the sieved product to obtain a pharmaceutical granule preparation.
- the pharmaceutical granule preparation containing isoleucine, leucine, and palin according to the present invention hides the bitterness peculiar to the branched-chain amino acid and is easy to take.
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Abstract
A medicinal granular preparation characterized by containing as the active ingredients three branched amino acids, i.e., isoleucine, leucine, and valine, and further containing at least one organic acid as an acidulating agent. Since the bitterness attributable to the branched amino acids is mitigated, the granular preparation is easy to take.
Description
明 細 書 Specification
分岐鎖アミノ酸を含有する医薬用顆粒製剤 技術分野 Pharmaceutical granules containing branched-chain amino acids
本発明は、 イソロイシン、 ロイシン及ぴバリンからなる 3種の分岐鎖アミノ酸 を有効成分として含有する医薬用顆粒製剤に関する。 本発明の医薬用顆粒製剤と は、 日本薬局方、 ヨーロッパ薬局方に記載された顆粒剤及ぴ散剤、 および日本薬 局方に記載された丸剤のことであり、 医薬用の顆粒剤、 散剤の粒度の範囲は日本 薬局方に規定された範囲である。 特に本発明は、 苦みの強いイソロイシン、 ロイ シン及びバリンからなる 3種の分岐鎖アミノ酸を有効成分として含有する医薬用 顆粒製剤の苦みを緩和して服用し易くした医薬用顆粒製剤に閼するものである。 背景技術 TECHNICAL FIELD The present invention relates to a granular pharmaceutical preparation containing three kinds of branched-chain amino acids consisting of isoleucine, leucine and valine as active ingredients. The pharmaceutical granule preparation of the present invention refers to granules and powders described in the Japanese Pharmacopoeia and European Pharmacopoeia, and pills described in the Japanese Pharmacopoeia, and pharmaceutical granules and powders The particle size range of is defined by the Japanese Pharmacopoeia. In particular, the present invention relates to a pharmaceutical granule containing three types of branched-chain amino acids consisting of isoleucine, leucine, and valine, which has a strong bitterness, as an active ingredient, wherein the pharmaceutical composition eases the bitterness and is easy to take. It is. Background art
イソロイシン、 ロイシン、 及びパリンからなる 3種の分岐鎖アミノ酸を有効成 分として含む医薬用顆粒製剤は肝疾患に有効な治療薬である。 この 3種のアミノ 酸を含む医薬用顆粒製剤は、 そのままでは苦く、 風味が悪く非常に服用しにくい という欠点がある。 Pharmaceutical granules containing three types of branched chain amino acids consisting of isoleucine, leucine and palin as active ingredients are effective therapeutic agents for liver diseases. Pharmaceutical granules containing these three types of amino acids have the drawbacks that they are bitter as they are, have poor flavor, and are very difficult to take.
日本特許第 2 9 7 1 8 5 5号公報には、 アミノ酸含有食品において、 その加熱 殺菌や長期保存によって発生するアミノ酸特有の風味 （一般的には獣臭） の発生 を抑制するために、 酸味料で p Hを酸性域に調整し、 さらに甘味料で風味を整え る方法が提案されている。 また、 日本特許出願公開公報、 特開平 1 0— 2 8 7 5 5 1号には、 不快な風味を有するアミノ酸類を配合した内服液剤の不快風味を改 善する方法として、 不快な風味を有するチアミン誘導体を配合することが提案さ れており、 不快な風味を有するアミノ酸としてイソロイシン、 ロイシン、 バリン 等も例示されているが、 この方法は、 特にアミノ酸としてメチォニンを含む場合 に有効であることが記載されている。 Japanese Patent No. 29711855 discloses that in foods containing amino acids, acidity is controlled in order to suppress the generation of flavors (generally animal odor) peculiar to amino acids generated by heat sterilization and long-term storage. A method has been proposed in which the pH is adjusted to an acidic range with a sweetener and the flavor is further adjusted with a sweetener. In addition, Japanese Patent Application Laid-Open Publication No. Hei 10-2875751 discloses a method for improving the unpleasant taste of an oral solution containing an amino acid having an unpleasant taste, which has an unpleasant flavor. It has been proposed to incorporate a thiamine derivative, and isoleucine, leucine, valine, etc. are exemplified as amino acids having an unpleasant flavor.However, this method may be effective particularly when methionine is contained as an amino acid. Has been described.
