JP4344532B2 - Composition for rhinitis - Google Patents
Composition for rhinitis Download PDFInfo
- Publication number
- JP4344532B2 JP4344532B2 JP2003121231A JP2003121231A JP4344532B2 JP 4344532 B2 JP4344532 B2 JP 4344532B2 JP 2003121231 A JP2003121231 A JP 2003121231A JP 2003121231 A JP2003121231 A JP 2003121231A JP 4344532 B2 JP4344532 B2 JP 4344532B2
- Authority
- JP
- Japan
- Prior art keywords
- rhinitis
- composition
- pharmaceutically acceptable
- acceptable salt
- emedastine
- 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.)
- Expired - Fee Related
Links
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Description
【０００１】
【発明の属する技術分野】
本発明は、アレルギー性鼻炎、急性鼻炎、副鼻腔炎、風邪などによる鼻炎症状の処置に有効な鼻炎用組成物に関する。より詳細には、鼻炎症状の中でも鼻汁分泌の抑制効果に優れた鼻炎用組成物に関する。
【０００２】
【従来の技術】
アレルギー性鼻炎、急性鼻炎、副鼻腔炎、風邪などによる鼻炎症状（くしゃみ、鼻づまり（鼻閉）、鼻みず（鼻汁過多）など）の不快感は誰しもが一度は経験しているところであり、鼻炎患者は一刻も早くその苦しみから逃れたいと思う。特に、鼻汁過多になると、鼻をかむ頻度が多くなり、鼻粘膜の炎症や鼻出血などの症状を併発することもしばしばみられ、早期の改善あるいは軽減が求められる。鼻炎症状の処置に使用される薬剤には種々のタイプのものが存在し、各種の症状を総合的に緩和する薬剤に加え、特定の症状に着目し、その症状に対して増強された効果を発揮する薬剤もある。例えば、優れた鼻汁分泌抑制効果は、ベラドンナ総アルカロイド、ヨウ化イソプロパミドなどの抗コリン薬（副交感神経遮断剤）を配合することにより得られる。
【０００３】
【発明が解決しようとする課題】
ところで、エメダスチンは、ヒスタミンに起因するアレルギー性鼻炎などの処置に有効な抗ヒスタミン薬として知られており、鼻汁分泌に対してもその抑制効果が確認されている（医学と薬学３５（６）１２７３（１９９６））、しかしながら、その効果は必ずしも十分なものではないので、エメダスチンを有効成分とする鼻汁分泌の抑制効果に優れた鼻炎用組成物が求められている。このような鼻炎用組成物を得ることができれば、エメダスチンの服用量を低減することが可能となることから、眠気などの副作用の回避といったような効果を得ることも可能となる。
そこで本発明は、鼻炎症状に対して改善効果の高い鼻炎用組成物、特に、鼻炎症状の中でも鼻汁分泌の抑制効果に優れることで、鼻汁過多の症状に対して改善効果の高い鼻炎用組成物を提供することを目的とする。
【０００４】
【課題を解決するための手段】
本発明者らは上記の点に鑑みて種々の検討を行った結果、エメダスチンとグリチルリチン酸を組み合わせて使用した場合、意外にも鼻汁分泌に対して優れた抑制効果が得られることを知見した。
【０００５】
本発明は上記の知見に基づいてなされたものであり、本発明の鼻炎用組成物は、請求項１記載の通り、エメダスチンまたはその薬学的に許容される塩、および、グリチルリチン酸またはその薬学的に許容される塩を含有することを特徴とする。
また、請求項２記載の鼻炎用組成物は、請求項１記載の鼻炎用組成物において、エメダスチンまたはその薬学的に許容される塩１重量部に対して、グリチルリチン酸またはその薬学的に許容される塩を０．２重量部〜６００重量部含有することを特徴とする。
また、本発明の鼻炎用組成物は、請求項３記載の通り、エメダスチンまたはその薬学的に許容される塩０．０５ｍｇ〜５ｍｇ（エメダスチン換算量）、および、グリチルリチン酸またはその薬学的に許容される塩０．１ｍｇ〜３００ｍｇ（グリチルリチン酸換算量）を含有することを特徴とする。
また、本発明の鼻汁分泌抑制剤は、請求項４記載の通り、エメダスチンまたはその薬学的に許容される塩、および、グリチルリチン酸またはその薬学的に許容される塩を含有することを特徴とする。
また、請求項５記載の鼻炎用組成物は、請求項１乃至３のいずれかに記載の鼻炎用組成物において、アレルギー性鼻炎、急性鼻炎、副鼻腔炎、風邪のいずれかによる鼻炎症状に適用されるものであることを特徴とする。
