JP2016008189A - Antipyretic analgesic formulation - Google Patents
Antipyretic analgesic formulation Download PDFInfo
- Publication number
- JP2016008189A JP2016008189A JP2014128927A JP2014128927A JP2016008189A JP 2016008189 A JP2016008189 A JP 2016008189A JP 2014128927 A JP2014128927 A JP 2014128927A JP 2014128927 A JP2014128927 A JP 2014128927A JP 2016008189 A JP2016008189 A JP 2016008189A
- Authority
- JP
- Japan
- Prior art keywords
- ibuprofen
- caffeine
- tablet
- antipyretic analgesic
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000003907 antipyretic analgesic agent Substances 0.000 title claims abstract description 21
- 239000000203 mixture Substances 0.000 title claims description 17
- 238000009472 formulation Methods 0.000 title claims description 11
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- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 45
- 229960001680 ibuprofen Drugs 0.000 claims abstract description 44
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- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims abstract description 31
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- 229960004459 apronal Drugs 0.000 claims abstract description 26
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Abstract
【課題】イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインを含有する解熱鎮痛製剤において、ウイスカーの発生やそれに伴う不快な臭いの発生を抑制することのできる技術を提供すること。【解決手段】イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインをそれぞれ質量比で１０：３：４の割合で含有することを特徴とする解熱鎮痛製剤。【選択図】なしAn antipyretic analgesic preparation containing ibuprofen, allylisopropylacetylurea and caffeine provides a technique capable of suppressing the generation of whiskers and the unpleasant odor associated therewith. An antipyretic analgesic preparation comprising ibuprofen, allylisopropylacetylurea and caffeine in a mass ratio of 10: 3: 4, respectively. [Selection figure] None
Description
本発明は、解熱鎮痛製剤に関し、更に詳細には、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインを活性医薬品成分として含有し、これらの活性医薬品成分を特定の割合で配合することによって、収納容器内での曇りや臭いの発生を抑制した解熱鎮痛製剤に関する。 The present invention relates to an antipyretic analgesic preparation, and more specifically, contains ibuprofen, allylisopropylacetylurea and caffeine as active pharmaceutical ingredients, and by blending these active pharmaceutical ingredients in a specific ratio, It is related with the antipyretic analgesic formulation which suppressed generation | occurrence | production of the cloudiness and smell of the.
イブプロフェン、アリルイソプロピルアセチル尿素及び無水カフェインを含有する解熱鎮痛剤は、１９９０年９月１日にイブＡ錠（エスエス製薬社製）として発売されたものであり、イブプロフェン単独の製剤の効きはじめがやや弱いという弱点を克服し、早くよく効くイブプロフェン含有の解熱鎮痛薬として汎用されている。このイブＡ錠には、活性医薬品成分として、イブプロフェン、アリルイソプロピルアセチル尿素及び無水カフェインが２錠中にそれぞれ１５０ｍｇ、６０ｍｇ及び８０ｍｇ配合されているが、イブＡ錠と同量のイブプロフェン、アリルイソプロピルアセチル尿素及び無水カフェインを配合した解熱鎮痛薬が一般用医薬品として本邦で数多く販売されるに至り、さらに、酸化マグネシウム、メタケイ酸アルミン酸マグネシウム、乾燥水酸化アルミニウムゲルなどの制酸剤を配合した解熱鎮痛薬も含めると、解熱鎮痛薬は３０種類以上に上っている。 An antipyretic analgesic agent containing ibuprofen, allylisopropylacetylurea and anhydrous caffeine was released on September 1, 1990 as Eve A Tablets (manufactured by SS Pharmaceutical Co., Ltd.). It is widely used as an antipyretic analgesic containing ibuprofen, which overcomes the weakness of the weakness and works quickly. In this Eve A tablet, 150 mg, 60 mg and 80 mg of ibuprofen, allylisopropylacetylurea and anhydrous caffeine are blended as active pharmaceutical ingredients in 2 tablets, respectively, but the same amount of ibuprofen and allylisopropyl as in Eve A tablet. Numerous antipyretic analgesics containing acetylurea and anhydrous caffeine have been sold in Japan as over-the-counter drugs, and in addition, antacids such as magnesium oxide, magnesium aluminate metasilicate, and dry aluminum hydroxide gel were formulated. Including antipyretic analgesics, there are over 30 antipyretic analgesics.
ところで、イブプロフェンは、融点が７５〜７７℃と比較的に低く、また昇華性であるため、ガラス瓶等の密閉容器の内壁に再結晶が形成されて、曇り（ウイスカー）が生じることが知られている。また、カフェインも昇華性であるため保存容器内に曇りが生じ、さらに、製剤の表面や保管容器内にカフェインが針状結晶となって成長することも知られている。そして、これら昇華性の活性医薬品成分に、他の活性医薬品成分や賦形剤などを混合すると、融点降下が生じるため、活性医薬品成分を単独で配合する場合よりもさらに昇華し易くなることが知られている。 By the way, since ibuprofen has a relatively low melting point of 75 to 77 ° C. and is sublimable, it is known that recrystallization is formed on the inner wall of a closed container such as a glass bottle and cloudiness (whisker) occurs. Yes. Further, since caffeine is also sublimable, it is known that clouding occurs in the storage container, and caffeine grows as needle-like crystals on the surface of the preparation and in the storage container. In addition, it is known that mixing other active pharmaceutical ingredients or excipients with these sublimable active pharmaceutical ingredients causes a melting point drop, which makes it easier to sublime than when the active pharmaceutical ingredient is blended alone. It has been.
また、上記解熱鎮痛薬のような固形製剤は、通常、ＰＴＰ包装、プラスチックボトル、ガラス瓶等の密閉した容器内で保存し、安定性を確保した包装形態で販売されている。しかし、昇華しやすい活性医薬品成分が含まれている固形製剤では、製品の保存時にガラス瓶やＰＴＰ容器などの密封容器の内側に曇りが生じる場合があり、また、密封容器を開封する時に活性医薬品成分由来の不快な臭いを感じることも知られており、商品価値の低下の問題を生じる。特に、店頭で在庫され販売される一般用医薬品は、店内の空調の運転状況、日光の照射、季節及び朝晩の気温及び湿度変動などにより、様々な過酷な環境にさらされることがあるため、想定外に外観の劣化が生じてしまうことがある。 In addition, solid preparations such as antipyretic analgesics are usually stored in sealed containers such as PTP packaging, plastic bottles, glass bottles, etc., and sold in a packaging form that ensures stability. However, in solid preparations containing active pharmaceutical ingredients that are easily sublimated, clouding may occur inside sealed containers such as glass bottles and PTP containers during product storage, and active pharmaceutical ingredients may be used when opening sealed containers. It is also known to feel an unpleasant odor from the origin, resulting in a problem of a decrease in commercial value. In particular, over-the-counter drugs that are stocked and sold in stores may be exposed to various harsh environments, depending on the air conditioner operating conditions, sunlight exposure, seasonal and morning / night temperature and humidity fluctuations, etc. The appearance may be deteriorated outside.