しかし、 苦みの強い分岐アミノ酸であるイソロイシン、 ロイシン、 パリンを有 効成分とする医薬用顆粒製剤の苦みを抑えることを目的として酸味剤を添加、 使 用した例はない。
また、 甘味剤として従来から使用されているショ糖、 ブドウ糖、 果糖などを顆 粒中に配合すること、 あるいはこれらの糖で矯味コ一ティング層を設けることに よってアミノ酸特有の風味の悪さを隠蔽することはできるが、 イソロイシン、 口 ィシン、 及びバリンのようなアミノ酸を有効成分として含む医薬用顆粒製剤の場 合、 ショ糖、 ブドウ糖、 果糖などの糖成分が有効成分であるイソロイシン、 ロイ シン、 及ぴバリンに接触すると、 いわゆるメイラード反応を起こして医薬用顆粒 製剤が着色し、 保存安定性が悪くなるため、 避けなければならない。 発明の開示 However, there is no example of adding or using a sour agent for the purpose of suppressing the bitterness of a pharmaceutical granule formulation containing the highly bitter branched amino acids isoleucine, leucine and palin as active ingredients. In addition, sucrose, glucose, fructose, etc., which are conventionally used as sweeteners, are blended in the granules, or a flavoring coating layer is provided with these sugars to mask the poor flavor inherent in amino acids. However, in the case of a granular pharmaceutical preparation containing an amino acid such as isoleucine, oral isine, and valine as an active ingredient, sucrose, glucose, fructose, and other sugar components are isoleucine, leucine, Contact with valine causes the so-called Maillard reaction, which causes the coloration of the pharmaceutical granule formulation and impairs the storage stability, and must be avoided. Disclosure of the invention
本発明は、 肝疾患に対する有効な治療薬であるイソロイシン、 ロイシン及びバ リンからなる 3種の分岐鎖アミノ酸を有効成分とする医薬用顆粒製剤に、 酸味剤 として有機酸を添加し、 必要に応じてメイラ一ド反応等による着色等を起こさな い矯味剤や着香剤をさらに添加することにより、 分岐鎖アミノ酸特有の苦みや風 味の悪さを改善して服用にあたって不快感の少ない医薬用顆粒製剤を提供するこ とを目的とするものである。 The present invention relates to a pharmaceutical granule preparation containing three types of branched-chain amino acids consisting of isoleucine, leucine and valine, which are effective therapeutic agents for liver disease, as an active ingredient, by adding an organic acid as an acidulant, Pharmaceutical granules with less discomfort in taking by improving the bitterness and unpleasant taste peculiar to branched-chain amino acids by further adding flavoring agents and flavoring agents that do not cause coloring due to the Maillard reaction etc. It is intended to provide a formulation.
上記の課題を解決するための本発明は、 イソロイシン、 ロイシン、 及ぴバリン からなる 3種の分岐鎖アミノ酸を有効成分として製造されている医薬用顆粒製剤 中に有機酸である酸味剤を含有せしめ、 必要に応じてメイラ一ド反応等による着 色等を起こさない矯味剤を添加することを基本的な手段とするものであり、 以下 の各発明を含包する。 The present invention for solving the above-mentioned problem is to provide a pharmaceutical granule manufactured using three kinds of branched-chain amino acids consisting of isoleucine, leucine, and valine as an active ingredient, so as to contain a sour agent as an organic acid. The basic means is to add a flavoring agent that does not cause coloring or the like due to the Maillard reaction or the like as necessary, and includes the following inventions.
(1 ) イソロイシン、 ロイシン及びパリンからなる 3種の分岐鎖アミノ酸を有効成 分として含有し、 かつ酸味剤として医薬品添加剤として許容されている 1種類以 上の有機酸を含有することを特徴とする医薬用顆粒製剤。 (1) It is characterized by containing three types of branched-chain amino acids consisting of isoleucine, leucine and palin as an active ingredient and containing one or more organic acids that are acceptable as pharmaceutical additives as sour agents. Pharmaceutical granules.
(2) 前記イソロイシン、 ロイシン及びパリンからなる 3種の分岐鎖アミノ酸は、 それらの配合割合が重量比で、 イソロイシン/ロイシン/バリン = 1 1 . 9〜 (2) The three types of branched-chain amino acids consisting of isoleucine, leucine, and palin are mixed at a weight ratio of isoleucine / leucine / valine = 11.9 to
2 . 2 / 1 . ：!〜 1 . 3であることを特徴とする（1 ) 項記載の医薬用顆粒製剤。2.2 / 1 .: The pharmaceutical granule preparation according to the above item (1), which is! -1.3.
(3) 前記イソロイシン、 ロイシン及ぴバリンからなる 3種の分岐鎖アミノ酸は、 粒度が 2 0〜7 0 0 πι、 好ましくは 5 0〜5 0 0 μ であるイソ口イシン粒子 及びロイシンと粒度が 1 mm以下のパリンとを含むィソロイシン、 ロイシン及び
バリンからなる 3種の分岐鎖アミノ酸の粒子を造粒原料として使用して製造され ていることを特徴とする（1 ) 項又は（2) 項に記載の医薬用顆粒製剤。 (3) The three types of branched-chain amino acids consisting of isoleucine, leucine and pervaline have a particle size of 20 to 700 μπ, preferably 50 to 500 μm Isoloisin, leucine and The pharmaceutical granule preparation according to the above mode (1) or (2), which is produced using particles of three kinds of branched-chain amino acids consisting of valine as a granulation raw material.
なお、 上記医薬用顆粒製剤における分岐鎖アミノ酸の粒度は、 以下の方法で測 定した数値である。 The particle size of the branched-chain amino acid in the pharmaceutical granule is a numerical value measured by the following method.