また、請求項６記載の鼻炎用組成物は、請求項５記載の鼻炎用組成物において、鼻炎症状が鼻汁過多であることを特徴とする。
また、請求項７記載の鼻炎用組成物は、請求項１、２、３、５、６のいずれかに記載の鼻炎用組成物において、キサンチン類、副交感神経遮断剤、解熱鎮痛薬成分、抗炎症薬成分、抗ヒスタミン薬成分、抗アレルギー成分、ビタミン類から選択される少なくとも１種をさらに含有することを特徴とする。
また、請求項８記載の鼻炎用組成物は、請求項７記載の鼻炎用組成物において、キサンチン類がカフェイン、テオフィリン、テオブロミン、ジプロフィリン、プロキシフィリン、ペントキシフィリンまたはその薬学的に許容される塩、安息香酸ナトリウムカフェインから選択される少なくとも１種であることを特徴とする。
また、請求項９記載の鼻炎用組成物は、請求項７記載の鼻炎用組成物において、副交感神経遮断剤がダツラエキス、ベラドンナ総アルカロイド、ベラドンナエキス、ヨウ化イソプロパミド、ロートエキスから選択される少なくとも１種であることを特徴とする。
【０００６】
【発明の実施の形態】
本発明の鼻炎用組成物は、エメダスチンまたはその薬学的に許容される塩、および、グリチルリチン酸またはその薬学的に許容される塩を含有することを特徴とするものであり、とりわけ鼻汁分泌抑制剤としての利用価値が高い。グリチルリチン酸は鼻炎症状の処置に使用される薬剤に消炎剤として配合される場合があり、また、肥満細胞からのヒスタミン遊離抑制作用を有することが知られている（和漢医薬学会誌６，２９４−２９５，１９８９）。しかしながら、グリチルリチン酸とエメダスチンとの組み合わせについてはこれまでに検討されたことはなく、両者を組み合わせることにより鼻汁分泌に対して優れた抑制効果が得られることは、いかなる先行文献にも記載されておらず、また、いかなる先行文献からも予測できるものではない。なお、特開２０００−９５６７５号公報、特開２００１−３０２５１８号公報、特開２００１−３０２５４５号公報には、鼻炎用組成物などの医薬組成物の配合成分として多種多様の化合物が記載されており、その中にエメダスチンとグリチルリチン酸も記載されているが、両者を組み合わせた鼻炎用組成物の開示はない。
【０００７】
本発明の鼻炎用組成物の一成分として使用されるエメダスチンは公知の化合物であり（例えば、米国特許第４４３０３４３号公報に記載）、その薬学的に許容される塩としては、塩酸塩、硝酸塩、硫酸塩、リン酸塩、シュウ酸塩、マレイン酸塩、フマル酸塩、臭化水素酸塩、エナント酸塩などが挙げられるが、中でも、塩酸塩、フマル酸塩が好ましい。
【０００８】
本発明の鼻炎用組成物の一成分として使用されるグリチルリチン酸またはその薬学的に許容される塩としては、グリチルリチン酸、グリチルリチン酸ジカリウム、グリチルリチン酸モノアンモニウム、グリチルリチン酸ジアンモニウムなどが挙げられる。また、グリチルリチン酸を含有する生薬や生薬エキス類を使用することもできる。このような生薬や生薬エキス類を使用する場合、グリチルリチン酸の含有量を考慮し、所定量のグリチルリチン酸が本発明の鼻炎用組成物に含有されるように使用することに留意すべきである。グリチルリチン酸を含有する生薬や生薬エキス類の具体例としては、カンゾウ、カンゾウ末（粉末）、カンゾウエキス、カンゾウ粗エキス、葛根湯エキス、桂枝湯エキス、柴胡桂枝湯エキス、小柴胡湯エキス、小青竜湯エキス、麦門冬湯エキス、麻黄湯エキスなどが挙げられる。これらは単独で、または２種類以上を併用して使用することができる。
【０００９】
本発明の鼻炎用組成物における、エメダスチンまたはその薬学的に許容される塩、および、グリチルリチン酸またはその薬学的に許容される塩の好適な配合割合は、前者１重量部に対して、後者０．２重量部〜６００重量部であるが、より好適な配合割合は、前者１重量部に対して、後者５重量部〜２００重量部である。
【００１０】
本発明の鼻炎用組成物による、エメダスチンまたはその薬学的に許容される塩の１日当たりの投与量は、効果を十分に発揮させつつも副作用の発現を回避する観点から、エメダスチン換算量として、０．０５ｍｇ〜５ｍｇが好ましく、０．２ｍｇ〜４．５ｍｇがより好ましく、０．５ｍｇ〜４ｍｇがさらに好ましい。また、グリチルリチン酸またはその薬学的に許容される塩の１日当たりの投与量は、グリチルリチン酸換算量として、０．１ｍｇ〜３００ｍｇが好ましく、０．３ｍｇ〜２５０ｍｇがより好ましく、１ｍｇ〜２００ｍｇがさらに好ましい。従って、本発明の鼻炎用組成物は、１回または複数回の投与により１日当たりの投与量がエメダスチンまたはその薬学的に許容される塩については０．０５ｍｇ〜５ｍｇ（エメダスチン換算量）、グリチルリチン酸またはその薬学的に許容される塩については０．１ｍｇ〜３００ｍｇ（グリチルリチン酸換算量）となるように製剤化されて使用されることが好ましい。
【００１１】
