JP6286096B1 - Pharmaceutical tablets - Google Patents
Pharmaceutical tablets Download PDFInfo
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- JP6286096B1 JP6286096B1 JP2017149425A JP2017149425A JP6286096B1 JP 6286096 B1 JP6286096 B1 JP 6286096B1 JP 2017149425 A JP2017149425 A JP 2017149425A JP 2017149425 A JP2017149425 A JP 2017149425A JP 6286096 B1 JP6286096 B1 JP 6286096B1
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- pharmaceutical tablet
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Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
【課題】打錠性に優れた医薬用錠剤を提供する。【解決手段】（Ａ）フェキソフェナジン塩酸塩、及び （Ｂ）メチルエフェドリン塩酸塩又はプソイドエフェドリン塩酸塩を含む医薬用錠剤であって、（Ａ）成分／（Ｂ）成分で示される重量比が、特定の比率である、医薬用錠剤を調製する。より具体的には、（Ａ）フェキソフェナジン塩酸塩、及び（Ｂ）メチルエフェドリン塩酸塩を含む医薬用錠剤であって、（Ａ）成分／（Ｂ）成分で示される重量比が、１．３〜１．９である、医薬用錠剤を調製する。また、（Ａ）フェキソフェナジン塩酸塩、及び（Ｂ）プソイドエフェドリン塩酸塩を含む医薬用錠剤であって、（Ａ）成分／（Ｂ）成分で示される重量比が、０．５〜１．０、（Ｂ）成分の含有量が、該錠剤全量の１２重量％以下である医薬用錠剤を調製する。【選択図】なしDisclosed is a pharmaceutical tablet having excellent tabletability. A pharmaceutical tablet comprising (A) fexofenadine hydrochloride and (B) methylephedrine hydrochloride or pseudoephedrine hydrochloride, wherein the weight ratio indicated by (A) component / (B) component is: Prepare pharmaceutical tablets at a specific ratio. More specifically, it is a pharmaceutical tablet comprising (A) fexofenadine hydrochloride and (B) methylephedrine hydrochloride, wherein the weight ratio represented by (A) component / (B) component is 1. A pharmaceutical tablet is prepared, which is 3-1.9. Moreover, it is a pharmaceutical tablet containing (A) fexofenadine hydrochloride and (B) pseudoephedrine hydrochloride, and the weight ratio indicated by (A) component / (B) component is 0.5 to 1.0. (B) The content of the component is prepared as a pharmaceutical tablet that is 12% by weight or less of the total amount of the tablet. [Selection figure] None
Description
本発明は、医薬用錠剤に関する。より詳細には、（Ａ）フェキソフェナジン塩酸塩、及び（Ｂ）メチルエフェドリン塩酸塩又はプソイドエフェドリン塩酸塩を含む医薬用錠剤に関する。 The present invention relates to a pharmaceutical tablet. More particularly, the present invention relates to a pharmaceutical tablet containing (A) fexofenadine hydrochloride and (B) methylephedrine hydrochloride or pseudoephedrine hydrochloride.
アレルギー用薬として、ケミカルメディエーター遊離抑制薬や、抗ヒスタミン薬、ロイコトリエン拮抗薬等、様々なメカニズムを有する薬剤が知られている。このようなアレルギー用薬のうち、抗ヒスタミン薬として、古くから種々の薬剤が開発されている。特に眠気に関する副作用の少ない抗ヒスタミン薬もいくつか知られており、中でもフェキソフェナジンは、鎮静作用がほとんどなく、臨床において広く用いられている。フェキソフェナジンとしては、主としてフェキソフェナジン塩酸塩が用いられている。 As allergic drugs, chemical mediator release inhibitors, antihistamines, leukotriene antagonists and other drugs having various mechanisms are known. Among such allergic drugs, various drugs have long been developed as antihistamines. Several antihistamines with particularly few side effects related to sleepiness are known, and among them, fexofenadine has almost no sedative action and is widely used in clinical practice. As fexofenadine, fexofenadine hydrochloride is mainly used.
メチルエフェドリン塩酸塩（例えば、ｄｌ−メチルエフェドリン塩酸塩）は、エフェドリンと類似の作用機序、すなわちα作用、及びβ作用を有し、気管支拡張作用、中枢性の鎮咳作用を有することが知られており（非特許文献１）、さらに、交感神経興奮薬として長い間汎用されている成分である。 Methylephedrine hydrochloride (for example, dl-methylephedrine hydrochloride) has a mechanism of action similar to that of ephedrine, that is, alpha action and beta action, and is known to have bronchodilator action and central antitussive action. (Non-patent Document 1) and a component that has been widely used for a long time as a sympathomimetic drug.
プソイドエフェドリン塩酸塩は、交感神経刺激薬として知られており、交感神経を刺激し、鼻粘膜の血管平滑筋を収縮させ、鼻閉を改善することができるとして使用されている成分である。 Pseudoephedrine hydrochloride is known as a sympathomimetic drug, and is a component that is used to stimulate sympathetic nerves, contract vascular smooth muscles of the nasal mucosa, and improve nasal congestion.
本発明は、良好な状態の医薬用錠剤を提供することを目的とする。 An object of this invention is to provide the pharmaceutical tablet of a favorable state.
本発明者らは、鋭意検討を行った結果、（Ａ）フェキソフェナジン塩酸塩、及び （Ｂ）メチルエフェドリン塩酸塩又はプソイドエフェドリン塩酸塩を含む医薬用錠剤であって、特定の（Ｂ）成分の含有量及び（Ａ）成分と（Ｂ）成分の重量の特定範囲の割合によって、硬度が適度な値であり、あるいは摩損度が低い良好な医薬用錠剤が得られることを見出し、本発明を完成するに至った。 As a result of intensive studies, the present inventors have found that (A) fexofenadine hydrochloride, and (B) methylephedrine hydrochloride or pseudoephedrine hydrochloride, a pharmaceutical tablet comprising a specific component (B) The present invention was completed by finding that a good pharmaceutical tablet having a moderate hardness or low friability can be obtained depending on the content and the ratio of the specific ranges of the weights of the components (A) and (B). It came to do.
すなわち、本発明は、下記に掲げる医薬用錠剤を提供する。
項１．
（Ａ）フェキソフェナジン塩酸塩、及び
（Ｂ）メチルエフェドリン塩酸塩
を含む医薬用錠剤であって、
（Ａ）成分／（Ｂ）成分で示される重量比が、１．３〜１．９である、
医薬用錠剤。
項２．
（Ｂ）成分の含有量が、該錠剤全量の１２重量％以下である項１に記載の医薬用錠剤。
項３．
前記（Ａ）成分／（Ｂ）成分で示される重量比が、５／３である、請求項１又は２記載の医薬用錠剤。
項４．
（Ａ）フェキソフェナジン塩酸塩、及び
（Ｂ）プソイドエフェドリン塩酸塩
を含む医薬用錠剤であって、
（Ａ）成分／（Ｂ）成分で示される重量比が、０．５〜１．０、
（Ｂ）成分の含有量が、該錠剤全量の１２重量％以下である医薬用錠剤。
項５．
前記（Ｂ）成分の含有量が、該錠剤全量の８重量％以上である項４に記載の医薬用錠剤。
項６．
前記（Ａ）成分／（Ｂ）成分で示される重量比が、１である、項４又は５記載の医薬用錠剤。
項７．
前記（Ａ）成分／（Ｂ）成分で示される重量比が、０．５である、項４又は５記載の医薬用錠剤。
項８．
硬度５０Ｎ以上である、項１〜７のいずれか１項記載の医薬用錠剤。
項９．
摩損度０．８％以下である、項１〜８のいずれか１項記載の医薬用錠剤。
項１０．
前記（Ａ）成分の一日投与量が、１２０ｍｇである、項１〜９のいずれか１項記載の医薬用錠剤。
項１１．
さらに、抗コリン成分を含有する、項１〜１０のいずれか１項記載の医薬用錠剤。
項１２．
さらに、滑沢剤を含有する、項１〜１１のいずれか１項記載の医薬用錠剤。
項１３．
重量が３０ｍｇ〜８００ｍｇである、項１〜１２のいずれか１項記載の医薬用錠剤。
項１４．
錠径が３．０ｍｍ〜１２．０ｍｍ、及び 錠厚が２．０ｍｍ〜７．０ｍｍである、項１〜１３のいずれか1項記載の医薬用錠剤。
That is, the present invention provides the following pharmaceutical tablets.
Item 1.
(A) fexofenadine hydrochloride, and
(B) a pharmaceutical tablet comprising methylephedrine hydrochloride,
The weight ratio indicated by (A) component / (B) component is 1.3 to 1.9,
Pharmaceutical tablet.
Item 2.
Item 2. The pharmaceutical tablet according to Item 1, wherein the content of the component (B) is 12% by weight or less of the total amount of the tablet.
Item 3.
The pharmaceutical tablet according to claim 1 or 2, wherein a weight ratio represented by the component (A) / component (B) is 5/3.
Item 4.
(A) fexofenadine hydrochloride, and
(B) a pharmaceutical tablet comprising pseudoephedrine hydrochloride,
The weight ratio represented by (A) component / (B) component is 0.5 to 1.0,
(B) The pharmaceutical tablet whose content of a component is 12 weight% or less of the tablet whole quantity.
Item 5.
Item 5. The pharmaceutical tablet according to Item 4, wherein the content of the component (B) is 8% by weight or more of the total amount of the tablet.
Item 6.
Item 6. The pharmaceutical tablet according to Item 4 or 5, wherein the weight ratio represented by the component (A) / component (B) is 1.
Item 7.
Item 6. The pharmaceutical tablet according to Item 4 or 5, wherein a weight ratio represented by the component (A) / component (B) is 0.5.
Item 8.
Item 8. The pharmaceutical tablet according to any one of Items 1 to 7, having a hardness of 50 N or more.
Item 9.
Item 9. The pharmaceutical tablet according to any one of Items 1 to 8, which has a friability of 0.8% or less.
Item 10.
Item 10. The pharmaceutical tablet according to any one of Items 1 to 9, wherein the daily dose of the component (A) is 120 mg.
Item 11.
Furthermore, the pharmaceutical tablet of any one of claim | item 1 -10 containing an anticholinergic component.
Item 12.
Furthermore, the pharmaceutical tablet of any one of claim | item 1 -11 containing a lubricant.
Item 13.
Item 13. The pharmaceutical tablet according to any one of Items 1 to 12, having a weight of 30 mg to 800 mg.
Item 14.
Item 14. The pharmaceutical tablet according to any one of Items 1 to 13, wherein the tablet diameter is 3.0 mm to 12.0 mm, and the tablet thickness is 2.0 mm to 7.0 mm.
