JP2004002408A - Composition for rhinitis - Google Patents
Composition for rhinitis Download PDFInfo
- Publication number
- JP2004002408A JP2004002408A JP2003121231A JP2003121231A JP2004002408A JP 2004002408 A JP2004002408 A JP 2004002408A JP 2003121231 A JP2003121231 A JP 2003121231A JP 2003121231 A JP2003121231 A JP 2003121231A JP 2004002408 A JP2004002408 A JP 2004002408A
- Authority
- JP
- Japan
- Prior art keywords
- rhinitis
- pharmaceutically acceptable
- acceptable salt
- composition
- 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.)
- Granted
Links
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Abstract
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、本発明の鼻炎用組成物の鼻汁分泌抑制効果を高める方法は、請求項５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させ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]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a composition for rhinitis which is effective for treating rhinitis caused by allergic rhinitis, acute rhinitis, sinusitis, cold and the like. More specifically, the present invention relates to a composition for rhinitis that is excellent in suppressing nasal secretion among rhinitis symptoms.
[0002]
[Prior art]
Allergic rhinitis, acute rhinitis, sinusitis, nasal inflammation caused by colds (sneezing, nasal congestion (nasal congestion), nasal discharge (excessive nasal discharge), etc.) have been experienced by everyone once. Rhinitis patients want to escape their suffering as soon as possible. In particular, when the nasal discharge is excessive, the frequency of blowing the nose increases, and symptoms such as inflammation of the nasal mucosa and epistaxis are often observed. Therefore, early improvement or reduction is required. There are various types of drugs used for the treatment of rhinitis symptoms.In addition to drugs that comprehensively alleviate various symptoms, attention is paid to a specific symptom, and the enhanced effect on that symptom is Some drugs work. For example, an excellent nasal secretion inhibitory effect can be obtained by blending an anticholinergic drug (parasympathetic blocker) such as belladonna total alkaloid and isopropamide iodide.
[0003]
[Problems to be solved by the invention]
By the way, emedastine is known as an effective antihistamine for treating allergic rhinitis caused by histamine, and its inhibitory effect on nasal secretion has been confirmed (Medical & Pharmacy 35 (6) 1273). (1996)) However, since the effect is not always sufficient, there is a need for a composition for rhinitis which contains emedastine as an active ingredient and has an excellent effect of suppressing nasal secretion. If such a composition for rhinitis can be obtained, the dose of emedastine can be reduced, so that effects such as avoidance of side effects such as drowsiness can also be obtained.
Accordingly, the present invention provides a composition for rhinitis having a high effect of improving rhinitis, particularly a composition for rhinitis having an excellent effect of suppressing nasal secretion in rhinitis. The purpose is to provide.
[0004]
[Means for Solving the Problems]
The present inventors have conducted various studies in view of the above points, and as a result, have found that when emedastine and glycyrrhizic acid are used in combination, an excellent inhibitory effect on nasal secretion is unexpectedly obtained.
[0005]
The present invention has been made based on the above findings, and the composition for rhinitis of the present invention, as described in claim 1, comprises emedastine or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutically acceptable salt thereof. It is characterized by containing a salt acceptable.
The composition for rhinitis according to claim 2 is the composition for rhinitis according to claim 1, wherein glycyrrhizic acid or a pharmaceutically acceptable salt thereof is added to 1 part by weight of emedastine or a pharmaceutically acceptable salt thereof. 0.2 to 600 parts by weight of a salt.
Further, as described in claim 3, the composition for rhinitis of the present invention comprises emedastine or a pharmaceutically acceptable salt thereof in an amount of 0.05 mg to 5 mg (emedastine equivalent amount), and glycyrrhizic acid or a pharmaceutically acceptable salt thereof. 0.1 to 300 mg (equivalent to glycyrrhizic acid).
Further, the nasal secretion inhibitor of the present invention contains emedastine or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutically acceptable salt thereof as described in claim 4. .