レーザー回折/散乱式粒度分布測定装置 （堀場製作所製、 L A— 9 1 0 ) を用 レ 、 2 —プロパノール 2 0 O m 1 を循環槽に入れて攪拌、 超音波照射しながら 5 分間循環させた後、 ブランク測定 （測定時は超音波 O F F ) を行う。 続いて、 循 環槽に 2 —プロパノ一ル 2 0 0 m lを入れ透過率が約 8 5 %になるように測定ァ ミノ酸試料を投入する。 攪拌、 超音波照射をしながら 4分間循環させ、 超音波を 停止した 5分後に粒径測定を行う。 平均粒径は体積基準のメジアン径を用いた。 Using a laser diffraction / scattering particle size distribution analyzer (LA-910, manufactured by HORIBA, Ltd.), 2-propanol 20 Om1 was placed in a circulation tank and stirred and circulated for 5 minutes while irradiating with ultrasonic waves. Then, perform blank measurement (ultrasonic wave is turned off during measurement). Subsequently, 200 ml of 2-propanol is put into the circulation tank, and the amino acid sample to be measured is introduced so that the transmittance becomes about 85%. Circulate for 4 minutes while stirring and irradiating with ultrasonic wave, and measure the particle size 5 minutes after stopping the ultrasonic wave. The median diameter based on volume was used as the average particle diameter.
(4) 前記酸味剤がクェン酸、 リンゴ酸、 酢酸、 酒石酸及ぴァスコルビン酸から選 ばれる少なくとも 1種であることを特徴とする（1) 項〜（3) 項のいずれか 1項に 記載の医薬用顆粒製剤。 (4) The method according to any one of items (1) to (3), wherein the sour agent is at least one selected from cunic acid, malic acid, acetic acid, tartaric acid, and ascorbic acid. Pharmaceutical granule preparation.
(5) 前記酸味剤に加えて、 さらにアスパルテーム、 サッカリン、 サッカリンナト リウム、 グリチルリチン酸及びその塩類、 アセスルファム K、 マンニトール、 ェ リスリ ト一ル、 ソルビトール、 キシリ トール、 トレハロ一ス、 カカオ末及びメン トール等からなる群から選ばれる少なくとも 1種の矯味剤を含有することを特徴 とする（1) 項〜（4) 項のいずれか 1項に記載の医薬用顆粒製剤。 (5) In addition to the acidulant, aspartame, saccharin, sodium saccharin, glycyrrhizic acid and salts thereof, acesulfame K, mannitol, erythritol, sorbitol, xylitol, trehalose, cocoa powder and menthol The pharmaceutical granule preparation according to any one of (1) to (4), further comprising at least one flavoring agent selected from the group consisting of:
(6) さらに着香剤を含有することを特徴とする（1) 項〜（5) 項のいずれか 1項に 記載の医薬用顆粒製剤。 (6) The pharmaceutical granule preparation according to any one of (1) to (5), further comprising a flavoring agent.
本発明の医薬用顆粒製剤は、 イソロイシン、 ロイシン及ぴパリンからなる 3種 の分岐鎖アミノ酸の粒子を造粒して製造されている医薬用顆粒製剤である。 本発明の医薬用顆粒製剤は、 イソロイシン、 ロイシン及びパリンの配合割合が 重量比で、 イソロイシン/口イシン Ζバリン = 1 / 1 . 9〜 2 · 2 / 1 . 1〜 1 . 3であることが好ましい。 The pharmaceutical granule of the present invention is a pharmaceutical granule produced by granulating particles of three types of branched-chain amino acids consisting of isoleucine, leucine and paparin. In the pharmaceutical granule preparation of the present invention, the mixing ratio of isoleucine, leucine and palin is by weight, and isoleucine / mouthrin / valine = 1 / 1.9 to 2.2 / 2 / 1.1 to 1.3. preferable.
本発明の医薬用顆粒製剤に使用される酸味剤は無水クェン酸、 クェン酸、 cU- リンゴ酸、 酒石酸、 d-酒石酸、 ァスコルビン酸、 酢酸、 乳酸、 コハク酸、 マレイ ン酸、 マロン酸、 L-グルタミン酸塩酸塩等の有機酸である。 特に好ましくは無水 クェン酸、 クェン酸、 d l - リンゴ酸、 酒石酸、 d-酒石酸、 ァスコルビン酸、 酢酸
等が挙げられる。 The sour agent used in the pharmaceutical granule preparation of the present invention is citric anhydride, cunic acid, cU-malic acid, tartaric acid, d-tartaric acid, ascorbic acid, acetic acid, lactic acid, succinic acid, maleic acid, malonic acid, L -Organic acids such as glutamate hydrochloride. Particularly preferred are citric anhydride, citric acid, dl-malic acid, tartaric acid, d-tartaric acid, ascorbic acid, and acetic acid. And the like.