本発明によれば、良好な医薬用錠剤を提供することができる。 According to the present invention, a good pharmaceutical tablet can be provided.
本発明は、（Ａ）フェキソフェナジン塩酸塩、及び （Ｂ）メチルエフェドリン塩酸塩又はプソイドエフェドリン塩酸塩を含む医薬用錠剤であって、（Ａ）成分／（Ｂ）成分で示される重量比が、特定割合である、医薬用錠剤に関する。 The present invention is a pharmaceutical tablet comprising (A) fexofenadine hydrochloride, and (B) methylephedrine hydrochloride or pseudoephedrine hydrochloride, wherein the weight ratio indicated by (A) component / (B) component is: It relates to a pharmaceutical tablet in a specific proportion.
［（Ａ）フェキソフェナジン塩酸塩］
本発明で用いられる、フェキソフェナジン（（ＲＳ）−２−［４−［１−ヒドロキシ−４−［４−（ヒドロキシ−ジフェニル−メチル）−１−ピペリジル］ブチル］フェニル］−２−メチル−プロピオン）の塩酸塩（本明細書中、（Ａ）成分と記載することもある）は、第２世代抗ヒスタミン薬として公知の化合物である。フェキソフェナジン塩酸塩は、市販品にて入手するか、公知の製造方法によって製造することができる。
[(A) Fexofenadine hydrochloride]
Fexofenadine ((RS) -2- [4- [1-hydroxy-4- [4- (hydroxy-diphenyl-methyl) -1-piperidyl] butyl] phenyl] -2-methyl- used in the present invention Propion) hydrochloride (sometimes referred to herein as component (A)) is a compound known as a second-generation antihistamine. Fexofenadine hydrochloride can be obtained as a commercial product or can be produced by a known production method.
フェキソフェナジンは、Ｒ体、Ｓ体のいずれであってもよく、光学分離したものを用いてもラセミ体を用いてもよい。 Fexofenadine may be either R-form or S-form, and optically separated or racemic form may be used.
本発明の医薬用錠剤における（Ａ）成分の用量（投与量）は、（Ｂ）成分の量、他の成分の種類や量、及び服用者の状態（体重、年齢、性別、症状、体調等）に応じて適宜設定でき、限定はされないが、本発明の効果をより顕著に発揮させる観点から、通常、１日あたりの経口投与量は、フェキソフェナジン塩酸塩として、好ましくは、約１０〜約２４０ｍｇとすることができ、より好ましくは、約１０〜約２００ｍｇ、さらに好ましくは、約２０〜約１６０ｍｇ、さらにより好ましくは、約３０〜約１４０ｍｇ、特に好ましくは、約６０〜約１２０ｍｇとすることができる。あるいは、最も好ましくは、1日辺り１２０ｍｇとすることである。 The dose (dosage) of component (A) in the pharmaceutical tablet of the present invention is the amount of component (B), the type and amount of other components, and the condition of the user (weight, age, sex, symptoms, physical condition, etc.) However, from the viewpoint of exerting the effects of the present invention more remarkably, the oral dose per day is usually about 10 to 10 as fexofenadine hydrochloride. About 240 mg, more preferably about 10 to about 200 mg, more preferably about 20 to about 160 mg, even more preferably about 30 to about 140 mg, particularly preferably about 60 to about 120 mg. be able to. Or most preferably, it is 120 mg per day.
本発明の医薬用錠剤における（Ａ）成分の総含有量は、上記の服用量となるように適宜設定できる。限定はされないが、本発明の効果をより顕著に発揮させる観点から、例えば、医薬用錠剤の総量を基準として、１重量％以上とすることができ、好ましくは３重量％以上、より好ましくは５重量％以上、さらにより好ましくは１０重量％以上とすることができ、９０重量％以下とすることができ、好ましくは６０重量％以下とすることができ、より好ましくは５０重量％以下とすることができる。
（Ａ）成分の総含有量は、例えば、医薬用錠剤の総量を基準として、１〜９０重量％とすることができ、好ましくは３〜６０重量％、より好ましくは５〜６０重量％、さらにより好ましくは１０〜５０重量％とすることができる。
The total content of the component (A) in the pharmaceutical tablet of the present invention can be appropriately set so as to be the above dose. Although not limited, from the viewpoint of more prominently exerting the effects of the present invention, for example, it can be 1% by weight or more, preferably 3% by weight or more, more preferably 5%, based on the total amount of pharmaceutical tablets. % By weight or more, even more preferably 10% by weight or more, 90% by weight or less, preferably 60% by weight or less, more preferably 50% by weight or less. Can do.
The total content of component (A) can be, for example, 1 to 90% by weight, preferably 3 to 60% by weight, more preferably 5 to 60% by weight, based on the total amount of pharmaceutical tablets. More preferably, it can be 10 to 50% by weight.
[（Ｂ−１）メチルエフェドリン塩酸塩]
本発明で用いられる、メチルエフェドリン（（１ＲＳ，２ＳＲ）−２−ジメチルアミノ−１−フェニルプロパン−１−オール）塩酸塩（本明細書中、単に（Ｂ）成分と記載することもある）は、エフェドリンと類似の作用機序、すなわちα作用、及びβ作用を有し、気管支拡張作用、中枢性の鎮咳作用を有することが知られている公知の化合物である。メチルエフェドリン塩酸塩は、市販品にて入手するか、又は公知の方法に従って製造することができる。
[(B-1) methylephedrine hydrochloride]
As used in the present invention, methylephedrine ((1RS, 2SR) -2-dimethylamino-1-phenylpropan-1-ol) hydrochloride (sometimes referred to simply as component (B) in this specification) is It is a known compound that has a mechanism of action similar to that of ephedrine, that is, an α action and a β action, and is known to have a bronchodilating action and a central antitussive action. Methylephedrine hydrochloride can be obtained as a commercial product or can be produced according to a known method.
メチルエフェドリンは、Ｒ体、Ｓ体のいずれであってもよく、光学分離したものを用いてもラセミ体を用いてもよい。 Methylephedrine may be either R-form or S-form, and optically separated or racemic form may be used.
本発明の医薬用錠剤における（Ｂ−１）成分の用量（投与量）は、（Ａ）成分の量、他の成分の種類や量、及び服用者の状態（体重、年齢、性別、症状、体調等）に応じて適宜設定でき、限定はされないが、本発明の効果をより顕著に発揮させる観点から、（Ｂ−１）成分が含まれる場合には、通常、１日あたりの経口投与量は、メチルエフェドリン塩酸塩として、約１０〜約２００ｍｇとすることができ、より好ましくは、約２２〜約１６０ｍｇ、さらにより好ましくは、約３０〜約１４０ｍｇ、特に好ましくは、約６０〜約１００ｍｇとすることができる。あるいは、最も好ましくは、1日あたり７２ｍｇとすることである。 The dose (dosage) of component (B-1) in the pharmaceutical tablet of the present invention is the amount of component (A), the type and amount of other components, and the condition of the user (weight, age, sex, symptoms, Can be appropriately set according to the physical condition etc., and is not limited, but from the viewpoint of more prominently exerting the effects of the present invention, when the component (B-1) is included, the oral dose per day is usually Can be from about 10 to about 200 mg as methylephedrine hydrochloride, more preferably from about 22 to about 160 mg, even more preferably from about 30 to about 140 mg, particularly preferably from about 60 to about 100 mg. can do. Alternatively, it is most preferably 72 mg per day.
本発明の医薬用錠剤における（Ｂ−１）成分の総含有量は、上記の服用量となるように適宜設定でき、医薬用錠剤の総量の１２重量％以下であることが好ましい。本願発明の効果および（Ａ）成分／（Ｂ−１）成分の適性な数値設定の観点から、１２重量％以下で、効能を生じる範囲で濃度は低くてもよい。本発明の医薬用錠剤における（Ｂ−１）成分の総含有量は、（Ｂ−１）成分が含まれる場合には、限定はされないが、本発明の効果をより顕著に発揮させる観点から、例えば、医薬用錠剤の総量を基準として、０．１重量％以上とすることができ、好ましくは１重量％以上、より好ましくは５重量％以上、さらにより好ましくは８重量％以上とすることができ、場合により１０重量％以上とすることができる。本発明の医薬用錠剤における（Ｂ−１）成分の総含有量は、１２重量％以下であり、本発明の効果をより顕著に発揮させる観点から、好ましくは、１１．５重量％以下とすることができ、より好ましくは、１１重量％以下とすることができる。 The total content of the component (B-1) in the pharmaceutical tablet of the present invention can be appropriately set to be the above dose, and is preferably 12% by weight or less of the total amount of the pharmaceutical tablet. From the viewpoint of the effect of the present invention and the appropriate numerical setting of the component (A) / component (B-1), the concentration may be as low as 12% by weight or less within the range where the effect is produced. The total content of the component (B-1) in the pharmaceutical tablet of the present invention is not limited when the component (B-1) is included, but from the viewpoint of more prominently exerting the effects of the present invention. For example, based on the total amount of pharmaceutical tablets, it can be 0.1% by weight or more, preferably 1% by weight or more, more preferably 5% by weight or more, and even more preferably 8% by weight or more. In some cases, it can be 10% by weight or more. The total content of the component (B-1) in the pharmaceutical tablet of the present invention is 12% by weight or less, and preferably 11.5% by weight or less from the viewpoint of more prominently exerting the effects of the present invention. More preferably, it can be 11 weight% or less.
（Ｂ−１）成分の総含有量は、（Ｂ−１）成分が含まれる場合には、例えば、医薬用錠剤の総量を基準として、０．１〜１２重量％とすることができ、好ましくは１〜１２重量％、より好ましくは５〜１２重量％、さらにより好ましくは８〜１２重量％とすることができる。場合により、１０〜１１重量％とすることができる。 The total content of the component (B-1) can be 0.1 to 12% by weight based on the total amount of the pharmaceutical tablet, for example, when the component (B-1) is included, Can be 1 to 12% by weight, more preferably 5 to 12% by weight, and even more preferably 8 to 12% by weight. Depending on the case, it can be 10 to 11 weight%.
[（Ｂ−２）プソイドエフェドリン塩酸塩]
本発明で用いられる、プソイドエフェドリン（（１Ｓ，２Ｓ）−２−（メチルアミノ）−１−フェニル−１−プロパノール）塩酸塩（本明細書中、（Ｂ）成分と記載することもある）は、エフェドリンと類似の作用機序、すなわちα作用、及びβ作用を有し、気管支拡張作用、中枢性の鎮咳作用を有することが知られている公知の化合物である。プソイドエフェドリン塩酸塩は、市販品にて入手するか、又は公知の方法に従って製造することができる。
[(B-2) pseudoephedrine hydrochloride]
Pseudoephedrine ((1S, 2S) -2- (methylamino) -1-phenyl-1-propanol) hydrochloride (sometimes referred to as (B) component in the present specification) used in the present invention is: It is a known compound that has an action mechanism similar to that of ephedrine, that is, an α action and a β action, and is known to have a bronchodilator action and a central antitussive action. Pseudoephedrine hydrochloride can be obtained as a commercial product or can be produced according to a known method.