Further, the method for enhancing the nasal secretion inhibitory effect of the composition for rhinitis of the present invention is as described in claim 5, wherein emedastine or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutically acceptable salt thereof. It is characterized by containing.
[0006]
BEST MODE FOR CARRYING OUT 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, and particularly, a nasal secretion inhibitor. High value of use. Glycyrrhizic acid is sometimes used as an anti-inflammatory agent in drugs used for the treatment of rhinitis symptoms, and is known to have an inhibitory action on histamine release from mast cells (Japanese Society of Pharmaceutical Sciences 6,294-). 295, 1989). However, a combination of glycyrrhizic acid and emedastine has not been studied so far, and it has been described in any prior literature that an excellent inhibitory effect on nasal secretion can be obtained by combining both. Nor is it predictable from any prior literature. In addition, JP-A-2000-95675, JP-A-2001-302518, and JP-A-2001-302545 describe various compounds as compounding components of a pharmaceutical composition such as a composition for rhinitis. Although emedastine and glycyrrhizic acid are also described therein, there is no disclosure of a composition for rhinitis combining the two.
[0007]
Emedastine used as one component of the composition for rhinitis of the present invention is a known compound (for example, described in US Pat. No. 4,430,343), and pharmaceutically acceptable salts thereof include hydrochloride, nitrate, Sulfate, phosphate, oxalate, maleate, fumarate, hydrobromide, enanthate and the like can be mentioned, and among them, hydrochloride and fumarate are preferable.
[0008]
Examples of glycyrrhizic acid or a pharmaceutically acceptable salt thereof used as one component of the composition for rhinitis of the present invention include glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, diammonium glycyrrhizinate and the like. Crude drugs and crude drug extracts containing glycyrrhizic acid can also be used. When using such crude drugs and crude drug extracts, it should be noted that the prescribed amount of glycyrrhizic acid is used in the composition for rhinitis of the present invention in consideration of the content of glycyrrhizic acid. . Specific examples of crude drugs and crude drug extracts containing glycyrrhizic acid include licorice, licorice powder (powder), licorice extract, licorice crude extract, kakkonto extract, keishito extract, saikokeishito extract, shosaikoto extract, Sho-seiryu-to extract, Bakumondo-to extract, Mao-to extract and the like can be mentioned. These can be used alone or in combination of two or more.
[0009]
In the composition for rhinitis of the present invention, a suitable mixing ratio of emedastine or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutically acceptable salt thereof is 0 parts by weight to 1 part by weight of the former. The amount is from 0.2 to 600 parts by weight, and a more preferable blending ratio is from 5 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 composition for rhinitis of the present invention is 0% in terms of emedastine in terms of emedastine from the viewpoint of avoiding the occurrence of side effects while exerting the effect sufficiently. 0.05 mg-5 mg are preferred, 0.2 mg-4.5 mg are more preferred, and 0.5 mg-4 mg are still more preferred. 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, and even more preferably 1 mg to 200 mg in terms of glycyrrhizic acid. . Therefore, the composition for rhinitis of the present invention can be administered in a single or multiple doses at a daily dose of 0.05 mg to 5 mg (emedastine-equivalent amount) for emedastin or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid. Alternatively, a pharmaceutically acceptable salt thereof is preferably formulated and used in an amount of 0.1 mg to 300 mg (equivalent to glycyrrhizic acid).
[0011]
The composition for rhinitis of the present invention includes tablets, coated tablets, granules, fine granules, powders, capsules, solutions, syrups, and other oral administration preparations, dropping solutions, coating solutions, spraying solutions and the like. For nasal administration, nasal instillation, nasal drops, cold medicine, etc., allergic rhinitis, acute rhinitis, sinusitis, nasal allergic symptoms due to pollen and house dust, cold, etc. Used for treatment. Formulation of the composition for rhinitis of the present invention comprises emedastine or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutically acceptable salt thereof as required with an excipient, a binder, and a lubricant. Known additives such as an agent, a disintegrant, a coating agent, a flavoring agent, a flavoring agent, a coloring agent, a preservative, a dispersant, and a solvent are added according to various preparation forms, and the reaction is carried out according to a conventional method.
