WO2003063854A1 - Chewable tablet containing branched amino acids - Google Patents
Chewable tablet containing branched amino acids Download PDFInfo
- Publication number
- WO2003063854A1 WO2003063854A1 PCT/JP2003/000579 JP0300579W WO03063854A1 WO 2003063854 A1 WO2003063854 A1 WO 2003063854A1 JP 0300579 W JP0300579 W JP 0300579W WO 03063854 A1 WO03063854 A1 WO 03063854A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- producing
- chewable
- granules
- leucine
- isoleucine
- Prior art date
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- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- 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 pharmaceutical tuple agent containing three kinds of branched-chain amino acids of isoleucine, leucine and parin as active ingredients.
- compositions containing three types of branched-chain amino acids consisting of isoleucine, leucine and palin as active ingredients are effective remedies for liver diseases, and currently commercially available preparations are mainly granules.
- a single dose is about 5 g, which is much larger than that of a general preparation, and there is a problem that it is difficult to take.
- a chewable preparation that is taken or dissolved in the mouth and taken is the preferred dosage form.
- the amount of the branched-chain amino acid mixture to be taken is too large compared to other drugs, so that the binding between powders is low and sticking is likely to occur as a tableting obstacle during tableting. .
- substances with strong binding properties such as cellulosic compounds, are added to prevent tableting disorders.However, formulations produced by such a method suffer from the bitterness inherent to branched-chain amino acids in the oral cavity. The difficulty was that it was difficult to take. Disclosure of the invention
- An object of the present invention is to provide a method for producing a chutable agent which does not generate stateing at the time of tableting in a process of producing a tiable agent containing three types of branched chain amino acids of isoleucine, leucine and parin as active ingredients.
- an object of the present invention is to suppress the odor and bitterness peculiar to the branched-chain amino acid and to have excellent stability during handling and storage.
- the present inventors have conducted intensive studies, and as a result, have found that a series of processes for producing a chewable agent containing only three types of branched-chain amino acids of isoloucine, leucine, and valine as active ingredients.
- the tableting step when granules containing isoleucine, leucine and palin, which are the raw materials for tableting, are coated with a liquid containing a binder component and then the granules are compressed, sticking is prevented, and
- the present inventors have found that the odor and bitterness peculiar to the three kinds of branched-chain amino acids can be reduced, and have completed the present invention.
- the present invention includes the following items.
- the binder component in the coating solution is mannitol, erythritol, sorbitol, xylitol, trehalose, ethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylethylcellulose, polyvinylpyrrolid.
- the method according to (1) which is at least one selected from dong, carboxyvinyl polymer, polypropylene alcohol, gum arabic and sodium alginate.
- the sweetener component in the coating liquid is aspartame, saccharin, saccharin sodium, glycyrrhizic acid, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, Acesulfame K: The manufacture of the chewable according to any one of (1) to (3), characterized by being at least one selected from mannitol, erythritol, sorbitol, xylitol and trehalose. Method.
- the step of producing the granule is a step of producing a granule by adding an acid aqueous solution to a particle mixture containing the three kinds of branched-chain amino acid particles as an active ingredient and granulating the mixture.
- the step of tableting the coated granules to produce a wobbled preparation is a step performed by mixing a magnesium compound into the coated granules (1) to (5). 2.
- the step of producing a while preparation by tableting the coated granules is a step of producing a while preparation having a hardness of 20 to 150 N.
- the particle mixture containing the three types of branched-chain amino acid particles of isoleucine, leucine, and parin as active ingredients is characterized by having masses of isoleucine, leucine, and palin, (1) to (6). 3.
- a chewable agent having a hardness of 20 to 15 ON which is manufactured by the method for manufacturing a chutable agent according to any one of the above (1) to (8).
- a chewable having a hardness of 30 to 120 N which is manufactured by the method for manufacturing a chewable according to any one of the above (1) to (8).
- a tiable agent having a hardness of 40 to 100 N which is produced by the method for producing a tiable agent according to any one of the above (1) to (8).
- a pharmaceutical preparation for healing a liver disease comprising the whiable preparation according to any one of the above (9) to (11).
- the chewable agent of the present invention is a medicinal while agent manufactured using three types of branched-chain amino acids consisting of isoleucine, leucine and palin as active ingredients.
- the one used as isoleucine which is one of the active ingredients, is generally a particle having a particle size of 1 mm or less produced by a fermentation method.
- the particle size is no particular limitation on the particle size as long as it meets the standards of either the Pharmacopoeia or the European Pharmacopoeia.
- Leucine is generally manufactured by fermentation or extraction and has a particle size of 1 mm or less, or as long as it meets the specifications of the Japanese Pharmacopoeia, the United States Pharmacopeia, or the European Pharmacopoeia. However, there is no particular restriction on the particle size.
- particles having a particle size of 1 mm or less which are generally produced by a fermentation method or a synthesis method, are used.
- any of the standards of the Japanese Pharmacopoeia, U.S. There is no particular restriction on the particle size as long as it satisfies.
- Binder components mannitol, erythritol, sorbitol, xylitol, trehalose, ethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, lipoxylmethylethylcellulose, polyvinylpyrroli Don, lipoxyvinyl polymer, polyvinyl alcohol, gum arabic, sodium alginate, etc.
- the sweetener that can be used in the coating solution together with the binder is selected from, for example, those exemplified below and used.
- Sweetener components aspartame, saccharin, saccharin sodium, glycyrrhizic acid, monoammonium daricyllytinate, diammonium glycyrrhizinate, diammonium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, acesulfame K and the like.
- sweetener component it is desirable to avoid using a reducing sugar or the like that may cause a Maillard reaction with the three kinds of branched-chain amino acids.
