JP3637968B1 - Gastric disintegrating tablets - Google Patents

Gastric disintegrating tablets Download PDF

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JP3637968B1
JP3637968B1 JP2004000939A JP2004000939A JP3637968B1 JP 3637968 B1 JP3637968 B1 JP 3637968B1 JP 2004000939 A JP2004000939 A JP 2004000939A JP 2004000939 A JP2004000939 A JP 2004000939A JP 3637968 B1 JP3637968 B1 JP 3637968B1
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tablet
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glutamine
crospovidone
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JP2005194225A (en
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泰伸 秋山
貴仁 富山
利安 小林
嘉樹 鈴木
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Abstract

【課題】 服用後胃内で容易に崩壊し薬効成分を放出する水溶性アズレンおよびL−グルタミンを含有する胃内崩壊性錠剤を提供すること。
【解決手段】 水溶性アズレンおよびL−グルタミンからなる薬効成分と、粘着剤との重量比が、99.5:0.5から60:40であり、必要により、さらに結合剤、崩壊剤、賦形剤などを含有する胃内崩壊性錠剤。上記粘着剤はヒドキシプロピルセルロース、メチルセルロース、ヒドロキシプロピルメチルセルロース、プルラン、ポリビニルアルコールおよびクロスポビドンからなる群から選ばれる少なくとも1種である。
【選択図】 なし
PROBLEM TO BE SOLVED: To provide an orally disintegrating tablet containing water-soluble azulene and L-glutamine that easily disintegrates in the stomach after taking and releases a medicinal component.
SOLUTION: The weight ratio of the medicinal component consisting of water-soluble azulene and L-glutamine and the pressure-sensitive adhesive is 99.5: 0.5 to 60:40. A gastric disintegrating tablet containing a dosage form or the like. The pressure-sensitive adhesive is at least one selected from the group consisting of hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, pullulan, polyvinyl alcohol and crospovidone.
[Selection figure] None

Description

本発明は、胃内崩壊性錠剤に関する。さらに詳しくは、錠剤として必要な機械強度を示す硬度、摩損度を良好に維持しつつ服用後胃内で容易に崩壊する胃内崩壊性錠剤に関する。   The present invention relates to an orally disintegrating tablet. More specifically, the present invention relates to a gastric disintegrating tablet that easily disintegrates in the stomach after administration while maintaining good hardness and friability indicating the mechanical strength necessary for the tablet.

水溶性アズレンおよびL−グルタミンからなる製剤は、経口投与により抗胃潰瘍作用、抗十二指腸潰瘍作用、抗胃炎作用等の広範な作用を有する製剤であり、すでに医療用としてその優れた有用性は確立されている。その経口投与製剤としては顆粒剤、細粒剤、散剤、カプセル剤、錠剤といった剤形が使用されている。   A preparation comprising water-soluble azulene and L-glutamine is a preparation having a wide range of effects such as anti-gastric ulcer action, anti-duodenal ulcer action, and anti-gastritis action by oral administration, and its excellent usefulness for medical use has already been established. ing. As the preparation for oral administration, dosage forms such as granules, fine granules, powders, capsules and tablets are used.

しかしながら、顆粒、細粒、散剤においては、こぼれ易かったり、高齢者等が服用するとき入れ歯と歯茎との間に入り込み不快であるとか、ざらつきがあり患者コンプライアンス上の問題がある。さらに顆粒、細粒、散剤は調剤の際に1回分毎に分包しなければならず手間がかかり非効率的である。   However, granules, fine granules, and powders are easily spilled, and when taken by an elderly person, they are uncomfortable because they enter between the dentures and gums. Furthermore, granules, fine granules, and powders must be packaged every time when dispensing, which is troublesome and inefficient.

カプセル剤においては、L−グルタミンの投与量が多いことから大きなカプセル剤となり、嚥下しにくく、口腔粘膜や食道壁に付着してしまうなどの問題がある。   In capsules, since the dose of L-glutamine is large, it becomes a large capsule, which makes it difficult to swallow and adheres to the oral mucosa and esophageal wall.

錠剤においては、L−グルタミンの投与量が1〜2g/日と多いことから大きな錠剤となり嚥下しにくく、口腔内崩壊性の錠剤では不快なえぐ味があり、発泡性の錠剤では口腔内で発泡し刺激があるなどの問題点がある。   In tablets, since the dose of L-glutamine is as high as 1 to 2 g / day, it becomes a large tablet and is difficult to swallow. There are problems such as irritation.

また、錠剤においては、製剤の大部分を占めるグルタミンに圧縮成形性が欠如しているため、錠剤硬度が上がりにくく、錠剤状になっても角が欠け易く、外観上、商品価値上、品質管理上から問題がある。   In addition, in tablets, glutamine, which accounts for the majority of the formulation, lacks compression moldability, so it is difficult to increase tablet hardness, and corners are easily lost even when it is tablet-like. There is a problem from above.

このため、水溶性アズレンとL−グルタミンを含有する製剤であっても、上記したような欠点がなく、流通上においても、調剤上においても問題を生じない製剤の開発が患者、医師、薬剤師などの医療関係者から望まれている。   For this reason, even if it is a formulation containing water-soluble azulene and L-glutamine, it is possible to develop a formulation that does not have the above-described drawbacks and does not cause problems in distribution and dispensing. It is desired by medical personnel in Japan.

特許文献1には、水溶性アズレンおよびL−グルタミンからなる製剤の経口投与可能な剤形として、顆粒、細粒、散剤、これらをコーティングしたもの、カプセル剤および錠剤が開示されている。しかしながら、特許文献1は易崩壊性かつ低摩損性錠剤の組成にはなんら言及もしていないし示唆も与えていない。   Patent Document 1 discloses granules, fine granules, powders, coatings thereof, capsules and tablets as dosage forms that can be administered orally with a preparation comprising water-soluble azulene and L-glutamine. However, Patent Document 1 does not mention or suggest any composition of easily disintegratable and low friable tablets.

特許文献2には、口腔内の水や唾液により吸水膨潤後の硬度が容易に低下し嚥下容易な口腔内易崩壊性錠剤が開示されている。本剤は口腔内発泡錠であり、胃内易崩壊性錠剤の組成にはなんら言及していないし示唆も与えていない。   Patent Document 2 discloses an easily disintegratable tablet in the oral cavity in which the hardness after water absorption and swelling is easily reduced by oral water or saliva, and easy to swallow. This agent is an effervescent tablet in the mouth and does not mention or give any suggestion to the composition of easily disintegrating tablets in the stomach.