本発明の医薬用顆粒製剤に使用される矯味剤はアスパルテーム、 サッカリン、 サッカリンナトリゥム、 グリチルリチン酸、 グリチルリチン酸モノアンモニゥム、 グリチルリチン酸二アンモニゥム、 グリチルリチン酸二カリウム、 グリチルリチ ン酸ニナトリウム、 グリチルリチン酸三ナトリウム、 アセスルファム K、 マンニ トール、 エリスリ トール、 ソルビトール、 キシリ トール、 トレ八ロース、 カカオ 末等である。 . Flavoring agents used in the pharmaceutical granule preparation of the present invention include aspartame, saccharin, saccharin sodium, glycyrrhizic acid, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, Acesulfame K, mannitol, erythritol, sorbitol, xylitol, Torehachirose, cocoa powder, etc. .
本発明の医薬用顆粒製剤に使用される着香剤としては、 各種フレーバーを用い ることができるが、 例としてはレモンフレーバ一、 オレンジフレーバー、 グレー プフルーツフレーバー、 チョコレ一トフレーバー、 （Π-メントール、 卜メント一 ル等が挙げられる。 Various flavors can be used as the flavoring agent used in the pharmaceutical granule preparation of the present invention, and examples thereof include lemon flavor, orange flavor, grapefruit flavor, chocolate flavor, and (、-). Menthol, menthol and the like.
本発明の医薬用顆粒製剤において、 有効成分の一つであるイソロイシンは、 一 般的には発酵法で製造されている粒度が l mm以下、 好ましくは 2 0〜7 0 0 m、 より好ましくは 5 0〜5 0 0 の粒子であり、 日本薬局方、 ヨーロッパ薬 局方、 アメリカ薬局方のいずれかの規格を満たすものである。 In the pharmaceutical granule preparation of the present invention, isoleucine, one of the active ingredients, generally has a particle size produced by a fermentation method of 1 mm or less, preferably 20 to 700 m, more preferably These particles are 50 to 500 particles and meet any of the standards of the Japanese Pharmacopoeia, the European Pharmacopoeia, and the United States Pharmacopeia.
また、 ロイシンとしては、 一般的には発酵法又は抽出法で製造されている粒度 が l mm以下の粒子であり、 好ましくは 2 0 ~ 7 0 0 m、 より好ましくは 5 0 〜5 0 0 i mの粒子であり、 日本薬局方、 ヨーロッパ薬局方、 アメリカ薬局方の いずれかの規格を満たす医薬用顆粒製剤を製造することができる限り特に制限は ない。 Further, leucine is a particle generally produced by a fermentation method or an extraction method and having a particle size of 1 mm or less, preferably 20 to 700 m, more preferably 50 to 500 im. There is no particular limitation as long as it can produce a pharmaceutical granule that meets any of the standards of the Japanese Pharmacopoeia, the European Pharmacopoeia, and the United States Pharmacopeia.
また、 バリンとしては、 一般的には発酵法もしくは合成法で製造されている粒 度が l mm以下の粒子で、 日本薬局方、 ヨーロッパ薬局方、 アメリカ薬局方のい ずれかの規格を満たす医薬用顆粒製剤を製造することができる限り特に制限はな い。 In addition, valine is generally a particle manufactured by fermentation or synthesis and having a particle size of 1 mm or less, and meets any of the standards of the Japanese Pharmacopoeia, European Pharmacopoeia, and the United States Pharmacopeia. There is no particular limitation as long as a granular preparation can be produced.
本発明の医薬用顆粒製剤を構成する粒子を造粒するために、 結合剤を使用する ことができる。 結合剤としては、 メチルセルロース、 ヒドロキシプロピルセル口 —ス、 ヒドロキシプロピルメチルセルロース、 ヒドロキシプロピルメチルセル口 ースフタレート等のセルロース誘導体、 トウモロコシデンプン、 コムギデンプン 等のデンプン類、 ポリビニルピロリ ドン、 ポリピニルアルコール、 アクリル酸ポ
リマ一などの合成高分子類、 寒天、 ゼラチン、 キサンタンガム、 アラビアガム等 であり、 医薬用として使用できるものであれば特に制限なく使用できる。 また、 その使用量も通常の造粒が可能な範囲である限り任意である。 A binder can be used to granulate the particles constituting the pharmaceutical granule preparation of the present invention. Examples of the binder include cellulose derivatives such as methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and hydroxypropylmethylcellulose, starches such as corn starch and wheat starch, polyvinylpyrrolidone, polypinyl alcohol, and acrylic acid. Po Synthetic polymers such as lima, agar, gelatin, xanthan gum, gum arabic and the like can be used without particular limitation as long as they can be used for medicine. Also, the amount used is arbitrary as long as normal granulation is possible.