プソイドエフェドリンは、Ｒ体、Ｓ体のいずれであってもよく、光学分離したものを用いてもラセミ体を用いてもよい。 The pseudoephedrine may be either R-form or S-form, and optically separated or racemic form may be used.
本発明の医薬用錠剤における（Ｂ−２）成分の用量（投与量）は、（Ａ）成分の量、他の成分の種類や量、及び服用者の状態（体重、年齢、性別、症状、体調等）に応じて適宜設定でき、限定はされないが、本発明の効果をより顕著に発揮させる観点から、（Ｂ−２）成分が含まれる場合には、通常、１日あたりの経口投与量は、例えば、プソイドエフェドリン塩酸塩として、約２０〜約４００ｍｇとすることができ、より好ましくは、約２０〜約３００ｍｇ、さらにより好ましくは、約３０〜約２８０ｍｇ、特に好ましくは、約６０〜約２４０ｍｇとすることができる。 The dose (dose) of the component (B-2) in the pharmaceutical tablet of the present invention is the amount of the component (A), the type and amount of the other components, and the state of the user (weight, age, sex, symptoms, It can be appropriately set according to the physical condition etc., and is not limited, but from the viewpoint of more prominently exerting the effects of the present invention, when the component (B-2) is included, the oral dose per day is usually Can be, for example, about 20 to about 400 mg as pseudoephedrine hydrochloride, more preferably about 20 to about 300 mg, even more preferably about 30 to about 280 mg, and particularly preferably about 60 to about 240 mg. It can be.
本発明の医薬用錠剤における（Ｂ−２）成分の総含有量は、上記の服用量となるように適宜設定でき、本願発明の効果および（Ａ）成分／（Ｂ−２）成分の適性な数値設定の観点から、医薬用錠剤の総量の１２重量％以下であることが好ましい。本発明の医薬用錠剤における（Ｂ−２）成分の総含有量は、（Ｂ−２）成分が含まれる場合には、限定はされないが、本発明の効果をより顕著に発揮させる観点から、例えば、医薬用錠剤の総量を基準として、０．１重量％以上とすることができ、好ましくは１重量％以上、より好ましくは５重量％以上、さらにより好ましくは８重量％以上とすることができ、場合により１０重量％以上とすることができる。本発明の医薬用錠剤における（Ｂ−２）成分の総含有量は、１２重量％以下であり、本発明の効果をより顕著に発揮させる観点から、好ましくは、１１．５重量％以下とすることができ、より好ましくは、１１重量％以下とすることができる。 The total content of the component (B-2) in the pharmaceutical tablet of the present invention can be appropriately set so as to be the above dose, and the effect of the present invention and the suitability of the component (A) / (B-2) From the viewpoint of setting numerical values, it is preferably 12% by weight or less of the total amount of the pharmaceutical tablet. The total content of the component (B-2) in the pharmaceutical tablet of the present invention is not limited when the component (B-2) is included, but from the viewpoint of more prominently exerting the effects of the present invention, For example, based on the total amount of pharmaceutical tablets, it can be 0.1% by weight or more, preferably 1% by weight or more, more preferably 5% by weight or more, and even more preferably 8% by weight or more. In some cases, it can be 10% by weight or more. The total content of the component (B-2) in the pharmaceutical tablet of the present invention is 12% by weight or less, and preferably 11.5% by weight or less from the viewpoint of exhibiting the effects of the present invention more remarkably. More preferably, it can be 11 weight% or less.
（Ｂ−２）成分の総含有量は、（Ｂ−２）成分が含まれる場合には、例えば、医薬用錠剤の総量を基準として、０．１〜１２重量％とすることができ、好ましくは１〜１２重量％、より好ましくは５〜１２重量％、さらにより好ましくは、８〜１２重量％とすることができ、場合により、１０〜１１重量％とすることができる。 The total content of the component (B-2) can be 0.1 to 12% by weight, for example, based on the total amount of the pharmaceutical tablet when the component (B-2) is included. Can be 1 to 12% by weight, more preferably 5 to 12% by weight, even more preferably 8 to 12% by weight, and optionally 10 to 11% by weight.
本発明の医薬用錠剤は、（Ｂ−１）成分又は（Ｂ−２）成分のいずれか一方を含有していれば良く、場合により、（Ｂ−１）成分および（Ｂ−２）成分の両方を含有しても良い。本発明の医薬用錠剤は、好ましくは、（Ｂ−１）成分又は（Ｂ−２）成分のいずれか一方を含有するものである。 The pharmaceutical tablet of the present invention may contain either one of the component (B-1) or the component (B-2). Depending on the case, the pharmaceutical tablet of the component (B-1) and the component (B-2) Both may be contained. The pharmaceutical tablet of the present invention preferably contains either (B-1) component or (B-2) component.
本発明の医薬用錠剤の（Ｂ）成分の総含有量は、限定はされないが、本発明の効果をより顕著に発揮させる観点から、例えば、医薬用錠剤の総量を基準として、（Ｂ−１）又は（Ｂ−２）それぞれ単一の（Ｂ）成分につき、０．１重量％以上とすることができ、好ましくは１重量％以上、より好ましくは５重量％以上、さらにより好ましくは８重量％以上とすることができ、場合により１０重量％以上とすることができる。本発明の医薬用錠剤における（Ｂ）成分の総含有量は、限定はされないが、本発明の効果をより顕著に発揮させる観点から、例えば、医薬用錠剤の総量を基準として、（Ｂ−１）又は（Ｂ−２）それぞれ単一の（Ｂ）成分につき、１２重量％以下であり、本発明の効果をより顕著に発揮させる観点から、好ましくは、１１．５重量％以下とすることができ、より好ましくは、１１重量％以下とすることができる。但し、（Ｂ）成分としては、（Ｂ−１）又は（Ｂ−２）成分のそれぞれ単独であることが好ましいことから、（Ｂ）成分の合計量としても、これらの値であることが好ましい。 The total content of the component (B) of the pharmaceutical tablet of the present invention is not limited, but from the viewpoint of more prominently exerting the effects of the present invention, for example, based on the total amount of the pharmaceutical tablet (B-1 ) Or (B-2) Each of the single component (B) may be 0.1% by weight or more, preferably 1% by weight or more, more preferably 5% by weight or more, and still more preferably 8% by weight. % Or more, and in some cases, 10% by weight or more. The total content of the component (B) in the pharmaceutical tablet of the present invention is not limited, but from the viewpoint of exhibiting the effects of the present invention more remarkably, for example, based on the total amount of the pharmaceutical tablet (B-1 ) Or (B-2) Each of the single component (B) is 12% by weight or less, and preferably 11.5% by weight or less from the viewpoint of more prominently exerting the effects of the present invention. More preferably, it can be made into 11 weight% or less. However, since the component (B) is preferably each of the components (B-1) or (B-2), the total amount of the component (B) is preferably those values. .
（Ｂ）成分の総含有量は、例えば、医薬用錠剤の総量を基準として、（Ｂ−１）又は（Ｂ−２）それぞれ単一の（Ｂ）成分につき、０．１〜１２重量％とすることができ、好ましくは１〜１２重量％、より好ましくは５〜１２重量％、さらにより好ましくは７〜１２重量％、最も好ましくは８〜１２重量％とすることができ、場合により、１０〜１１重量％とすることができる。 The total content of component (B) is, for example, 0.1 to 12% by weight for each single component (B) based on the total amount of pharmaceutical tablets (B-1) or (B-2). Preferably 1 to 12% by weight, more preferably 5 to 12% by weight, even more preferably 7 to 12% by weight, most preferably 8 to 12% by weight. It can be set to ˜11% by weight.
本発明による効果を奏する観点から、（Ａ）成分の総含有量と（Ｂ−１）成分の総含有量との配合比率を（Ａ）成分／（Ｂ−１）成分で示される重量比とした場合、１．３〜１．９の範囲内である。好ましくは、（Ａ）成分／（Ｂ−１）成分で示される重量比は、１．３〜１．８の範囲内であり、より好ましくは、１．３〜１．７の範囲内であり、最も好ましくは５／３である。 From the standpoint of achieving the effect of the present invention, the blending ratio of the total content of the component (A) and the total content of the component (B-1) is a weight ratio represented by the component (A) / (B-1). In this case, it is within the range of 1.3 to 1.9. Preferably, the weight ratio represented by component (A) / component (B-1) is in the range of 1.3 to 1.8, more preferably in the range of 1.3 to 1.7. Most preferably, it is 5/3.
本発明による効果を奏する観点から、（Ａ）成分の総含有量と（Ｂ−２）成分の総含有量との配合比率を（Ａ）成分／（Ｂ−２）成分で示される重量比とした場合、０．５〜１．０の範囲内である。好ましくは、（Ａ）成分／（Ｂ−２）成分で示される重量比は、０．５又は１である。 From the standpoint of achieving the effect of the present invention, the blending ratio of the total content of the component (A) and the total content of the component (B-2) is the weight ratio indicated by the component (A) / (B-2). In this case, it is in the range of 0.5 to 1.0. Preferably, the weight ratio represented by (A) component / (B-2) component is 0.5 or 1.
本発明の医薬用錠剤には、さらに、（Ａ）成分及び（Ｂ）成分以外の任意の成分を含ませることができる。このような任意成分は、その１種又は２種以上を適宜組み合わせることも可能である。このような任意の成分の代表的な一例として、好ましくは、トロパンアルカロイド又はその誘導体などの抗コリン成分が挙げられる。 The pharmaceutical tablet of the present invention may further contain any component other than the component (A) and the component (B). Such optional components can be used alone or in combination of two or more thereof. A typical example of such an optional component is preferably an anticholinergic component such as a tropane alkaloid or a derivative thereof.