本発明の鼻炎用組成物は、錠剤、被覆錠剤、顆粒剤、細粒剤、散剤、カプセル剤、液剤、シロップ剤などの経口投与用製剤や、滴下用液剤、塗布用液剤、噴霧用液剤などの経鼻投与用製剤などに製剤化され、鼻炎用内服薬、鼻炎用点鼻薬、風邪薬などとして、アレルギー性鼻炎、急性鼻炎、副鼻腔炎、花粉やハウスダストなどによる鼻のアレルギー症状、感冒などの処置に使用される。本発明の鼻炎用組成物の製剤化は、エメダスチンまたはその薬学的に許容される塩、および、グリチルリチン酸またはその薬学的に許容される塩に必要に応じて賦形剤、結合剤、滑沢剤、崩壊剤、コーティング剤、矯味剤、矯臭剤、着色剤、保存剤、分散剤、溶剤などの公知の添加剤を各種製剤形態に応じて加え、常法に従って行われる。
【００１２】
本発明の鼻炎用組成物に対し、キサンチン類を組み合わせると、抗ヒスタミン薬の副作用である眠気について改善された組成物を得ることができるため、併用すると特に好適である。キサンチン類としては、例えば、カフェイン、テオフィリン、テオブロミン、ジプロフィリン、プロキシフィリン、ペントキシフィリンまたはその薬学的に許容される塩や、安息香酸ナトリウムカフェインなどが例示できる。これらのキサンチン類は、通常１ｍｇ以上であれば効果を発揮することができるので、配合量の下限は１ｍｇが好ましく、５ｍｇがより好ましい。また、上限は特に制限はないが、経済性や投与量を考慮すると５００ｍｇが好ましく、３００ｍｇがより好ましい。
また、本発明の鼻炎用組成物に対し、さらに副交感神経遮断剤を組み合わせるとより好ましい。副交感神経遮断剤としては、ダツラエキス、ベラドンナ総アルカロイド、ベラドンナエキス、ヨウ化イソプロパミド、ロートエキスなどが例示できる。副交感神経遮断剤の配合量の下限は、効果を有効に発揮させるためには０．１ｍｇが好ましく、０．２ｍｇがより好ましい。また、上限は副交感神経遮断剤の種類にも依存するが１００ｍｇが好ましく、６０ｍｇがより好ましい。副交感神経遮断剤の配合割合は、その下限はエメダスチン１重量部に対して０．０５重量部以上であることが好ましく、０．１重量部以上であることがより好ましい。また、その上限はエメダスチン１重量部に対して２００重量部以下が好ましく、１５０重量部以下がより好ましい。
本発明の鼻炎用組成物には、必要に応じてさらに種々の成分（薬理活性成分や生理活性成分を含む）を組み合わせることができる。このような成分の種類は特に制限されず、例えば、解熱鎮痛薬成分、抗炎症薬成分、抗ヒスタミン薬成分、抗アレルギー成分、ビタミン類などが例示できる。本発明において好適な成分としては、例えば、次のような成分が例示できる。
解熱鎮痛薬成分としては、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、イブプロフェン、ケトプロフェン、サリチル酸ナトリウムおよびラクチルフェネチジンなどが例示できる。
抗炎症薬成分としては、例えば、インドメタシン、ジクロフェナク、プラノプロフェン、ピロキシカム、イプシロン−アミノカプロン酸、ベルベリン、リゾチーム、アラントイン、アズレン、ブロメラインまたはその薬学的に許容される塩（例えば、塩化ベルベリン、硫酸ベルベリン、ジクロフェナクナトリウム、塩化リゾチームなど）などが例示できる。
抗ヒスタミン薬成分としては、例えば、クロルフェニラミン、クレマスチン、ジフェンヒドラミン、イプロヘプチン、イソチペンジル、ジフェテロール、ジフェニルピラリン、トリプロリジン、トリペレナミン、トンジルアミン、プロメタジン、メトジラジン、カルビノキサミン、アリメマジン、プロメタジン、メブヒドロリン、フェネタジン、ケトチフェン、アゼラスチン、オキサトミド、メキタジン、テルフェナジン、エピナスチン、アステミゾール、エバスチン、セチリジン、レボカバスチン、オロパタジンまたはその薬学的に許容される塩などが例示できる。
抗アレルギー成分としては、例えば、クロモグリク酸、トラニラスト、アンレキサノクス、イブジラスト、ペミロラスト、タザノラストまたはその薬学的に許容される塩などが例示できる。
ビタミン類としては、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、リコピンまたはその薬学的に許容される塩（例えば、酢酸レチノール、パルミチン酸レチノールなど）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、ニコチニックアルコール、パントテン酸、パンテノール、ビオチン、コリン、イノシトールまたはその薬学的に許容される塩（例えば、塩酸チアミン、硝酸チアミン、塩酸ジセチアミン、塩酸フルスルチアミン、酪酸リボフラビン、リン酸リボフラビンナトリウム、フラビンアデニンジヌクレオチドナトリウム、塩酸ピリドキシン、リン酸ピリドキサール、リン酸ピリドキサールカルシウム、塩酸ヒドロキソコバラミン、酢酸ヒドロキソコバラミン、パントテン酸カルシウム、パントテン酸ナトリウムなど）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、その誘導体またはその薬学的に許容される塩（例えば、アスコルビン酸ナトリウム、エリソルビン酸ナトリウムなど）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またはその薬学的に許容される塩など）、ビタミンＥ類［例えば、トコフェロール、その誘導体、ユビキノン誘導体またはその薬学的に許容される塩（酢酸トコフェロール、ニコチン酸トコフェロール、コハク酸トコフェロール、コハク酸トコフェロールカルシウムなど）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、エリオシトリンまたはその薬学的に許容される塩（塩化カルニチンなど）など］が例示できる。