このように昇華しやすい活性医薬品成分であるイブプロフェンのウイスカー防止方法としては、イブプロフェン含有素錠に、素錠質量５〜６０％の量の糖衣を施すことや（特許文献１）、イブプロフェン含有素錠と外層フィルムコーティングとの間に、糖類の層を形成させる方法（特許文献２）等、素錠に糖類を被覆させる方法が報告されている。また、イブプロフェン含有素錠に直接フィルムコーティングを行う方法も報告されており、フィルムコーティング液の組成としては、例えば、プロピレングリコール、グリセリンまたはコポリビドン及び水溶性高分子基剤（特許文献３）、水溶性高分子及びトリアセチン（特許文献４）、ポリビニルアルコール及びケイ酸（特許文献５）、ポリビニルアルコール、パラフィン、カルナウバロウ及び特定量の酸化チタン（特許文献６）等が開示されている。 As a method for preventing whisker of ibuprofen, which is an active pharmaceutical ingredient that is easily sublimated in this way, sugar coating of 5-60% of the uncoated tablet mass is applied to the uncoated tablet containing ibuprofen (Patent Document 1), ibuprofen-containing uncoated tablet There have been reported methods for coating uncoated tablets with saccharides, such as a method for forming a saccharide layer between the outer layer and the outer film coating (Patent Document 2). In addition, a method of directly film-coating ibuprofen-containing uncoated tablets has also been reported. Examples of the composition of the film coating solution include propylene glycol, glycerin or copolyvidone, a water-soluble polymer base (Patent Document 3), and a water-soluble composition. Polymers and triacetin (Patent Document 4), polyvinyl alcohol and silicic acid (Patent Document 5), polyvinyl alcohol, paraffin, carnauba wax and a specific amount of titanium oxide (Patent Document 6) are disclosed.
さらに、イブプロフェンのウイスカー防止方法としては、イブプロフェン含有固形製剤を密閉容器に保存の際、ポリビニルピロリドン、酸化マグネシウム、炭酸水素ナトリウム等の物質（特許文献７）、シルカゲルや塩化カルシウム等の乾燥剤（特許文献８）を同製剤に共存させて密閉容器で保存する方法が報告されている。また、イブプロフェン含有粉体に、クエン酸、酒石酸、リンゴ酸及びコハク酸から選択される酸を粉末状で添加して混合する方法も報告されている（特許文献９）。 Furthermore, as a method for preventing whisker of ibuprofen, when storing a solid preparation containing ibuprofen in a sealed container, a substance such as polyvinylpyrrolidone, magnesium oxide, sodium hydrogen carbonate (Patent Document 7), a desiccant such as silica gel or calcium chloride (patent) There has been reported a method in which Document 8) is stored in a closed container in the same preparation. In addition, a method has been reported in which an acid selected from citric acid, tartaric acid, malic acid and succinic acid is added in powder form to the ibuprofen-containing powder and mixed (Patent Document 9).
一方、カフェインのウイスカー防止方法としては、カフェインに特定の物質を添加させること、例えば、含水二酸化ケイ素（特許文献１０）、制酸剤及び含水二酸化ケイ素（特許文献１１）、ポリビニルピロリドン類（特許文献１２）、グリチルリチン酸類（特許文献１３）等をカフェインに添加混合し、顆粒剤や錠剤を製造する方法が開示されている。また、カフェインに高分子重合体を添加し、混練押出処理（特許文献１４）や多軸エクストルーダーによる押し出し処理（特許文献１５）をする方法も報告されている。 On the other hand, as a method of preventing whisker of caffeine, a specific substance is added to caffeine, for example, hydrous silicon dioxide (Patent Document 10), antacid and hydrous silicon dioxide (Patent Document 11), polyvinylpyrrolidones ( Patent Document 12), glycyrrhizic acids (Patent Document 13) and the like are added to and mixed with caffeine to produce granules and tablets. In addition, a method of adding a polymer to caffeine and performing a kneading extrusion process (Patent Document 14) or an extrusion process using a multi-axis extruder (Patent Document 15) has also been reported.
さらに、カフェインのウイスカー防止方法としては、カフェインを平衡相対湿度７５％以下の条件で水分制御を行って湿式造粒する方法（特許文献１６）や、カフェイン以外の薬物を顆粒状とし、この顆粒状薬物にカフェインを粉末で添加する方法（特許文献１７）が報告されている。 Furthermore, as a method for preventing whisker of caffeine, a method of performing wet granulation by controlling moisture under conditions of equilibrium relative humidity of 75% or less (Patent Document 16), or a drug other than caffeine is granulated, A method of adding caffeine as a powder to this granular drug has been reported (Patent Document 17).
また、イブプロフェンとカフェインの両方を含有する製剤のウイスカーによる曇り防止方法としては、これらの成分を含有する素錠にカルボキシメチルセルロース類をコーティングする方法や、イブプロフェン及びカフェインにカルボキシメチルセルロース類を添加して造粒する方法が報告されている（特許文献１８）。 In addition, as a method of preventing fogging by a whisker of a preparation containing both ibuprofen and caffeine, a method for coating uncoated tablets containing these components with carboxymethylcelluloses, or adding carboxymethylcelluloses to ibuprofen and caffeine. And a method of granulating is reported (Patent Document 18).
しかしながら、これらの方法は、イブプロフェン、アリルイソプロピルアセチル尿素及び無水カフェインが配合されている一般用医薬品として市販されている解熱鎮痛製剤に適用した場合、何れも効果が不十分であったり、過酷な環境下では効果を示さないものであった。また、上記方法は、製造工程が複雑であるため、コストがかさみ採用するのが困難であるという問題も有していた。 However, when these methods are applied to antipyretic analgesics that are marketed as over-the-counter drugs containing ibuprofen, allylisopropylacetylurea and anhydrous caffeine, all of these methods are ineffective or severe. It was not effective under the environment. In addition, the above-described method has a problem that the manufacturing process is complicated, so that the cost is high and it is difficult to adopt the method.