[抗コリン成分]
本発明において、抗コリン成分としては、トロパン骨格を持つアルカロイド又はその誘導体が例示される。具体的にはトロパンアルカロイド（アトロピン、スコポラミン、ヒヨスチアミンなど）及びその誘導体（例えば、メチルアトロピン、メチルスコポラミン、ブチルスコポラミンなどの四級アンモニウム化誘導体など）並びにそれらのアルカロイドを含有する成分（ダツラエキス、ベラドンナ総アルカロイド、ベラドンナコン、ベラドンナエキス、ロートコン総アルカロイド、ロートコン、ロートエキス、ヨウ化イソプロパミド、メチルスコポラミン又はその塩、ブチルスコポラミン又はその塩等）が挙げられる。なお、これらは、薬学上許容される塩や溶媒和物の状態であってもよい。これらのうち、本発明の医薬用錠剤の打錠性により良い影響を及ぼすことができる観点から、ベラドンナ総アルカロイドが特に好ましい。
[Anticholine component]
In the present invention, the anticholinergic component is exemplified by alkaloids having a tropane skeleton or derivatives thereof. Specifically, tropane alkaloids (atropine, scopolamine, hyoscyamine and the like) and derivatives thereof (for example, quaternary ammonium derivatives such as methylatropine, methyl scopolamine and butyl scopolamine) and components containing these alkaloids (datsura extract, belladonna Total alkaloid, belladon nacon, belladonna extract, rotcon total alkaloid, rotcon, funnel extract, isopropamide iodide, methyl scopolamine or a salt thereof, butyl scopolamine or a salt thereof, and the like. These may be in the form of a pharmaceutically acceptable salt or solvate. Among these, the belladonna total alkaloid is particularly preferable from the viewpoint that it can have a better influence on the tabletability of the pharmaceutical tablet of the present invention.
ここで、塩の好適な具体例としては、臭化物塩（例えば、ブチルスコポラミン臭化物など）、臭化水素酸塩（例えば、スコポラミン臭化水素酸塩水和物など）、クエン酸塩（例えば、ロートコン総アルカロイドクエン酸塩など）などが挙げられる。また、溶媒和物としては、水和物等が挙げられる。 Here, preferable specific examples of the salt include bromide salts (for example, butyl scopolamine bromide), hydrobromides (for example, scopolamine hydrobromide hydrate), citrates (for example, rotocon total And alkaloid citrate). Examples of solvates include hydrates.
抗コリン成分として、１種又は２種以上を組み合わせて使用することができる。 As an anticholinergic component, one or a combination of two or more can be used.
本発明の医薬用錠剤に抗コリン成分が含まれる場合には、抗コリン成分は、通常、成人に対して、１日あたり有効成分の量として、通常、０．０１〜１００ｍｇを投与することができ、例えばベラドンナ総アルカロイドの場合には、０．０１〜１ｍｇ、好ましくは０．４〜０．６ｍｇ、ロートエキス、ベラドンナエキス、ダツラエキスでは１〜１００ｍｇ、ヨウ化イソプロパミドの場合には０．１〜１０ｍｇを１日１回ないし数回に分けて経口投与することができる。 When the anti-cholinergic component is contained in the pharmaceutical tablet of the present invention, the anti-cholinergic component can be administered usually in an amount of 0.01 to 100 mg as an active ingredient amount per day for an adult. For example, in the case of belladonna total alkaloid, 0.01 to 1 mg, preferably 0.4 to 0.6 mg, funnel extract, belladonna extract, duck extract, 1 to 100 mg, and in the case of iodopropamide, 0.1 to 1 mg. 10 mg can be orally administered once to several times a day.
本発明の医薬用錠剤に抗コリン成分が含まれる場合には、抗コリン成分の総含有量は、例えば、医薬用錠剤の総量を基準として、例えばベラドンナ総アルカロイドの場合には０．０２〜０．１重量％、好ましくは０．０３〜０．１重量％、より好ましくは０．０３〜０．０６重量％とすることができる。場合により０．０２〜０．０６重量％程度に調整することもできる。ロートエキス、ベラドンナエキス、ダツラエキスの場合は、０．１〜４０重量％とすることができる。ヨウ化イソプロパミドの場合には０．０１〜４重量％とすることができる。 When the anticholinergic component is contained in the pharmaceutical tablet of the present invention, the total content of the anticholinergic component is, for example, 0.02 to 0 in the case of belladonna total alkaloid, for example, based on the total amount of the pharmaceutical tablet. 0.1 wt%, preferably 0.03 to 0.1 wt%, more preferably 0.03 to 0.06 wt%. In some cases, it may be adjusted to about 0.02 to 0.06% by weight. In the case of a funnel extract, belladonna extract, or duck extract, it can be 0.1 to 40% by weight. In the case of isopropamide iodide, it can be 0.01 to 4% by weight.
本発明による効果を奏する観点から、（Ａ）成分と抗コリン成分との配合割合は、（Ａ）成分１重量部に対し、抗コリン成分 ０．００３重量部〜０．０１５重量部とすることが好ましい。 From the viewpoint of achieving the effect of the present invention, the blending ratio of the component (A) and the anticholinergic component is 0.003 part by weight to 0.015 part by weight with respect to 1 part by weight of the component (A). Is preferred.
本発明の医薬用錠剤には、さらに、（Ａ）成分及び（Ｂ）成分以外の任意の成分として、好ましくは、滑沢剤を含ませることができる。 The pharmaceutical tablet of the present invention may preferably further contain a lubricant as an optional component other than the components (A) and (B).
[滑沢剤]
本発明において、滑沢剤としては、限定はされないが、ステアリン酸マグネシウムあるいはステアリン酸カルシウムなどのステアリン酸塩が好ましく用いられる。この他に、蔗糖脂肪酸エステル、フマル酸ステアリルナトリウム、ステアリン酸、タルク、硬化油又はポリエチレングリコールなども用いられる。
[lubricant]
In the present invention, the lubricant is not limited, but stearates such as magnesium stearate or calcium stearate are preferably used. In addition, sucrose fatty acid ester, sodium stearyl fumarate, stearic acid, talc, hydrogenated oil, polyethylene glycol, etc. are also used.
滑沢剤として、１種又は２種以上を組み合わせて使用することができる。 As the lubricant, one kind or a combination of two or more kinds can be used.
本発明の医薬用錠剤に滑沢剤が含まれる場合には、滑沢剤の総含有量は、例えば、医薬用錠剤の総量を基準として、０．００１〜３．５重量％とすることができ、好ましくは０．００３〜３．０重量％、より好ましくは０．００５〜２．５重量％、さらにより好ましくは０．０１〜２．０重量％とすることができる。 When the pharmaceutical tablet of the present invention contains a lubricant, the total content of the lubricant is, for example, 0.001 to 3.5% by weight based on the total amount of the pharmaceutical tablet. Preferably 0.003 to 3.0% by weight, more preferably 0.005 to 2.5% by weight, and even more preferably 0.01 to 2.0% by weight.
本発明の医薬用錠剤に滑沢剤が含まれる場合には、（Ａ）成分と滑沢剤との配合割合は、（Ａ）成分１重量部に対し、滑沢剤０．０００２〜０．２０重量部であることが好ましい。 When the pharmaceutical tablet of the present invention contains a lubricant, the blending ratio of the component (A) to the lubricant is 0.0002 to 0.000 lubricant per 1 part by weight of the component (A). It is preferably 20 parts by weight.
本発明の医薬用錠剤は、良好な錠剤を製造する観点から、さらに以下に挙げる結合剤を含有することも好ましい。 The pharmaceutical tablet of the present invention preferably further contains the following binders from the viewpoint of producing a good tablet.
[結合剤]
結合剤は、医薬上、薬理学的に又は生理学的に許容されることを限度として特に制限されず、水難溶性結合剤として、低置換度ヒドロキシプロピルセルロース、水溶性結合剤として、タンパク質、水溶性セルロース系高分子、デンプン類、水溶性ビニル系高分子、ポリエーテル類のいずれであってもよい。
[Binder]
The binder is not particularly limited as long as it is pharmaceutically, pharmacologically or physiologically acceptable, and as a poorly water-soluble binder, low-substituted hydroxypropylcellulose, as a water-soluble binder, protein, water-soluble Any of cellulose polymers, starches, water-soluble vinyl polymers, and polyethers may be used.
タンパク質としては、具体的に、ゼラチン、精製ゼラチン等が挙げられる。水溶性セルロース系高分子としては、具体的に、カルメロース又はその塩、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、メチルセルロース、ヒドロキシエチルセルロース等が挙げられる。デンプン類としては、具体的に、デンプン（コムギデンプン、トウモロコシデンプン、バレイショデンプン等）、アルファー化デンプン、デキストリン、シクロデキストリン、カルボキシメチルスターチ、ヒドロキシプロピルスターチ、ヒドロキシエチルスターチ、部分アルファー化デンプン等が挙げられる。水溶性ビニル系高分子としては、具体的に、ポリビニルピロリドン、ポリビニルアルコール、カルボキシビニルポリマー、コポリドン等が挙げられる。アクリル系高分子としては、ポリアクリル酸ナトリウム等が挙げられる。ポリエーテル類として、具体的に、マクロゴール等が挙げられる。 Specific examples of the protein include gelatin and purified gelatin. Specific examples of the water-soluble cellulose polymer include carmellose or a salt thereof, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, and hydroxyethylcellulose. Specific examples of starches include starch (wheat starch, corn starch, potato starch, etc.), pregelatinized starch, dextrin, cyclodextrin, carboxymethyl starch, hydroxypropyl starch, hydroxyethyl starch, partially pregelatinized starch and the like. It is done. Specific examples of the water-soluble vinyl polymer include polyvinyl pyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, and copolydon. Examples of the acrylic polymer include sodium polyacrylate. Specific examples of polyethers include macrogol.
これらの結合剤成分の製剤上の用途は結合剤以外であってもよい。上記の結合剤の中でも、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、メチルセルロースなどのセルロース系高分子；バレイショデンプン、トウモロコシデンプン、アルファー化デンプンなどのデンプン類；およびポリビニルピロリドン、ポリビニルアルコールなどからなるビニル系高分子；より選択される水溶性高分子の結合剤であることが特に好ましい。 The use of these binder components in the preparation may be other than the binder. Among the above-mentioned binders, cellulosic polymers such as hydroxypropylcellulose, hydroxypropylmethylcellulose and methylcellulose; starches such as potato starch, corn starch and pregelatinized starch; and vinyl polymers comprising polyvinylpyrrolidone, polyvinyl alcohol and the like A particularly preferred water-soluble polymer binder is more preferred.
本発明の医薬用錠剤に結合剤が含まれる場合には、結合剤の総含有量は、例えば、医薬用錠剤の総量を基準として、０.０１〜９０重量％とすることができ、好ましくは０．０５〜８０重量％、より好ましくは０．１〜７０重量％、さらにより好ましくは０．５〜６０重量％とすることができる。 When the pharmaceutical tablet of the present invention contains a binder, the total content of the binder can be, for example, 0.01 to 90% by weight based on the total amount of the pharmaceutical tablet, preferably The amount can be 0.05 to 80% by weight, more preferably 0.1 to 70% by weight, and still more preferably 0.5 to 60% by weight.
