JP2014516052A - ヒスタミン受容体活性阻害用の薬剤学的組成物、及び、睡眠障害、不安またはうつ病の予防または改善用食品組成物 - Google Patents
ヒスタミン受容体活性阻害用の薬剤学的組成物、及び、睡眠障害、不安またはうつ病の予防または改善用食品組成物 Download PDFInfo
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Abstract
【選択図】図26
Description
[実験動物]
ICRマウス(18−22g、雄性)及びSDラット(200−250g、雄性)は、それぞれ(株)コアテック及び(株)オリエントバイオから分譲されて実験動物用飼育箱に一週間適応させた後、実験に使った。動物の飼育は、温度23±1℃、湿度55±5%、明暗周期(明:午前9時−午後9時)、照度3000Luxの条件下になされ、飼料及び飲水は、自由に与えた。あらゆる動物は、韓国食品研究院動物管理委員会(KFRI−IACUC、Korea Food Research InstitutionalAnimal Care and Use Committee)の実験動物使用指針によって管理した。
ペントバルビタール睡眠誘導実験は、午後1時から5時の間の一定の時間内に進行し、グループ当たり、10匹(n=10)のマウスを実験前24時間絶食させた後に使った。あらゆる試料は、0.5%CMC−食塩水溶液を用いて製造し、ペントバルビタール投与45分前にマウスに経口投与(p.o.)した。一般対照群/実験群は、0.5%CMC−食塩水水溶液を10mg/kgの濃度で処理し、ジアゼパムは、代表的な睡眠剤のうち1つであって、抽出物の睡眠増進効果を比較するために、陽性対照群を薬物として使った。ペントバルビタール((株)翰林製薬)は、実験デザインによって45mg/kg(hypnotic dosage)の濃度で腹腔注射(i.p.)を通じて投与した。ペントバルビタール処理後、それぞれの個体を独立した空間に移して、入眠潜時(sleep latency)と睡眠時間(sleep duration)とを測定した。入眠潜時は、ペントバルビタールを腹腔注射した後、正反射(righting reflex)を1分以上喪失する時までの経過時間で設定し、睡眠時間は、再び正反射を回復する時までの時間で設定した。ペントバルビタール投与後、10分が経ても睡眠行動を見せていないマウスは、実験から除外した。
SDラット(Sprague−Dawley Rat、200−250g)を1週間適応させた後、脳波(Electroencephalogram、EEG)及び筋電図度(Electromyogram、EMG)の測定のために、電極挿入手術を実施した。ラットをペントバルビタール(50mg/kg、i.p.)で麻酔し、脳***(stereotaxic instrument)に頭部を固定させた。頭部皮下結合組織を切開した後、EEG及びEMGの測定のために、ステンレススチールスクリュー(stainless−steel screw)と銀電極ライン(silver electrode line)とを挿入した。以後、歯科用セメントで固定させて縫合した。手術部位の消毒及び抗生剤投与を3日間実施して、手術による炎症を予防し、7日間回復期間を置いた。測定環境に適応させるために、測定4日前から対照群に使う0.5%CMC−食塩水溶液を経口投与(p.o.)した後、レコーディング装置を連結して、本実験過程に順応するように誘導した。試料経口投与後、5分間安定化させた後、PAL−8200series(Pinnacle Technology Inc,Oregon,USA)を用いて、10:00から16:00まで6時間脳電図[electroencephalogram(EEG)]及び筋電図[electromyogram(EMG)]を測定した。EEG及びEMGのサンプリングレート(Sampling Rate)は、200Hzに設定し(epoch time:10s)、EEGは、0.1−25Hz、EMGは、10−100Hzのフィルター領域を設定してデータを記録した。睡眠構造分析は、FFT(Fast Fourier Transform)アルゴリズムによって行い、SleepSignプログラム(Ver.3.0,Kissei Comtec,Nagono,Japan)を利用した。分析結果は、覚醒(wake)、レム睡眠(REM sleep、rapid eye movement、theta band:6−10Hz)、ノンレム睡眠(NREM sleep、non−rapid eye movement、delta band:0.65−4Hz)に区分して表わした。入眠潜時は、10秒epoch単位のノンレム睡眠が12回以上連続して表われるのにかかる時間として設定した。