【００１３】
本発明は、また、エメダスチンまたはその薬学的に許容される塩、および、グリチルリチン酸またはその薬学的に許容される塩を含有させることで鼻炎用組成物の鼻汁分泌抑制効果を高める方法としても特徴付けることができる。鼻炎用組成物の鼻汁分泌抑制効果を高めるためのエメダスチンまたはその薬学的に許容される塩、および、グリチルリチン酸またはその薬学的に許容される塩の好適な配合割合は、前者１重量部に対して、後者０．２重量部〜６００重量部であるが、より好適な配合割合は、前者１重量部に対して、後者５重量部〜２００重量部である。
【００１４】
【実施例】
本発明を以下の試験例と実施例によってさらに詳細に説明するが、本発明はこれに限定されるものではない。
【００１５】
試験例１（モルモットを使用した鼻汁分泌抑制効果確認試験）
実験方法：
ハートレイ系雄性モルモット（体重２５０ｇ〜３５０ｇ）に対し、卵白アルブミン１０μｇおよび水酸化アルミニウムゲル２０ｍｇを腹腔内に投与し（感作０日）、その１週間後および２週間後に、同量の卵白アルブミンを含有する生理食塩液を同様の方法で投与することにより、能動感作を行った。さらに、感作２０、２２、２４日後に、それぞれ０．１、０．２５、０．５％の卵白アルブミンを含有する生理食塩液をモルモットの両鼻腔内に２０μｌずつ点鼻することにより、能動感作モルモットを作成した。
感作２８日後に、再度、２．５％の卵白アルブミンを含有する生理食塩液をモルモットの右鼻腔内に２０μｌ点鼻することにより、アレルギー反応を惹起させた。惹起１０分後からキャピラリーにて１０分間右鼻腔から鼻汁を回収し（麻酔下）、鼻汁分泌量を計測した。被験サンプルは以下の通りであり、惹起１時間前に経口投与した（ｎ＝３〜７）。なお、Ａ群のコントロール群は０．１％カルボキシメチルセルロースナトリウム溶液とした。Ｂ群〜Ｅ群はフマル酸エメダスチンおよび／またはグリチルリチン酸ジカリウムを０．１％カルボキシメチルセルロースナトリウム溶液に溶解して調製した。
【００１６】
Ａ群：コントロール群（0.1%カルボキシメチルセルロースナトリウム溶液）
Ｂ群：フマル酸エメダスチン0.05mg/kg
Ｃ群：グリチルリチン酸ジカリウム25mg/kg
Ｄ群：グリチルリチン酸ジカリウム200mg/kg
Ｅ群：フマル酸エメダスチン0.05mg/kg＋グリチルリチン酸ジカリウム25mg/kg
【００１７】
実験結果：
結果を図１に示す。図１から明らかなように、フマル酸エメダスチン単独投与群（Ｂ群）およびグリチルリチン酸ジカリウム単独投与群（Ｃ群とＤ群）において鼻汁分泌抑制効果が得られなかった両者の用量であっても、Ｅ群において両者を組み合わせて投与した場合（Ｂ群とＣ群の組み合わせ）、意外にも、優れた鼻汁分泌抑制効果が得られた。
【００１８】
【００１９】
【００２０】
【００２１】
【００２２】
【００２３】
【００２４】
【００２５】
【００２６】
【００２７】
【００２８】
【００２９】
【００３０】
【００３１】
【００３２】
【００３３】
【００３４】
【００３５】
【発明の効果】
本発明によれば、鼻炎症状に対して改善効果の高い鼻炎用組成物、特に、鼻炎症状の中でも鼻汁分泌の抑制効果に優れることで、鼻汁過多の症状に対して改善効果の高い鼻炎用組成物が提供される。
【図面の簡単な説明】
【図１】 実施例における鼻水分泌抑制効果を示すグラフである。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a composition for rhinitis that is effective for treating nasal inflammation caused by allergic rhinitis, acute rhinitis, sinusitis, cold, and the like. More particularly, the present invention relates to a composition for rhinitis that is excellent in the effect of suppressing nasal secretion among nasal inflammation symptoms.