- the chewable preparation of the present invention can generally contain a flavoring agent used in pharmaceutical preparations, foods and the like.
- a flavoring agent used in pharmaceutical preparations, foods and the like.
- various flavors are used. Examples include lemon flavor, orange flavor, grapefruit flavor, chocolate flavor, dl-menthol, 1-menthol, and the like.
- a usual production method such as a wet method or a dry method can be applied, and a high-speed stirring granulator, a fluidized bed granulator, or the like.
- Equipment such as a press, a planetary mixer, a dry press granulator, a crushing granulator, an extrusion granulator, a rolling granulator, a spray drying granulator, and a coating granulator are used.
- an acid solution is added to the raw material branched chain amino acid particles and granulation is performed, so that the specific volume of the granules can be reduced.
- various methods such as a fluidized-bed coating and a rolling-bed coating usually used for coating a granular material can be applied.
- tableting is usually performed at a tableting pressure of 0.3 to 1.2 tons. It is not limited to this. By performing tableting with such a tableting pressure, a chewable preparation having a hardness of 30 N or more and 150 N or less can be broken down, and the chewability in the oral cavity can be improved when the chewable preparation is taken.
- a magnesium compound such as magnesium stearate or talc
- the tableting properties of the raw material granules of the above Examples and Comparative Examples and the hardness of the obtained chewable tablets were measured with a hardness meter (TS-50N manufactured by Okada Seie Co., Ltd.).
- Example 1 No sticking 1.02 tons 78.3N
- Example 2 No sticking 0.86 tons 57.9N
- Example 3 No sticking 0.71 tons 53.5N Comparative
- Example 1 Sticking 1.10 tons 19.3N Industrial applicability
- the medicated chewable preparation produced according to the present invention is a preparation that can be rapidly chewed in the mouth and that is highly ingestible.
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Abstract
A process for chewable-tablet production free from sticking during tableting; and a chewable tablet containing three branched amino acids, i.e., isoleucine, leucine, and valine, as active ingredients, in which the odor and bitterness characteristic of the branched amino acids are diminished and which is excellent in handleability and storage stability. The process, which is for producing a chewable tablet containing three branched amino acids, i.e., isoleucine, leucine, and valine, as active ingredients, is characterized by comprising: a step in which a particle mixture comprising three branched amino acids, i.e., isoleucine, leucine, and valine, as active ingredients is granulated; a step in which the granules are coated with a coating fluid containing a binder ingredient to produce coated granules; and a step in which the coated granules are tableted to produce a chewable tablet.
Description
明 細 書 Specification
分岐鎖アミノ酸を含有するチユアブル剤 Chewables containing branched-chain amino acids
：分岐鎖アミノ酸を含有するチユアブル剤 : Chewable containing branched-chain amino acids
技術分野 Technical field
本発明は、 イソロイシン、 ロイシン及びパリンの 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チユアプル剤に関する。 背景技術 The present invention relates to a pharmaceutical tuple agent containing three kinds of branched-chain amino acids of isoleucine, leucine and parin as active ingredients. 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 として含む医薬用製剤は肝疾患に有効な治療薬であり、 現在市販されている製剤 は顆粒剤が主体である。 しかし、 上記 3種の分岐鎖アミノ酸粒子を有効成分とす る顆粒剤の場合、 その 1回服用量が約 5 gと一般の製剤と比較して著しく多く、 服用しにくいという難点があった。 Pharmaceutical preparations containing three types of branched-chain amino acids consisting of isoleucine, leucine and palin as active ingredients are effective remedies for liver diseases, and currently commercially available preparations are mainly granules. However, in the case of granules containing the above-mentioned three kinds of branched-chain amino acid particles as an active ingredient, a single dose is about 5 g, which is much larger than that of a general preparation, and there is a problem that it is difficult to take.
一般的に、 1回服用量が多い製剤を服用する場合、 口中で嚙むか又溶かして服 用するチユアブル剤が好ましい剤形といえるが、 分岐鎖アミノ酸混合物をチユア ブル剤とした場合、 1回で服用とする分岐鎖アミノ酸混合物の量が他の薬剤の場 合に比較してあまりに多いため、 粉体同士の結合性が低く、 打錠時の打錠障害と してスティッキングが発生しやすくなる。 このため、 セルロース系化合物などの 結合性の強い物質を添加し、 打錠障害の防止を図っているが、 このような方法に より製造された製剤は口腔内で分鎖鎖アミノ酸に特有の苦みがでて服用性が悪い ことが難点であった。 発明の開示 In general, when taking a large dose of a single dose, a chewable preparation that is taken or dissolved in the mouth and taken is the preferred dosage form. The amount of the branched-chain amino acid mixture to be taken is too large compared to other drugs, so that the binding between powders is low and sticking is likely to occur as a tableting obstacle during tableting. . For this reason, substances with strong binding properties, such as cellulosic compounds, are added to prevent tableting disorders.However, formulations produced by such a method suffer from the bitterness inherent to branched-chain amino acids in the oral cavity. The difficulty was that it was difficult to take. Disclosure of the invention
本発明の課題は、 イソロイシン、 ロイシン及びパリンの 3種の分岐鎖アミノ酸 を有効成分とするチユアブル剤の製造工程において、 打錠時にステイツキングが 発生しないチユアブル剤の製造方法を提供することにある。 An object of the present invention is to provide a method for producing a chutable agent which does not generate stateing at the time of tableting in a process of producing a tiable agent containing three types of branched chain amino acids of isoleucine, leucine and parin as active ingredients.