従って、本発明の課題は、従来技術よりも簡便に、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインを含有する解熱鎮痛製剤において、ウイスカーの発生やそれに伴う不快な臭いの発生を抑制することのできる技術を提供することである。 Therefore, the subject of the present invention is a technique capable of suppressing the generation of whiskers and the unpleasant odor associated therewith in an antipyretic analgesic preparation containing ibuprofen, allylisopropylacetylurea and caffeine, more simply than in the prior art. Is to provide.
本発明者らは、上記課題を解決するため、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインを含有する解熱鎮痛製剤について、その製剤処方の検討を行っていたところ、従来から使用されてきた各活性医薬品成分の質量比率において、イブプロフェンの比率を高めるのみで密閉容器に保存した時の曇りや開封時の不快な臭いを軽減できることを見出し、本発明を完成した。 In order to solve the above problems, the present inventors have been studying the formulation of an antipyretic analgesic preparation containing ibuprofen, allylisopropylacetylurea and caffeine. The present inventors completed the present invention by discovering that, by increasing the ratio of ibuprofen in terms of the mass ratio of the components, cloudiness when stored in a closed container and unpleasant odor when opened can be reduced.
すなわち、本発明は、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインをそれぞれ質量比で１０：３：４の割合で含有することを特徴とする解熱鎮痛製剤である。 That is, the present invention is an antipyretic analgesic preparation characterized by containing ibuprofen, allylisopropylacetylurea and caffeine in a mass ratio of 10: 3: 4, respectively.
また、本発明は、密封包装されたものである上記解熱鎮痛製剤である。 Further, the present invention is the antipyretic analgesic preparation which is hermetically packaged.
本発明によれば、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインを含有する解熱鎮痛製剤を密閉容器に保存したときの曇りの発生や不快な臭いの発生を抑制することができる。そのため、この解熱鎮痛製剤の商品価値を高めることが可能となる。 ADVANTAGE OF THE INVENTION According to this invention, generation | occurrence | production of the cloudiness and generation | occurrence | production of an unpleasant odor when the antipyretic analgesic formulation containing ibuprofen, allyl isopropyl acetyl urea, and caffeine are preserve | saved in a sealed container can be suppressed. Therefore, the commercial value of this antipyretic analgesic preparation can be increased.
本発明の解熱鎮痛製剤は、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインを単位製剤中に１０：３：４の比率で含有するものであり（以下、「本発明製剤」という）、必要に応じてその他の活性医薬品成分や製剤添加物を含有してもよい。 The antipyretic analgesic preparation of the present invention contains ibuprofen, allylisopropylacetylurea and caffeine in a unit preparation at a ratio of 10: 3: 4 (hereinafter referred to as “the preparation of the present invention”). Other active pharmaceutical ingredients and formulation additives may be included.
本発明製剤に含有するイブプロフェンは、その化学名が、（２ＲＳ）−２−［４−（２−メチルプロピル）フェニル］プロパン酸（英名：（２ＲＳ）−２−［４−（２−Ｍｅｔｈｙｌｐｒｏｐｙｌ） ｐｈｅｎｙｌ］ ｐｒｏｐａｎｏｉｃ ａｃｉｄ）であり、分子式は、Ｃ１３Ｈ１８Ｏ２で、その分子量は、２０６．２８、融点は、７５〜７７℃であるフェニルプロピオン酸系の非ステロイド抗炎症薬で、プロスタグランジン生合成阻害作用により、抗炎症・鎮痛・解熱作用を発揮するものである。 The chemical name of ibuprofen contained in the preparation of the present invention is (2RS) -2- [4- (2-methylpropyl) phenyl] propanoic acid (English name: (2RS) -2- [4- (2-Methylpropyl)). phenyl] propionic acid), a molecular formula of C 13 H 18 O 2 , a molecular weight of 206.28, and a melting point of 75-77 ° C. It exhibits anti-inflammatory, analgesic, and antipyretic effects by inhibiting gin biosynthesis.
また、本発明製剤に含有するアリルイソプロピルアセチル尿素は、その化学名が、２−イソプロピル−４−ペンテノイルウレア（英名：２−Ｉｓｏｐｒｏｐｙｌ−４−ｐｅｎｔｅｎｏｙｌｕｒｅａ）であり、分子式は、Ｃ９Ｈ１６Ｎ２Ｏ２で、その分子量は、１８４．２４、融点は、１９３〜１９８℃の穏和な鎮静薬で、痛みに伴う不安、不快感、恐怖心等の疼痛反応を除去することにより疼痛を緩和するとともに、鎮痛薬の作用を増強するものである。 Further, allyl isopropyl acetylurea contained in the preparation of the present invention has a chemical name of 2-isopropyl-4-pentenoylurea (English name: 2-Isopropyl-4-pentenoylurea) and a molecular formula of C 9 H 16 N. 2 O 2 is a mild sedative with a molecular weight of 184.24 and a melting point of 193-198 ° C., which relieves pain by eliminating painful reactions such as anxiety, discomfort, and fear At the same time, it enhances the action of analgesics.
