JP2015172029A - 末梢神経障害誘発感覚異常を改善する外用剤 - Google Patents
末梢神経障害誘発感覚異常を改善する外用剤 Download PDFInfo
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Abstract
Description
このうち、末梢神経障害で誘発される感覚異常は、薬物を使用してしばらく経過した後に手・足先の痺れ感、ほてり、感覚が鈍くなる等の症状を呈する。症状は、次第に上方の腕や脚に広がる。感覚異常の多くは両足・両手で起こるが、片足・片手だけのこともある。
以下に本発明を詳細に説明する。
生薬として芍薬(シャクヤク)および/または牡丹皮(ボタンピ)、それらのエキスが挙げられるが、芍薬または芍薬エキスが好ましい。
なお、感覚異常の指標としてvon Freyフィラメントを用いた感覚の過過敏症(アロディニア)の評価を用い、また、一部の実験では、電気生理学的に、末梢神経の神経活動評価を用いた。
<芍薬エキス1>
芍薬50g と純水400mLを煎じ器加え,とろ火で50分間煎じる。煎じ液を濾紙で濾過し、濾液を凍結乾燥する。得られた粉末状のエキス(13.4g、収率:26.8%)はサンプル瓶に入れ、冷蔵保管する。
<芍薬エキス2>
芍薬1kgと99.5%エタノール2Lをガラス容器(ナス型フラスコの上部に摺合ジムロート冷器を装着したガラス容器)に投入し、90分間加熱還流する。冷却後、上清を分取する。残渣に99.5%エタノール2Lを加え、90分間加熱還流する。冷却後、上清を分取する。この抽出操作を再度繰り返す。分取した上清を合わせ、減圧下に濃縮する。残渣を凍結乾燥し、得られた粉末状のエキス(112.4g)はサンプル瓶に入れ、冷蔵保管する。
マウス(ICR,5〜7週齢, 雄性)に、パクリタキセル(PTX、5mg/kg)単回腹腔内注射し、翌日よりA1アデノシン受容体作動薬(CPA:N6-Cyclopentyladenosine)およびその溶媒(VH2:エタノール)を20μLの容量で1日2回両足(足首から指先まで全体的に)に塗布した。アロディニアは、von Freyフィラメント(0.69 mN)を用いてスコア化(0 : 反応なし又は後肢を横にずらす行動、1 : 後肢の引き上げ行動 (lifting)、2 : 後肢の振り行動 (flinching) 又は刺激部位への舐め行動 (licking))して評価した。
マウス(ICR,5〜7週齢, 雄性)に、パクリタキセル(PTX、5mg/kg)単回腹腔内注射し、翌日よりペオニフロリンまたはその溶媒(VH2:エタノール)を20μLの容量で1日2回両足(足首から指先まで全体的に)に塗布した。アロディニアは、von Freyフィラメント(0.69 mN)を用いてスコア化(0 : 反応なし又は後肢を横にずらす行動、1 : 後肢の引き上げ行動 (lifting)、2 : 後肢の振り行動 (flinching) 又は刺激部位への舐め行動 (licking))して評価した。
マウス(ICR,5〜7週齢, 雄性)に、パクリタキセル(PTX、5mg/kg)単回腹腔内注射し、翌日より芍薬エキス1またはその溶媒(VH2:エタノール)を20μLの容量で1日2回両足(足首から指先まで全体的に)に塗布した。アロディニアは、von Freyフィラメント(0.69 mN)を用いてスコア化(0 : 反応なし又は後肢を横にずらす行動、1 : 後肢の引き上げ行動 (lifting)、2 : 後肢の振り行動 (flinching) 又は刺激部位への舐め行動 (licking))して評価した。
マウス(ICR,5〜7週齢, 雄性)に、パクリタキセル(PTX、5mg/kg)単回腹腔内注射し、翌日より芍薬エキス2またはその溶媒(VH2:エタノール)を20μLの容量で1日2回両足(足首から指先まで全体的に)に塗布した。アロディニアは、von Freyフィラメント(0.69 mN)を用いてスコア化(0 : 反応なし又は後肢を横にずらす行動、1 : 後肢の引き上げ行動 (lifting)、2 : 後肢の振り行動 (flinching) 又は刺激部位への舐め行動 (licking))して評価した。図の値は、平均±標準誤差示した(n = 6)。* p<0.05 vs. PTX+VH2 (Holm-Sidak テスト)。
マウス(ICR,5〜7週齢, 雄性)に、パクリタキセル(PTX、5mg/kg)単回腹腔内注射し、翌日よりペオニフロリン(PNF、1%)またはその溶媒(VH2:エタノール)を20μLの容量で1日2回両足(足首から指先まで全体的に)に塗布した。PTX投与後14日目に伏在神経における神経活動を電気生理学的に評価した。自発的発火及びvon Freyフィラメント(0.69 mN)による刺激による発火を記録した。
Claims (5)
- 末梢神経障害で誘発される感覚異常の改善作用を示すこと特徴とするアデノシンA1受容体アゴニストを含有する外用剤。
- アデノシンA1受容体アゴニストが生薬または生薬成分である請求項1に記載の外用剤。
- 生薬が芍薬および/または牡丹皮である請求項2に記載の外用剤。
- 生薬成分がペオニフロリンまたはペオニフロリンの関連化合物である請求項2に記載の外用剤。
- 末梢神経障害で誘発される感覚異常が抗がん剤によるものである請求項1〜4に記載の外用剤。
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KR20190129434A (ko) * | 2018-05-11 | 2019-11-20 | 대전대학교 산학협력단 | 당뇨병성 말초신경병증 치료를 위한 한약재 조성물 |
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JPH07138279A (ja) * | 1993-11-11 | 1995-05-30 | Hoyu Co Ltd | ペオニフロリンの安定化法 |
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EUROPEAN JOURNAL OF PAIN, vol. Vol.13, JPN6018007044, 2009, pages 22 - 27 * |
PHARMACOLOGY, BIOCHEMISTRY AND BEHAVIOR, vol. Vol.94, JPN6018007045, 2009, pages 88 - 97 * |
日本緩和医療薬学雑誌, vol. Vol.4, JPN6018026666, 2011, pages 1 - 13 * |
Cited By (2)
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KR20190129434A (ko) * | 2018-05-11 | 2019-11-20 | 대전대학교 산학협력단 | 당뇨병성 말초신경병증 치료를 위한 한약재 조성물 |
KR102066209B1 (ko) | 2018-05-11 | 2020-01-14 | 대전대학교 산학협력단 | 당뇨병성 말초신경병증 치료를 위한 한약재 조성물 |
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