また、本発明の課題は、分岐鎖アミノ酸に特有の臭いや苦味が抑制されており、 かつ、 取扱いや保存時の安定性にも優れている、 前記 3種の分岐鎖アミノ酸を有 効成分とするチユアブル剤を提供することにある。
上記課題を解決するため、 本発明者らは鋭意検討を重ねた結果、 有効成分とし てィソロイシン、 ロイシン及びバリンの 3種の分岐鎖アミノ酸のみを含有するチ ユアブル剤を製造する一連の工程における打錠工程において、 打錠原料となる、 イソロイシン、 ロイシン及びパリンを含有する顆粒に、 結合剤成分を含有する液 によるコ一ティングを施してから該顆粒を打錠するとスティッキングが防止され るとともに、 前記 3種の分岐鎖アミノ酸に特有の臭いや苦味をも低減し得ること を見出し、 本発明を完成するに至った。 本発明は、 以下の各項目を包含する。Further, an object of the present invention is to suppress the odor and bitterness peculiar to the branched-chain amino acid and to have excellent stability during handling and storage. To provide a chewable agent. In order to solve the above-mentioned problems, the present inventors have conducted intensive studies, and as a result, have found that a series of processes for producing a chewable agent containing only three types of branched-chain amino acids of isoloucine, leucine, and valine as active ingredients. In the tableting step, when granules containing isoleucine, leucine and palin, which are the raw materials for tableting, are coated with a liquid containing a binder component and then the granules are compressed, sticking is prevented, and The present inventors have found that the odor and bitterness peculiar to the three kinds of branched-chain amino acids can be reduced, and have completed the present invention. The present invention includes the following items.
( 1 ) イソロイシン、 ロイシン及びパリンの 3種の分岐鎖アミノ酸粒子を有効成 分として含有する粒子混合物を造粒して顆粒を製造する工程、 結合剤成分を含有 するコーティング液で該顆粒をコ一ティングしてコーティング顆粒を製造するェ 程、 及び該コ一ティング顆粒を打錠してチユアブル剤を製造する工程を有するこ とを特徴とする、 イソロイシン、 ロイシン及びパリンの 3種の分岐鎖アミノ酸を 有効成分として含有するチユアブル剤の製造方法。 (1) a step of granulating a particle mixture containing three types of branched-chain amino acid particles of isoleucine, leucine and palin as active ingredients to produce granules, and coagulating the granules with a coating solution containing a binder component. Coating to produce coated granules; and tableting the coated granules to produce a readable drug, wherein three types of branched-chain amino acids of isoleucine, leucine and parin are provided. A method for producing a chewable agent contained as an active ingredient.
( 2 ) 前記コーティング液における結合剤成分は、 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、 トレハロース、 ェチルセルロース、 メチルセ ルロース、 ヒドロキシプロピルセルロース、 ヒドロキシプロピルメチルセルロー ス、 カルボキシルメチルェチルセルロース、 ポリビニルピロリ ドン、 カルポキシ ビニルポリマー、 ポリピエルアルコール、 アラビアゴム及びアルギン酸ナ卜リウ ムから選ばれる 1種以上であることを特徴とする （ 1 ) 項記載のチユアブル剤の 製造方法。 (2) The binder component in the coating solution is mannitol, erythritol, sorbitol, xylitol, trehalose, ethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylethylcellulose, polyvinylpyrrolid. The method according to (1), which is at least one selected from dong, carboxyvinyl polymer, polypropylene alcohol, gum arabic and sodium alginate.
( 3 ) 前記コーティング液は甘味剤成分を含有することを特徴とする （ 1 ) 又は ( 2 ) 項に記載のチユアブル剤の製造方法。 (3) The method according to (1) or (2), wherein the coating liquid contains a sweetener component.
( 4 ) 前記コーティング液中の甘味剤成分は、 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、 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 トール及び卜レハロースから選 ばれる 1種以上であることを特徴とする （1 ) 〜 （3 ) 項のいずれか 1項に記載 のチユアブル剤の製造方法。
(5) 前記顆粒を製造する工程が、 前記 3種の分岐鎖アミノ酸粒子を有効成分と して含有する粒子混合物に酸水溶液を添加して造粒することによって顆粒を製造 する工程であることを特徴とする （1) 〜 （4) 項のいずれか 1項に記載のチュ アプル剤の製造方法。 (4) The sweetener component in the coating liquid is aspartame, saccharin, saccharin sodium, glycyrrhizic acid, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, Acesulfame K: The manufacture of the chewable according to any one of (1) to (3), characterized by being at least one selected from mannitol, erythritol, sorbitol, xylitol and trehalose. Method. (5) The step of producing the granule is a step of producing a granule by adding an acid aqueous solution to a particle mixture containing the three kinds of branched-chain amino acid particles as an active ingredient and granulating the mixture. The method for producing a tuple preparation according to any one of (1) to (4), which is characterized in that:
(6) 前記コーティング顆粒を打錠してチユアブル剤を製造する工程が、 前記コ —ティング顆粒にマグネシウム化合物を混合して行われる工程であることを特徴 とする （1) 〜 （5) 項のいずれか 1項に記載のチユアブル剤の製造方法。 (6) The step of tableting the coated granules to produce a wobbled preparation is a step performed by mixing a magnesium compound into the coated granules (1) to (5). 2. The method for producing a chuable according to claim 1.
(7) 前記コーティング顆粒を打錠してチユアブル剤を製造する工程が、 硬度が 20〜 1 50 Nのチユアブル剤を製造する工程であることを特徴とする （1) 〜 (6) 項のいずれか 1項に記載のチユアブル剤の製造方法。 (7) The step of producing a while preparation by tableting the coated granules is a step of producing a while preparation having a hardness of 20 to 150 N. (1) Any of (1) to (6) Or the method for producing a chewable according to item 1.