[0002]
[Prior art]
Allergic rhinitis, acute rhinitis, sinusitis, nasal inflammation caused by colds (sneezing, nasal congestion (nasal obstruction), nasal congestion (excessive nasal discharge), etc.) have been experienced by everyone once , Rhinitis patients want to get away from the suffering as soon as possible. In particular, excessive nasal discharge increases the frequency of biting the nose and often causes symptoms such as inflammation of the nasal mucosa and nasal bleeding, and early improvement or reduction is required. There are various types of drugs used for the treatment of nasal inflammation. In addition to drugs that comprehensively relieve various symptoms, attention is paid to specific symptoms and an enhanced effect on the symptoms. Some drugs work. For example, an excellent inhibitory effect on nasal secretion is obtained by blending an anticholinergic agent (parasympathetic nerve blocker) such as belladonna total alkaloids and isopropamide iodide.
[0003]
[Problems to be solved by the invention]
By the way, emedastine is known as an antihistamine effective for the treatment of allergic rhinitis caused by histamine, and its inhibitory effect on nasal secretion is also confirmed (Medicine and Pharmacy 35 (6) 1273). (1996)) However, since the effect is not necessarily sufficient, a composition for rhinitis which is excellent in the inhibitory effect on nasal secretion containing emedastine as an active ingredient is desired. If such a composition for rhinitis can be obtained, the dose of emedastine can be reduced, so that an effect such as avoidance of side effects such as sleepiness can be obtained.
Therefore, the present invention provides a composition for rhinitis having a high improvement effect on nasal inflammation, and in particular, a composition for rhinitis having a high improvement effect on symptoms of excessive nasal discharge by being excellent in the suppression effect of nasal discharge among nasal inflammation. The purpose is to provide.
[0004]
[Means for Solving the Problems]
As a result of various studies in view of the above points, the present inventors have surprisingly found that when emedastine and glycyrrhizic acid are used in combination, an excellent inhibitory effect on nasal secretion is obtained.
[0005]
The present invention has been made based on the above findings, and the composition for rhinitis of the present invention comprises emedastin or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutical thereof as described in claim 1. It contains an acceptable salt.
The rhinitis composition according to claim 2 is the nasal inflammation composition according to claim 1, wherein glycyrrhizic acid or a pharmaceutically acceptable salt thereof is used per 1 part by weight of emedastine or a pharmaceutically acceptable salt thereof. 0.2 to 600 parts by weight of the salt is contained.
Moreover, the composition for rhinitis of the present invention is emedastine or a pharmaceutically acceptable salt thereof of 0.05 mg to 5 mg (emedastine equivalent amount) and glycyrrhizic acid or a pharmaceutically acceptable salt thereof as described in claim 3. Containing 0.1 mg to 300 mg (as glycyrrhizic acid equivalent).
The nasal secretion inhibitor of the present invention comprises emedastine or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutically acceptable salt thereof as described in claim 4. .
The rhinitis composition according to claim 5 is applied to the rhinitis condition caused by any of allergic rhinitis, acute rhinitis, sinusitis and cold in the rhinitis composition according to any one of claims 1 to 3. It is characterized by being.
The rhinitis composition according to claim 6 is characterized in that in the rhinitis composition according to claim 5, the nasal inflammation is excessive.
