JP2022504207A - アスリートのオーバートレーニングの予防又は処置に用いる化合物 - Google Patents
アスリートのオーバートレーニングの予防又は処置に用いる化合物 Download PDFInfo
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- JP2022504207A JP2022504207A JP2021518512A JP2021518512A JP2022504207A JP 2022504207 A JP2022504207 A JP 2022504207A JP 2021518512 A JP2021518512 A JP 2021518512A JP 2021518512 A JP2021518512 A JP 2021518512A JP 2022504207 A JP2022504207 A JP 2022504207A
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Abstract
Description
・生化学的-コルチゾール増加及び遊離テストステロン濃度低下;
・免疫学的-感染に対する感受性増加;
・生理学的-パフォーマンス低下、筋肉の質量、痛み及び硬直、体重減少、心拍数変化;
・心理学的-不安感、落ち着きのなさ
に分類しうる。
-自律神経系:副交感神経優位型はオーバートレーニング症候群の多くの症状をおこす;
-中枢性疲労:脳でトリプトファン摂取が高まると、中枢性セロトニン及び気分障害が高まる;
-グルタミン:グルタミンが減少すると、免疫機能障害と感染症に対する感受性が亢進する;
-視床下部:視床下部とホルモン軸の調節不全により、オーバートレーニング症候群の多くの症状が誘発される;
-酸化ストレス:過剰な酸化ストレスは、筋肉を損傷し、かつ疲労につながる;
を含む様々な仮説がある。
これらの仮説はいずれも妥当のようであるが、個々のOTSのすべての症状を説明するものではない。
(i)(R)-3-ヒドロキシブチレート;
(ii)(R)-3-ヒドロキシブチレートエステル
(iii)(R)-3-ヒドロキシブチレート部分のオリゴマー化により得られるオリゴマー;
から選択される化合物、又は製薬上許容されるその塩若しくは溶媒和物を提供する。
(R)-3-ヒドロキシブチレートはケトン体であり、K N Frayn「代謝調節:ヒトの展望」による特定される。
- R1は、C1-C6アルキル基であり、アルキル基には5個までの-OR2置換基があり、
- ここで、R2は、水素、若しくはC1-C6アルキルを表すか、若しくは-OR2は(R)-3-ヒドロキシブチレート部分を表し;又は
- R1は、アルコールHOR1に由来する部分であり、ここで、前記アルコールは糖である)
で表される化合物である。
好ましくは、R2は、Hである。
-希釈剤、例えばラクトース、デキストロース、サッカロース、セルロース、トウモロコシデンプン又はジャガイモデンプン;
- シリカ、タルク、ステアリン酸、ステアリン酸マグネシウム又はステアリン酸カルシウム及び/又はポリエチレングリコール等の潤滑剤;
- デンプン、アラビアゴム、ゼラチン、メチルセルロース、カルボキシメチルセルロース、又はポリビニルピロリドン等の結合剤;
- デンプン、アルギン酸、アルギン酸塩又はデンプングリコール酸ナトリウム等の崩壊剤;
-発泡剤;
-染料;
-フレーバー;
-湿潤剤、例えば、レシチン、ポリソルベート、ラウリル硫酸塩;及び/又は
-担体;
の1又はそれ以上をさらに含みうる。
被験体
健常男性被験体(n=24)を募集した。男性は年齢が18~30歳で、身体は健常、身体活動に定期的に関与し、その健康状態は医学的スクリーニングで確認された。
表1に、試験設計(A)及び訓練(B)の概要を示す。
被験体には、試験前に少なくとも48時間は激しい身体活動を控えるよう指示した。試験前と試験後の間の初期筋肉グリコーゲン濃度の差を避けるため、被験体は詳細な食事指導を受けた。さらに、各実験セッション前の夕方、被験体は標準炭水化物富化食(~1500kcal、そのうち70E%炭水化物、20E%タンパク質、10E%脂肪)を摂取した。翌朝、実験室に到着すると、彼らは約750kcal(70%の炭水化物、20%のタンパク質、10%の脂肪)を含む標準炭水化物富化朝食を摂取した。朝食後、被験体は2時間休息した。
前試験後、参加者は3週間の監督下で完全制御運動トレーニングプログラムに登録された。トレーニングプログラムの各週は、朝のインターバルトレーニングと夕方の持久力トレーニングの6つのトレーニング日数で構成され、週に12回のトレーニングセッションを実施した(表2)。
3週間のトレーニング期間の最後のトレーニングセッションの1日後、被験体は前試験と同一の後試験に参加した。
試験後、被験体に1週間のトレーニング中止を指示した。この回復期間の3日後及び7日後に、試験前及び試験後に実施した多くの測定を繰り返した。
各トレーニングセッションの直後及び睡眠の30分前、被験体には、炭水化物1g/kg体重と乳清タンパク質分離株0.35g/kg体重を含む回復飲料(6D Recovery Shake,Medix,Oudenaarde,Belgium)が与えられた。さらに、被験体には、炭水化物/タンパク質回復飲料とともに摂取される別飲料として、ケトンエステル飲料又は等カロリープラセボ(PL;長鎖トリグリセリド)0.35g/kg体重が投与された。ケトンエステルサプリメント(G;登録商標)は純粋なD-β-ヒドロキシブチレート-R 1,3ブタンジオールモノエステルを供給した。当該栄養補助食品は、以前に広範に試験されている(例えば、非特許文献2参照)。
血液試料
Venoject(登録商標)系を用いて腕静脈からBD Vacutainer(登録商標)チューブに血液試料(2×5ml)を採取した。試料は、試験前及び試験後のTT30分の直前及び2時間後、及びトレーニング過負荷期間中の1、4、8、11、15及び18日目の絶食状態で採取した。血漿を遠心分離で直ちに分離した。血清及び血漿試料を用いて、高感度ELISAキットを用いて化学マーカーを評価した。
全夜尿(10pm~8am)を、10ml塩酸で調製したフラスコに各実験セッションの前夜に採取した。尿量アウトプットを記録し、よく混合した試料のアリコートを、市販の酵素免疫測定法(ELISA)(BA E-5400、LDN、ノルドホーン、ドイツ)を用いてノルアドレナリン濃度を単回測定してアッセイするまで-80℃で保存した。
結果を添付の図に示した。
図1は、運動前、運動直後、及びケトンエステル又はプラセボ飲料の摂取後30分後に採取した血液試料中のケトン(β-ヒドロキシブチレート)レベルを示す。6、13及び20日目に試料を採取した。血中β-ヒドロキシブチレート濃度は、ケトンエステル飲料の摂取後に有意に高いことが示された。ケトンエステルの摂取は、運動30分後に血中(R)-3-ヒドロキシブチレートを常に約2~3mmol/Lに上昇させる。
Claims (20)
- 被験体のオーバートレーニングの予防又は処置に用いる化合物であって、以下の:
(i)(R)-3-ヒドロキシブチレート;
(ii)(R)-3-ヒドロキシブチレートエステル