本発明の医薬用顆粒製剤における前記 3種の分岐鎖アミノ酸を含む顆粒製剤は、 高速攪拌造粒機、 流動層造粒機、 プラネタリ一ミキサー、 乾式圧扁造粒機、 破砕 造粒機、 押し出し造粒機、 転動造粒機、 噴霧乾燥造粒機、 コーティング造粒機な どの機器を使用しても製造することができる.が、 高速攪拌造粒機、 押し出し造粒 機が好ましい。 押し出し造粒法は、 可塑性を付与された粉末を多数の穴のあいた スクリーンから押し出すことにより造粒する方法であり、 前押し出し式造粒機、 ディスクペレツ夕一式造粒機、 リングダイ式造粒機、 バスケット式造粒機、 オシ レ一ティング式造粒機、 シリンダ一式造粒機等が使用される。 The granule preparation containing the three types of branched-chain amino acids in the pharmaceutical granule preparation of the present invention may be a high-speed stirring granulator, a fluidized bed granulator, a planetary mixer, a dry press granulator, a crush granulator, or an extruder. It can also be produced using equipment such as a granulator, a tumbling granulator, a spray-drying granulator, and a coating granulator. However, a high-speed stirring granulator or an extrusion granulator is preferable. Extrusion granulation is a method in which plasticized powder is extruded from a screen with many holes to granulate it.Pre-extrusion granulator, disc pellet pelletizer, ring die granulator Granulator, basket granulator, oscillating granulator, cylinder granulator, etc. are used.
高速攪拌造粒法とは、 粉に水あるいはバインダー液を投入あるいは噴霧し、 攪 拌羽根の回転によりせん断 ·転動 ·圧密化を行い造粒する方法であり、 竪型 ·横 型の攪拌造粒機が使用される。 The high-speed stirring granulation method is a method in which water or a binder solution is charged or sprayed into powder, and the powder is subjected to shearing, rolling, and consolidation by rotation of a stirring blade, and granulation is performed. A granulator is used.
流動層造粒法とは、 粉を流動させながら水あるいはバインダー液を噴霧し、 粉 を凝集させることにより行われる造粒法であり、 流動層型造粒機、 攪拌流動層型 造粒機、 転動流動層型造粒機、 攪拌転動流動層型造粒機が使用される。 The fluidized-bed granulation method is a granulation method performed by spraying water or a binder liquid while flowing the powder to agglomerate the powder.The fluidized-bed granulator, the stirred fluidized-bed granulator, A tumbling fluidized bed type granulator and a stirring tumbling fluidized bed type granulator are used.
乾式圧扁造粒法とは、 水あるいはバインダー液を使用せず粉を圧縮して成形す る方法であり、 ロールプレス、 プリケッティングマシン、 単発式打錠機、 口一夕 リ一式打錠機が使用される。 Dry compression granulation is a method of compacting powder without using water or a binder solution, and is used for roll pressing, pre-ketting machines, single-shot tablet presses, and single-table tablet presses. Machine is used.
転動造粒法とは、粉末を転がして造粒する方法のことであり、 ドラム型造粒機、 皿型造粒機、 振動造粒機、 円盤回転式造粒機が使用される。 発明を実施するための最良の形態 The tumbling granulation method is a method of rolling and granulating powder, and a drum-type granulator, a dish-type granulator, a vibrating granulator, and a disk-type granulator are used. BEST MODE FOR CARRYING OUT THE INVENTION
以下に、 実施例を挙げて本発明をより具体的に説明するが、 本発明は以下の実 施例によって限定されるものではない。 実施例 1 Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples. Example 1
高速攪拌造粒機 （ハイスピードミキサー、 深江バウテック社製） にイソ口イシ
ン (平均粒径 28 urn) 47. 60 g、 ロイシン （平均粒径 23 im) 95. 2High-speed stirring granulator (High-speed mixer, Fukae Bautech) (Average particle size 28 urn) 47.60 g, leucine (average particle size 23 im) 95.2
0 g、 ノ リン （平均粒径 22 urn) 57. 20 g、 無水クェン酸 10. 00 g、 ヒドロキシプロピルセル口一ス 5. 00 gを量り取り、 均一に混合した。 蒸留水 30. 00 gにレモンフレーバー微量を溶解させた液を結合液とし、 これを添加 し造粒を行った。 造粒物を棚段乾燥機を用い 60 で 2時間乾燥し顆粒を得た。0 g, 57.20 g of phosphorus (average particle size: 22 urn), 10.00 g of citric anhydride, and 5.00 g of hydroxypropyl cell mouth were weighed and uniformly mixed. A solution obtained by dissolving a trace amount of lemon flavor in 30.00 g of distilled water was used as a binding solution, and this was added to perform granulation. The granules were dried at 60 using a tray dryer for 2 hours to obtain granules.