米の水抽出物(RWE)は、粉砕試料100gに蒸留水1Lを入れて1時間100℃で加熱して製造し、米のエタノール抽出物(REE)は、粉砕試料に70%エタノールを10倍(w/v)加えて、50℃インキュベーターで1日間抽出して製造し、一日に90分間3回ずつ超音波処理した。あらゆる抽出物は、濾過及び減圧濃縮を経て凍結乾燥した後、粉末化して実験に使った。
籾殻の水抽出物(HWE)は、粉砕試料100gに蒸留水1Lを入れて1時間100℃で加熱して製造し、籾殻のエタノール抽出物(HEE)は、粉砕試料に70%エタノールを10倍(w/v)加えて、50℃インキュベーターで1日間抽出して製造し、一日に90分間3回ずつ超音波処理した。あらゆる抽出物は、濾過及び減圧濃縮を経て凍結乾燥した後、粉末化して実験に使った。
米ぬかの水抽出物(BWE)は、粉砕試料100gに蒸留水1Lを入れて1時間100℃で加熱して製造し、米ぬかのエタノール抽出物(BEE)は、粉砕試料に70%エタノールを10倍(w/v)加えて、50℃インキュベーターで1日間抽出して製造した。あらゆる抽出物は、濾過及び減圧濃縮を経て凍結乾燥した後、粉末化して実験に使った。米ぬかの水抽出物(BWE)の収率は、5.56%、米ぬかのエタノール抽出物(BEE)の収率は、7.02%で表われた。
製造例1の米の水抽出物(RWE)及びエタノール抽出物(REE)を50、100、250及び500mg/kgの濃度で経口投与(p.o.)した後、ペントバルビタール(45mg/kg、i.p.)による睡眠誘導効果を分析した。その結果、図1及び図2から見られるように、米の水抽出物(RWE)では、50mg/kgを除いた濃度で用量依存的な入眠潜時の減少と睡眠持続時間の増加(p<0.01)とが表われた。また、図3及び図4から見られるように、米のエタノール抽出物(REE)でも、50mg/kgを除いた濃度で用量依存的な入眠潜時の減少と睡眠持続時間の増加とが表われた。米の水抽出物(RWE)よりも米のエタノール抽出物(REE)で睡眠持続時間の増加が大きく表われ、入眠潜時は、米の水抽出物(RWE)と米のエタノール抽出物(REE)いずれも類似して減少する傾向を表わした。
製造例2の籾殻の水抽出物(HWE)及びエタノール抽出物(HEE)を50、100、250及び500mg/kgの濃度で経口投与(p.o.)した後、ペントバルビタール(45mg/kg、i.p.)による睡眠誘導効果を分析した。その結果、図5及び図6から見られるように、籾殻の水抽出物(HWE)では、有意的に入眠潜時の減少が表われ、250と500mg/kgの濃度で有意的に睡眠持続時間が有意的に増加した(p<0.01)。また、図7及び図8から見られるように、籾殻のエタノール抽出物(HEE)では、50mg/kgを除いた濃度で留意した入眠潜時の減少(p<0.01)が表われ、用量依存的な睡眠持続時間の増加が表われた(p<0.01)。籾殻の水抽出物(HWE)よりも籾殻のエタノール抽出物(HEE)で睡眠持続時間の増加が大きく表われ、入眠潜時は、籾殻の水抽出物(HWE)と籾殻のエタノール抽出物(HEE)いずれも類似して減少する傾向を表わした。
製造例3の米ぬか(BE)の水抽出物(BWE)及びエタノール抽出物(BEE)を50、100、250及び500mg/kgの濃度で経口投与(p.o.)した後、ペントバルビタール(45mg/kg、i.p.)による睡眠誘導効果を分析した。その結果、BWEで入眠潜時がいずれも有意的に減少(p<0.01)し(図9)、陽性対照群であるDZPよりも減少した入眠潜時を確認することができた。また、BWEで50mg/kg及び100mg/kgを除いた250mg/kg及び500mg/kgの濃度で用量依存的な睡眠時間の増加が表われた(図10)。BEEでは、BWEと同様に、DZPよりも減少した入眠潜時(図11)と250mg/kg及び500mg/kgの濃度で用量依存的な睡眠時間との増加を示した(図12)。睡眠誘導物質BEは、水とエタノール抽出物との差なしに有意的に減少した入眠潜時と250mg/kgと500mg/kgとで有意的に増加した睡眠時間とを示した。
BEE500mg/kgを経口投与後、入眠潜時と総睡眠時間とを図17に表わした。対照群の平均入眠潜時は、31.9分であり、BEEの入眠潜時は、26.2分で約5.7分程度短縮された。総睡眠時間では、対照群が165.4分であり、BEE500mg/kgを経口投与した時、248.6分で約83分が増加した。
油脂成分が多いBEEを用いて、さらに正確な単一睡眠誘導物質を得るために、BEE(製造例3の米ぬかのエタノール抽出物の液相分画)をヘキサン、ブタノール、水及び酢酸エチルの4種の溶媒を用いて分離精製した(図20)。
BEE−H(ヘキサン)、BEE−B(ブタノール)、BEE−W(水)及びBEE−E(酢酸エチル)の睡眠誘導増進効果を確認するために、50mg/kg及び250mg/kgの量で経口投与(p.o.)した後、ペントバルビタール(45mg/kg、i.p.)を腹腔注射して、入眠潜時と睡眠時間との変化を調べた(図21及び図22)。