(8) 前記イソロイシン、 ロイシン及びパリンの 3種の分岐鎖アミノ酸粒子を有 効成分として含有する粒子混合物は、 イソロイシン、 ロイシン及びパリンの質量 あることを特徴とする、 （1) 〜 （6)項のいずれか 1項に記載のチユアブル剤の 製造方法。 (8) The particle mixture containing the three types of branched-chain amino acid particles of isoleucine, leucine, and parin as active ingredients is characterized by having masses of isoleucine, leucine, and palin, (1) to (6). 3. The method for producing a chuable according to claim 1.
(9) 前記 （1) 〜 （8) 項のいずれか 1項に記載のチユアブル剤の製造方法に よって製造されていることを特徴とする、 硬度が 20〜1 5 ONであるチュアブ ル剤。 (9) A chewable agent having a hardness of 20 to 15 ON, which is manufactured by the method for manufacturing a chutable agent according to any one of the above (1) to (8).
(10) 前記 （1) 〜 （8) 項のいずれか 1項に記載のチユアブル剤の製造方法 によって製造されていることを特徴とする、 硬度が 30〜 120 Nであるチユア ブル剤。 (10) A chewable having a hardness of 30 to 120 N, which is manufactured by the method for manufacturing a chewable according to any one of the above (1) to (8).
(1 1) 前記 （1) 〜 （8) 項のいずれか 1項に記載のチユアブル剤の製造方法 によって製造されていることを特徴とする、 硬度が 40〜100Nであるチユア ブル剤。 (11) A tiable agent having a hardness of 40 to 100 N, which is produced by the method for producing a tiable agent according to any one of the above (1) to (8).
(12) 前記 （9) 〜 （1 1) 項のいずれか 1項に記載のチユアブル剤からなる 肝疾患治癒用医薬製剤。 (12) A pharmaceutical preparation for healing a liver disease, comprising the whiable preparation according to any one of the above (9) to (11).
本発明のチユアブル剤は、 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製造されている医薬用のチユアブル剤である。 本発明のチユアブル剤は、 イソロイシン、 ロイシン及びパリンの配合割合が質
量比で、 イソロイシン ロイシン バリン = 1ノ 1 . 9〜 2 . 2 / 1 . 1〜 1 .The chewable agent of the present invention is a medicinal while agent manufactured using three types of branched-chain amino acids consisting of isoleucine, leucine and palin as active ingredients. The chewable preparation of the present invention has a high mixing ratio of isoleucine, leucine and parin. In the quantitative ratio, isoleucine leucine valine = 1.9 to 2.2 / 1.1 to 1.1.
3であることが好ましい。 It is preferably 3.
本発明のチユアブル剤において、 有効成分の一つであるイソロイシンとして使 用されるものは、 一般的に発酵法で製造されている粒度が 1 mm以下の粒子であ るが、 日本薬局方、 米国薬局方、 欧州薬局方のいずれかの規格を満たすものであ る限り、 粒子の粒度に特に制約はない。 In the chewable preparation of the present invention, the one used as isoleucine, which is one of the active ingredients, is generally a particle having a particle size of 1 mm or less produced by a fermentation method. There is no particular limitation on the particle size as long as it meets the standards of either the Pharmacopoeia or the European Pharmacopoeia.
ロイシンとしては、 一般的に発酵法又は抽出法で製造されている粒度が 1 mm 以下の粒子であるか、 日本薬局方、 米国薬局方、 欧州薬局方のいずれかの規格を 満たすものである限り、 粒子の粒度に特に制約はない。 Leucine is generally manufactured by fermentation or extraction and has a particle size of 1 mm or less, or as long as it meets the specifications of the Japanese Pharmacopoeia, the United States Pharmacopeia, or the European Pharmacopoeia. However, there is no particular restriction on the particle size.
また、 パリンとしては、 一般的に発酵法もしくは合成法で製造されている粒度 が l mm以下の粒子が使用されるが、 日本薬局方、 米国薬局方、 欧州薬局方のい ずれかの規格を満たすものである限り、 粒子の粒度に特に制約はない。 In addition, as parin, particles having a particle size of 1 mm or less, which are generally produced by a fermentation method or a synthesis method, are used. However, any of the standards of the Japanese Pharmacopoeia, U.S. There is no particular restriction on the particle size as long as it satisfies.
本発明のチユアブル剤の製造工程において、 打錠前の顆粒のコ一ティング液に 使用される結合剤成分は、以下の成分の中から 1つ以上が選択され、使用される。 結合剤成分： マンニ卜ール、 エリスリ トール、 ソルビトール、 キシリ トール、 卜 レハロース、 ェチルセルロース、 メチルセルロース、 ヒドロキシプロピルセル口 ース、 ヒドロキシプロピルメチルセルロース、 力ルポキシルメチルェチルセル口 ース、 ポリビニルピロリ ドン、 力ルポキシビ二ルポリマー、 ポリビニルアルコー ル、 アラビアゴム、 アルギン酸ナトリウム等。 In the manufacturing process of the tablet preparation of the present invention, one or more of the following components are selected and used as the binder component used in the coating solution of the granules before tableting. Binder components: mannitol, erythritol, sorbitol, xylitol, trehalose, ethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, lipoxylmethylethylcellulose, polyvinylpyrroli Don, lipoxyvinyl polymer, polyvinyl alcohol, gum arabic, sodium alginate, etc.
また、 結合剤と共にコーティング液に使用することができる甘味剤は、 例えば 以下に例示したものから選択され、 使用される。 The sweetener that can be used in the coating solution together with the binder is selected from, for example, those exemplified below and used.
甘味剤成分 ： 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、ダ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力リウム、 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等。 Sweetener components: aspartame, saccharin, saccharin sodium, glycyrrhizic acid, monoammonium daricyllytinate, diammonium glycyrrhizinate, diammonium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, acesulfame K and the like.