1400 /im篩で篩分後、 篩上品を 1400 篩を用い強制篩過し、 篩下品と 充分混合を行い、 医薬用顆粒製剤を得た。 実施例 2 After sieving with a 1400 / im sieve, the sieved product was forcibly sieved using a 1400 sieve and thoroughly mixed with the sieved product to obtain a pharmaceutical granule formulation. Example 2
高速攪拌造粒機 （ハイスピードミキサー、 深江パゥテック社製） にイソ口イシ ン （平均粒径 28 m) 47. 60 g、 ロイシン （平均粒径 23 /xm) 95. 2 0 g、 ノ リン （平均粒径 22 ^m) 57. 20 g、 無水クェン酸 10. 00 g、 マンニトール 75. 00 g、 サッカリンナトリウム 0. 38 g、 ヒドロキシプロ ピルセルロース 5. 00 gを量り取り、 均一に混合した。 蒸留水 40. 00 gに レモンフレーバ一微量を溶解させた液を結合液とし、これを添加し造粒を行った。 造粒物を棚段乾燥機を用い 60°Cで 2時間乾燥し顆粒を得た。 1400 im篩で 篩分後、 篩上品を 1400 ιη篩を用い強制篩過し、 篩下品と充分混合を行い、 医薬用顆粒製剤を得た。 実施例 3 To a high-speed stirring granulator (high-speed mixer, manufactured by Fukae Powertech Co., Ltd.), 47.60 g of isoguchiine (average particle size 28 m), 95.2 g of leucine (average particle size 23 / xm), norin ( (Average particle size 22 ^ m) 57.20 g, 10.00 g of citric anhydride, 75.00 g of mannitol, 0.38 g of sodium saccharin, and 5.00 g of hydroxypropylcellulose were weighed and mixed uniformly. A solution obtained by dissolving a small amount of lemon flavor in 40.00 g of distilled water was used as a binding solution, and this was added to perform granulation. The granulated product was dried at 60 ° C for 2 hours using a tray dryer to obtain granules. After sieving with a 1400 im sieve, the sieved product was forcibly sieved using a 1400 ιη sieve, and sufficiently mixed with the sieved product to obtain a pharmaceutical granule preparation. Example 3
高速攪拌造粒機 （ハイスピードミキサー、 深江パゥテック社製） にイソ口イシ ン （平均粒径 28 m) 28. 56 g、 ロイシン （平均粒径 23 m) 57. 1 High-speed agitation granulator (high-speed mixer, Fukae Patetech Co., Ltd.) 28.56 g of isoguchiin (average particle size 28 m), leucine (average particle size 23 m) 57.1
2 g、 パリン （平均粒径 22 μπι) 34. 32 g、 リンゴ酸 2. 25 g、 トレ八 口一ス 30. 00 g、 アスパルテーム 90 g、 ヒドロキシプロピルセルロー ス 3. 00 gを量り取り、 均一に混合した。 蒸留水 20. 00 gにグレープフル ーッフレーバー微量を溶解させた液を結合液とし、 これを添加し造粒を行った。 造粒物を棚段乾燥機を用い 60°Cで 2時間乾燥し顆粒を得た。 1400 m篩で 篩分後、 篩上品を 1400 篩を用い強制篩過し、 篩下品と充分混合を行い、 医薬用顆粒製剤を得た。
実施例 4 2 g, palin (average particle size: 22 μπι) 34.32 g, malic acid 2.25 g, torayachiguchi 13.0 g, aspartame 90 g, hydroxypropylcellulose 3.00 g, weigh and uniform Was mixed. A solution obtained by dissolving a small amount of grape fresh flavor in 20.00 g of distilled water was used as a binding solution, and this was added to perform granulation. The granulated product was dried at 60 ° C for 2 hours using a tray dryer to obtain granules. After sieving with a 1400-m sieve, the sieved product was forcibly sieved using a 1400 sieve, and thoroughly mixed with the sieved product to obtain a pharmaceutical granule formulation. Example 4
高速攪拌造粒機 （ハイスピードミキサー、 深江パゥテック社製） にイソ口イシ ン （平均粒径 28 m) 38. 08 g、 ロイシン （平均粒径 23 ^m) 76. 1 6 g、 バリン (平均粒径 22 m) 45. 76 g、 酒石酸 3. 00 g、 マンニト ール 60. 00 g、 サッカリンナトリウム 0. 30 g、 ヒドロキシプロピルセル ロース 4. 00 gを量り取り、 均一に混合した。 蒸留水 45. 00 gにレモンフ レ一パー微量を溶解させた液を結合液とし、 これを添加し造粒を行った。 造粒物 を棚段乾燥機を用い 60 で 2時間乾燥し顆粒を得た。 1400 篩で篩分後、 篩上品を 1400 m篩を用い強制篩過し、 篩下品と充分混合を行い、 医薬用顆 粒製剤を得た。 実施例 5 ' In a high-speed stirring granulator (high-speed mixer, Fukae Patetech Co., Ltd.), 38.08 g of isoguchiin (average particle diameter 28 m), leucine (average particle diameter 23 ^ m) 76.16 g, valine (average) Particle size 22 m) 45.76 g, tartaric acid 3.00 g, mannitol 60.00 g, saccharin sodium 0.30 g, hydroxypropylcellulose 4.00 g were weighed and mixed uniformly. A solution obtained by dissolving a trace amount of lemon flapper in 45.00 g of distilled water was used as a binding solution, and the solution was added to perform granulation. The granulated product was dried at 60 using a tray dryer for 2 hours to obtain granules. After sieving with a 1400 sieve, the sieved product was forcibly sieved using a 1400 m sieve, and thoroughly mixed with the sieved product to obtain a pharmaceutical granule preparation. Example 5 '