更に、本発明製剤に含有するカフェインとしては、無水カフェイン、カフェイン水和物あるいはこれらの混合物を使用することができる。このうち無水カフェインは、化学名が、１，３，７−トリメチル−１Ｈ−プリン−２，６（３Ｈ，７Ｈ）−ジオン（英名：１，３，７−Ｔｒｉｍｅｔｈｙｌ−１Ｈ−ｐｕｒｉｎｅ−２，６（３Ｈ，７Ｈ）−ｄｉｏｎｅ）であり、その分子式は、Ｃ８Ｈ１０Ｎ４Ｏ２であり、分子量は、１９４．１９、融点は、２３５〜２３８℃である。また、カフェイン水和物は、化学名が、１，３，７−トリメチル−１Ｈ−プリン−２，６（３Ｈ，７Ｈ）−ジオン 一水和物（英名：１，３，７−Ｔｒｉｍｅｔｈｙｌ−１Ｈ−ｐｕｒｉｎｅ−２，６（３Ｈ，７Ｈ）−ｄｉｏｎｅ ｍｏｎｏｈｙｄｒａｔｅ）で、その分子式は、Ｃ８Ｈ１０Ｎ４Ｏ２・Ｈ２Ｏで、その分子量は、２１２．２１、融点は２３５〜２３８℃（乾燥後）である。これらは共に、中枢神経興奮作用を有し、神経機能を活発にして、不快感等の疼痛反応を除去することにより、疼痛を緩和し、更に、血管性頭痛に対しては脳血管を収縮して鎮痛作用を示すものである。 Furthermore, as the caffeine contained in the preparation of the present invention, anhydrous caffeine, caffeine hydrate or a mixture thereof can be used. Among these, anhydrous caffeine has a chemical name of 1,3,7-trimethyl-1H-purine-2,6 (3H, 7H) -dione (English name: 1,3,7-Trimethyl-1H-purine-2, 6 (3H, 7H) -dione), the molecular formula is C 8 H 10 N 4 O 2 , the molecular weight is 194.19, and the melting point is 235 to 238 ° C. Caffeine hydrate has a chemical name of 1,3,7-trimethyl-1H-purine-2,6 (3H, 7H) -dione monohydrate (English name: 1,3,7-Trimethyl- 1H-purine-2,6 (3H, 7H) -dione monohydrate), the molecular formula is C 8 H 10 N 4 O 2 .H 2 O, the molecular weight is 212.21, and the melting point is 235 to 238 ° C. (After drying). Both of these have central nervous excitability, relieve pain by activating neural functions and eliminating painful responses such as discomfort, and constricting cerebrovascular for vascular headaches. It shows analgesic action.
本発明製剤は、上記したように、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインをイブプロフェン：アリルイソプロピルアセチル尿素：カフェイン＝１０：３：４の比率で単位製剤中に配合するものである。具体的には、例えば錠剤の剤型で、１錠中にイブプロフェン５０ｍｇを配合する場合には、アリルイソプロピルアセチル尿素１５ｍｇとカフェイン２０ｍｇとを１錠中配合する。また、１錠中にイブプロフェン７５ｍｇを配合する場合には、アリルイソプロピルアセチル尿素２２．５ｍｇとカフェイン３０ｍｇとを１錠中配合する。同様に、１錠中にイブプロフェン１００ｍｇを配合する場合には、アリルイソプロピルアセチル尿素３０ｍｇとカフェイン４０ｍｇとを、１錠中にイブプロフェン１5０ｍｇを配合する場合には、アリルイソプロピルアセチル尿素４５ｍｇとカフェイン６０ｍｇとを、１錠中にイブプロフェン２００ｍｇを配合する場合には、アリルイソプロピルアセチル尿素６０ｍｇとカフェイン８０ｍｇとを、それぞれ１錠中に配合する。 As described above, in the preparation of the present invention, ibuprofen, allylisopropylacetylurea and caffeine are blended in the unit preparation at a ratio of ibuprofen: allylisopropylacetylurea: caffeine = 10: 3: 4. Specifically, for example, when 50 mg of ibuprofen is blended in one tablet in the form of a tablet, 15 mg of allylisopropylacetylurea and 20 mg of caffeine are blended in one tablet. When 75 mg of ibuprofen is blended in one tablet, 22.5 mg of allylisopropylacetylurea and 30 mg of caffeine are blended in one tablet. Similarly, when 100 mg of ibuprofen is blended in one tablet, 30 mg of allyl isopropyl acetylurea and 40 mg of caffeine are combined. When 200 mg of ibuprofen is blended in one tablet, 60 mg of allyl isopropyl acetylurea and 80 mg of caffeine are blended in each tablet.
本発明製剤では、必要に応じて、上記各医薬品成分の他、制酸剤を配合してもよい。制酸剤としては、例えば、アミノ酢酸（グリシン）、ケイ酸マグネシウム、合成ケイ酸アルミニウム、合成ヒドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウム・アミノ酢酸塩（アルミニウムグリシネート）、水酸化アルミニウムゲル、乾燥水酸化アルミニウムゲル、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・炭酸水素ナトリウムの共沈生成物、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、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、炭酸マグネシウム、メタケイ酸アルミン酸マグネシウム、ケイ酸アルミン酸マグネシウム、水酸化アルミナマグネシウム、水酸化マグネシウム、炭酸水素ナトリウム、沈降炭酸カルシウム、無水リン酸水素カルシウム、リン酸水素カルシウム等が挙げられる。なお、これらは、１種または２種以上を混合して添加しても良い。 In the preparation of the present invention, an antacid may be blended in addition to the above-mentioned pharmaceutical ingredients as necessary. Examples of antacids include aminoacetic acid (glycine), magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate (aluminum glycinate), aluminum hydroxide gel, and dry water. Aluminum oxide gel, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / calcium carbonate / magnesium carbonate coprecipitation product, magnesium hydroxide / potassium aluminum sulfate Co-precipitation products, magnesium carbonate, magnesium metasilicate aluminate, magnesium silicate aluminate, magnesium hydroxide magnesium, magnesium hydroxide, sodium bicarbonate, precipitated calcium carbonate, anhydrous hydrogen phosphate cal Um, calcium hydrogen phosphate and the like. In addition, you may add these 1 type or in mixture of 2 or more types.