[0012]
Combining the composition for rhinitis of the present invention with a xanthine can provide a composition improved with respect to drowsiness which is a side effect of an antihistamine, and therefore, it is particularly preferable to use the composition in combination. Examples of xanthines include caffeine, theophylline, theobromine, diprofylline, proxyphylline, pentoxifylline or pharmaceutically acceptable salts thereof, and sodium benzoate caffeine. These xanthines can exert their effects if they are usually 1 mg or more. Therefore, the lower limit of the amount is preferably 1 mg, more preferably 5 mg. The upper limit is not particularly limited, but is preferably 500 mg, more preferably 300 mg, in consideration of economy and dosage.
It is more preferable that the composition for rhinitis of the present invention is further combined with a parasympathetic blocker. Examples of parasympathetic blockers include datsura extract, belladonna total alkaloid, belladonna extract, isopropamide iodide, and funnel extract. The lower limit of the amount of the parasympathetic blocker is preferably 0.1 mg, more preferably 0.2 mg, in order to exert the effect effectively. The upper limit depends on the type of the parasympathetic blocker, but is preferably 100 mg, more preferably 60 mg. The lower limit of the blending ratio of the parasympathetic blocker is preferably at least 0.05 part by weight, more preferably at least 0.1 part by weight, per 1 part by weight of emedastine. The upper limit is preferably 200 parts by weight or less, more preferably 150 parts by weight or less, per 1 part by weight of emedastine.
Various components (including a pharmacologically active component and a physiologically active component) can be further combined with the rhinitis composition of the present invention, if necessary. The types of such components are not particularly limited, and examples thereof include antipyretic analgesic components, anti-inflammatory drug components, antihistamine drug components, anti-allergic components, 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, etenzamid, 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 (eg, berberine chloride, berberine sulfate) , Diclofenac sodium, lysozyme chloride).
Examples of the antihistamine component include, for example, chlorpheniramine, clemastine, diphenhydramine, iproheptin, isotipendil, dipheterol, diphenylpyraline, triprolidine, tripelenamine, tondylamine, promethazine, methdilazine, carbinoxamine, alimemazine, promethazine, mebuhydrozine, phenetine, phenetine, phenetine 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, and pharmaceutically acceptable salts thereof.
Examples of the vitamins include vitamins A (eg, retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene, and pharmaceutically acceptable salts thereof (eg, retinol acetate, retinol palmitate, and the like)), and vitamins. B class [for example, thiamine, thiamine disulfide, dicetiamine, octiamine, sicotiamine, bisibutiamine, bisbenthamine, prosultiamine, benfotiamine, fursultiamine, riboflavin, flavin adenine dinucleotide, pyridoxine, pyridoxal, hydroxocobalamin , Cyanocobalamin, methylcobalamin, deoxyadenocobalamin, folic acid, tetrahydrofolate, dihydrofolate, nicotinic acid, nicotinamide, nicotinic alcohol, pantothe Acid, panthenol, biotin, choline, inositol or a pharmaceutically acceptable salt thereof (for example, thiamine hydrochloride, thiamine nitrate, dicetiamine hydrochloride, fursultiamine hydrochloride, riboflavin butyrate, sodium riboflavin phosphate, sodium flavin adenine dinucleotide, Pyridoxine hydrochloride, pyridoxal phosphate, calcium pyridoxal phosphate, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, calcium pantothenate, sodium pantothenate, etc.), vitamin Cs [for example, ascorbic acid, erythorbic acid, derivatives thereof or pharmaceuticals thereof] (Eg, sodium ascorbate, sodium erythorbate, etc.) and vitamin Ds (eg, ergocalciferol, cholecalciferol) Hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotaxerol or a pharmaceutically acceptable salt thereof), vitamin Es [for example, tocopherol, a derivative thereof, a ubiquinone derivative or a pharmaceutically acceptable salt thereof (tocopherol acetate) , Tocopherol nicotinate, tocopherol succinate, calcium tocopherol succinate, etc.), and other vitamins [for example, hesperidin, carnitine, ferulic acid, γ-oryzanol, orotic acid, rutin, eriocitrin or a pharmaceutically acceptable salt thereof. (Eg, carnitine chloride).