特許文献3には、L−グルタミン、アズレンスルホン酸ナトリウムおよび崩壊剤を含む混合物を、乳糖含有水溶液を結合剤として用いて造粒し乾燥して得られる造粒物を圧縮成形して得られる実質的に発泡成分を含まない速崩錠または口腔内崩壊錠剤並びにその製造法が開示されている。速崩性ではあるが低摩損性錠剤組成に関してはなんら言及もしていないし示唆も与えていない。
特開昭59−27822号公報 特開2000−26286号公報 特開2003−212769号公報
Patent Document 3 discloses a substance obtained by compression molding a granulated product obtained by granulating and drying a mixture containing L-glutamine, sodium azulenesulfonate and a disintegrant using a lactose-containing aqueous solution as a binder. In particular, a rapidly disintegrating tablet or an orally disintegrating tablet containing no foaming component and a production method thereof are disclosed. There is no mention or suggestion regarding the composition of fast-disintegrating but low-friable tablets.
JP 59-27822 A JP 2000-26286 A JP 2003-212769 A

本発明の目的は、服用後胃内で崩壊する胃内崩壊性錠剤を提供することにある。   An object of the present invention is to provide an orally disintegrating tablet that disintegrates in the stomach after administration.

本発明の他の目的は、服用後胃内で容易に崩壊し薬効成分である水溶性アズレンおよびL−グルタミンを放出する易崩壊性、低摩損性の胃内崩壊性錠剤を提供することにある。   Another object of the present invention is to provide an easily disintegrating, low-friable gastro-disintegrating tablet that easily disintegrates in the stomach after administration and releases water-soluble azulene and L-glutamine as medicinal ingredients. .

本発明の他の目的は、錠剤としての機械的強度を示す錠剤硬度、摩損度を良好に維持しつつ、服用後容易に胃内で崩壊し薬効成分を放出する易崩壊性、低摩損性の胃内崩壊性錠剤を提供することにある。   Another object of the present invention is to maintain tablet hardness and friability, which show mechanical strength as a tablet, while easily disintegrating in the stomach after taking and releasing a medicinal component with low friability. It is to provide a gastric disintegrating tablet.

本発明のさらに他の目的は、製剤重量の増加を抑え、服用後容易に胃内で崩壊して薬効成分を放出し且つ服用し易い、易崩壊性、低摩損性の胃内崩壊性錠剤を提供することにある。   Still another object of the present invention is to provide an easily disintegrating, low-friable disintegrating tablet that suppresses an increase in the weight of the preparation, disintegrates easily in the stomach after taking, releases a medicinal component, and is easy to take. It is to provide.

本発明のさらに他の目的は、水溶性アズレンが錠剤中に均一に分散している、水溶性アズレンおよびL−グルタミンを含有する易崩壊性、低摩損性の胃内崩壊性錠剤を提供することにある。   Still another object of the present invention is to provide an easily disintegratable, low-friable gastro-disintegrating tablet containing water-soluble azulene and L-glutamine in which water-soluble azulene is uniformly dispersed in the tablet. It is in.

本発明のさらに他の目的は、水溶性アズレンの安定性に優れた、水溶性アズレンおよびL−グルタミンを含有する易崩壊性、低摩損性の胃内崩壊性錠剤を提供することにある。   Still another object of the present invention is to provide an easily disintegratable, low-friable gastroerodible tablet containing water-soluble azulene and L-glutamine, which is excellent in the stability of water-soluble azulene.

本発明のさらに他の目的および利点は、以下の説明から明らかになろう。   Still other objects and advantages of the present invention will become apparent from the following description.

本発明によれば、本発明の上記目的および利点は、(A)水溶性アズレンおよびL−グルタミンからなる胃腸障害改善薬効成分、
(B)ヒドロキシプロピルセルロース、メチルセルロース、ヒドロキシプロピルメチルセルロース、プルランおよびポリビニルアルコールよりなる群から選ばれる少なくとも1種からなる粘着剤、ならびに
(C)結合剤または崩壊剤からなり、
(A)成分対(B)成分の重量比が99.5:0.5〜60:40であり、且つ
(A)成分および(B)成分の合計重量100重量部に対し(C)成分が1〜300重量部であり、そして
日本薬局方記載摩損度試験器を用いて測定した10分後の摩損度が3%以下である、
ことを特徴とする胃内崩壊性錠剤によって達成される。
According to the present invention, the above objects and advantages of the present invention, (A) gastrointestinal disorder improving medicinal Ingredients comprising a water-soluble azulene and L- glutamine,
(B) hydroxypropyl cellulose, methylcellulose, hydroxypropyl methylcellulose, at least one selected from pullulan and polyvinyl alcohol by Li Cheng group adhesive, and
(C) consists of a binder or disintegrant ,
(A) component to (B) weight ratio of component 99.5: 0.5 to 60: Ri 40 der, and,
The friability after 10 minutes when the component (C) is 1 to 300 parts by weight with respect to 100 parts by weight of the total weight of the component (A) and the component (B), and measured using a friability tester described in the Japanese Pharmacopoeia. Is 3% or less,
This is achieved by a gastric disintegrating tablet.

本発明により、服用後胃内で容易に崩壊し薬効成分を放出する崩壊性、低摩損性錠剤が提供される。   The present invention provides a disintegrating, low-abrasion tablet that easily disintegrates in the stomach after administration and releases a medicinal component.

また、本発明により、錠剤としての機械的強度を示す錠剤硬度、摩損度を良好に維持しつつ、服用後容易に胃内で崩壊し薬効成分を放出する調剤し易い、水溶性アズレンおよびL−グルタミンを含有する胃内崩壊性、低摩損性錠剤が提供される。   In addition, according to the present invention, water-soluble azulene and L-, which are easy to be dispensed, easily disintegrate in the stomach and release a medicinal component after taking, while maintaining good tablet hardness and friability indicating mechanical strength as a tablet. A gastric disintegrating, low friable tablet containing glutamine is provided.

また本発明により、製剤重量の増加を抑え、服用後容易に胃内で崩壊し薬効成分を放出する服用し易い、水溶性アズレンおよびL−グルタミンを含有する胃内崩壊性、低摩損性錠剤が提供される。   In addition, according to the present invention, there is provided an easily disintegrating gastric disintegrating and low-friable tablet containing water-soluble azulene and L-glutamine that suppresses an increase in the weight of a preparation and easily disintegrates in the stomach after taking and releases a medicinal ingredient. Provided.

また本発明により、水溶性アズレンが錠剤中に均一に分散している、水溶性アズレンおよびL−グルタミンを含有する胃内崩壊性、低摩損性錠剤が提供される。   The present invention also provides a gastric disintegrating, low-friable tablet containing water-soluble azulene and L-glutamine in which water-soluble azulene is uniformly dispersed in the tablet.

さらに、本発明により、水溶性アズレンの安定性に優れた、水溶性アズレンおよびL−グルタミンを含有する胃内崩壊性、低摩損性錠剤が提供される。   Furthermore, the present invention provides a gastric disintegrating, low-friable tablet containing water-soluble azulene and L-glutamine, which is excellent in the stability of water-soluble azulene.