これら制酸剤の配合量は、制酸剤の種類によって異なるが、イブプロフェン４５０ｍｇ〜６００ｍｇに対して１０〜５０００ｍｇを用いることが好ましく、さらに好ましくは１６〜４０００ｍｇである。より詳細には、イブプロフェン４５０ｍｇ〜６００ｍｇに対して、制酸剤としてアミノ酢酸や、水酸化アルミニウム・炭酸水素ナトリウムの共沈生成物を使用する場合は、３０〜９００ｍｇ程度、ケイ酸マグネシウム、合成ケイ酸アルミニウム、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲルを使用する場合は、１００〜３０００ｍｇ程度、合成ヒドロタルサイトを使用する場合は、１３３〜４０００ｍｇ程度、酸化マグネシウムを使用する場合は、１６〜５００ｍｇ程度、ジヒドロキシアルミニウム・アミノ酢酸塩、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、メタケイ酸アルミン酸マグネシウム、沈降炭酸カルシウム、リン酸水素カルシウムを使用する場合は、５０〜１５００ｍｇ程度、水酸化アルミニウムゲル、乾燥水酸化アルミニウムゲルを使用する場合は、乾燥水酸化アルミニウムゲルとして３３〜１０００ｍｇ程度、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を使用する場合は、６０〜１８００ｍｇ程度、炭酸マグネシウム、ケイ酸アルミン酸マグネシウム、水酸化アルミナマグネシウムを使用する場合は、６６〜２０００ｍｇ程度、水酸化マグネシウム、無水リン酸水素カルシウムを使用する場合は、４０〜１２００ｍｇ程度、炭酸水素ナトリウムを使用する場合は、８３〜２５００ｍｇ程度とすることが好ましい。 Although the compounding quantity of these antacids changes with kinds of antacid, it is preferable to use 10-5000 mg with respect to ibuprofen 450 mg-600 mg, More preferably, it is 16-4000 mg. More specifically, when using aminoacetic acid or a coprecipitation product of aluminum hydroxide / sodium bicarbonate as an antacid for 450 mg to 600 mg of ibuprofen, about 30 to 900 mg, magnesium silicate, synthetic silica When using aluminum oxide, aluminum hydroxide / magnesium carbonate mixed dry gel, about 100-3000 mg, when using synthetic hydrotalcite, about 133-4000 mg, when using magnesium oxide, about 16-500 mg When using dihydroxyaluminum / aminoacetate, aluminum hydroxide / calcium carbonate / magnesium carbonate coprecipitation product, magnesium metasilicate aluminate, precipitated calcium carbonate, calcium hydrogen phosphate, about 50 to 1500 mg Aluminum When using um gel and dry aluminum hydroxide gel, about 33-1000 mg as dry aluminum hydroxide gel, when using coprecipitation product of magnesium hydroxide and potassium aluminum sulfate, about 60-1800 mg, magnesium carbonate, When using magnesium aluminate silicate and magnesium aluminate hydroxide, about 66 to 2000 mg, when using magnesium hydroxide and anhydrous calcium hydrogen phosphate, about 40 to 1200 mg, when using sodium bicarbonate, It is preferable to be about 83 to 2500 mg.
本発明製剤には、さらに必要に応じて、ビタミンＢ1、ビタミンＢ2、ビタミンＣ、ヘスペリジン及びこれらの誘導体並びにこれらの塩類や、地竜、カンゾウ、ケイヒ、シャクヤク、ボタンピ、カノコソウ、ショウキョウ、チンピなどの生薬を添加することもできる。 In the preparation of the present invention, vitamin B 1 , vitamin B 2 , vitamin C, hesperidin and derivatives thereof and salts thereof, earth dragon, licorice, cinnamon, peonies, button pi, valerian, ginger, Herbal medicine such as chimpi can also be added.
本発明製剤の製造に当たっては、上記した各成分に加え、さらに、製剤分野で一般的に使用され得る賦形剤、結合剤、崩壊剤、滑沢剤等の製剤添加剤を利用することができる。本発明製剤に配合できる製剤添加剤としては、賦形剤、結合剤、崩壊剤、滑沢剤の他、各種担体、安定（化）剤、界面活性剤、可塑剤、滑沢化剤、可溶（化）剤、還元剤、緩衝剤、甘味剤、基剤、吸着剤、矯味剤、懸濁（化）剤、抗酸化剤、光沢化剤、コーティング剤、剤皮、湿潤剤、湿潤調整剤、充填剤、消泡剤、清涼化剤、着色剤、着香剤、香料、糖衣剤、等張化剤、軟化剤、乳化剤、粘稠化剤、粘稠剤、発泡剤、ｐＨ調整剤、稀釈剤、分散剤、崩壊補助剤、崩壊延長剤、芳香剤、防湿剤、防腐剤、保存剤、溶解剤、溶解補助剤、溶剤、流動化剤、帯電防止剤、増量剤、保湿剤、付湿剤等の製剤添加物を挙げることができる。該添加剤の例は、薬食発１２０４第１号（薬事行政法令）、医薬品添加物事典２００７（日本医薬品添加剤協会編集、薬事日報社）及び第８版食品添加物公定書（日本食品添加物協会）に記載されている。 In producing the preparation of the present invention, in addition to the above-described components, formulation additives such as excipients, binders, disintegrants, lubricants and the like that can be generally used in the pharmaceutical field can be used. . Pharmaceutical additives that can be incorporated into the preparation of the present invention include excipients, binders, disintegrants, lubricants, various carriers, stabilizers, surfactants, plasticizers, lubricants, Solubilizing agent, reducing agent, buffering agent, sweetener, base, adsorbent, flavoring agent, suspending agent, antioxidant, brightening agent, coating agent, skin, wetting agent, wetting adjustment Agent, filler, antifoaming agent, cooling agent, coloring agent, flavoring agent, fragrance, sugar coating agent, tonicity agent, softening agent, emulsifier, thickening agent, thickening agent, foaming agent, pH adjusting agent , Diluents, dispersants, disintegration aids, disintegration extenders, fragrances, desiccants, preservatives, preservatives, solubilizers, solubilizers, solvents, fluidizers, antistatic agents, extenders, moisturizers, There may be mentioned preparation additives such as moisturizing agents. Examples of such additives are: Yakushoku 1204 1 (Pharmaceutical Administration Law), Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association, Yakuji Nippo) and 8th edition Food Additives Official (Japan Food Additives) (Association of Things).
上記製剤添加剤のうち、賦形剤としては、例えば、乳糖、デンプン、コーンスターチ、アルファー化デンプン、部分アルファー化デンプン、結晶セルロース、低置換度ヒドロキシプロピルセルロース、ヒドロキシプロピルセルロース、精製白糖、糖アルコール類、軽質無水ケイ酸、ケイ酸カルシウム、酸化チタン、沈降炭酸カルシウム等が挙げられる。これらの賦形剤は１種または２種以上を使用することができる。 Among the above preparation additives, examples of the excipient include lactose, starch, corn starch, pregelatinized starch, partially pregelatinized starch, crystalline cellulose, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, purified sucrose, and sugar alcohols. , Light anhydrous silicic acid, calcium silicate, titanium oxide, precipitated calcium carbonate and the like. These excipients can be used alone or in combination of two or more.