高速攪拌造粒機 （ハイスピードミキサー、 深江パゥテック社製） にイソ口イシ ン （平均粒径 51 ^m) 38. 08 g、 ロイシン （平均粒径 59 ^m) 76. 1 6 g、 パリン （平均粒径 22 m) 45. 76 g、 酢酸 80 g、 マンニト一 ル 60. 00 g、 サッカリンナトリウム 0. 30 g、 ヒドロキシプロピルセル口 ース 4. 00 gを量り取り、 均一に混合した。 蒸留水 45. 00 gにオレンジフ レーバー微量を溶解させた液を結合液とし、 これを添加し造粒を行った。 造粒物 を棚段乾燥機を用い 60°Cで 2時間乾燥し顆粒を得た。 1400 篩で篩分後、 篩上品を 1400 m篩を用い強制篩過し、 篩下品と充分混合を行い、 医薬用顆 粒製剤を得た。 比較例 1 In a high-speed stirring granulator (high-speed mixer, Fukae Patetech Co., Ltd.), 38.08 g of isoguchiin (average particle diameter 51 ^ m), 76.16 g of leucine (average particle diameter 59 ^ m), palin ( Average particle size: 22 m) 45.76 g, acetic acid 80 g, mannitol 60.00 g, saccharin sodium 0.30 g, hydroxypropylcellulose 4.00 g were weighed out and mixed uniformly. A solution obtained by dissolving a small amount of orange flavor in 45.00 g of distilled water was used as a binding solution, and the solution was added to perform granulation. The granulated product was dried at 60 ° C for 2 hours using a tray dryer to obtain granules. After sieving with a 1400 sieve, the sieved product was forcibly sieved using a 1400 m sieve, and thoroughly mixed with the sieved product to obtain a pharmaceutical granule preparation. Comparative Example 1
高速攪拌造粒機 （八ィスピードミキサー、 深江パゥテック社製） にイソ口イシ ン （平均粒径 28 m) 38. 08 g、 ロイシン （平均粒径 23 im) 76. 1 6 g、 バリン （平均粒径 22 /m) 45. 76 g、 ヒドロキシプロピルセルロー ス 4. 00 gを量り取り、 均一に混合した。 蒸留水 40. 00 gにレモンフレ一 バー微量を溶解させた液を結合液とし、 これを添加し造粒を行った。 造粒物を棚
段乾燥機を用い 6 0 °Cで 2時間乾燥し顆粒を得た。 1 4 0 0 /x m篩で篩分後、 篩 上品を 1 4 0 0 篩を用い強制篩過し、 篩下品と充分混合を行い、 医薬用顆粒 製剤を得た。 実験例 1 High-speed agitation granulator (8-speed mixer, manufactured by Fukae Patetech Co., Ltd.), 38.08 g of isoguchiine (average particle size 28 m), leucine (average particle size 23 im) 76.16 g, valine (average (Particle size 22 / m) 45.76 g and hydroxypropyl cellulose 4.00 g were weighed out and mixed uniformly. A solution obtained by dissolving a trace amount of lemon flavor in 40.00 g of distilled water was used as a binding solution, and this was added to perform granulation. Shelves with granules The granules were dried at 60 ° C for 2 hours using a stage dryer. After sieving with a 1400 / xm sieve, the sieved product was forcibly sieved using a 1400 sieve, and thoroughly mixed with the sieved product to obtain a pharmaceutical granule preparation. Experimental example 1
実施例 1〜 5で得た医薬用顆粒製剤、 比較例 1で得た医薬用顆粒製剤において ブラインド性を確保した状態で成人男性 5名のパネラーを用い服用し官能評価を 行った。 服用のしゃすさ、 服用後の 3種の分岐鎖アミノ酸 （B C A A) の医薬用 顆粒製剤の苦味、 後味の残り具合について評価を行った。 In the pharmaceutical granule preparations obtained in Examples 1 to 5 and the pharmaceutical granule preparation obtained in Comparative Example 1, sensory evaluation was performed using 5 adult male panelists while ensuring blindness. We evaluated the bitterness and residual aftertaste of the medicinal granule preparation of the three types of branched-chain amino acids (BCAA) after taking it and taking it.
判断基準は次の通りである。 The criteria are as follows.
◎： 良好、 もしくは全く気にならない。 ◎: Good or not at all.
〇： あまり気にならない。 〇: I don't care much.
△ :やや気になる、 もしくはやや苦い。 △: slightly anxious or slightly bitter.
X ：飲みにくレ 、 もしくは苦い。 表 1 X: Difficult to drink or bitter. table 1
以上のとおり、 本発明によるイソロイシン、 ロイシン、 及びパリンを含んでな る医薬用顆粒製剤は、 該分岐鎖アミノ酸特有の苦みが隠蔽され、 服用し易い医薬
用顆粒製剤である,
As described above, the pharmaceutical granule preparation containing isoleucine, leucine, and palin according to the present invention hides the bitterness peculiar to the branched-chain amino acid and is easy to take. Granule preparation,
Claims
1 . イソロイシン、 ロイシン及びパリンからなる 3種の分岐鎖アミノ酸を有効成 分として含有し、 かつ酸味剤として医薬品添加剤として許容されている少なくと も 1種の有機酸を含有することを特徴とする医薬用顆粒製剤。 1. It contains three types of branched-chain amino acids consisting of isoleucine, leucine and palin as an active ingredient, and contains at least one organic acid that is acceptable as a pharmaceutical additive as a sour agent. Pharmaceutical granules.