本発明の医薬用錠剤に結合剤が含まれる場合には、本発明の効果をより顕著に奏するという観点や、コスト対効果の観点から、（Ａ）成分の総量１重量部に対し、結合剤を、好ましくは０．０００１〜５．５重量部、より好ましくは０．０００２〜４．５重量部、さらに好ましくは０．００１〜４．０重量部含有する。 When the pharmaceutical tablet of the present invention contains a binder, the binder is used with respect to 1 part by weight of the total amount of the component (A) from the viewpoint of more remarkable effects of the present invention and cost effectiveness. Is preferably 0.0001 to 5.5 parts by weight, more preferably 0.0002 to 4.5 parts by weight, and still more preferably 0.001 to 4.0 parts by weight.
本発明の医薬用錠剤は、所望により、さらに、（Ａ）成分および（Ｂ）成分に加えて、その他の生理活性成分を含有してもよい。
このような生理活性成分としては、例えば
（１）交感神経興奮成分（例えば、フェニレフリン、フェニルプロパノールアミン、エフェドリン、エチレフリン、メトキサミン、ミドドリン、メトキシフェナミンなど）、
（２）消炎酵素類（例えば、リゾチーム、セラペプターゼ、ブロメライン、プロナーゼなど）
（３）生薬、及び生薬由来成分（例えば、ショウキョウ、ニンジン、マオウ、ケイヒ、ケイガイ、サイシン、シンイ、ナンテンジツ、オウヒ、ビャクシ、ゼンコ、キキョウ、シャゼンシ、ゴオウ、ガジュツ、ビャクジュツ、ソウジュツ、ゲンチアナ、ウイキョウ、オンジ、オウバク、オウレン、チクセツニンジン、チンピ、チョウジ、セネガ、シャゼンソウ、シャジンなど）、
（４）キサンチン誘導体（例えば、カフェイン、テオフィリン、アミノフィリン、テオブロミン、ジプロフェイリン、プロキシフィリン、ペントキシフィリンなど）、
（５）解熱鎮痛薬成分（例えば、アスピリン、アスピリンアルミニウム、アセトアミノフェン、エテンザミド、サザピリン、サリチルアミド、サリチル酸ナトリウム、ラクチルフェネチジン、イブプロフェン、ケトプロフェンなど）、
（６）鎮咳薬成分（例えば、アクロラミド、クロペラスチン、ペントキシベリン（カルベタペンタン）、チペピジン、ジブナート、デキストロメトルファン、コデイン、ジヒドロコデイン、ノスカピンなど）、
（７）去痰薬（例えば、グアヤコールスルホン酸カリウム、グアイフェネシンなど）、
（８）ビタミン類（例えば、ビタミンＡ類［例えば、レチナール、レチノール、レチノイン酸、カロチン、デヒドロレチナール、リコピンなど］、ビタミンＢ類［例えば、チアミン、チアミンジスルフィド、ジセチアミン、オクトチアミン、シコチアミン、ビスイブチアミン、ビスベンチアミン、プロスルチアミン、ベンフォチアミン、フルスルチアミン、リボフラビン、フラビンアデニンジヌクレオチド、ピリドキシン、ピリドキサール、ヒドロキソコバラミン、シアノコバラミン、メチルコバラミン、デオキシアデノコバラミン、葉酸、テトラヒドロ葉酸、ジヒドロ葉酸、ニコチン酸、ニコチン酸アミド、ニコチニルアルコール、パントテン酸、パンテノール、ビオチン、コリン、イノシトールなど］、ビタミンＣ類［例えば、アスコルビン酸、エリソルビン酸、又はその誘導体など］、ビタミンＤ類［例えば、エルゴカルシフェロール、コレカルシフェロール、ヒドロキシコレカルシフェロール、ジヒドロキシコレカルシフェロール、ジヒドロタキステロールなど］、ビタミンＥ類［例えば、トコフェロールおよびその誘導体、ユビキノン誘導体など］、その他のビタミン類［例えば、ヘスペリジン、カルニチン、フェルラ酸、γ−オリザノール、オロチン酸、ルチン、エリオシトリンなど］など）、および
（９）粘膜保護成分（例えば、アミノ酢酸、乾燥水酸化アルミニウムゲル、ジヒドロキシアルミニウム・アミノ酢酸塩などのアルミニウム系粘膜保護剤；メタケイ酸アルミン酸マグネシウム、ケイ酸アルミニウム、ヒドロタルサイト、水酸化アルミナマグネシウム、水酸化アルミニウムゲル、水酸化アルミニウム・炭酸水素ナトリウムの共沈生成物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸カルシウム・炭酸マグネシウムの共沈生成物、炭酸マグネシウム、酸化マグネシウム、水酸化マグネシウム、ケイ酸マグネシウム、水酸化マグネシウム・硫酸アルミニウムカリウムの共沈生成物などのマグネシウム系粘膜保護剤など）などが挙げられる。
これらの生理活性成分は、フリー体であっても、塩であってもよい。
If desired, the pharmaceutical tablet of the present invention may further contain other physiologically active components in addition to the components (A) and (B).
Examples of such physiologically active components include (1) sympathomimetic components (for example, phenylephrine, phenylpropanolamine, ephedrine, ethylephrine, methoxamine, middolin, methoxyphenamine, etc.),
(2) Anti-inflammatory enzymes (eg lysozyme, serrapeptase, bromelain, pronase)
(3) herbal medicine and herbal medicine-derived components (for example, shrimp, carrot, maoh, keihi, kei-gai, saishin, shin-i, nantenjitsu, haku-ji, bakushi, zenko, kyoto, shazenshi, gooh, gadju, juniper, sojutsu, gentian, fennel , Onji, Awaku, Auren, Chikutsujinjin, Chimpi, Clove, Senega, Shazenso, Shajin, etc.)
(4) xanthine derivatives (for example, caffeine, theophylline, aminophylline, theobromine, diprofeline, proxyphylline, pentoxyphylline),
(5) antipyretic analgesic components (for example, aspirin, aspirin aluminum, acetaminophen, etenzamide, sazapyrine, salicylamide, sodium salicylate, lactylphenetidine, ibuprofen, ketoprofen, etc.)
(6) Antitussive components (for example, achloramide, cloperastine, pentoxyberine (carbettapentane), tipepidine, dibutate, dextromethorphan, codeine, dihydrocodeine, noscapine, etc.)
(7) expectorants (for example, potassium guaiacol sulfonate, guaifenesin, etc.),
(8) vitamins (for example, vitamins A [for example, retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene, etc.), vitamins B [for example, thiamine, thiamine disulfide, discetiamine, octothiamine, chicotiamine, bisive Thiamine, bisbenchamine, prosultiamine, benfotiamine, fursultiamine, riboflavin, flavin adenine dinucleotide, pyridoxine, pyridoxal, hydroxocobalamin, cyanocobalamin, methylcobalamin, deoxyadenocobalamin, folate, tetrahydrofolate, dihydrofolate, nicotine Acid, nicotinamide, nicotinyl alcohol, pantothenic acid, panthenol, biotin, choline, inositol, etc.], vitamin C [eg ascorb Acid, erythorbic acid, or derivatives thereof], vitamin Ds (eg ergocalciferol, cholecalciferol, hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotaxosterol etc.), vitamin Es (eg tocopherol and Derivatives thereof, ubiquinone derivatives, etc.], other vitamins [eg, hesperidin, carnitine, ferulic acid, γ-oryzanol, orotic acid, rutin, eriocitrin, etc.], and (9) mucosal protective components (eg, aminoacetic acid) , Dry aluminum hydroxide gel, Aluminum-based mucosal protective agents such as dihydroxyaluminum / aminoacetate; Magnesium aluminate metasilicate, Aluminum silicate, Hydrotalcite, Magnesium aluminate hydroxide, Hydroxide Aluminum fluoride gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / calcium carbonate / magnesium carbonate coprecipitation product, magnesium carbonate, magnesium oxide, hydroxylation And magnesium-based mucosal protective agents such as coprecipitation products of magnesium, magnesium silicate, magnesium hydroxide and potassium aluminum sulfate).
These physiologically active ingredients may be free forms or salts.
[基剤又は担体]
本発明の医薬用錠剤は、本発明の効果を損なわない範囲で、医薬品、医薬部外品、として用いられ得る、公知の基剤又は担体と共に混合して製剤化することができる。その他に、本発明の医薬用錠剤には、賦形剤（例えば、ショ糖、乳糖、結晶セルロース、乳糖水和物、マンニトール、軽質無水ケイ酸など）、滑沢剤（例えば、ショ糖脂肪酸エステル、ステアリン酸マグネシウム、タルクなど）、崩壊剤（例えば、低置換度ヒドロキシプロピルセルロース、クロスポビドン、クロスカルメロースナトリウムなど）、発泡剤（例えば、炭酸水素ナトリウムなど）、流動化剤（例えば、メタケイ酸アルミン酸ナトリウム、軽質無水ケイ酸など）、コーティング剤（ヒドロキシプロピルメチルセルロース、ポリビニルアルコールなど）、着色剤（例えば、酸化鉄、酸化チタンなど）などが挙げられる。これらの添加物の製剤上の用途は上記以外であってもよい。また、これらの基剤、担体、及び／又は添加剤は、１種を単独で又は２種以上を組み合わせて使用できる。
[Base or carrier]
The pharmaceutical tablet of the present invention can be formulated by mixing with a known base or carrier that can be used as a pharmaceutical product or quasi-drug as long as the effects of the present invention are not impaired. In addition, the pharmaceutical tablet of the present invention includes excipients (for example, sucrose, lactose, crystalline cellulose, lactose hydrate, mannitol, light anhydrous silicic acid, etc.), lubricants (for example, sucrose fatty acid esters). , Magnesium stearate, talc, etc.), disintegrant (eg, low-substituted hydroxypropylcellulose, crospovidone, croscarmellose sodium, etc.), foaming agent (eg, sodium bicarbonate), fluidizing agent (eg, metasilicic acid, etc.) Sodium aluminate, light anhydrous silicic acid, etc.), coating agents (hydroxypropylmethylcellulose, polyvinyl alcohol, etc.), and coloring agents (eg, iron oxide, titanium oxide, etc.). The use of these additives in the preparation may be other than those described above. These bases, carriers, and / or additives can be used alone or in combination of two or more.
