JP7376870B2 - 抗不安医薬組成物およびそれを含む加工食品 - Google Patents
抗不安医薬組成物およびそれを含む加工食品 Download PDFInfo
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- JP7376870B2 JP7376870B2 JP2019127709A JP2019127709A JP7376870B2 JP 7376870 B2 JP7376870 B2 JP 7376870B2 JP 2019127709 A JP2019127709 A JP 2019127709A JP 2019127709 A JP2019127709 A JP 2019127709A JP 7376870 B2 JP7376870 B2 JP 7376870B2
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- VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 1
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- TVHVQJFBWRLYOD-UHFFFAOYSA-N rosmarinic acid Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=Cc2ccc(O)c(O)c2)C=O TVHVQJFBWRLYOD-UHFFFAOYSA-N 0.000 description 1
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Description
GABAA受容体はすべて神経細胞に発現しており、GABAによって活性化するGABAB(代謝型)、GABAC(イオンチャネル型)受容体などがある。よって、神経細胞への直接的なGABAの投与ではGABAA受容体単独の活性をみることは非常に難しい。そこで、GABAA受容体を評価用の細胞に発現させ、評価対象化合物をその細胞に灌流する。評価対象化合物によって、GABAA受容体が活性すれば、GABAA受容体チャネルが開くため、細胞の内外に電流が流れる。この電流を測定することで、GABAA受容体活性能を評価した。
以下の操作は可能な限り、無菌的に行った。メスのアフリカツメガエルを氷水の中で約1時間放置し、強制的に冬眠させた後、必要分の卵母細胞を約5mmの塊となるように取り出し、コラゲナーゼ溶液に浸した。卵母細胞をコラゲナーゼ溶液に入れ、温室20~25℃で1~1.5時間浸した後にBarth溶液で洗い流し、顕微鏡下で、Barth溶液の入ったシャーレ中で卵母細胞の表面を覆っている卵胞膜をピンセットで取り除いた。卵胞膜を取り除いた卵母細胞を20℃のサーモプレート上で保存した。
卵母細胞ひとつひとつに合成した牛由来のα1、β1のmRNAを50nL(α1は0.08μg/oocyte,β1は0.09μg/oocyte)ずつインジェクションした。その後、インジェクションした卵母細胞は、Barth溶液が入った新しいシャーレに入れ、20℃でインキュベートし、GABAA受容体を発現させた(図2)。
二電極膜電位固定法で膜電位を-70mVに固定し、細胞膜を通過するイオンを電流測定電極で測定した。アンプはオーサイトクランプ装置(TEV-200A VOLTAGE CLAMP)を用い、電流値をPower Lab/200でAD変換し、ソフトChartで取り込んだ。図3はリガンドであるGABAを灌流させた時の、GABAA受容体の標準的な測定状態を示したものである。図3を参照して、横軸が時間(sec)であり、縦軸が電流(μA)を表している。GABAは、計測開始後5秒目から25秒目まで灌流した。図3では、この間、細胞膜を通過する電流が計測されているのがわかる。
図8にはピログルタミン酸のGABAA受容体活性化能の試験結果を示す。図8(a)は、GABA単体の結果であり、図8(b)は、GABA単体に対するピログルタミン酸の比率を示している。横軸はいずれも濃度(μM)を示している。なお、この実験では、ピログルタミン酸を灌流する場合に、GABAは共存させていない。つまり、ピログルタミン酸は、単独でGABAと同じ効果を有している。
次に実際の抗不安効果をマウスを用いて確認した。
9週齢のC57BL/6NCrlCrlj雄性マウス(日本チャールスリバー社)を購入後、動物飼育室で飼育順応させて高架式十字迷路試験を行った。マウスは4匹ずつ、ペーパーチップ床敷を敷いたポリカーボネート製ケージ(30×20×15cm)に入れ、飼料と水道水を自由に摂取させて飼育した。飼料は、動物用固形飼料MF(オリエンタル酵母工業株式会社)を用いた。動物実験室内は、12時間毎の明暗(明期:20時より8時、暗期:8時より20時)、室温23℃及び湿度60%に調節した。
実験に使用した高架式十字迷路は床上40cmにあり、直行する4本のアーム(6×30cm)とそれらが交差する部分のプラットホーム(9×9cm)から構成されている。2本のオープンアーム(高さ2cmのふち付き)には側壁がないが、2本のクローズアームは灰色不透明の側壁(高さ10cm)付きでその他の床も灰色不透明になっている。
水は自由摂取させたが、コントロール、抗不安化合物、比較例のサンプル物質の投与前から高架式十字迷路試験終了まで、3~5時間マウスは絶食とした。各サンプル物質をマウスの体重に応じた量(79mg/kg BW)だけ腹腔内投与した。なお、ほうじ茶水出し2倍希釈およびほうじ茶煮出し2倍希釈については、5ml/kg BWの量を腹腔内投与した。投与してから1時間後にマウスを高架式十字迷路のプラットホーム部分に置き、頭をオープン方向に向けて試験を開始し、10分間、オープンとクローズのそれぞれのアームへの侵入回数と滞在時間を観察し、記録した。プラットホームから四肢全部がアーム部分に出た場合を、アームへの移行として記録した。
Claims (6)
- 2-エチル-3,5-ジメチルピラジンと2-エチル-3,6-ジメチルピラジンを含み、カテキン類を含まない抗不安組成物。
- さらに2,3,5-トリメチルピラジン、2,3-ジエチル-5-メチルピラジン、3,7-ジメチル-2,6-オクタジエン-1-オール、4-ヒドロキシ-2,5-ジメチル-3(2H)-フラノンから選ばれる少なくとも1種の抗不安化合物を含む請求項1に記載された抗不安組成物。
- ピログルタミン酸をさらに含むことを特徴とする請求項1または2の請求項に記載された抗不安組成物。
- GABAをさらに含むことを特徴とする請求項1乃至3の何れか一の請求項に記載された抗不安組成物。
- 請求項1乃至4の何れか一の請求項に記載された抗不安組成物を含む医薬組成物。
- 請求項1乃至4の何れか一の請求項に記載された抗不安組成物を含む加工食品。
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Citations (1)
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JP2014019649A (ja) | 2012-07-12 | 2014-02-03 | Kinki Univ | Gaba様組成物 |
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JP2014019649A (ja) | 2012-07-12 | 2014-02-03 | Kinki Univ | Gaba様組成物 |
Non-Patent Citations (5)
Title |
---|
Biol. Pharm. Bull.,2001年,Vol.24, No.9,pp.1068-1071 |
Food Chemistry,2008年,Vol.108,pp.840-846 |
Fundam. Clin. Pharmacol.,1988年,Vol.2,pp.77-82 |
J Sci Food Agric,2018年,Vol.99,pp.1780-1786 |
日本食品科学工学会誌,2016年,Vol.63, No.9,pp.394-404 |
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