以下に本発明に付き詳細に説明する。抗炎症、抗潰瘍作用に関してL−グルタミンおよび水溶性アズレン(グアイアズレンスルホン酸塩)は、既にそれぞれ単独および配合剤として、胃潰瘍、十二指腸潰瘍、胃炎等の胃腸障害のための医療用薬剤として使用されている。水溶性アズレンの投与量は通常4.5〜6mg/日と少量であるのに対し、L−グルタミンの投与量は通常1〜2g/日とかなり大量である。L−グルタミンの投与量が多い上にL−グルタミン粉末の圧縮成形性が乏しいため、錠剤化しようとすると、多量の添加剤を必要とし、大型の錠剤とならざるを得ず、かつ胃内での早い崩壊性を付与しつつ錠剤の機械的強度を維持することが求められる。   The present invention will be described in detail below. Regarding anti-inflammatory and anti-ulcer activity, L-glutamine and water-soluble azulene (guaiazulene sulfonate) are already used alone and in combination as medical drugs for gastrointestinal disorders such as gastric ulcer, duodenal ulcer and gastritis. Yes. The dosage of water-soluble azulene is usually as small as 4.5 to 6 mg / day, whereas the dosage of L-glutamine is usually as large as 1 to 2 g / day. Since the dose of L-glutamine is large and the compression moldability of L-glutamine powder is poor, when trying to tablet, a large amount of additive is required, and it must be a large tablet. Therefore, it is required to maintain the mechanical strength of the tablet while imparting fast disintegration property.

本発明の胃内崩壊性錠剤の崩壊性は、日本薬局方記載崩壊試験法で精製水を試験液として測定したとき、180秒以下が好ましく、90秒以下がより好ましく、60秒以下が特に好ましい。   The disintegration property of the gastric disintegrating tablet of the present invention is preferably 180 seconds or less, more preferably 90 seconds or less, and particularly preferably 60 seconds or less, when purified water is measured as a test solution by the disintegration test method described in the Japanese Pharmacopoeia. .

本発明の胃内崩壊性錠剤の硬度は、錠剤硬度計(エルベェッカ社製、TBH200型)で測定したとき、50N以上が好ましく、60N以上がより好ましく、70N以上が特に好ましい。   The hardness of the gastric disintegrating tablet of the present invention is preferably 50 N or more, more preferably 60 N or more, and particularly preferably 70 N or more, as measured with a tablet hardness meter (TBH200 type, manufactured by Elbekka).

本発明の胃内崩壊性錠剤の摩損度は、日本薬局方記載摩損度試験器を用いて10分間回転したとき(10分後の摩損度)、3%以下であり、2%以下が好ましく、1%以下が特に好ましい。 Friability gastric disintegrating tablet of the present invention, when rotated for 10 minutes using a Japanese Pharmacopoeia friability tester (Friability after 10 minutes), 3% or less, 2% or less is better good 1% or less is particularly preferable.

本発明の錠剤において、薬効成分である水溶性アズレンおよびL−グルタミンの含量は、粘着剤との合計重量に基づいて、99.5〜60重量%であり、99〜70重量%が好ましく、98.5〜80重量%が特に好ましい。   In the tablet of the present invention, the content of water-soluble azulene and L-glutamine as medicinal ingredients is 99.5 to 60% by weight, preferably 99 to 70% by weight, based on the total weight with the adhesive, 98 5 to 80% by weight is particularly preferable.

粘着剤としては、ヒドロキシプロピルセルロース、メチルセルロース、ヒドロキシプロピルメチルセルロース、プルランおよびポリビニルアルコールが用いられる。これらは1種または2種以上一緒に用いることができる。これらのうち、ヒドロキシプロピルセルロース、プルランがより好ましい。 As the adhesive, hydroxycarboxylic cellulose, methyl cellulose, hydroxypropyl methyl cellulose, pullulan and polyvinyl alcohol used. These can be used alone or in combination of two or more. Of these, hydroxypropylcellulose and pullulan are more preferred.

本発明の錠剤に用いられる粘着剤は、薬効成分との合計重量に対し、0.5〜40重量%であり、1〜30重量%が好ましく、1.5〜20重量%が特に好ましい。   The pressure-sensitive adhesive used in the tablet of the present invention is 0.5 to 40% by weight, preferably 1 to 30% by weight, particularly preferably 1.5 to 20% by weight, based on the total weight with the medicinal ingredients.

本発明の錠剤は、さらに、胃内投与前の錠剤においては結合剤として作用し、一旦胃内に投与された後には崩壊剤として作用する、結合剤または崩壊剤を含有する。 Tablets of the present invention may further act as a binder in the tablet prior to intragastric administration, once after being administered into the stomach to act as a disintegrant, you a binder or disintegrant.

かかる結合剤または崩壊剤としては、例えば結晶セルロース、カルボキシメチルセルロースカルシウム、クロスポビドン、クロスカルボキシメチルセルロースナトリウム、カルボキシメチルスターチナトリウムなどが挙げられる。これらのうち、結晶セルロース、カルボキシメチルセルロースカルシウム、クロスポビドンが好ましい。これらは1種または2種以上で用いられる。   Examples of the binder or disintegrant include crystalline cellulose, carboxymethylcellulose calcium, crospovidone, croscarboxymethylcellulose sodium, carboxymethyl starch sodium, and the like. Of these, crystalline cellulose, carboxymethylcellulose calcium, and crospovidone are preferred. These are used alone or in combination of two or more.

かかる結合剤または崩壊剤は、薬効成分と粘着剤の合計重量100重量部に対し、1〜300重量部、好ましくは5〜200重量部で用いられる。 Such binder or disintegrant, against the total weight 100 parts by weight of the medicinal component adhesive, 1-300 parts by weight, good Mashiku is used in 5 to 200 parts by weight.

また、本発明の錠剤には、必要に応じ、その他の添加剤が含有されていてもよい。その他の添加剤としては、経口医薬品に添加することができる成分であれば特に制限はないが、例えば、賦形剤、流動化剤、滑沢剤、安定化剤、着色剤、矯味剤および着香剤が挙げられる。これらは単独または組み合わせて使用される。錠剤中におけるこれらの濃度は、それぞれ、例えば微量〜10重量%が好ましく、微量〜7重量%がより好ましく、微量〜5重量%が特に好ましい。   Moreover, the tablet of this invention may contain the other additive as needed. Other additives are not particularly limited as long as they are components that can be added to oral pharmaceuticals. For example, excipients, fluidizers, lubricants, stabilizers, coloring agents, flavoring agents, and dressings. A fragrance is mentioned. These are used alone or in combination. Each of these concentrations in the tablet is, for example, preferably from a trace amount to 10% by weight, more preferably from a trace amount to 7% by weight, and particularly preferably from a trace amount to 5% by weight.