なお、 甘味剤成分としては、 前記 3種の分岐鎖アミノ酸とメイラード反応を起 こすような還元糖などの使用は避けることが望ましい。 As the sweetener component, it is desirable to avoid using a reducing sugar or the like that may cause a Maillard reaction with the three kinds of branched-chain amino acids.
本発明のチユアブル剤は、 一般的に、 医薬製剤や食品等に使用されている矯味 剤を含有することができる。 そのような矯味剤としては、 各種フレーバーを用い
ることができるが、 例としては、 レモンフレーパー、 オレンジフレーバー、 グレ ープフルーツフレーバー、 チョコレー卜フレーバ一、 d l—メントール、 1ーメ ントール等が挙げられる。 The chewable preparation of the present invention can generally contain a flavoring agent used in pharmaceutical preparations, foods and the like. As such a flavoring agent, various flavors are used. Examples include lemon flavor, orange flavor, grapefruit flavor, chocolate flavor, dl-menthol, 1-menthol, and the like.
本発明のチユアプル剤の製造工程における前記顆粒製造のための造粒方法とし ては、 湿式法、 乾式法等の通常行われている製造方法を適用でき、 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、 破碎造粒機、 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が使 用される。 顆粒製造の際に、 原料分岐鎖アミノ酸粒子に酸溶液を添加して造粒す ることにより、 顆粒の比容積を小さくすることができるので好ましい。 As the granulation method for producing the granules in the production process of the tuples of the present invention, a usual production method such as a wet method or a dry method can be applied, and a high-speed stirring granulator, a fluidized bed granulator, or the like. Equipment such as a press, a planetary mixer, a dry press granulator, a crushing granulator, an extrusion granulator, a rolling granulator, a spray drying granulator, and a coating granulator are used. At the time of granule production, an acid solution is added to the raw material branched chain amino acid particles and granulation is performed, so that the specific volume of the granules can be reduced.
また、 本発明のチユアブル剤の製造工程における前記顆粒のコ一ティング方法 としては、 通常、 粒状物のコーティングに使用される流動層コーティング、 転動 層コーティング等の各種方法を適用できる。 In addition, as a method of coating the granules in the production process of the chewable preparation of the present invention, various methods such as a fluidized-bed coating and a rolling-bed coating usually used for coating a granular material can be applied.
また、 本発明のチユアブル剤の製造工程における前記コ一ティグ顆粒からチュ アプル剤を製造するための打錠工程では、 通常 0. 3トン以上 1. 2トン以下の 打錠圧で打錠が行われるが、 これに限るものではない。 このような打錠圧で打錠 することにより硬度 30 N以上 1 50 N以下のチユアブル剤を打綻でき、 このチ ユアブル剤を服用するとき口腔内での咀嚼性が改善できる。 前記コ一ティグ顆粒 を打錠する際に、 該コーティング顆粒にステアリン酸マグネシウムやタルクのよ うなマグネシウム化合物を添加混合して打錠するとチユアブル剤の保存時の着色 が防止できるので好ましい。 発明を実施するための最良の形態 In the tableting process for producing a tuple from the coated granules in the process for producing the tabletable tablet of the present invention, tableting is usually performed at a tableting pressure of 0.3 to 1.2 tons. It is not limited to this. By performing tableting with such a tableting pressure, a chewable preparation having a hardness of 30 N or more and 150 N or less can be broken down, and the chewability in the oral cavity can be improved when the chewable preparation is taken. When the above-mentioned coated granules are tableted, it is preferable to add and mix a magnesium compound such as magnesium stearate or talc to the coated granules and tablet them, since coloring during storage of the chewable can be prevented. BEST MODE FOR CARRYING OUT THE INVENTION
本発明の具体例を以下に実施例として示すが、 本発明はこれらによって限定さ れるものではない。 実施例 1 EXAMPLES Specific examples of the present invention will be shown below as examples, but the present invention is not limited thereto. Example 1
ロイシン 285. 6 g、 ノ'リン 17 1. 6 g、 イソロイシン 142. 9 g、 ヒ ドロキシプロピルセルロース 1 5. l g、 カカオ末 19. 6 g、 蒸留水 285. 0 gを秤量後、 スクリーン径 0. 5 mmで押し出し造粒機 （ダルトン社製 DG—
L I ) で練合し、 造粒し、 流動層造粒機 （フロイント産業社製 S F C— M I N) で乾燥させた。 同様な操作を繰り返して得られた顆粒 8 8 8. 3 g秤量し、 別に エリスリ トール 3 1 5. 1 g、 サッカリンナトリウム 2. 1 8を蒸留水8 8 0 8 に溶かしたコーティング液としてコ一ティングを行った。 このようにして得られ たコ一ティング顆粒 3 44. 5 g、 ァクチゾル 6. 0 g、 チョコレートフレーバ 一 0. 3 g、 ステアリン酸マグネシウム 1 0. 8 gを混合してチユアブル剤製造 用の原料顆粒を製造した。 この原料顆粒を打錠機 （畑鐡ェ所、 HT— AP 6 S S -II) で 1. 0 2 トンで打錠してチユアブル錠を製造した。 実施例 2 After Leucine 285. 6 g, Roh 'phosphate 17 1. 6 g, isoleucine 142. 9 g, hydroxycarboxylic cellulose 1 5. lg, cocoa powder 19. 6 g, distilled water 285. 0 g weighed, screen size Extrusion granulator at 0.5 mm (Dalton DG— LI), granulated, and dried with a fluid bed granulator (SFC-MIN manufactured by Freund Corporation). 88.8.3 g of granules obtained by repeating the same operation were weighed and separately coated as a coating solution obtained by dissolving 35.1 g of erythritol and 2.18 g of saccharin sodium in distilled water 8808. Was done. 344.5 g of the coating granules thus obtained, 6.0 g of actisol, 0.3 g of chocolate flavor, and 10.8 g of magnesium stearate were mixed to obtain raw granules for the production of whitable preparations. Was manufactured. The raw granules were tableted with a tableting machine (Hata Tetsusho, HT-AP 6 SS-II) at 1.02 ton to produce chewable tablets. Example 2