また、結合剤としては、例えば、ゼラチン、アラビアゴム末、メチルセルロース、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、ヒドロキシプロピルセルロース、ヒプロメロース、ポリビニルピロリドン、ポリビニルアルコール、ポリビニルアルコール・アクリル酸・メタクリル酸メチル共重合体、ポリビニルアルコール・ポリエチレングリコール・グラフトコポリマー、プルラン、デキストリン、カルボキシメチルセルロースカルシウム、カルボキシメチルセルロースナトリウム、メタクリル酸コポリマー等のアクリル酸誘導体、セラック、カルボキシビニルポリマー、カルボキシメチルスターチナトリウム、カルボキシメチルエチルセルロース、酢酸フタル酸セルロース等が挙げられる。これらの結合剤は１種または２種以上を使用することができる。 Examples of the binder include gelatin, gum arabic powder, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, hypromellose, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, polyvinyl Alcohol / polyethylene glycol / graft copolymer, pullulan, dextrin, carboxymethylcellulose calcium, sodium carboxymethylcellulose, acrylic acid derivatives such as methacrylic acid copolymer, shellac, carboxyvinyl polymer, sodium carboxymethyl starch, carboxymethylethylcellulose, cellulose acetate phthalate, etc. Can be mentioned. These binders can use 1 type (s) or 2 or more types.
更に、崩壊剤としては、例えば、クロスカルメロースナトリウム、クロスポビドン、クロスリンクドインソルブルポリビニルピロリドン、カルメロースカルシウム、カルボキシメチルスターチナトリウム、バレイショデンプン、コーンスターチ、アルファー化デンプン等が挙げられる。これらの崩壊剤は１種または２種以上を使用することができる。 Furthermore, examples of the disintegrant include croscarmellose sodium, crospovidone, cross-linked insoluble polyvinylpyrrolidone, carmellose calcium, sodium carboxymethyl starch, potato starch, corn starch, pregelatinized starch and the like. These disintegrants can be used alone or in combination of two or more.
更にまた、滑沢剤としては、例えば、タルク、ステアリン酸、ステアリン酸マグネシウム、ショ糖脂肪酸エステル類、ポリエチレングリコール等が挙げられる。これらの滑沢剤は１種または２種以上を使用することができる。 Furthermore, examples of the lubricant include talc, stearic acid, magnesium stearate, sucrose fatty acid esters, polyethylene glycol and the like. These lubricants can be used alone or in combination of two or more.
以上説明した本発明製剤は、錠剤の他、カプレット、硬カプセル剤、口腔内崩壊錠、チュアブル錠、細粒剤、顆粒剤、ドライシロップ剤などの内服固形製剤として提供される。また、必要に応じてフィルムコーティングや糖衣を施し、上記製剤のコーティング製剤とすることもできる。これらの剤型には、通常行われている製剤化方法（津田恭介・上野寿著、「医薬品開発基礎講座ＸＩ 薬剤製造法（上）（下）」、地人書館、１９７１年発行；仲井由宣著、「製剤工学ハンドブック」、地人書館、１９８３年発行；仲井由宣著、「医薬品の開発１１ 製剤の単位操作と機械」、廣川書店、１９８９年発行；橋田充著、「経口投与製剤の設計と評価」、薬業時報社、１９９５年発行；橋田充著、「経口投与製剤の処方設計」、薬業時報社、１９９５年発行）により製造することができる。また、マイクロカプセル、ナノカプセル、マイクロスフィアー、ナノスフィアー等の微小粒子を用いてもよい。 The preparations of the present invention described above are provided as solid preparations for internal use such as caplets, hard capsules, orally disintegrating tablets, chewable tablets, fine granules, granules, and dry syrups in addition to tablets. In addition, if necessary, film coating or sugar coating can be applied to form a coating preparation of the above preparation. These dosage forms include the usual formulation methods (Yusuke Tsuda and Toshi Ueno, “Pharmaceutical Development Basic Course XI Pharmaceutical Production Method (top) (bottom)”, Jinshokan, 1971; Yu Nakai Nobu, “Formulation Engineering Handbook”, Jinshokan, published in 1983; Nakano, Yoshinobu, “Pharmaceutical Development 11 Unit Operation and Machine of Drugs”, Yodogawa Shoten, 1989; Hashida, Mitsuru, “Oral Preparations” ”Design and Evaluation”, published by Yakuho Jihosha, 1995; Mitsuru Hashida, “Prescription Design of Orally Administered Drugs”, Yakuho Jihosha, 1995). Moreover, you may use microparticles, such as a microcapsule, a nanocapsule, a microsphere, and a nanosphere.
本発明製剤の投与量は、従来品と同様であり、通常、１回量を１日３回限度とし、なるべく空腹時をさけて水又はぬるま湯で服用するのが好ましい。 The dosage of the preparation of the present invention is the same as that of the conventional product. Usually, it is preferable to take the amount once a maximum of 3 times a day and take water or lukewarm water as much as possible to avoid fasting.
斯くして得られる本発明の解熱鎮痛製剤は、ガラス瓶、プラスチックボトル、ＰＴＰ包装、アルミヒートシール包装等の密閉容器に保存することにより解熱鎮痛医薬品とすることができ、かつ、保存の際の曇りや不快な臭いの発生を抑制することができる。 The antipyretic analgesic preparation of the present invention thus obtained can be made into an antipyretic analgesic drug by storing it in a closed container such as a glass bottle, plastic bottle, PTP packaging, aluminum heat seal packaging, etc., and clouding during storage And the generation of unpleasant odors can be suppressed.
次に、実施例および比較例を示し、本発明を更に具体的に説明するが、本発明はこれらに何ら制約されるものではない。 Next, although an Example and a comparative example are shown and this invention is demonstrated more concretely, this invention is not restrict | limited at all by these.
実 施 例 １
フィルムコーティング錠の製造：
（１）イブプロフェン３００ｇ、アリルイソプロピルアセチル尿素９０ｇ、無水カフェイン１２０ｇ、トウモロコシデンプン６０ｇ、結晶セルロース２５５ｇ、軽質無水ケイ酸３０ｇ、低置換度ヒドロキシプロピルセルロース１５０ｇおよびタルク６３ｇを秤量し、高速攪拌造粒機で、精製水を添加して、湿式造粒を行った。整粒後、流動層で乾燥したのち、２４メッシュの篩を通過させ、これにタルク１２ｇを混合し打錠用顆粒を製した。常法により、１錠あたり３６０ｍｇになるようにロータリー打錠機で圧縮成型し、素錠を得た。この素錠にヒプロメロース、酸化チタン、マクロゴール及び水（７：２．５：０．５：９０）からなるフィルムコーティング剤を通気式コーティング装置にて噴霧し、直径約９ｍｍ、３６５ｍｇ／錠のフィルムコーティング錠として発明品１を得た。
Example 1
Production of film-coated tablets:
(1) 300 g of ibuprofen, 90 g of allyl isopropyl acetylurea, 120 g of anhydrous caffeine, 60 g of corn starch, 255 g of crystalline cellulose, 30 g of light anhydrous silicic acid, 150 g of low-substituted hydroxypropyl cellulose and 63 g of talc, and a high-speed stirring granulator Then, purified water was added and wet granulation was performed. After sizing, after drying in a fluidized bed, it was passed through a 24-mesh sieve, and 12 g of talc was mixed therewith to produce tableting granules. According to a conventional method, the tablet was compression-molded with a rotary tableting machine to obtain 360 mg per tablet to obtain an uncoated tablet. A film coating agent composed of hypromellose, titanium oxide, macrogol and water (7: 2.5: 0.5: 90) is sprayed onto the uncoated tablets using a ventilated coating apparatus, and the film has a diameter of about 9 mm and 365 mg / tablet. Invention 1 was obtained as a coated tablet.