[0013]
The present invention is also characterized as a method for increasing the nasal secretion inhibitory effect of a composition for rhinitis by including emedastine or a pharmaceutically acceptable salt thereof, and glycyrrhizic acid or a pharmaceutically acceptable salt thereof. be able to. The preferred compounding ratio of emedastine or a pharmaceutically acceptable salt thereof and glycyrrhizic acid or a pharmaceutically acceptable salt thereof for enhancing the nasal secretion suppressing effect of the composition for rhinitis is 1 part by weight of the former. The latter is 0.2 parts by weight to 600 parts by weight, but a more preferable compounding ratio is 1 part by weight of the former to 5 parts by weight to 200 parts by weight.
[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 (Test for confirming nasal secretion using guinea pig)
experimental method:
Hartley male guinea pigs (body weight 250 g to 350 g) were intraperitoneally administered with 10 μg of ovalbumin and 20 mg of aluminum hydroxide gel (
Twenty-eight days after sensitization, an allergic reaction was induced again by instilling 20 μl of a physiological saline solution containing 2.5% ovalbumin into the right nasal cavity of the guinea pig. Ten minutes after the induction, nasal secretions were collected from the right nasal cavity for 10 minutes using a capillary (under anesthesia), and the amount of nasal secretions was measured. The test samples were as follows, and were orally administered 1 hour before induction (n = 3 to 7). The control group A was a 0.1% sodium carboxymethylcellulose solution. Groups B to 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% sodium carboxymethylcellulose 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 evident from FIG. 1, even when the dose of both the emedastine fumarate-only administration group (group B) and the dipotassium glycyrrhizinate administration group (group C and D) did not achieve the nasal secretion suppression effect, When both were administered in combination in Group E (combination of Group B and Group C), a surprisingly excellent nasal secretion inhibitory effect was 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 ameliorating effect on rhinitis, particularly a composition for rhinitis having a high ameliorating effect on symptoms of nasal discharge due to being excellent in suppressing nasal secretion even in rhinitis. Things are provided.
[Brief description of the drawings]
FIG. 1 is a graph showing the effect of suppressing nasal secretion in Examples.
Claims (5)
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| JP2003121231A JP4344532B2 (en) | 2002-04-26 | 2003-04-25 | Composition for rhinitis |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2021042260A (en) * | 2020-12-21 | 2021-03-18 | 小林製薬株式会社 | Fimbria motility activator of upper respiratory tract mucosa |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000095675A (en) * | 1998-09-22 | 2000-04-04 | Rohto Pharmaceut Co Ltd | Oral solid pharmaceutical composition for treating rhinitis of intraoral soluble type or mastication type |
| JP2001302545A (en) * | 2000-02-15 | 2001-10-31 | Rohto Pharmaceut Co Ltd | Refreshing agent |
| 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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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000095675A (en) * | 1998-09-22 | 2000-04-04 | Rohto Pharmaceut Co Ltd | Oral solid pharmaceutical composition for treating rhinitis of intraoral soluble type or mastication type |
| JP2001302545A (en) * | 2000-02-15 | 2001-10-31 | Rohto Pharmaceut Co Ltd | Refreshing agent |
| JP2001302518A (en) * | 2000-02-15 | 2001-10-31 | Rohto Pharmaceut Co Ltd | Method for improving action and agent for improving action |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2021042260A (en) * | 2020-12-21 | 2021-03-18 | 小林製薬株式会社 | Fimbria motility activator of upper respiratory tract mucosa |
| JP7719601B2 (en) | 2020-12-21 | 2025-08-06 | 小林製薬株式会社 | ciliary movement activator for the upper respiratory tract mucosa |
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