The rhinitis composition according to claim 7 is the rhinitis composition according to any one of claims 1, 2, 3, 5 and 6, wherein xanthines, parasympathetic nerve blocker, antipyretic analgesic component, It further comprises at least one selected from an inflammatory component, an antihistamine component, an antiallergic component, and vitamins.
The rhinitis composition according to claim 8 is the rhinitis composition according to claim 7, wherein the xanthines are caffeine, theophylline, theobromine, diprofylline, proxyphylline, pentoxifylline or a pharmaceutically acceptable salt thereof. It is at least one selected from a salt and sodium caffeine benzoate.
The rhinitis composition according to claim 9 is the rhinitis composition according to claim 7, wherein the parasympathetic nerve blocker is selected from datsura extract, belladonna total alkaloid, belladonna extract, iodopropamide, funnel extract. It is a seed.
[0006]
DETAILED DESCRIPTION OF THE INVENTION
The composition for rhinitis of the present invention is characterized by containing emedastine or a pharmaceutically acceptable salt thereof and glycyrrhizic acid or a pharmaceutically acceptable salt thereof. The utility value is high. Glycyrrhizic acid is sometimes added as an anti-inflammatory agent to a drug used for the treatment of nasal inflammation, and is known to have an inhibitory action on histamine release from mast cells (Journal of Japanese-Wan Pharmaceutical Society 6,294- 295, 1989). However, the combination of glycyrrhizic acid and emedastine has not been studied so far, and it is described in any prior literature that an excellent inhibitory effect on nasal secretion can be obtained by combining the two. Moreover, it cannot be predicted from any prior literature. JP-A-2000-95675, JP-A-2001-302518, and JP-A-2001-302545 describe a wide variety of compounds as ingredients of pharmaceutical compositions such as rhinitis compositions. Although emedastine and glycyrrhizic acid are also described therein, there is no disclosure of a composition for rhinitis combining both.
[0007]
Emedastine used as one component of the rhinitis composition of the present invention is a known compound (for example, described in U.S. Pat. No. 4,430,343), and pharmaceutically acceptable salts thereof include hydrochloride, nitrate, Examples thereof include sulfate, phosphate, oxalate, maleate, fumarate, hydrobromide, and enanthate, among which hydrochloride and fumarate are preferable.
[0008]
Examples of glycyrrhizic acid or a pharmaceutically acceptable salt thereof used as one component of the rhinitis composition of the present invention include glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, and diammonium glycyrrhizinate. In addition, crude drugs and herbal extracts containing glycyrrhizic acid can also be used. When using such herbal medicines or herbal extracts, it should be noted that in consideration of the content of glycyrrhizic acid, a predetermined amount of glycyrrhizic acid is used in the composition for rhinitis of the present invention. . Specific examples of herbal medicines and herbal extracts containing glycyrrhizic acid include licorice, licorice powder (powder), licorice extract, licorice crude extract, kakkonto extract, katsune-tou extract, saiko kei-to extract, sho-saiko-to extract, Examples include Shosei Ryuyu Extract, Mumon Fuyuyu Extract, Maoyu Extract, etc. These can be used alone or in combination of two or more.
[0009]
In the composition for rhinitis of the present invention, the preferred mixing ratio of emedastine or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutically acceptable salt thereof is 0 part by weight with respect to 1 part by weight of the former. .2 parts by weight to 600 parts by weight, but a more preferable blending ratio is 5 parts by weight to 200 parts by weight with respect to 1 part by weight of the former.
[0010]
The daily dose of emedastine or a pharmaceutically acceptable salt thereof according to the rhinitis composition of the present invention is 0 as an amount converted to emedastin from the viewpoint of avoiding the onset of side effects while sufficiently exerting the effect. 0.05 mg to 5 mg is preferable, 0.2 mg to 4.5 mg is more preferable, and 0.5 mg to 4 mg is more preferable. In addition, the daily dose of glycyrrhizic acid or a pharmaceutically acceptable salt thereof is preferably 0.1 mg to 300 mg, more preferably 0.3 mg to 250 mg, further preferably 1 mg to 200 mg, in terms of glycyrrhizic acid. . Therefore, the composition for rhinitis of the present invention has a daily dose of 0.05 mg to 5 mg (emedastine equivalent amount) or glycyrrhizic acid for emedastine or a pharmaceutically acceptable salt thereof by single or multiple administrations. Or about the pharmaceutically acceptable salt, it is preferable to formulate and use it so that it may become 0.1 mg-300 mg (glycyrrhizic acid conversion amount).