賦形剤としては、例えば、デンプン、ソルビトール、デキストラン、マンニトール、トレハロース、乳糖などが挙げられる。   Examples of the excipient include starch, sorbitol, dextran, mannitol, trehalose, and lactose.

流動化剤または滑沢剤としては、例えばタルク、軽質無水ケイ酸、ケイ酸カルシウム、合成ケイ酸アルミニウム、ステアリン酸マグネシウム、ステアリン酸カルシウム、ステアリン酸、ショ糖脂肪酸エステルなどが挙げられる。   Examples of the fluidizing agent or lubricant include talc, light anhydrous silicic acid, calcium silicate, synthetic aluminum silicate, magnesium stearate, calcium stearate, stearic acid, and sucrose fatty acid ester.

流動化剤および滑沢剤は、それぞれ、錠剤化する成分材料の粉体としての流動性を改善するためや、打錠工程におけるスティッキング、キャッピング、ラミネーションなどの打錠障害や、打錠用杵臼のキシミ、磨耗を防止するために、通常、錠剤化する成分材料中に添加される成分である。錠剤内部に滑沢剤があまりに多量に含有されると、その撥水性のために錠剤の崩壊性が低下することがあるので、錠剤内部にはあまりに多量の滑沢剤を含有させないことが好ましい。   Fluidizers and lubricants are used to improve the fluidity of powdered component materials, tableting obstacles such as sticking, capping and lamination in the tableting process, and In order to prevent wear and tear, it is a component that is usually added to the component material to be tableted. When a too large amount of lubricant is contained in the tablet, the disintegration property of the tablet may be lowered due to its water repellency. Therefore, it is preferable not to contain a too large amount of lubricant in the tablet.

安定化剤としては、例えば塩化セチルピリジニウム、塩化ベンザルコニウム、塩化ベンセトニウムなどが挙げられる。   Examples of the stabilizer include cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride.

着色剤としては、例えば、β−カロテン、食用青色1号などの食用色素、黄酸化鉄、褐色酸化鉄、黒酸化鉄、カラメル、酸化チタンなどが挙げられる。   Examples of the colorant include edible pigments such as β-carotene and edible blue No. 1, yellow iron oxide, brown iron oxide, black iron oxide, caramel, and titanium oxide.

矯味剤としては、例えばアスパルテーム、グルコース、フルクトース、キシリトール、サッカリン、アスコルビン酸などが挙げられ、また着香剤としては、例えばメントール、オレンジエキス、レモンパウダーなどが挙げられる。   Examples of the flavoring agent include aspartame, glucose, fructose, xylitol, saccharin, and ascorbic acid. Examples of the flavoring agent include menthol, orange extract, and lemon powder.

なお、本発明の錠剤には、炭酸塩と有機酸等の組合せからなる発泡成分は、実質的に含まれていないことが好ましい。   In addition, it is preferable that the foaming component which consists of a combination of carbonate and an organic acid etc. is not substantially contained in the tablet of this invention.

本発明の錠剤は、薬効成分(A)、ヒドロキシプロピルセルロースまたはプルラン、結晶セルロース、カルボキシメチルセルロースカルシウムおよびクロスポビドンを含有しそしてこれらの合計重量を基準にして薬効成分(A)が20〜90重量%、より好ましくは30〜90重量%、ヒドロキシプロピルセルロースまたはプルランが0.2〜20重量%、より好ましくは1〜10重量%、結晶セルロースが5〜60重量%、より好ましくは5〜50重量%、カルボキシメチルセルロースカルシウムが0.5〜20重量%、より好ましくは0.5〜10重量%、およびクロスポビドンが0.5〜20重量%、より好ましくは0.5〜10重量%であるものである。   The tablet of the present invention contains a medicinal component (A), hydroxypropylcellulose or pullulan, crystalline cellulose, carboxymethylcellulose calcium and crospovidone, and the medicinal component (A) is 20 to 90% by weight based on the total weight thereof. More preferably 30 to 90% by weight, hydroxypropylcellulose or pullulan 0.2 to 20% by weight, more preferably 1 to 10% by weight, crystalline cellulose 5 to 60% by weight, more preferably 5 to 50% by weight. Carboxymethylcellulose calcium is 0.5 to 20% by weight, more preferably 0.5 to 10% by weight, and crospovidone is 0.5 to 20% by weight, more preferably 0.5 to 10% by weight. is there.

本発明の錠剤は、例えば水溶性アズレンおよびL−グルタミンと結合剤または崩壊剤、とからなる混合物に粘着剤水溶液またはアルコール溶液、または粘着剤粉体と水またはアルコールを溶媒として用いて造粒し、乾燥して得られる造粒物を圧縮成形することにより製造されるかまたは上記により得られた造粒物にさらに結合剤、崩壊剤等の添加物を添加混合し得られた粉体を圧縮成形することにより製造される。 Tablets of the present invention, for example, water-soluble azulene and L- glutamine and binding material mixture or disintegrant, using a mixture in the pressure-sensitive adhesive aqueous or alcoholic solution comprising city, or an adhesive powder and water or an alcohol as a solvent granulation A powder obtained by compression-molding a granulated product obtained by drying or by adding additives such as a binder and a disintegrant to the granulated product obtained by the above process Manufactured by compression molding.

上記粘着剤水溶液またはアルコール溶液中の粘着剤の濃度は特に制限はないが、0.5〜30重量%が好ましく、0.5〜20重量%がより好ましく、1〜10重量%が特に好ましい。   Although there is no restriction | limiting in particular in the density | concentration of the adhesive in the said adhesive aqueous solution or alcohol solution, 0.5-30 weight% is preferable, 0.5-20 weight% is more preferable, 1-10 weight% is especially preferable.

粘着剤は、造粒性と可塑性のある膜状物を形成する性質を有することが望ましい。これにより圧縮成形性の欠如している薬効成分粉末造粒物の内部および表面に可塑性のある膜状物を形成し、圧縮成形性を向上させ錠剤化を可能にしたと言える。粘着剤は、5重量%水溶液の25℃における粘度が0.1〜500mPa・sであるものが好ましく、0.5〜200mPa・sであるものがより好ましく、1〜100mPa・sであるものが特に好ましい。



The pressure-sensitive adhesive desirably has a property of forming a film-like product having granulation properties and plasticity. As a result, it can be said that a film-like product having plasticity is formed inside and on the surface of the medicinal component powder granulated product lacking in compression moldability, thereby improving the compression moldability and enabling tableting. The pressure-sensitive adhesive preferably has a 5% by weight aqueous solution having a viscosity at 25 ° C. of 0.1 to 500 mPa · s , more preferably 0.5 to 200 mPa · s , and 1 to 100 mPa · s. Those are particularly preferred.