ロイシン 2 8 5. 6 g、 ノ リン 1 7 1. 6 0 g、 イソロイシン 1 4 2. 8 0 g、 ヒドロキシプロピルセルロース 1 5. 0 g、 カカオ末 1 9. 5 g、 蒸留水 2 8 5. O gを秤量後、 スクリーン径 0. 5 mmで押し出し造粒機 （ダルトン社製 DG— L 1 ) で練合した。 これを、 流動層造粒機 （フロイント産業社製 S F C— M I N) で乾燥させた、 同様な操作を繰り返した。 これを 8 8 8. 3 0 g秤量し、 別にマ ンニトール 3 1 5. 0 g、 サッカリンナトリウム 2. 1 0 8を蒸留水8 8 0 に 溶かしたコーティング液とし、 コーティングを行った。 このコーティング顆粒 3 4 5. 5 g、 クロスポピドン 1 8. 0 g、 クロスカルメロースナトリウム 6. 0 g、 チョコレートフレーパ一 0. 3 g、 ステアリン酸マグネシウム 1 1. 4 gを 混合させチユアブル剤用顆粒を製造した。 この顆粒を打錠機 （畑鐡ェ所社製 HT — AP 6 S S— Π) で 0. 8 6 トンで打錠しチユアブル錠を製造した。 実施例 3 Leucine 285.6 g, Norin 171.70 g, Isoleucine 142.80 g, Hydroxypropylcellulose 15.0 g, Cocoa powder 19.5 g, Distilled water 288.5 After weighing Og, the mixture was kneaded with an extrusion granulator (DG-L1 manufactured by Dalton) with a screen diameter of 0.5 mm. This was dried with a fluid bed granulator (SFC-MIN) manufactured by Freund Corporation, and the same operation was repeated. This was weighed 88.8.30 g, and coated separately using a coating solution in which 35.0 g of mannitol and 2.108 of saccharin sodium were dissolved in 880 of distilled water. 34.5.5 g of the coated granules, 18.0 g of crospopidone, 6.0 g of croscarmellose sodium, 0.3 g of chocolate flavour, and 11.4 g of magnesium stearate are mixed and used for chewable preparations. Granules were produced. The granules were tableted at 0.86 ton with a tableting machine (HT-AP6SS-II manufactured by Hattetsu Corporation) to produce chewable tablets. Example 3
ロイシン 2 8 5. 6 g、 ノ リン 1 7 1. 6 0 g、 イソロイシン 1 42. 8 g、 コリ ドン K 9 0 7. 5 g、 無水クェン酸 3 0. 0 g、 蒸留水 2 8 0. 0 gを秤量 後、 スクリーン径 0. 5 mmで押し出し造粒機 （ダルトン社製 DG_L 1 ) で練 合した。 これを、 流動層造粒機 （フロイント産業社製 S F C— M I N) で乾燥さ せた、 同様な操作を繰り返した。 これを 5 1 0. O g秤量し、 別にマンニトール 1 8 0. 2 g、 サッカリンナトリウム 1. 2 gを蒸留水 1 0 6 3. O gに溶かし
コ一ティング液とし、 スプレーにてコーティングを行った。 このコーティング顆 粒 345. 5 g、 クロスポピドン 18. 0 g、 クロスカルメロースナトリウム 6. 0 g、 レモンオイル 0. 3 g、 ステアリン酸マグネシウム 1 1. 4 gを混合させ チユアブル剤用顆粒を製造した。 この顆粒を打錠機 （畑鐡ェ所社製 HT— AP 6 S S— II) で 0. 71 トンで打錠しチユアブル錠を製造した。 比較例 1 Leucine 285.6 g, Norin 171.70 g, Isoleucine 142.8 g, Kollidone K 97.5 g, Cyanic anhydride 30.0 g, Distilled water 280. After weighing 0 g, the mixture was kneaded with an extrusion granulator (DG_L 1 manufactured by Dalton) with a screen diameter of 0.5 mm. This was dried using a fluid bed granulator (SFC-MIN manufactured by Freund Corporation), and the same operation was repeated. This was weighed to 50.1 Og, and then separately dissolved 180.2 g of mannitol and 1.2 g of saccharin sodium in 106 g of distilled water. Coating was performed by spraying with a coating liquid. 345.5 g of the coated granules, 18.0 g of crospopidone, 6.0 g of croscarmellose sodium, 0.3 g of lemon oil, and 11.4 g of magnesium stearate were mixed to produce granules for chewable preparations. . The granules were tableted at 0.71 ton with a tableting machine (HT-AP 6 SS-II manufactured by Hattetsu Corporation) to produce chewable tablets. Comparative Example 1
ロイシン 285. 6 g、 ノ リン 1 71. 6 g、 イソロイシン 142. 8 g、 ヒ ドロキシプロピルセルロース 1 5. 0 g、 カカオ末 19. 5 g、 蒸留水 285. 0 gを枰量後、 スクリーン径 0. 5 mmで押し出し造粒機 （ダルトン社製 DG— L 1) で練合した。 これを、 流動層造粒機 （フロイント産業社製 SFC— M I N) で乾燥させた。 得られた顆粒 253. 8 g、 クロスポピドン 6. 0 g、 ステアリ ン酸マグネシウム 10. 8 gを混合してチユアブル剤製造用の原料顆粒を製造し た。 この原料顆粒をそのまま打錠機 （畑鐡ェ所、 HT— AP 6 S S— II) で 1. 10 トンで打錠してチユアブル錠を製造した。 試験例 After weighing 285.6 g of leucine, 171.6 g of phosphorus 174.2 g of isoleucine, 15.0 g of hydroxypropylcellulose, 19.5 g of cocoa powder, and 285.0 g of distilled water, screen It was kneaded with an extrusion granulator (DG-L1 manufactured by Dalton) with a diameter of 0.5 mm. This was dried using a fluid bed granulator (SFC-MIN, manufactured by Freund Corporation). 253.8 g of the obtained granules, 6.0 g of crospopidone, and 10.8 g of magnesium stearate were mixed to produce raw material granules for the production of chewables. The raw granules were directly compressed at 1.10 tonnes using a tableting machine (Hata Tetsusho, HT-AP6SS-II) to produce chewable tablets. Test example
前記の実施例及び比較例の原料顆粒の打錠性及び得られたチユアブル錠の硬度 を硬度計 （岡田精ェ社製 T S— 50 N) にて測定した。 The tableting properties of the raw material granules of the above Examples and Comparative Examples and the hardness of the obtained chewable tablets were measured with a hardness meter (TS-50N manufactured by Okada Seie Co., Ltd.).