（２）イブプロフェン６６０ｇ、アリルイソプロピルアセチル尿素１９８ｇ、無水カフェイン２６４ｇ、酸化マグネシウム３３０ｇおよび低置換度ヒドロキシプロピルセルロース４８１．８ｇを高速攪拌造粒機で混合後、精製水を添加し練合した。次に、０．６ｍｍスクリーンで押し出し造粒後、流動層乾燥機にて乾燥した。この乾燥顆粒を１７５８ｇ量り取り、結晶セルロース１６５．６ｇ、クロスカルメロースナトリウム１２０ｇ、軽質無水ケイ酸１６．２ｇ、タルク２４ｇ、ステアリン酸マグネシウム１６．２ｇを混合し打錠用顆粒を製した。常法により、１錠あたり３５０ｍｇになるようにロータリー打錠機で圧縮成型し、素錠を得た。この素錠にヒドロキシプロピルメチルセルロース、酸化チタン、マクロゴール及び水（７：２．５：０．５：９０）からなるフィルムコーティング剤を通気式コーティング装置にて噴霧し、直径約９ｍｍ、３６０ｍｇ／錠のフィルムコーティング錠として発明品２を得た。 (2) 660 g of ibuprofen, 198 g of allyl isopropyl acetylurea, 264 g of anhydrous caffeine, 330 g of magnesium oxide and 481.8 g of low-substituted hydroxypropylcellulose were mixed with a high-speed stirring granulator, and purified water was added and kneaded. Next, it was extruded and granulated with a 0.6 mm screen, and then dried with a fluidized bed dryer. 1758 g of this dried granule was weighed and mixed with 165.6 g of crystalline cellulose, 120 g of croscarmellose sodium, 16.2 g of light anhydrous silicic acid, 24 g of talc, and 16.2 g of magnesium stearate to produce granules for tableting. According to a conventional method, the tablet was compression-molded with a rotary tableting machine so as to be 350 mg per tablet to obtain an uncoated tablet. This uncoated tablet is sprayed with a film coating agent composed of hydroxypropylmethylcellulose, titanium oxide, macrogol and water (7: 2.5: 0.5: 90) with a breathable coating apparatus, and has a diameter of about 9 mm, 360 mg / tablet. Invention 2 was obtained as a film-coated tablet.
比 較 例 １
上記実施例１（１）において、使用イブプロフェンを２２５ｇに変更し、素錠質量を３３５ｍｇ及びフィルムコーティング錠質量を３４０ｍｇと変更する以外は同様にしてフィルムコーティング錠を得た。これを比較品１とした。
Comparative Example 1
A film-coated tablet was obtained in the same manner as in Example 1 (1) except that the ibuprofen used was changed to 225 g, the uncoated tablet mass was changed to 335 mg, and the film-coated tablet mass was changed to 340 mg. This was designated as comparative product 1.
上記実施例１（２）において、使用イブプロフェンを４９５ｇに変更し、乾燥顆粒の使用量を１６０８ｇ、素錠質量を３２５ｍｇ及びフィルムコーティング錠質量を３３５ｍｇに変更とする以外は、同様にしてフィルムコーティング錠を得た。これを比較品２とした。 In the above Example 1 (2), except that the ibuprofen used was changed to 495 g, the amount of dry granules used was changed to 1608 g, the uncoated tablet mass was changed to 325 mg, and the film coated tablet mass was changed to 335 mg, the film coated tablet was similarly used. Got. This was designated as comparative product 2.
上記発明品１〜２及び比較品１〜２のフィルムコーティング錠１錠当たりの各成分の組成を表１に示す。 Table 1 shows the composition of each component per film-coated tablet of the invention products 1-2 and comparative products 1-2.
試 験 例 １
保存試験：
上記発明品１〜２及び比較品１〜２をそれぞれ１シート１０錠のＰＴＰ包装にて１錠ごとに密閉包装し、２シートを紙箱に入れた。それらを、４０℃で８時間加熱送風後、室温(２３℃)で１６時間送風することを１サイクルとして、これを６カ月間繰り返して保管した。保管後のＰＴＰ包装の透明部分の曇りを下記の評価基準に従って評価した。結果を表２に示す。
Test example 1
Storage test:
The invention products 1 and 2 and the comparative products 1 and 2 were each hermetically packaged in a PTP package of 10 tablets per sheet, and 2 sheets were placed in a paper box. These were heated and heated at 40 ° C. for 8 hours, and then blown at room temperature (23 ° C.) for 16 hours as one cycle, and this was repeated for 6 months and stored. The cloudiness of the transparent part of the PTP package after storage was evaluated according to the following evaluation criteria. The results are shown in Table 2.
＜曇りの評価基準＞
（評 価） （内 容）
−： 曇りを全く認めない
±： 曇りをほとんど認めない
＋： 曇りを認める
＋＋： 強く曇りを認める
＋＋＋： 著しく強く曇りを認める
<Evaluation criteria for cloudiness>
(Evaluation) (Contents)
-: No cloudiness
±: Almost no cloudiness
+: Cloudiness is recognized ++: Strong cloudiness is recognized ++++: Cloudiness is recognized extremely strongly
この結果から、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインをそれぞれ質量比で１０：３：４の割合で有する本発明製剤は、曇りが全く認められないのに対し、同じ成分を異なる比率（１５：６：８）で使用する比較品では曇りが発生することが明らかになった。 From this result, the formulation of the present invention having ibuprofen, allylisopropylacetylurea and caffeine in a mass ratio of 10: 3: 4, respectively, has no cloudiness at all, whereas the same component has a different ratio (15: It became clear that fogging occurred in the comparative product used in 6: 8).