なお、上記添加剤は、錠剤の製造工程のいずれの段階で添加されてもよく、例えば、水溶性アズレンおよびL−グルタミンと崩壊剤の一部とからなる混合物に混合して使用されてもよく、又、水溶性アズレンおよびL−グルタミンと崩壊剤からなる混合物を粘着剤を用いて造粒して得られる造粒物に混合してもよい。   The additive may be added at any stage of the tablet production process, and may be used, for example, by mixing with a mixture comprising water-soluble azulene and L-glutamine and a part of the disintegrant. Alternatively, a mixture of water-soluble azulene and L-glutamine and a disintegrant may be mixed with a granulated product obtained by granulating using a pressure-sensitive adhesive.

造粒法としては、特に制限はないが、高速攪拌造粒、攪拌造粒、流動層造粒、転動流動層造粒、押し出し造粒等の湿式造粒法が好ましい。造粒物の粒度、硬度、流動性、水分などは、特に限定されず、ついで行われる打錠工程および得られた錠剤物性に支障を来たさない範囲であれば、任意に設定される。   The granulation method is not particularly limited, but wet granulation methods such as high-speed stirring granulation, stirring granulation, fluidized bed granulation, rolling fluidized bed granulation, and extrusion granulation are preferable. The particle size, hardness, fluidity, moisture, and the like of the granulated product are not particularly limited, and can be arbitrarily set as long as they do not interfere with the subsequent tableting process and the obtained tablet physical properties.

造粒温度としては、特に制限はないが、造粒物温度が高温になることは好ましくなく、30〜70℃が好ましく、30〜60℃がより好ましく、30〜50℃がさらに好ましい。   Although there is no restriction | limiting in particular as granulation temperature, It is not preferable that a granulated material temperature becomes high temperature, 30-70 degreeC is preferable, 30-60 degreeC is more preferable, 30-50 degreeC is further more preferable.

造粒物の乾燥法としては、特に制限はないが、例えば通風乾燥法、流動層乾燥法、減圧乾燥法などが挙げられる。乾燥温度としては、特に制限はないが、30〜70℃が好ましく、30〜60℃がより好ましく、30〜50℃がさらに好ましい。   The drying method of the granulated product is not particularly limited, and examples thereof include a ventilation drying method, a fluidized bed drying method, and a vacuum drying method. Although there is no restriction | limiting in particular as drying temperature, 30-70 degreeC is preferable, 30-60 degreeC is more preferable, and 30-50 degreeC is further more preferable.

錠剤の製造法は、特に制限はないが、例えばロータリー式打錠機を用いて行うことができる。打錠用の杵、臼に滑沢剤を塗布する装置を備えないものも使用できるが、杵、臼に滑沢剤を塗布する装置を備えたものを用いることもできる。圧縮成形は、滑沢剤を塗布した杵、臼または塗布していない杵、臼を用いて行うことができる。   The method for producing the tablet is not particularly limited, but can be performed using, for example, a rotary tableting machine. Tableting punches and those that do not have a device for applying a lubricant to the die can be used, but those that are provided with a device for applying a lubricant to the punches and die can also be used. The compression molding can be performed by using a pestle, a mortar or an unapplied mortar or mortar to which a lubricant is applied.

以下、実施例を挙げ本発明をさらに詳述する。本発明は実施例により何ら制限されるものではない。   Hereinafter, the present invention will be described in more detail with reference to examples. The present invention is not limited in any way by the examples.

実施例1
L−グルタミン(味の素(株)製)2,475g、グアイアズレンスルホン酸ナトリウム(アルプス薬品(株)製)7.5g、結晶セルロース(旭化成(株)製)392.5g、ヒドキシプロピルセルロース(日本曹達(株)製)150gを攪拌造粒機(パウレック社製、FM−VG25型)に入れ、1分間混合した。さらに、300gのエチルアルコールを加え、3分間造粒し、得られた造粒物を通風型乾燥機で乾燥して乾燥造粒物を得た。得られた造粒物を0.5mm篩で整粒し、これに、結晶セルロース1,220g、カルボキシメチルセルロースカルシウム(五徳薬品工業(株)製)90g、クロスポビドン(BASF社製)90gを加え、混合し、さらにステアリン酸マグネシウム75gを加え、打錠用粉体を得た。直径9mm平杵を装着したロータリー型打錠機(畑鉄工所製、HT−AP18型)を使用し打錠圧900Kgで、錠剤重量300mgの胃内崩壊性錠剤を得た。
Example 1
L-glutamine (manufactured by Ajinomoto Co., Inc.) 2,475 g, sodium guaiazulene sulfonate (manufactured by Alps Pharmaceutical Co., Ltd.) 7.5 g, crystalline cellulose (manufactured by Asahi Kasei Co., Ltd.) 392.5 g, hydroxypropyl cellulose (Nihon Soda) 150 g of (manufactured by Co., Ltd.) was put into a stirring granulator (manufactured by Paulek, FM-VG25 type) and mixed for 1 minute. Furthermore, 300 g of ethyl alcohol was added and granulated for 3 minutes, and the resulting granulated product was dried with a ventilation dryer to obtain a dried granulated product. The obtained granulated product was sized with a 0.5 mm sieve, to which was added 1,220 g of crystalline cellulose, 90 g of carboxymethylcellulose calcium (manufactured by Gotoku Pharmaceutical Co., Ltd.), 90 g of crospovidone (manufactured by BASF), After mixing, 75 g of magnesium stearate was further added to obtain a tableting powder. A gastric disintegrating tablet having a tablet weight of 300 mg was obtained at a tableting pressure of 900 kg using a rotary tableting machine (manufactured by Hata Iron Works, model HT-AP18) equipped with a 9 mm diameter flat punch.

実施例2
L−グルタミン990g、グアイアズレンスルホン酸ナトリウム3.0g、結晶セルロース157gを流動層造粒機(フロイント産業(株)製、FLO−5マルチ型)に入れ、2分間混合した。ヒドキシプロピルセルロース60gを1,150gの精製水に溶解した粘着剤溶液により、約80分間噴霧造粒・乾燥し、造粒物を得た。得られた造粒物を0.5mm篩で整粒し、これに、結晶セルロース488g、カルボキシメチルセルロースカルシウム36g、クロスポビドン36gを加え、混合し、さらにステアリン酸マグネシウム30gを加え、打錠用粉体を得た。直径9mm平杵を装着したロータリー型打錠機を使用し打錠圧900Kgで、錠剤重量300mgの胃内崩壊性錠剤を得た。
Example 2
990 g of L-glutamine, 3.0 g of sodium guaiazulene sulfonate, and 157 g of crystalline cellulose were placed in a fluidized bed granulator (Freund Sangyo Co., Ltd., FLO-5 multi type) and mixed for 2 minutes. A granulated product was obtained by spray granulation and drying for about 80 minutes with an adhesive solution in which 60 g of hydroxypropylcellulose was dissolved in 1,150 g of purified water. The resulting granulated product is sized with a 0.5 mm sieve, to which 488 g of crystalline cellulose, 36 g of carboxymethylcellulose calcium and 36 g of crospovidone are added and mixed, and further 30 g of magnesium stearate is added, and powder for tableting Got. A gastric disintegrating tablet having a tablet weight of 300 mg was obtained with a tableting pressure of 900 kg using a rotary tableting machine equipped with a 9 mm diameter flat punch.