【表 1】 【table 1】
ステッキングの有無 打鲑圧 硬度 （N) With or without sticking Pressing pressure Hardness (N)
実施例 1 ステッキング無 1. 02卜ン 78. 3N 実施例 2 ステッキング無 0. 86トン 57. 9N 実施例 3 ステッキング無 0. 71卜ン 53. 5N 比較例 1 ステッキンク 1. 10卜ン 19. 3N
産業上の利用可能性 Example 1 No sticking 1.02 tons 78.3N Example 2 No sticking 0.86 tons 57.9N Example 3 No sticking 0.71 tons 53.5N Comparative Example 1 Sticking 1.10 tons 19.3N Industrial applicability
本発明により、 イソロイシン、 ロイシン及びバリンを有効成分とする医薬用チ ユアブル剤の製造時の打錠工程において、 ステイツキングが防止され、 そのため 生産効率が大幅に改善され、 その効果は明らかである。 また、 この発明により製 造される医薬用チユアブル剤は口内で速やかに咀嚼できる、 服用性の高い製剤で ある。
ADVANTAGE OF THE INVENTION According to this invention, in the tableting process at the time of the manufacture of the pharmaceutical pills containing isoleucine, leucine and valine as an active ingredient, the sticking is prevented, the production efficiency is largely improved, and the effect is obvious. In addition, the medicated chewable preparation produced according to the present invention is a preparation that can be rapidly chewed in the mouth and that is highly ingestible.
Claims
1 . イソロイシン、 ロイシン及びパリンの 3種の分岐鎖アミノ酸粒子を有効成分 として含有する粒子混合物を造粒して顆粒を製造する工程、 結合剤成分を含有す るコーティング液で該顆粒をコ一ティングしてコーティング顆粒を製造する工程、 及び該コーティング顆粒を打錠してチユアブル剤を製造する工程を有することを 特徴とする、 イソロイシン、 ロイシン及びパリンの 3種の分岐鎖アミノ酸を有効 成分として含有するチユアブル剤の製造方法。 1. A step of granulating a particle mixture containing three types of branched chain amino acid particles of isoleucine, leucine and palin as active ingredients to produce granules, and coating the granules with a coating solution containing a binder component Comprising three types of branched chain amino acids, isoleucine, leucine and palin, as active ingredients, characterized by comprising the steps of: A method for producing a chewable.
2 .前記コーティング液における結合剤成分は、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、 卜レハロース、 ェチルセルロース、 メチルセル口 ース、 ヒドロキシプロピルセルロース、 ヒドロキシプロピルメチルセルロース、 カルボキシルメチルェチルセルロース、 ポリビニルピロリ ドン、 カルボキシビ二 ルポリマー、 ポリビニルアルコール、 アラビアゴム及びアルギン酸ナトリウムか ら選ばれる 1種以上であることを特徴とする請求の範囲第 1項に記載のチュアブ ル剤の製造方法。 2. The binder component in the coating solution is mannitol, erythritol, sorbitol, xylitol, trehalose, ethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylethylcellulose, polyvinylpyrrolidone. 2. The method according to claim 1, wherein the method is at least one selected from the group consisting of carboxyvinyl polymer, polyvinyl alcohol, gum arabic and sodium alginate.
3 . 前記コーティング液は甘味剤成分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項に記載のチユアブル剤の製造方法。 3. The method according to claim 1, wherein the coating solution contains a sweetener component.
4 . 前記コーティング液中の甘味剤成分は、 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、 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 —ル、 エリスリ トール、 ソルビトール、 キシリ トール及びトレハロースから選ば れる 1種以上であ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 に記載のチユアブル剤の製造方法。 4. The sweetener component in the coating liquid is aspartame, saccharin, saccharin sodium ', glycyrrhizic acid, glycyrrhizinate monoammonium, glycyrrhizinate diammonium, dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, acesulfame 4. The method according to claim 1, wherein the drug is at least one selected from the group consisting of K, mannitol, erythritol, sorbitol, xylitol and trehalose. Method.
5 . 前記顆粒を製造する工程が、 前記 3種の分岐鎖アミノ酸粒子を有効成分とし て含有する粒子混合物に酸水溶液を添加して造粒することによって顆粒を製造す る工程であることを特徴とする請求の範囲第 1項〜第 4項のいずれか 1項に記載 のチユアブル剤の製造方法。 5. The step of producing the granules is a step of producing a granule by adding an aqueous acid solution to a particle mixture containing the three kinds of branched-chain amino acid particles as an active ingredient and granulating the mixture. The method for producing a chuable according to any one of claims 1 to 4.