[錠剤の性質]
本発明の医薬用錠剤は、内服用固形製剤であり、限定はされないが、素錠、口腔内速崩壊錠、口腔内速溶解錠、チュアブル錠、発泡錠、トローチ剤、ドロップ剤、フィルムコーティング錠、糖衣錠、カプレット剤、丸剤などであり得る。本発明によれば、結合剤などを多量に添加せずとも製剤的に打錠性の良い医薬用錠剤が得られる為、服用に支障がない量で必要に応じて様々な大きさの医薬用錠剤とすることができる。これらは、例えば、限定はされないが、１錠あたりの重量が、３０〜８００ｍｇであることが好ましく、１００〜８００ｍｇであることがより好ましく、３００〜８００ｍｇであることがさらに好ましく、３００〜６００ｍｇであることがさらにより好ましく、３００〜５００ｍｇであることが最も好ましい。測定は、汎用の天秤を用いて測定することができる。
[Tablet properties]
The pharmaceutical tablet of the present invention is a solid preparation for internal use, and is not limited to, but is not limited to, uncoated tablet, intraoral quick disintegrating tablet, intraoral quick dissolving tablet, chewable tablet, effervescent tablet, troche, drop agent, film-coated tablet Sugar-coated tablets, caplets, pills and the like. According to the present invention, a pharmaceutical tablet with good tableting properties can be obtained without adding a large amount of a binder or the like. It can be a tablet. Although these are not limited, for example, the weight per tablet is preferably 30 to 800 mg, more preferably 100 to 800 mg, further preferably 300 to 800 mg, and 300 to 600 mg. Even more preferably, it is most preferably 300-500 mg. The measurement can be performed using a general-purpose balance.
本発明の医薬用錠剤は、好ましい形態では、錠径が３.０〜１２．０ｍｍ、錠厚が２．０〜７．０ｍｍである。錠厚、錠径は汎用のノギス等を用いて測定することができる。 In a preferred form, the pharmaceutical tablet of the present invention has a tablet diameter of 3.0 to 12.0 mm and a tablet thickness of 2.0 to 7.0 mm. The tablet thickness and the tablet diameter can be measured using a general purpose caliper or the like.
本発明の医薬用錠剤の「摩損度」は、衝撃に対する錠剤の磨耗性やもろさを示す値をいい、具体的には、第十七改正日本薬局方に収載される錠剤の摩損度試験法を参考に、内径約２８７ｍｍ、深さ約３８ｍｍの透明で内面は滑らかなプラスチック性ドラム型の試験器に錠剤を入れ、２４〜２６回転／１分間の回転速度で１００回転させたのち、全錠剤の質量を精密に量り、初期質量に対する減少質量の質量百分率を算出することにより求められる値をいう。 The “friability” of the pharmaceutical tablet of the present invention refers to a value indicating the wear and brittleness of the tablet with respect to impact, and specifically, the tablet friability test method listed in the 17th revised Japanese Pharmacopoeia. For reference, put the tablet in a plastic drum type tester with an inner diameter of about 287 mm and a depth of about 38 mm and a smooth inner surface. After rotating the tablet 100 times at a rotation speed of 24 to 26 rotations per minute, It is a value obtained by accurately measuring the mass and calculating the mass percentage of the reduced mass with respect to the initial mass.
本発明の医薬用錠剤は、耐摩損度を有する。好ましい実施形態において、本発明の錠剤の摩損度は１％以下である。より好ましくは、本発明の錠剤の摩損度は０．８％以下であり、さらに好ましくは０．７％以下、特に好ましくは０．５％以下である。 The pharmaceutical tablet of the present invention has a wear resistance. In a preferred embodiment, the friability of the tablet of the present invention is 1% or less. More preferably, the friability of the tablet of the present invention is 0.8% or less, more preferably 0.7% or less, and particularly preferably 0.5% or less.
本発明の医薬用錠剤は、その硬度は、本発明の効果を奏し得る限り特に限定されないが、好ましくは、４９Ｎ以上、より好ましくは、５０Ｎ以上、さらに好ましくは５３Ｎ以上とすることができる。本発明の医薬用錠剤の硬度は、４９〜２００Ｎとすることができ、より好ましくは、５０〜１５０Ｎとすることができ、さらに好ましくは、５３〜１２０Ｎとすることができる。本発明の硬度は、硬度計（ＰＴＢ３１１Ｅ, ファーマテスト社製）を用いて、測定した値である。 The hardness of the pharmaceutical tablet of the present invention is not particularly limited as long as the effects of the present invention can be achieved, but it is preferably 49N or more, more preferably 50N or more, and even more preferably 53N or more. The hardness of the pharmaceutical tablet of the present invention can be 49 to 200 N, more preferably 50 to 150 N, and still more preferably 53 to 120 N. The hardness of the present invention is a value measured using a hardness meter (PTB311E, manufactured by Pharma Test).
医薬用錠剤をこのような硬度にすることによって、製剤安定性が高められ、充填包装時、錠剤輸送時、携帯時などに、錠剤の欠損が抑制される。 By setting the pharmaceutical tablet to such a hardness, the formulation stability is enhanced, and tablet defects are suppressed during filling and packaging, tablet transportation, and carrying.
[製造方法]
本発明の医薬用錠剤は、公知の方法により製造することができる。必要に応じて、滅菌工程を含めることができる。製剤は、第１７改正日本薬局方総則に従い、又はこれに準拠して、各成分を混合することにより製造することもできる。
[Production method]
The pharmaceutical tablet of the present invention can be produced by a known method. If necessary, a sterilization step can be included. The preparation can also be produced by mixing each component according to or in accordance with the 17th revised Japanese Pharmacopoeia General Rules.
本発明の医薬用錠剤は、当該技術分野における慣用の方法をそのまま又は適宜応用して製造することもできる。例えば、粉末状の活性成分と製薬上許容される賦形剤などの担体成分とを混合して、この混合物を圧縮成形することにより調製する直打法を採用することができる。ドロップ剤は型に注入する方法で調製してもよい。さらに、造粒法と打錠法等を組み合わせて調製することもできる。例えば、間接圧縮法、例えば、湿式顆粒打錠法、乾式顆粒打錠法などを使用することもできる。 The pharmaceutical tablet of the present invention can also be produced by applying a conventional method in the technical field as it is or appropriately. For example, it is possible to employ a direct compression method in which a powdered active ingredient and a carrier component such as a pharmaceutically acceptable excipient are mixed and this mixture is compression-molded. You may prepare a drop agent by the method of inject | pouring into a type | mold. Furthermore, it can also be prepared by combining a granulation method and a tableting method. For example, an indirect compression method such as a wet granule tableting method or a dry granule tableting method can be used.
ここで、造粒法としては、押出造粒法、粉砕造粒法、乾式圧密造粒法、流動層造粒法、転動造粒法、高速攪拌造粒法などを適宜組み合わせて使用することができる。 Here, as the granulation method, an extrusion granulation method, a pulverization granulation method, a dry compaction granulation method, a fluidized bed granulation method, a rolling granulation method, a high-speed stirring granulation method, or the like may be used in an appropriate combination. Can do.
本発明の医薬用錠剤は、コーティングを施した、糖衣錠やフィルムコーティング錠でもあり得る。さらに、本発明の医薬用錠剤は、単層錠であっても、二層錠などの積層錠であってもよい。本発明において、医薬用錠剤は、湿式顆粒打錠法で調製された単層錠でもあり得る。 The pharmaceutical tablet of the present invention may be a sugar-coated tablet or a film-coated tablet with a coating. Furthermore, the pharmaceutical tablet of the present invention may be a monolayer tablet or a laminated tablet such as a bilayer tablet. In the present invention, the pharmaceutical tablet may be a monolayer tablet prepared by a wet granule tableting method.
[包装]
本発明の医薬用錠剤は、任意の包装形態で提供され得る。例えば、包装形態は、ＳＰ包装やＰＴＰ包装などのように１錠又は１回服用量毎に個装する形態であってもよいし、或いは、任意の容器（例えば、ガラス製又はプラスチック製の瓶容器、或いは合成樹脂やアルミ箔などを積層加工したフィルムでできたパウチ型包装容器など）の中に複数回服用量（例えば、多数の錠剤）を一緒にまとめて充填し、服用のつど繰り返し開封されて継続的に使用される形態をとってもよい。多数の錠剤を一緒にまとめて包装体に充填する後者の形態は、コスト的に有利である。特に、ジッパー等によって開閉自在な取出口を有するパウチ型包装容器（ジッパー式パウチ型包装容器など）に多数の錠剤を一緒にまとめて充填する形態を有利に使用することができる。
[Packaging]
The pharmaceutical tablet of the present invention can be provided in any packaging form. For example, the packaging form may be a form in which each tablet or individual dose is individually packaged, such as SP packaging or PTP packaging, or any container (for example, a glass or plastic bottle) Multiple doses (for example, many tablets) are packed together in a container, or a pouch-type packaging container made of a laminated film of synthetic resin, aluminum foil, etc.), and opened repeatedly after each dose. And may be used continuously. The latter form in which a large number of tablets are packed together and filled into a package is advantageous in terms of cost. In particular, a form in which a large number of tablets are packed together in a pouch-type packaging container (such as a zipper-type pouch-type packaging container) having an opening that can be opened and closed by a zipper or the like can be advantageously used.
[用途]
本明細書中において、医薬用錠剤とは、例えば、医薬品、医薬部外品などに幅広く利用することができる錠剤であり得る。
本発明の医薬用錠剤は、症状として、ダニやハウスダスト、花粉などのアレルゲンが原因で発症するアレルギー性鼻炎（通年性アレルギー性鼻炎、および季節性アレルギー性鼻炎（花粉症の鼻炎症状など）を含む）あるいは蕁麻疹、並びに、湿疹・皮膚炎、皮膚そう痒症、アトピー性皮膚炎等の皮膚疾患に伴うそう痒に効果が高い。本発明の医薬用錠剤は、特に、アレルギー性鼻炎患者のアレルギー症状の軽減に有用である。特に、くしゃみ、鼻水、鼻づまりなどの鼻のアレルギー症状を緩和する。
[Usage]
In the present specification, the pharmaceutical tablet may be a tablet that can be widely used for, for example, pharmaceuticals, quasi drugs, and the like.
The pharmaceutical tablet of the present invention has symptoms such as allergic rhinitis (perennial allergic rhinitis and seasonal allergic rhinitis, such as nasal inflammation in hay fever) caused by allergens such as mites, house dust, and pollen. Or urticaria, and pruritus associated with skin diseases such as eczema / dermatitis, cutaneous pruritus and atopic dermatitis. The pharmaceutical tablet of the present invention is particularly useful for reducing allergic symptoms in patients with allergic rhinitis. In particular, relieve nasal allergy symptoms such as sneezing, runny nose and stuffy nose.