[0011]
The composition for rhinitis of the present invention is a preparation for oral administration such as tablets, coated tablets, granules, fine granules, powders, capsules, liquids, syrups, etc., dripping liquids, coating liquids, spraying liquids, etc. Intranasal preparations, nasal drops, nasal drops, cold medicines, allergic rhinitis, acute rhinitis, sinusitis, nasal allergy symptoms such as pollen and house dust, colds, etc. Used in the treatment of. Formulation of the rhinitis composition of the present invention can be carried out by adding an excipient, a binder, a lubricant as needed to emedastine or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutically acceptable salt thereof. Known additives such as agents, disintegrants, coating agents, flavoring agents, flavoring agents, coloring agents, preservatives, dispersants, solvents and the like are added according to various preparation forms, and are performed according to conventional methods.
[0012]
When the xanthines are combined with the rhinitis composition of the present invention, a composition improved with regard to drowsiness, which is a side effect of antihistamines, can be obtained. Examples of xanthines include caffeine, theophylline, theobromine, diprofylline, proxyphylline, pentoxifylline or a pharmaceutically acceptable salt thereof, sodium benzoate caffeine, and the like. Since these xanthines can exhibit an effect as long as they are usually 1 mg or more, the lower limit of the compounding amount is preferably 1 mg, and more preferably 5 mg. The upper limit is not particularly limited, but 500 mg is preferable and 300 mg is more preferable in consideration of economy and dosage.
Moreover, it is more preferable to further combine a parasympathetic nerve blocker with the rhinitis composition of the present invention. Examples of parasympathetic nerve blockers include duck extract, belladonna total alkaloids, belladonna extract, iodopropamide, and funnel extract. The lower limit of the compounding amount of the parasympathetic nerve blocker is preferably 0.1 mg and more preferably 0.2 mg in order to effectively exert the effect. Moreover, although an upper limit is dependent also on the kind of parasympathetic nerve blocker, 100 mg is preferable and 60 mg is more preferable. The lower limit of the blending ratio of the parasympathetic nerve blocker is preferably 0.05 parts by weight or more, more preferably 0.1 parts by weight or more with respect to 1 part by weight of emedastine. Moreover, the upper limit is preferably 200 parts by weight or less, more preferably 150 parts by weight or less with respect to 1 part by weight of emedastine.
In the composition for rhinitis of the present invention, various components (including pharmacologically active components and physiologically active components) can be further combined as necessary. The kind of such component is not particularly limited, and examples thereof include antipyretic analgesic component, anti-inflammatory component, antihistamine component, antiallergic component, vitamins and the like. Examples of suitable components in the present invention include the following components.
Examples of the antipyretic analgesic component include aspirin, aspirin aluminum, acetaminophen, etenzamide, sazapyrine, salicylamide, ibuprofen, ketoprofen, sodium salicylate, and lactylphenetidine.
Examples of the anti-inflammatory drug component include indomethacin, diclofenac, pranoprofen, piroxicam, epsilon-aminocaproic acid, berberine, lysozyme, allantoin, azulene, bromelain or a pharmaceutically acceptable salt thereof (for example, berberine chloride, berberine sulfate). , Diclofenac sodium, lysozyme chloride, etc.).
Antihistamine components include, for example, chlorpheniramine, clemastine, diphenhydramine, iproheptin, isothipentyl, dipheterol, diphenylpyralin, triprolidine, tripelenamine, tondilamine, promethazine, methodirazine, carbinoxamine, alimemazine, promethazine, methhydrozetin, phenethazine, And oxatomide, mequitazine, terfenadine, epinastine, astemizole, ebastine, cetirizine, levocabastine, olopatadine or a pharmaceutically acceptable salt thereof.
Examples of the antiallergic component include cromoglycic acid, tranilast, amlexanox, ibudilast, pemirolast, tazanolast or a pharmaceutically acceptable salt thereof.
Examples of vitamins include vitamin A [for example, retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene or a pharmaceutically acceptable salt thereof (for example, retinol acetate, retinol palmitate, etc.), vitamins, etc. Class B [for example, thiamine, thiamine disulfide, dicetiamine, octothiamine, chicotiamine, bisibhiamine, bisbenchamine, prosultiamine, benfotiamine, fursultiamine, riboflavin, flavin adenine dinucleotide, pyridoxine, pyridoxal, hydroxocobalamin , Cyanocobalamin, methylcobalamin, deoxyadenocobalamin, folic acid, tetrahydrofolic acid, dihydrofolic acid, nicotinic acid, nicotinamide, nicotinic alcohol, pantothe Acid, panthenol, biotin, choline, inositol or a pharmaceutically acceptable salt thereof (eg, thiamine hydrochloride, thiamine nitrate, dicetiamine hydrochloride, fursultiamine hydrochloride, riboflavin butyrate, sodium riboflavin phosphate, sodium flavin adenine dinucleotide, Pyridoxine hydrochloride, pyridoxal phosphate, pyridoxal calcium phosphate, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, calcium pantothenate, sodium pantothenate, etc.)], vitamin C [eg ascorbic acid, erythorbic acid, derivatives thereof or pharmaceuticals thereof Acceptable salts (eg, sodium ascorbate, sodium erythorbate, etc.), vitamin Ds (eg, ergocalciferol, cholecalciferol) Hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotaxosterol or a pharmaceutically acceptable salt thereof), vitamin E [eg, tocopherol, a derivative thereof, a ubiquinone derivative or a pharmaceutically acceptable salt thereof (tocopherol acetate) , Tocopherol nicotinate, tocopherol succinate, calcium tocopherol succinate, etc.)], other vitamins [eg hesperidin, carnitine, ferulic acid, γ-oryzanol, orotic acid, rutin, eriocitrin or pharmaceutically acceptable thereof Salt (such as carnitine chloride)].