実施例3
L−グルタミン2,475g、グアイアズレンスルホン酸ナトリウム7.5g、結晶セルロース1,612.5g、カルボキシメチルセルロースカルシウム150g、クロスポビドン150g、ヒドキシプロピルセルロース150gを攪拌造粒機に入れ、1分間混合した。さらに、425gのエチルアルコールを加え、3分間造粒し、得られた造粒物を通風型乾燥機で乾燥し、乾燥造粒物を得た。得られた造粒物を0.5mm篩で整粒し、これに、ステアリン酸マグネシウム75gを加え、打錠用粉体を得た。直径9mm平杵を装着したロータリー型打錠機を使用し打錠圧1,000Kgで、錠剤重量300mgの胃内崩壊性錠剤を得た。
Example 3
2,475 g of L-glutamine, 7.5 g of sodium guaiazulene sulfonate, 1,612.5 g of crystalline cellulose, 150 g of carboxymethylcellulose calcium, 150 g of crospovidone, and 150 g of hydroxypropylcellulose were placed in a stirring granulator and mixed for 1 minute. Furthermore, 425 g of ethyl alcohol was added and granulated for 3 minutes, and the resulting granulated product was dried with a ventilation dryer to obtain a dried granulated product. The obtained granulated product was sized with a 0.5 mm sieve, and 75 g of magnesium stearate was added thereto to obtain a tableting powder. A gastric disintegrating tablet having a tablet weight of 300 mg was obtained at a tableting pressure of 1,000 kg using a rotary tableting machine equipped with a 9 mm diameter flat plate.

実施例4
L−グルタミン2,475g、グアイアズレンスルホン酸ナトリウム7.5g、結晶セルロース1,867.5g、ヒドキシプロピルセルロース150gを高速攪拌造粒機に入れ、1分間混合した。さらに、450gのエチルアルコールを加え、3分間造粒し、得られた造粒物を通風型乾燥機で乾燥し、造粒物を得た。得られた造粒物を0.5mm篩で整粒し、打錠用粉体を得た。打錠用粉体を臼内に充填する前に上杵、下杵の表面、臼壁にステアリン酸マグネシウムを塗布する装置を装着したロータリー型打錠機(菊水社製、VIRGO φ518ss型)を使用し、直径9mm平杵、打錠圧800Kgで打錠し、錠剤重量300mgの胃内崩壊性錠剤を得た。
Example 4
2,475 g of L-glutamine, 7.5 g of sodium guaiazulene sulfonate, 1,867.5 g of crystalline cellulose, and 150 g of hydroxypropyl cellulose were placed in a high-speed stirring granulator and mixed for 1 minute. Furthermore, 450 g of ethyl alcohol was added, granulated for 3 minutes, and the resulting granulated product was dried with a ventilating dryer to obtain a granulated product. The obtained granulated product was sized with a 0.5 mm sieve to obtain a tableting powder. Use rotary type tableting machine (Kikusui Co., Ltd., VIRGO φ518ss type) equipped with a device that applies magnesium stearate to the surface of the upper and lower punches and the wall of the die before filling the powder for tableting into the die. The tablet was tableted with a 9 mm diameter flat tablet and a tableting pressure of 800 kg to obtain a gastric disintegrating tablet having a tablet weight of 300 mg.

実施例5
L−グルタミン2,475g、グアイアズレンスルホン酸ナトリウム7.5g、結晶セルロース1,678.5g、カルボキシメチルセルロースカルシウム90g、クロスポビドン90g、ヒドキシプロピルセルロース150gを高速攪拌造粒機に入れ、1分間混合した。さらに、430gのエチルアルコールを加え、3分間造粒し、得られた造粒物を通風型乾燥機で乾燥し、造粒物を得た。得られた造粒物を0.5mm篩で整粒し、打錠用粉体を得た。打錠用粉体を臼内に充填する前に上杵、下杵の表面、臼壁にステアリン酸マグネシウムを塗布する装置を装着したロータリー型打錠機を使用し、直径9mm平杵、打錠圧800Kgで打錠し、錠剤重量300mgの胃内崩壊性錠剤を得た。
Example 5
L-glutamine 2,475 g, sodium guaiazulene sulfonate 7.5 g, crystalline cellulose 1,678.5 g, carboxymethylcellulose calcium 90 g, crospovidone 90 g, and hydroxypropylcellulose 150 g were placed in a high speed stirring granulator and mixed for 1 minute. . Furthermore, 430 g of ethyl alcohol was added and granulated for 3 minutes, and the resulting granulated product was dried with a ventilation dryer to obtain a granulated product. The obtained granulated product was sized with a 0.5 mm sieve to obtain a tableting powder. Before filling tableting powder into the mortar, use a rotary tableting machine equipped with a device that applies magnesium stearate to the surface of the upper and lower ridges and the mortar wall. Tableting was performed at a pressure of 800 kg to obtain a gastric disintegrating tablet having a tablet weight of 300 mg.

実施例6
L−グルタミン990g、グアイアズレンスルホン酸ナトリウム3.0g、結晶セルロース157gを流動層造粒機に入れ、1分間混合した。プルラン60gを1,150gの精製水に溶解した粘着剤溶液により、約80分間噴霧造粒・乾燥し、造粒物を得た。得られた造粒物を0.5mm篩で整粒し、これに、結晶セルロース482g、カルボキシメチルセルロースカルシウム72g、クロスポビドン36gを加え、混合し、打錠用粉体を得た。打錠用粉体を臼内に充填する前に上杵、下杵の表面、臼壁にステアリン酸マグネシウムを塗布する装置を装着したロータリー型打錠機を使用し、直径9mm平杵、打錠圧900Kgで打錠し、錠剤重量300mgの胃内崩壊性錠剤を得た。
Example 6
990 g of L-glutamine, 3.0 g of sodium guaiazulene sulfonate, and 157 g of crystalline cellulose were put into a fluid bed granulator and mixed for 1 minute. Using an adhesive solution in which 60 g of pullulan was dissolved in 1,150 g of purified water, spray granulation and drying were performed for about 80 minutes to obtain a granulated product. The obtained granulated product was sized with a 0.5 mm sieve, and 482 g of crystalline cellulose, 72 g of carboxymethylcellulose calcium and 36 g of crospovidone were added and mixed to obtain a powder for tableting. Before filling tableting powder into the mortar, use a rotary tableting machine equipped with a device that applies magnesium stearate to the surface of the upper and lower ridges and the mortar wall. Tableting was performed at a pressure of 900 kg to obtain a gastric disintegrating tablet having a tablet weight of 300 mg.