［良好な打錠性の付与方法］
本発明は、さらに、（Ａ）フェキソフェナジン塩酸塩と、（Ｂ）メチルエフェドリン塩酸塩又はプソイドエフェドリン塩酸塩を含み、（Ａ）成分／（Ｂ）成分で示される重量比を、特定の比率とすることで、該医薬用錠剤の打錠性を向上させる方法に関する。ここで、その特定の比率とは、（Ａ）成分／（Ｂ−１）メチルエフェドリン塩酸塩の場合の重量比として、１．３〜１．９である。また、特定の比率は、（Ａ）成分／（Ｂ−２）プソイドエフェドリン塩酸塩の場合の重量比として、０．５〜１．０である。
[Method for imparting good tabletability]
The present invention further includes (A) fexofenadine hydrochloride and (B) methylephedrine hydrochloride or pseudoephedrine hydrochloride, and the weight ratio represented by (A) component / (B) component is expressed as a specific ratio. Thus, the present invention relates to a method for improving the tabletability of the pharmaceutical tablet. Here, the specific ratio is 1.3 to 1.9 as a weight ratio in the case of (A) component / (B-1) methylephedrine hydrochloride. Moreover, a specific ratio is 0.5-1.0 as a weight ratio in the case of (A) component / (B-2) pseudoephedrine hydrochloride.
当該方法においても、上記の本発明の医薬用錠剤における各成分の濃度、製剤、容器材質の条件等と同様の条件を採用する。 Also in this method, the same conditions as the concentration of each component, formulation, container material condition, etc. in the above-mentioned pharmaceutical tablet of the present invention are employed.
次に、実施例や試験例により本発明を具体的に説明するが、本発明は以下の実施例や試験例に限定されるものではない。 Next, the present invention will be specifically described with reference to examples and test examples, but the present invention is not limited to the following examples and test examples.
表１に示す実施例の組成の医薬用錠剤を、常法に従って調製した。
[実施例１]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩１２０ｇ、ｄｌ−メチルエフェドリン塩酸塩７２ｇ、ベラドンナ総アルカロイド０．４ｇ、乳糖水和物５２１ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕の後、ステアリン酸マグネシウム７ｇを混合し、打錠用粉とした。この打錠用粉を下記に示す条件にて打錠を行った。
Pharmaceutical tablets having the compositions of the examples shown in Table 1 were prepared according to a conventional method.
[Example 1]
Based on the formulation shown in Table 1, 120 g of fexofenadine hydrochloride, 72 g of dl-methylephedrine hydrochloride, 0.4 g of belladonna total alkaloid, and 521 g of lactose hydrate were mixed in a vinyl tube. Then, after crushing the mixture with a crusher (Comil QC-194S, manufactured by Paulek), 7 g of magnesium stearate was mixed to obtain a powder for tableting. This tableting powder was tableted under the following conditions.
[実施例２]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩１２０ｇ、ｄｌ−メチルエフェドリン塩酸塩７９.２ｇ、ベラドンナ総アルカロイド０．４ｇ、乳糖水和物５１３．４ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕の後、ステアリン酸マグネシウム７ｇを混合し、打錠用粉とした。この打錠用粉を下記に示す条件にて打錠を行った。
[Example 2]
Based on the formulation shown in Table 1, 120 g of fexofenadine hydrochloride, 79.2 g of dl-methylephedrine hydrochloride, 0.4 g of belladonna total alkaloid, and 513.4 g of lactose hydrate were mixed in a vinyl tube. Then, after crushing the mixture with a crusher (Comil QC-194S, manufactured by Paulek), 7 g of magnesium stearate was mixed to obtain a powder for tableting. This tableting powder was tableted under the following conditions.
[実施例３]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩１５６ｇ、ｄｌ−メチルエフェドリン塩酸塩９３．６ｇ、ベラドンナ総アルカロイド０．４ｇ、Ｄ-マンニトール６６７ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕し、造粒用粉とした。この造粒用粉を流動層造粒機（ＭＰ-０１Ｄ、パウレック社製）に投入し、そこに吸気温度設定７５℃、風量０．３５〜０．６６ｍ3／ｈの条件下、５％ポリビニルピロリドン水溶液を１８７ｇ噴霧し、それを乾燥・篩過して顆粒を得た。得られた顆粒のうち７１３ｇにステアリン酸マグネシウム７．０ｇを投入、混合して打錠用粉を得た。この打錠用粉を下記に示す条件にて打錠を行った。
[Example 3]
Based on the formulation shown in Table 1, 156 g of fexofenadine hydrochloride, 93.6 g of dl-methylephedrine hydrochloride, 0.4 g of belladonna total alkaloid, and 667 g of D-mannitol were mixed in a vinyl tube. Thereafter, the mixture was pulverized with a pulverizer (Comil QC-194S, manufactured by Paulek) to obtain a granulating powder. This granulating powder is put into a fluidized bed granulator (MP-01D, manufactured by POWREC Co., Ltd.), and there is 5% polyvinyl under conditions of an intake air temperature setting of 75 ° C. and an air volume of 0.35 to 0.66 m 3 / h. 187 g of pyrrolidone aqueous solution was sprayed and dried and sieved to obtain granules. In 713 g of the obtained granules, 7.0 g of magnesium stearate was added and mixed to obtain tableting powder. This tableting powder was tableted under the following conditions.
[実施例４]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩１２０ｇ、ｄｌ−メチルエフェドリン塩酸塩８６．４ｇ、ベラドンナ総アルカロイド０．４ｇ、乳糖水和物５０６．２ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕の後、ステアリン酸マグネシウム７ｇを混合し、打錠用粉とした。この打錠用粉を下記に示す条件にて打錠を行った。
[Example 4]
Based on the formulation shown in Table 1, 120 g of fexofenadine hydrochloride, 86.4 g of dl-methylephedrine hydrochloride, 0.4 g of belladonna total alkaloid, and 506.2 g of lactose hydrate were mixed in a vinyl tube. Then, after crushing the mixture with a crusher (Comil QC-194S, manufactured by Paulek), 7 g of magnesium stearate was mixed to obtain a powder for tableting. This tableting powder was tableted under the following conditions.
実施例１〜４の打錠条件は以下に示す通りである。
[打錠条件]
使用機器：ロータリー式打錠機（ＶＩＲＧＯ１８Ｋ、菊水製作所製）
使用杵：９.５ｍｍφ二段Ｒ
本圧：１８ｋＮ
予圧：２ｋＮ
回転盤回転数：７０ｒｐｍ
攪拌羽根回転数：１０ｒｐｍ
The tableting conditions of Examples 1 to 4 are as shown below.
[Tabletting conditions]
Equipment used: Rotary tablet press (VIRGO18K, manufactured by Kikusui Seisakusho)
Use bowl: 9.5mmφ double stage R
Main pressure: 18kN
Preload: 2kN
Turntable speed: 70 rpm
Agitation blade rotation speed: 10rpm
[実施例５]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩６４．８ｇ、ｄ-プソイドエフェドリン塩酸塩６４．８ｇ、ベラドンナ総アルカロイド０．３ｇ、乳糖水和物２５４．８５ｇ、Ｄ-マンニトール１５０ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕の後、ステアリン酸マグネシウム５．２５ｇを混合し、打錠用粉とした。この打錠用粉を下記に示す条件にて打錠を行った。
[Example 5]
Based on the formulation described in Table 1, in a vinyl tube, fexofenadine hydrochloride 64.8g, d-pseudoephedrine hydrochloride 64.8g, belladonna total alkaloid 0.3g, lactose hydrate 254.85g, D-mannitol 150g Were mixed. Thereafter, the mixture was crushed with a crusher (Comil QC-194S, manufactured by Paulek), and then 5.25 g of magnesium stearate was mixed to obtain a powder for tableting. This tableting powder was tableted under the following conditions.
実施例５の打錠条件は以下に示す通りである。
[打錠条件]
使用機器：ロータリー式打錠機（ＶＩＲＧＯ１８Ｋ、菊水製作所製）
使用杵：９.５ｍｍφ隅角
本圧：１０ｋＮ
予圧：１ｋＮ
回転盤回転数：７０ｒｐｍ
攪拌羽根回転数：１０ｒｐｍ
The tableting conditions of Example 5 are as shown below.
[Tabletting conditions]
Equipment used: Rotary tablet press (VIRGO18K, manufactured by Kikusui Seisakusho)
Use bowl: 9.5mmφ corner actual pressure: 10kN
Preload: 1kN
Turntable speed: 70 rpm
Agitation blade rotation speed: 10rpm
[比較例]
同様にして、表１に示す比較例の医薬用錠剤を、常法に従って調製した。
[Comparative example]
Similarly, pharmaceutical tablets of comparative examples shown in Table 1 were prepared according to a conventional method.
[比較例１]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩１０ｇ、ｄｌ−メチルエフェドリン塩酸塩７２ｇ、ベラドンナ総アルカロイド０．４ｇ、乳糖水和物６３１ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕の後、ステアリン酸マグネシウム７ｇを混合し、打錠用粉とした。この打錠用粉を下記に示す条件にて打錠を行った。
[Comparative Example 1]
Based on the formulation shown in Table 1, 10 g of fexofenadine hydrochloride, 72 g of dl-methylephedrine hydrochloride, 0.4 g of belladonna total alkaloid, and 631 g of lactose hydrate were mixed in a vinyl tube. Then, after crushing the mixture with a crusher (Comil QC-194S, manufactured by Paulek), 7 g of magnesium stearate was mixed to obtain a powder for tableting. This tableting powder was tableted under the following conditions.
[比較例２]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩１０ｇ、ｄｌ−メチルエフェドリン塩酸塩７９．２ｇ、ベラドンナ総アルカロイド０．４ｇ、乳糖水和物６１３．４ｇ、結晶セルロース１０ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕の後、ステアリン酸マグネシウム７ｇを混合し、打錠用粉とした。この打錠用粉を下記に示す条件にて打錠を行った。
[Comparative Example 2]
Based on the formulation described in Table 1, 10 g of fexofenadine hydrochloride, 79.2 g of dl-methylephedrine hydrochloride, 0.4 g of belladonna total alkaloid, 613.4 g of lactose hydrate, and 10 g of crystalline cellulose are mixed in a vinyl tube. did. Then, after crushing the mixture with a crusher (Comil QC-194S, manufactured by Paulek), 7 g of magnesium stearate was mixed to obtain a powder for tableting. This tableting powder was tableted under the following conditions.