(iii)(R)-3-ヒドロキシブチレート部分のオリゴマー化により得られるオリゴマー;
から選択される化合物、又は製薬上許容されるその塩若しくは溶媒和物。 - R1は、1、2又は3-OR2置換基で置換されたC1-C6アルキルである、請求項2に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- R2は、Hである、請求項2又は3に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- R1は、式-CH2-CH(OH)-CH2(OH)又は-CH2-CH2-CH(OH)-CH3である、請求項2~4のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- R1は、アルコールHOR1由来の部分であり、前記アルコールは、アルトロース、アラビノース、デキストロース、エリトロース、フルクトース、ガラクトース、グルコース、グロース、アイドース、ラクトース、リキソース、マンノース、リボース、リブロース、スクロース、タロース、トレオース、及びキシロースから選択される糖である、請求項2に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- 前記化合物は、オーバートレーニング症候群の予防又は処置に用いられる、請求項1~3のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- 被験体のオーバートレーニングに関連する1又はそれ以上の生理学的、心理学的、免疫学的又は生化学的変化を予防又は処置する、請求項1~9のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- 少なくとも1日、好ましくは少なくとも2、3、4、5又は6日、より好ましくは少なくとも1週間、好ましくは少なくとも2週間、より好ましくは少なくとも3週間、オーバートレーニングの症状の発症の遅延に用いる、請求項1~10のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- オーバートレーニングに伴うパワー損失の低減に用いる、請求項1~11のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- さらに、骨塩含有量を増加又は維持するのに用いる、請求項1~12のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- 前記被験体は、アスリート、好ましくは持久力が必要なアスリートである、請求項1~13のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- 前記被験体は、オーバートレーニング、好ましくはオーバートレーニング症候群に罹患する、請求項1~14のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物。
- 請求項1~15のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物、及び場合によっては、1又はそれ以上の製薬上許容される賦形剤を含む、オーバートレーニングの防止又は処置に用いる医薬組成物。
- 請求項1~15のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物、並びに、場合によっては、さらに、水及び、香味剤、タンパク質、炭水化物、糖質、脂肪、繊維、ビタミンとミネラルの1又はそれ以上、を含む、オーバートレーニングの防止又は処置に用いる栄養組成物。
- さらに、中鎖トリグリセリドを含む、請求項17に記載の栄養組成物であって、好ましくは、前記中鎖トリグリセリドは、式CH2Ra-CH2Rb-CH2Rc(式中、Ra、Rb及びRcは、炭素原子が5~12個の脂肪酸である)を有する、栄養組成物。
- 被験体のオーバートレーニングの防止又は処置に用いる薬剤の製造に用いる、請求項1~15のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物又は請求項16~18のいずれか一項に記載の組成物の使用。
- 請求項1~15のいずれか一項に記載の化合物、又は製薬上許容されるその塩若しくは溶媒和物又は請求項16~18のいずれか一項に記載の組成物を、それが必要な被験体に投与することを含む、被験体のオーバートレーニングを防止又は処置する方法。
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PCT/GB2019/052797 WO2020070506A1 (en) | 2018-10-04 | 2019-10-03 | Compounds for use in preventing or treating athlete overtraining |
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US20150283163A1 (en) * | 2014-04-04 | 2015-10-08 | Organic Medical Ventures, L.L.C. | Muscle treatment composition and method making same |
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- 2019-10-03 AU AU2019351925A patent/AU2019351925A1/en active Pending
- 2019-10-03 EP EP19787377.1A patent/EP3860584A1/en active Pending
- 2019-10-03 WO PCT/GB2019/052797 patent/WO2020070506A1/en unknown
Also Published As
Publication number | Publication date |
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EP3860584A1 (en) | 2021-08-11 |
GB2592803B (en) | 2022-11-09 |
GB2592803A (en) | 2021-09-08 |
US20210338612A1 (en) | 2021-11-04 |
KR20210079304A (ko) | 2021-06-29 |
GB202105967D0 (en) | 2021-06-09 |
GB2577723A (en) | 2020-04-08 |
CN112996498A (zh) | 2021-06-18 |
CA3114889A1 (en) | 2020-04-09 |
AU2019351925A1 (en) | 2021-04-15 |
WO2020070506A1 (en) | 2020-04-09 |
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