比較例1
L−グルタミン990g、グアイアズレンスルホン酸ナトリウム3.0g、結晶セルロース777gを攪拌造粒機に入れ、1分間混合した。精製水540g混合物に添加し、5分間練合を行い、練合物を得、1.0mmのスクリーンを備えた押し出し造粒機(菊水製作所製、RG−5型)で造粒した。得られた造粒物を通風型乾燥機で乾燥し、乾燥造粒物を得た。得られた乾燥造粒物を28号金網で整粒し、これに、ステアリン酸マグネシウム30gを加え、打錠用粉体を得た。直径9mm平杵を装着したロータリー型打錠機を使用し打錠圧1,000Kgで、錠剤重量300mgの錠剤を得た。
Comparative Example 1
990 g of L-glutamine, 3.0 g of sodium guaiazulene sulfonate, and 777 g of crystalline cellulose were put into a stirring granulator and mixed for 1 minute. The mixture was added to 540 g of purified water and kneaded for 5 minutes to obtain a kneaded product, which was granulated with an extrusion granulator (manufactured by Kikusui Seisakusho, model RG-5) equipped with a 1.0 mm screen. The obtained granulated product was dried with a ventilation dryer to obtain a dried granulated product. The obtained dried granulated product was sized with No. 28 wire mesh, and 30 g of magnesium stearate was added thereto to obtain a powder for tableting. A tablet with a tablet weight of 300 mg was obtained at a tableting pressure of 1,000 Kg using a rotary tableting machine equipped with a 9 mm diameter flat punch.

比較例2
L−グルタミン990g、グアイアズレンスルホン酸ナトリウム3.0g、結晶セルロース807gを攪拌造粒機に入れ、1分間混合した。精製水540g混合物に添加し、5分間練合を行い、練合物を得、1.0mmのスクリーンを備えた押し出し造粒機で造粒した。得られた造粒物を通風型乾燥機で乾燥し、乾燥造粒物を得た。得られた乾燥造粒物を28号金網で整粒し、打錠用粉体を得た。打錠用粉体を臼内に充填する前に上杵、下杵の表面、臼壁にステアリン酸マグネシウムを塗布する装置を装着したロータリー型打錠機を使用し、直径8mm平杵、打錠圧1,000Kgで打錠し、錠剤重量300mgの錠剤を得た。
Comparative Example 2
990 g of L-glutamine, 3.0 g of sodium guaiazulene sulfonate, and 807 g of crystalline cellulose were put into a stirring granulator and mixed for 1 minute. The mixture was added to 540 g of purified water and kneaded for 5 minutes to obtain a kneaded product, which was granulated with an extrusion granulator equipped with a 1.0 mm screen. The obtained granulated product was dried with a ventilation dryer to obtain a dried granulated product. The obtained dried granulated product was sized using a No. 28 wire mesh to obtain a powder for tableting. Use a rotary tableting machine equipped with a device that applies magnesium stearate to the surface of the upper and lower punches and the wall of the die before filling the powder for tableting into the die. Tableting was performed at a pressure of 1,000 kg to obtain a tablet having a tablet weight of 300 mg.

比較例3
L−グルタミン1,980g、グアイアズレンスルホン酸ナトリウム6.0g、クロスポビドン100gを攪拌造粒機に入れ、1分間混合した。乳糖100gを精製水300gに加温溶解させた室温水溶液を加え、3分間練合し、練合物を得、1.0mmのスクリーンを備えた押し出し造粒機で造粒した。得られた造粒物を通風型乾燥機で乾燥し、乾燥造粒物を得た。得られた乾燥造粒物を28号金網で整粒し、打錠用粉体を得た。これに、ステアリン酸マグネシウム22gを加え、打錠用粉体を得た。直径9mm平杵を装着したロータリー型打錠機を使用し打錠圧1,000Kgで、錠剤重量300mgの錠剤を得た。
Comparative Example 3
1,980 g of L-glutamine, 6.0 g of sodium guaiazulene sulfonate, and 100 g of crospovidone were placed in a stirring granulator and mixed for 1 minute. A room temperature aqueous solution in which 100 g of lactose was heated and dissolved in 300 g of purified water was added and kneaded for 3 minutes to obtain a kneaded product, which was granulated by an extrusion granulator equipped with a 1.0 mm screen. The obtained granulated product was dried with a ventilation dryer to obtain a dried granulated product. The obtained dried granulated product was sized using a No. 28 wire mesh to obtain a powder for tableting. To this, 22 g of magnesium stearate was added to obtain a tableting powder. A tablet with a tablet weight of 300 mg was obtained at a tableting pressure of 1,000 Kg using a rotary tableting machine equipped with a 9 mm diameter flat punch.

試験例1
上記した実施例1〜5および比較例1〜3で得られた錠剤について、錠剤崩壊性試験、錠剤硬度試験および錠剤摩損度試験を行った。錠剤崩壊性試験は、日本薬局方記載崩壊試験法に則り水を試験液として行ない、6錠の平均値を算出した。錠剤硬度試験は、錠剤硬度計(エルベェッカ社製、TBH200)を用い、各錠剤10錠の平均値を算出した。また、錠剤摩損度試験は、日本薬局方記載錠剤摩損度試験器(富山産業(株)製、TFT−120型)を用い、1分間25回転で15分間回転し、摩損度を測定した。結果を表1に示した。なお、各打錠工程中のスティッキング、キャッピング、ラミネーションなどの打錠障害の有無についても併記した。
Test example 1
The tablets obtained in Examples 1 to 5 and Comparative Examples 1 to 3 were subjected to a tablet disintegration test, a tablet hardness test, and a tablet friability test. In the tablet disintegration test, water was used as a test solution in accordance with the disintegration test method described in the Japanese Pharmacopoeia, and the average value of 6 tablets was calculated. In the tablet hardness test, an average value of 10 tablets was calculated using a tablet hardness meter (TBH200, manufactured by Elbekka). In addition, the tablet friability test was carried out using a tablet friability tester described in the Japanese Pharmacopoeia (manufactured by Toyama Sangyo Co., Ltd., TFT-120 type) and rotated for 15 minutes at 25 rpm for 1 minute to measure the friability. The results are shown in Table 1. The presence or absence of tableting troubles such as sticking, capping and lamination during each tableting process is also described.