6 . 前記コーティング顆粒を打錠してチユアブル剤を製造する工程が、 前記コー
ティング顆粒にマグネシウム化合物を混合して行われる工程であることを特徴と する請求の範囲第 1項〜第 5項のいずれか 1項に記載のチユアブル剤の製造方法 c 6. The step of tableting the coated granules to produce a chewable preparation comprises: 6. A process c for producing a chewable according to any one of claims 1 to 5, characterized in that the process is carried out by mixing a magnesium compound into the granules.
7. 前記コーティング顆粒を打錠してチユアブル剤を製造する工程が、 硬度が 2 0〜 1 5 0 Nのチユアブル剤を製造する工程であることを特徴とする請求の範囲 第 1項〜第 6項のいずれか 1項に記載のチュアプル剤の製造方法。 7. The step of producing a whitable preparation by tableting the coated granules is a step of producing a tiable preparation having a hardness of 20 to 150 N. Item 14. The method for producing a tuple preparation according to any one of Items 1.
8. 前記イソロイシン、 ロイシン及びパリンの 3種の分岐鎖アミノ酸粒子を有効 成分として含有する粒子混合物は、 イソロイシン、 ロイシン及びパリンの質量比 がイソロイシン/ロイシン/バリン = 1 / 1. 9〜 2. 2/ 1. 1〜 1. 3であ ることを特徴とする、 請求の範囲第 1項〜第 7項のいずれか 1項に記載のチユア ブル剤の製造方法。 8. In the particle mixture containing the three kinds of branched-chain amino acid particles of isoleucine, leucine and parin as active ingredients, the mass ratio of isoleucine, leucine and palin is isoleucine / leucine / valine = 1 / 1.9 to 2.2. / 11. The method for producing a tiable according to any one of claims 1 to 7, wherein the method is 1.1 to 1.3.
9. 前記請求の範囲第 1項〜第 8項のいずれか 1項に記載のチユアブル剤の製造 方法によって製造されていることを特徴とする、 硬度が 2 0〜 1 5 O Nであるチ ユアブル剤。 9. A chewable agent having a hardness of 20 to 15 ON, characterized in that it is manufactured by the method for manufacturing a chuble agent according to any one of claims 1 to 8. .
1 0. 前記請求の範囲第 1項〜第 8項のいずれか 1項に記載のチユアブル剤の製 造方法によって製造されていることを特徴とする、 硬度が 3 0〜 1 2 0 Nである チユアブル剤。 10. A hardness of 30 to 120 N, characterized by being produced by the method for producing a chewable agent according to any one of claims 1 to 8. Chewables.
1 1. 前記請求の範囲第 1項〜第 8項のいずれか 1項に記載のチュアプル剤の製 造方法によって製造されていることを特徴とする、 硬度が 4 0〜 1 0 0 Nである チユアブル剤。 . 1 1. It is produced by the method for producing a tuple according to any one of claims 1 to 8, wherein the hardness is 40 to 100 N. Chewables. .
1 2. 前記請求の範囲第 9項〜第 1 1項のいずれか 1項に記載のチユアブル剤か らなる肝疾患治癒用医薬製剤。
1 2. A pharmaceutical preparation for healing a liver disease, comprising the chewable preparation according to any one of claims 9 to 11.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002016479A JP3341768B1 (en) | 2002-01-25 | 2002-01-25 | Chewable preparation containing branched-chain amino acids |
| JP2002-16479 | 2002-01-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2003063854A1 true WO2003063854A1 (en) | 2003-08-07 |
Family
ID=19192004
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2003/000579 WO2003063854A1 (en) | 2002-01-25 | 2003-01-23 | Chewable tablet containing branched amino acids |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP3341768B1 (en) |
| WO (1) | WO2003063854A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109619383A (en) * | 2018-12-13 | 2019-04-16 | 张家港中宝生物技术有限公司 | A kind of preparation method of compound amino acid |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070224265A1 (en) * | 2004-04-14 | 2007-09-27 | Takahiro Hara | Tablet Comprising Branched Chain Amino Acid and Method for Producing the Same |
| JPWO2006090640A1 (en) * | 2005-02-23 | 2008-07-24 | 太陽化学株式会社 | Amino acid-containing tablet composition and tablet production method |
| JP2007008872A (en) * | 2005-06-30 | 2007-01-18 | Lion Corp | Method for producing granulated granule and the resultant granulated granule, and solid preparation |
| JP4565219B2 (en) * | 2008-12-26 | 2010-10-20 | アサヒビール株式会社 | Polyphenol-containing granule or polyphenol-containing chewable tablet and method for producing the same |
| JP6435161B2 (en) * | 2014-10-20 | 2018-12-05 | 株式会社ファンケル | Amino acid-containing composition |
| JP7001332B2 (en) * | 2016-03-29 | 2022-01-19 | 小林製薬株式会社 | Granulation |
| JP7065454B2 (en) * | 2017-05-08 | 2022-05-12 | アリメント工業株式会社 | Fine particle mixed food with improved reaction stability |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09194381A (en) * | 1996-01-17 | 1997-07-29 | Kowa Co | Chewable tablets containing calcium salt |
-
2002
- 2002-01-25 JP JP2002016479A patent/JP3341768B1/en not_active Expired - Fee Related
-
2003
- 2003-01-23 WO PCT/JP2003/000579 patent/WO2003063854A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09194381A (en) * | 1996-01-17 | 1997-07-29 | Kowa Co | Chewable tablets containing calcium salt |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109619383A (en) * | 2018-12-13 | 2019-04-16 | 张家港中宝生物技术有限公司 | A kind of preparation method of compound amino acid |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2003221326A (en) | 2003-08-05 |
| JP3341768B1 (en) | 2002-11-05 |
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