[0013]
The present invention is also characterized as a method for enhancing the nasal secretion inhibiting effect of a composition for rhinitis by containing emedastine or a pharmaceutically acceptable salt thereof and glycyrrhizic acid or a pharmaceutically acceptable salt thereof. be able to. The preferred mixing ratio of emedastine or a pharmaceutically acceptable salt thereof and glycyrrhizic acid or a pharmaceutically acceptable salt thereof for enhancing the nasal secretion suppression effect of the rhinitis composition is 1 part by weight of the former. The latter is 0.2 part by weight to 600 parts by weight, and a more preferable blending ratio is 5 parts by weight to 200 parts by weight with respect to 1 part by weight of the former.
[0014]
【Example】
The present invention will be described in more detail with reference to the following test examples and examples, but the present invention is not limited thereto.
[0015]
Test Example 1 (Confirmation of nasal secretion suppression effect using guinea pig)
experimental method:
Ovalbumin 10 μg and
28 days after sensitization, an allergic reaction was induced by nasally irrigating 20 μl of physiological saline containing 2.5% ovalbumin into the right nasal cavity of the guinea pig. Ten minutes after the induction, nasal discharge was collected from the right nasal cavity for 10 minutes with a capillary (under anesthesia), and the amount of nasal discharge was measured. The test samples were as follows, and were orally administered 1 hour before induction (n = 3 to 7). The control group of Group A was a 0.1% sodium carboxymethyl cellulose solution. Group B to Group E were prepared by dissolving emedastine fumarate and / or dipotassium glycyrrhizinate in a 0.1% sodium carboxymethylcellulose solution.
[0016]
Group A: Control group (0.1% carboxymethylcellulose sodium solution)
Group B: Emedastine fumarate 0.05 mg / kg
Group C: Dipotassium glycyrrhizinate 25 mg / kg
Group D: Dipotassium glycyrrhizinate 200 mg / kg
Group E: Emedastine fumarate 0.05 mg / kg + dipotassium glycyrrhizinate 25 mg / kg
[0017]
Experimental result:
The results are shown in FIG. As is clear from FIG. 1, even in the doses of both of which the nasal secretion inhibitory effect was not obtained in the emedastine fumarate single administration group (Group B) and the dipotassium glycyrrhizinate single administration group (Group C and Group D), When both were administered in combination in Group E (a combination of Group B and Group C), an excellent nasal secretion suppression effect was unexpectedly obtained.
[0018]
[0019]
[0020]
[0021]
[0022]
[0023]
[0024]
[0025]
[0026]
[0027]
[0028]
[0029]
[0030]
[0031]
[0032]
[0033]
[0034]
[0035]
【The invention's effect】
According to the present invention, a composition for rhinitis having a high improving effect on rhinitis symptoms, in particular, a composition for rhinitis having a high improving effect on symptoms of excessive nasal discharge by being excellent in the suppression effect of nasal discharge among nasal inflammation symptoms. Things are provided.
[Brief description of the drawings]
FIG. 1 is a graph showing a nasal secretion suppression effect in Examples.
Claims (9)
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| JP2003121231A JP4344532B2 (en) | 2002-04-26 | 2003-04-25 | Composition for rhinitis |
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| JP2003121231A JP4344532B2 (en) | 2002-04-26 | 2003-04-25 | Composition for rhinitis |
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| CN121648113A (en) * | 2026-02-06 | 2026-03-13 | 华中科技大学同济医学院附属同济医院 | Application of Vitamin B7 in the Preparation of Drugs for Treating Allergic Rhinitis |
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| JP2001302518A (en) * | 2000-02-15 | 2001-10-31 | Rohto Pharmaceut Co Ltd | Method for improving action and agent for improving action |
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