2 . 前記酸味剤がクェン酸、 リンゴ酸、 酢酸、 酒石酸及びァスコルビン酸から選 ばれる少なくとも 1種であることを特徴とする請求の範囲第 1項記載の医薬用顆 粒製剤。 2. The pharmaceutical granule preparation according to claim 1, wherein the sour agent is at least one selected from cunic acid, malic acid, acetic acid, tartaric acid and ascorbic acid.
3 . 前記酸味剤に加えて、 さらにアスパルテーム、 サッカリン、 サッカリンナト リウム、 グリチルリチン酸及びその塩類、 アセスルファム K、 マンニトール、 ェ リスり トール、 ソルビトール、 キシリ トール、 トレ八ロース、 カカオ末及びメン 卜一ルからなる群から選ばれる少なくとも 1種の矯味剤を含有することを特徴と する請求の範囲第 1項又は第 2項に記載の医薬用顆粒製剤。 3. In addition to the above-mentioned acidulants, aspartame, saccharin, sodium saccharin, glycyrrhizic acid and salts thereof, acesulfame K, mannitol, erythritol, sorbitol, xylitol, torehaulose, cacao powder and menthol 3. The pharmaceutical granule preparation according to claim 1, which comprises at least one flavoring agent selected from the group consisting of:
4 . 前記酸味剤に加えて、 さらに着香剤を含有することを特徴とする請求の範囲 第 1項〜第 3項のいずれか 1項に記載の医薬用顆粒製剤。
4. The pharmaceutical granule preparation according to any one of claims 1 to 3, further comprising a flavoring agent in addition to the sour agent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000-371665 | 2000-12-06 | ||
| JP2000371665A JP3259731B1 (en) | 2000-12-06 | 2000-12-06 | Pharmaceutical granules containing branched-chain amino acids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2002049638A1 true WO2002049638A1 (en) | 2002-06-27 |
Family
ID=18841351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2001/010527 WO2002049638A1 (en) | 2000-12-06 | 2001-12-03 | Medicinal granular preparation containing branched amino acids |
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| Country | Link |
|---|---|
| JP (1) | JP3259731B1 (en) |
| WO (1) | WO2002049638A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004016261A1 (en) * | 2002-08-12 | 2004-02-26 | Yuuichi Murayama | Method for suppressing proliferation of abnormal prion protein with leucine, isoleucine or valine |
| US7138142B2 (en) | 2002-01-24 | 2006-11-21 | Ajinomoto Co., Inc. | Process for producing granules containing branched amino acids |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004305201A (en) * | 2002-11-27 | 2004-11-04 | Hayashibara Biochem Lab Inc | Method for controlling formation of acrylamide and use of the same |
| TWI503128B (en) | 2007-07-31 | 2015-10-11 | Ajinomoto Kk | A granule preparation containing an amino acid with excellent taste |
| JP5756727B2 (en) * | 2011-09-30 | 2015-07-29 | ハウス食品グループ本社株式会社 | Granule |
| KR101598609B1 (en) * | 2013-01-17 | 2016-02-29 | 풍림무약주식회사 | Preparation method of granules containing amino acid |
| JP2018154598A (en) * | 2017-03-21 | 2018-10-04 | 株式会社明治 | Amino acid-containing granules and method for producing the same |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0725838A (en) * | 1993-05-13 | 1995-01-27 | Yotsuba Yuka Kk | Orally administering agent for preventing or recovering fatigue |
| JPH10287551A (en) * | 1997-04-11 | 1998-10-27 | Taisho Pharmaceut Co Ltd | Liquid agent for internal use improved in unpleasant flavor of amino acid |
| JP2000004836A (en) * | 1998-06-22 | 2000-01-11 | Meiji Milk Prod Co Ltd | Production of amino acid-containing food having good flavor |
-
2000
- 2000-12-06 JP JP2000371665A patent/JP3259731B1/en not_active Expired - Lifetime
-
2001
- 2001-12-03 WO PCT/JP2001/010527 patent/WO2002049638A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0725838A (en) * | 1993-05-13 | 1995-01-27 | Yotsuba Yuka Kk | Orally administering agent for preventing or recovering fatigue |
| JPH10287551A (en) * | 1997-04-11 | 1998-10-27 | Taisho Pharmaceut Co Ltd | Liquid agent for internal use improved in unpleasant flavor of amino acid |
| JP2000004836A (en) * | 1998-06-22 | 2000-01-11 | Meiji Milk Prod Co Ltd | Production of amino acid-containing food having good flavor |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7138142B2 (en) | 2002-01-24 | 2006-11-21 | Ajinomoto Co., Inc. | Process for producing granules containing branched amino acids |
| WO2004016261A1 (en) * | 2002-08-12 | 2004-02-26 | Yuuichi Murayama | Method for suppressing proliferation of abnormal prion protein with leucine, isoleucine or valine |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3259731B1 (en) | 2002-02-25 |
| JP2002173423A (en) | 2002-06-21 |
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