Figure 0003637968
Figure 0003637968

表1の結果から、実施例1〜5の胃内崩壊性錠剤は、いずれも、錠剤の崩壊が早く容易であり、錠剤硬度は十分高く、錠剤摩損度は15分回転後も1%以下と錠剤に欠けや割れを生じることなく実用上なんら問題を生ずることがないことが示された。一方、比較例1〜3の錠剤では、錠剤硬度、錠剤摩損度、打錠性のいずれかに問題があり、実用性が乏しいことが示された。   From the results of Table 1, all of the gastric disintegrating tablets of Examples 1 to 5 are fast and easy to disintegrate the tablet, the tablet hardness is sufficiently high, and the tablet friability is 1% or less even after 15 minutes of rotation. It has been shown that there are no practical problems without chipping or cracking of the tablet. On the other hand, it was shown that the tablets of Comparative Examples 1 to 3 had problems in any of tablet hardness, tablet friability, and tabletability, and their practicality was poor.

すなわち、実施例1〜5の錠剤は、錠剤として実用上必要とされる硬度、摩損度を有し、崩壊性は1分以内であり、かつ打錠性が良好であり、優れた崩壊性と優れた摩損度を有する易崩壊性、低摩損性錠剤であることが明らかとなった。   That is, the tablets of Examples 1 to 5 have hardness and friability required for practical use as tablets, disintegration is within 1 minute, and tableting properties are good. It was revealed that the tablet was an easily disintegratable and low friable tablet having excellent friability.

また、実施例1〜5の錠剤は、打錠工程において、スティッキングなどの打錠障害が発生しなかったのに対し、比較例1、2ではスティッキングが観察された。   In the tablets of Examples 1 to 5, no sticking troubles such as sticking occurred in the tableting process, whereas in Comparative Examples 1 and 2, sticking was observed.

試験例4
実施例2および5で得られた錠剤のグアイアズレンスルホン酸ナトリウムの含量均一性ならびに経時安定性を測定した。結果を表2に示した。
Test example 4
The tablets obtained in Examples 2 and 5 were measured for content uniformity of sodium guaiazulenesulfonate and stability over time. The results are shown in Table 2.

Figure 0003637968
Figure 0003637968

表2の結果から、本発明の錠剤のグアイアズレンスルホン酸ナトリウムの含量均一性および経時安定性が優れることが示された。 From the results in Table 2, it was shown that the tablet of the present invention was excellent in content uniformity and temporal stability of sodium guaiazulene sulfonate.

Claims (6)

(A)水溶性アズレンおよびL−グルタミンからなる胃腸障害改善薬効成分、
(B)ヒドロキシプロピルセルロース、メチルセルロース、ヒドロキシプロピルメチルセルロース、プルランおよびポリビニルアルコールよりなる群から選ばれる少なくとも1種からなる粘着剤、ならびに
(C)結合剤または崩壊剤からなり、
(A)成分対(B)成分の重量比が99.5:0.5〜60:40であり、且つ
(A)成分および(B)成分の合計重量100重量部に対し(C)成分が1〜300重量部であり、そして
日本薬局方記載摩損度試験器を用いて測定した10分後の摩損度が3%以下である、
ことを特徴とする胃内崩壊性錠剤。
(A) gastrointestinal disorder improving medicinal Ingredients comprising a water-soluble azulene and L- glutamine,
(B) hydroxypropyl cellulose, methylcellulose, hydroxypropyl methylcellulose, at least one selected from pullulan and polyvinyl alcohol by Li Cheng group adhesive, and
(C) consists of a binder or disintegrant ,
(A) component to (B) weight ratio of component 99.5: 0.5 to 60: Ri 40 der, and,
The friability after 10 minutes when the component (C) is 1 to 300 parts by weight with respect to 100 parts by weight of the total weight of the component (A) and the component (B), and measured using a friability tester described in the Japanese Pharmacopoeia. Is 3% or less,
A gastric disintegrating tablet characterized by the above.
結合剤または崩壊剤(C)が、結晶セルロース、カルボキシメチルセルロースカルシウムおよびクロスポビドンよりなる群から選ばれる少なくとも1種である請求項に記載の錠剤。 The tablet according to claim 1 , wherein the binder or disintegrant (C) is at least one selected from the group consisting of crystalline cellulose, carboxymethylcellulose calcium and crospovidone. 賦形剤、流動化剤、滑沢剤、安定化剤、着色剤、矯味剤および着香剤からなる群から選ばれる少なくとも1種をさらに含有する請求項1または2に記載の錠剤。 The tablet according to claim 1 or 2 , further comprising at least one selected from the group consisting of an excipient, a fluidizing agent, a lubricant, a stabilizer, a colorant, a corrigent and a flavoring agent. 薬効成分(A)、ヒドロキシプロピルセルロースまたはプルラン、結晶セルロース、カルボキシメチルセルロースカルシウムおよびクロスポビドンを含有しそしてこれらの合計重量を基準にして薬効成分(A)が20〜90重量%、ヒドロキシプロピルセルロースまたはプルランが0.2〜20重量%、結晶セルロースが5〜60重量%、カルボキシメチルセルロースカルシウムが0.5〜20重量%およびクロスポビドンが0.5〜20重量%である請求項1〜のいずれかに記載の錠剤。 Contains medicinal component (A), hydroxypropylcellulose or pullulan, crystalline cellulose, carboxymethylcellulose calcium and crospovidone, and 20 to 90% by weight of medicinal component (A) based on the total weight thereof, hydroxypropylcellulose or pullulan There 0.2-20 wt%, crystalline cellulose 5 to 60 wt%, carboxymethyl claim 1-3 cellulose calcium 0.5 to 20 wt% and crospovidone is 0.5 to 20 wt% Tablet as described in 1. 薬効成分(A)が30〜90重量%、ヒドロキプロピルセルロースまたはプルランが1〜10重量%、結晶セルロースが5〜50重量%、カルボキシメチルセルロースカルシウムが0.5〜10重量%およびクロスポビドンが0.5〜10重量%である請求項に記載の錠剤。 The medicinal component (A) is 30 to 90% by weight, hydroxypropylcellulose or pullulan is 1 to 10% by weight, crystalline cellulose is 5 to 50% by weight, carboxymethylcellulose calcium is 0.5 to 10% by weight, and crospovidone is 0.1% by weight. The tablet according to claim 4 , which is 5 to 10% by weight. 日本薬局方記載崩壊試験法にて測定した精製水を試験液とする崩壊性が180秒以下である請求項1〜のいずれかに記載の錠剤。 The tablet according to any one of claims 1 to 5 , which has a disintegration property of 180 seconds or less using purified water measured by a disintegration test method described in the Japanese Pharmacopoeia.
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