[比較例３]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩１３ｇ、ｄｌ−メチルエフェドリン塩酸塩１０３ｇ、ベラドンナ総アルカロイド０．５２ｇ、Ｄ-マンニトール８０１ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕し、造粒用粉とした。この造粒用粉を流動層造粒機（ＭＰ-０１Ｄ、パウレック社製）に投入し、そこに吸気温度設定７５℃、風量０．３５〜０．６６ｍ3／ｈの条件下、５％ポリビニルピロリドン水溶液を１８７ｇ噴霧し、それを乾燥・篩過して顆粒を得た。得られた顆粒のうち７１３ｇにステアリン酸マグネシウム７．０ｇを投入、混合して打錠用粉を得た。この打錠用粉を下記に示す条件にて打錠を行った。
[Comparative Example 3]
Based on the formulation shown in Table 1, 13 g of fexofenadine hydrochloride, 103 g of dl-methylephedrine hydrochloride, 0.52 g of belladonna total alkaloid, and 801 g of D-mannitol were mixed in a vinyl tube. Thereafter, the mixture was pulverized with a pulverizer (Comil QC-194S, manufactured by Paulek) to obtain a granulating powder. This granulating powder is put into a fluidized bed granulator (MP-01D, manufactured by POWREC Co., Ltd.), and there is 5% polyvinyl under conditions of intake air temperature setting of 75 ° C. and air volume of 0.35 to 0.66 m 3 / h. 187 g of pyrrolidone aqueous solution was sprayed and dried and sieved to obtain granules. In 713 g of the obtained granules, 7.0 g of magnesium stearate was added and mixed to obtain tableting powder. This tableting powder was tableted under the following conditions.
[比較例４]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩５４ｇ、ｄｌ−メチルエフェドリン塩酸塩１０８ｇ、ベラドンナ総アルカロイド０．４ｇ、乳糖水和物５５０．６ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕の後、ステアリン酸マグネシウム７ｇを混合し、打錠用粉とした。この打錠用粉を下記に示す条件にて打錠を行った。
[Comparative Example 4]
Based on the formulation shown in Table 1, 54 g of fexofenadine hydrochloride, 108 g of dl-methylephedrine hydrochloride, 0.4 g of belladonna total alkaloid, and 550.6 g of lactose hydrate were mixed in a vinyl tube. Then, after crushing the mixture with a crusher (Comil QC-194S, manufactured by Paulek), 7 g of magnesium stearate was mixed to obtain a powder for tableting. This tableting powder was tableted under the following conditions.
[比較例５]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩１０．８ｇ、ｄ-塩酸プソイドエフェドリン６４．８ｇ、ベラドンナ総アルカロイド０．３ ｇ、乳糖水和物３０１．３５ｇ、結晶セルロース７．５ｇ、Ｄ-マンニトール１５０ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕の後、ステアリン酸マグネシウム５．２５ｇを混合し、打錠用粉とした。この打錠用粉を実施例６と同様の条件にて打錠を行った。
[Comparative Example 5]
Based on the formulation shown in Table 1, 10.8 g of fexofenadine hydrochloride, 64.8 g of d-pseudoephedrine hydrochloride, 0.3 g of belladonna total alkaloids, 301.35 g of lactose hydrate, crystalline cellulose 7. 5 g and 150 g of D-mannitol were mixed. Thereafter, the mixture was crushed with a crusher (Comil QC-194S, manufactured by Paulek), and then 5.25 g of magnesium stearate was mixed to obtain a powder for tableting. This tableting powder was tableted under the same conditions as in Example 6.
[比較例６]
表１に記載の処方に基づき、ビニールチューブ内でフェキソフェナジン塩酸塩４３．２ｇ、ｄ-塩酸プソイドエフェドリン８６．４ｇ、ベラドンナ総アルカロイ０．３ｇ、乳糖水和物２５４．８５ｇ、Ｄ-マンニトール１５０ｇを混合した。その後、混合物を解砕機（コーミルＱＣ-１９４Ｓ、パウレック製）にて解砕の後、ステアリン酸マグネシウム５．２５ｇを混合し、打錠用粉とした。この打錠用粉を実施例６と同様の条件にて打錠を行った。
[Comparative Example 6]
Based on the formulation described in Table 1, 43.2 g of fexofenadine hydrochloride, 86.4 g of d-pseudoephedrine hydrochloride, 0.3 g of belladonna total alkaloy, 254.85 g of lactose hydrate, and 150 g of D-mannitol in a vinyl tube. Mixed. Thereafter, the mixture was crushed with a crusher (Comil QC-194S, manufactured by Paulek), and then 5.25 g of magnesium stearate was mixed to obtain a powder for tableting. This tableting powder was tableted under the same conditions as in Example 6.
（評価方法）
［硬度測定］
実施例及び比較例で得た錠剤５もしくは６錠を無作為に選択し、硬度計（ＰＴＢ３１１Ｅ, ファーマテスト社製）を用いて硬度を測定し、その平均値を求めた。
(Evaluation method)
[Hardness measurement]
Tablets 5 or 6 obtained in Examples and Comparative Examples were randomly selected, and the hardness was measured using a hardness meter (PTB311E, manufactured by Pharmatest), and the average value was obtained.
［摩損度］
実施例及び比較例の錠剤を、上述した日本薬局方に収載の摩損度試験法を参考に、内径約２８７ｍｍ、深さ約３８ｍｍの透明で内面は滑らかなプラスチック性ドラム型の試験器に錠剤を入れ、２４〜２６回転／１分間の回転速度で１００回転させたのち、全錠剤の質量を精密に量り、初期質量に対する減少質量の質量百分率を算出することにより値を求めた。
[Degree of wear]
Referring to the friability test method listed in the above-mentioned Japanese Pharmacopoeia for the tablets of Examples and Comparative Examples, the tablets are placed in a plastic drum type tester having an inner diameter of about 287 mm and a depth of about 38 mm and a smooth inner surface. Then, after rotating 100 times at a rotational speed of 24 to 26 rotations per minute, the mass of all tablets was precisely measured, and the value was determined by calculating the mass percentage of the reduced mass with respect to the initial mass.
実施例１〜５においては、硬度及び摩損度のいずれも良好な打錠性の高い錠剤を得ることができた。 In Examples 1 to 5, it was possible to obtain tablets with good tableting properties in both hardness and friability.
実施例の錠剤の摩損度は、表２に示す通り、（Ａ）／（Ｂ）以外の条件が類似する比較例と比べた場合に良好であった。なお、比較例１においては打錠中に打錠障害（キャッピング）が見られた。以下、表１、２中の数値の単位は、ｍｇ／錠である。 As shown in Table 2, the friability of the tablet of the example was good when compared with a comparative example having similar conditions other than (A) / (B). In Comparative Example 1, a tableting failure (capping) was observed during tableting. Hereinafter, the unit of numerical values in Tables 1 and 2 is mg / tablet.
ここで、実施例１〜４、比較例１〜４の錠剤の錠厚は、５．０〜５．２ｍｍ、錠径は、９．５ｍｍであった。実施例５、および比較例５および６の錠剤の錠厚は、４．１〜４．２ｍｍ、錠径は、９．５ｍｍであった。
以下、本発明の製剤処方例を示す。表３〜４に記載の処方例１〜９の分量に基づき１錠あたり３６０mgの錠剤を常法により調製し、１日あたり２錠服用とした。なお、表中の数値の単位は、ｍｇ／日である。これらの製剤は、アレルギー用薬として有効に用いられる。すべての製剤は、ＰＰ製容器等に収容して用いることも可能である。 Hereinafter, formulation examples of the present invention will be shown. Based on the amounts of Formulation Examples 1 to 9 shown in Tables 3 to 4, 360 mg tablets per tablet were prepared by a conventional method, and 2 tablets were taken per day. The unit of numerical values in the table is mg / day. These preparations are effectively used as allergy drugs. All the preparations can be used in a container made of PP.
Claims (10)
（Ｂ）メチルエフェドリン塩酸塩
を含む医薬用錠剤であって、
（Ａ）成分／（Ｂ）成分で示される重量比が、５／３であり、硬度５０Ｎ以上、摩損度１．０％以下である医薬用錠剤。 (A) fexofenadine hydrochloride, and
(B) a pharmaceutical tablet comprising methylephedrine hydrochloride,
A pharmaceutical tablet having a weight ratio of (A) component / (B) component of 5/3, a hardness of 50N or more and a friability of 1.0% or less.
（Ｂ）プソイドエフェドリン塩酸塩
を含む医薬用錠剤であって、
（Ａ）成分／（Ｂ）成分で示される重量比が、１．０、
（Ｂ）成分の含有量が、該錠剤全量の８重量％以上１２重量％以下であり、硬度５０Ｎ以上、摩損度１．０％以下である医薬用錠剤。 (A) fexofenadine hydrochloride, and
(B) a pharmaceutical tablet comprising pseudoephedrine hydrochloride,
The weight ratio represented by (A) component / (B) component is 1.0,
(B) The pharmaceutical tablet whose content of a component is 8 weight% or more and 12 weight% or less of the whole tablet quantity, hardness 50N or more, and friability 1.0% or less.
の医薬用錠剤。 The pharmaceutical tablet according to any one of claims 1 to 5, wherein a daily dose of the component (A) is 120 mg.
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|---|---|---|---|---|
| JP2002212067A (en) * | 2001-01-15 | 2002-07-31 | Taisho Pharmaceut Co Ltd | Composition for treating cold |
| JP2002255816A (en) * | 2001-03-05 | 2002-09-11 | Taisho Pharmaceut Co Ltd | Composition for treating cold |
| JP2003048834A (en) * | 2001-08-01 | 2003-02-21 | Taisho Pharmaceut Co Ltd | Pharmaceutical composition |
| JP2009543780A (en) * | 2006-07-11 | 2009-12-10 | ミューチュアル ファーマシューティカル カンパニー，インク． | Controlled release formulations and kits |
| CN103463085A (en) * | 2013-09-22 | 2013-12-25 | 广东环球制药有限公司 | Rapidly released fexofenadine pills and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2002212067A (en) * | 2001-01-15 | 2002-07-31 | Taisho Pharmaceut Co Ltd | Composition for treating cold |
| JP2002255816A (en) * | 2001-03-05 | 2002-09-11 | Taisho Pharmaceut Co Ltd | Composition for treating cold |
| JP2003048834A (en) * | 2001-08-01 | 2003-02-21 | Taisho Pharmaceut Co Ltd | Pharmaceutical composition |
| JP2009543780A (en) * | 2006-07-11 | 2009-12-10 | ミューチュアル ファーマシューティカル カンパニー，インク． | Controlled release formulations and kits |
| CN103463085A (en) * | 2013-09-22 | 2013-12-25 | 广东环球制药有限公司 | Rapidly released fexofenadine pills and preparation method thereof |
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| JP2019026644A (en) * | 2017-08-01 | 2019-02-21 | ロート製薬株式会社 | Pharmaceutical tablet |
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