試 験 例 ２
臭いの発生試験：
上記発明品１〜２及び比較品１〜２をそれぞれ５０錠無色透明ガラス瓶に入れて密閉し、５０℃で１０日保管した。ガラス瓶の蓋を開けた直後の臭いを下記の評価基準に従って評価した。結果を表３に示す。
Test example 2
Odor generation test:
The invention products 1 and 2 and comparative products 1 and 2 were each sealed in 50 colorless and transparent glass bottles and stored at 50 ° C. for 10 days. The odor immediately after opening the lid of the glass bottle was evaluated according to the following evaluation criteria. The results are shown in Table 3.
＜臭いの評価基準＞
（評 価） （内容）
−： 不快な臭いが全くない
±： 不快な臭いがほとんどない
＋： 不快な臭いがある
＋＋： 強く不快な臭いがある
<Odor evaluation criteria>
(Evaluation) (Content)
-: No unpleasant odor
±: Almost no unpleasant odor
+: Unpleasant odor ++: Strong and unpleasant odor
この結果から明らかなように、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインをそれぞれ質量比で１０：３：４の割合で有する本発明製剤では、開封時の不快な臭いが全く〜ほとんどないのに対し、同じ成分を異なる比率で使用する比較品では開封時に強い不快な臭いがあった。 As is apparent from the results, the preparation of the present invention having ibuprofen, allylisopropylacetylurea and caffeine at a mass ratio of 10: 3: 4 respectively has no unpleasant odor at the time of opening. The comparative product using the same components in different ratios had a strong unpleasant odor when opened.
実 施 例 ２
錠剤の製造：
イブプロフェン４００ｇ、アリルイソプロピルアセチル尿素１２０ｇ、無水カフェイン１６０ｇ、結晶セルロース１６０ｇ、軽質無水ケイ酸４０ｇ、低置換度ヒドロキシプロピルセルロース１２０ｇおよびタルク５０ｇを秤量し、高速攪拌造粒機で、精製水を添加して、湿式造粒を行った。整粒後、流動層で乾燥したのち、２４メッシュの篩を通過させ、これにタルク１０ｇを混合し打錠用顆粒を製した。常法により、１錠あたり５３０ｍｇになるようにロータリー打錠機で圧縮成型して発明品３を得た。
Example 2
Tablet production:
Weigh 400 g of ibuprofen, 120 g of allylisopropylacetylurea, 160 g of anhydrous caffeine, 160 g of crystalline cellulose, 40 g of light anhydrous silicic acid, 120 g of low-substituted hydroxypropylcellulose and 50 g of talc, and add purified water with a high-speed stirring granulator. Then, wet granulation was performed. After sizing, after drying in a fluidized bed, it was passed through a 24-mesh sieve, and 10 g of talc was mixed therewith to produce tableting granules. Inventive product 3 was obtained by compression molding with a rotary tableting machine at 530 mg per tablet by a conventional method.
比 較 例 ２
上記実施例２において、使用イブプロフェン量を３００ｇに変更し、また１錠あたりの質量を４８０ｍｇと変更とする以外は、同様にして錠剤を得た。これを比較品３とした。
Comparative Example 2
A tablet was obtained in the same manner as in Example 2 except that the amount of ibuprofen used was changed to 300 g and the mass per tablet was changed to 480 mg. This was designated as comparative product 3.
上記発明品３及び比較品３の錠剤１錠当たりの各成分の組成を表４に示す。 Table 4 shows the composition of each component per tablet of Invention Product 3 and Comparative Product 3.
試 験 例 ３
保存試験及び臭いの発生試験：
発明品３と比較品３をそれぞれ１シート１０錠のＰＴＰ包装にて１錠ごとに密閉包装し、２シートを紙箱に入れ、試験例１と同様に保存し、上記保存試験と同様の評価基準で、曇りを評価した。また、発明品３と比較品３をそれぞれ５０錠無色透明ガラス瓶に入れて密閉し、試験例２と同様に保存し、上記臭いの発生試験と同様の評価基準で、臭いを評価した。結果を表５に示す。
Test example 3
Storage test and odor generation test:
Inventive product 3 and comparative product 3 are each hermetically packaged in PTP packaging of 10 tablets per sheet, put 2 sheets in a paper box, stored in the same manner as in Test Example 1, and the same evaluation criteria as in the above storage test Then, cloudiness was evaluated. Inventive product 3 and comparative product 3 were each sealed in 50 colorless transparent glass bottles, sealed, stored in the same manner as in Test Example 2, and the odor was evaluated according to the same evaluation criteria as in the odor generation test. The results are shown in Table 5.
この実験から、イブプロフェン、アリルイソプロピルアセチル尿素及びカフェインをそれぞれ質量比で１０：３：４の割合で有する本発明製剤は、ＰＴＰ包装中でも曇りが全く発生せず、また不快な臭いもほとんどなかったのに対し、同じ成分を異なる比率で使用する比較品では強い曇りが発生し、また開封時に強い不快臭が感じられることが明らかになった。 From this experiment, the formulation of the present invention having ibuprofen, allylisopropylacetylurea and caffeine at a mass ratio of 10: 3: 4 respectively did not cause any cloudiness even during PTP packaging, and had almost no unpleasant odor. On the other hand, it was revealed that a comparative product using the same components at different ratios produced strong haze and a strong unpleasant odor was felt when opened.
本発明によれば、イブプロフェンとアリルイソプロピルアセチル尿素及びカフェインを含有する解熱鎮痛製剤において、その配合比率を変更することで、容易に密封容器に保存の際、曇りや不快な臭いを防止ないし低減することができる。 According to the present invention, in an antipyretic analgesic preparation containing ibuprofen, allylisopropylacetylurea and caffeine, by changing the mixing ratio, cloudiness and unpleasant odor can be easily prevented or reduced when stored in a sealed container. can do.
従って、本発明により簡単に曇りや不快臭を防ぎ、商品価値の低下を防止することが可能となるので、固形の解熱鎮痛剤の製造において広く利用しうるものである。
Therefore, the present invention can easily prevent fogging and unpleasant odors and prevent a decline in commercial value, and thus can be widely used in the production of solid antipyretic analgesics.
Claims (4)
The antipyretic analgesic preparation according to claim 3, wherein the sealed package is a PTP package, a glass bottle, a plastic bottle or an aluminum pillow package.
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