米ぬかのエタノール抽出物(BEE)の溶媒分画物のin vivo実験結果、他の分画物に比べて、n−ヘキサン分画の活性が有意的に優れているために、n−ヘキサン分画のサブ分画を製造した。n−ヘキサン分画(BEE−H、2176g)のうち、365gに対して、SiO2カラムクロマトグラフィー(以下、c.c.)を進行したが、この際、カラムは、直径13cmに高さ15cmでシリカゲルレジンを充填した。溶出溶媒は、n−ヘキサン:EtOAc=10:1の非極性溶媒から次第に極性を高めて、n−ヘキサン:EtOAc=7:1→2:1の比率で使い、その結果、総12つのサブ分画(BEE−H−1〜BEE−H−12)を得た(図23参照)。
BEE−H分画のサブ分画であるBEE−H−1ないしBEE−H−11の睡眠誘導増進効果を確認するために、50mg/kg及び250mg/kgの濃度で経口投与(p.o.)した後、ペントバルビタール(45mg/kg、i.p.)を腹腔注射して、入眠潜時と睡眠時間との変化を調べた。
(1)BEE−H−2分画
BEE−Hを小分画した結果、総12つの分画(BEE−H−1〜BEE−H−12)を得た。これらに対して、in vivo活性をテストした結果、BEE−H−2、BEE−H−10及びBEE−H−11分画物で高い活性結果を表わし、そのうち、BEE−H−2の2次小分画の製造を進行した。BEE−H−2(8.2g)に対して、ODS c.c.(φ4×7cm、アセトン:H2O=1:1)を実施して、同じ分画は、再び集めて濃縮後、5つの分画(BEE−H−2−1〜BEE−H−2−5)に分け、SiO2とODS TLCとで物質を確認した(図28)。
(2)BEE−H−10分画
BEE−Hを小分画した結果、総12つの分画(BEE−H−1〜BEE−H−12)を得た。これらに対して、in vivo活性をテストした結果、BEE−H−2、BEE−H−10、BEE−H−11分画物で高い活性結果を表わし、そのうち、BEE−H−10の2次小分画の製造を進行した。BEE−H−10(9.5g)に対して、SiO2 c.c.(φ6×17cm、n−hexane:EtOAc=10:1→6:1→4:1→2:1→1:1→CHCl3−MeOH=8:1→1:1)を実施して、23つの分画(BEE−H−10−1〜BEE−H10−23)に分け、SiO2とODS TLCとで物質を確認した(図29参照)。
(3)BEE−H−11分画
BEE−Hを小分画した結果、総12つの分画(BEE−H−1〜BEE−H−12)を得た。これらに対して、in vivo活性をテストした結果、BEE−H−2、BEE−H−10、BEE−H−11分画物で高い活性結果を表わし、そのうち、BEE−H−11の2次小分画の製造を進行した。BEE−H−11(810mg)に対して、SiO2 c.c.(φ5×10cm、n−hexane:EtOAc=10:1→5:1→3:1→1:1→CHCl3−MeOH=8:1→5:1→1:1)を実施して、13つの分画(BEE−H−11−1〜BEE−H11−13)に分け、SiO2とODS TLCとで物質を確認した(図30参照)。
BEE−H−2分画が、GPCRの活性を抑制するか否かをMillipore Corporation(アメリカ)に依頼して、GPCRProfilerTM方法によって分析した。実験結果、7つのGPCR受容体(セロトニン1A受容体、アデノシン1受容体、ヒスタミン1受容体、ヒスタミン2受容体、アセチルコリン2受容体、バソプレシン1A受容体、及びニューロペプチドY2受容体)に50%以上の抑制効果があった(図31参照)。
製造例1の米の水抽出物(RWE)と製造例3の米ぬかのエタノール抽出物(BEE)との睡眠作用機作を確認するために、ヒスタミン受容体効能剤である2−ピリジルエチレンアミン二塩酸塩が、米ぬかのエタノール抽出物の睡眠誘導効果に及ぼす影響を調べた。
Claims (19)
- 米、米ぬか、または籾殻の抽出物を有効成分として含むヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記ヒスタミン受容体活性阻害用の薬剤学的組成物は、アレルギー性鼻炎;炎症性腸疾患;喘息;気管支炎;嘔吐;胃及び十二指腸潰瘍;胃食道逆流;睡眠障害;不安;及びうつ病の予防または治療のためのものであることを特徴とする請求項1に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記睡眠障害の予防または治療は、入眠潜時の減少、睡眠持続時間の増加、またはノンレム睡眠の増加であることを特徴とする請求項2に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記米、米ぬか、または籾殻の抽出物は、水、有機溶媒、またはこれらの混合物を用いて抽出された、米、米ぬか、または籾殻の抽出物であることを特徴とする請求項1に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記有機溶媒は、低級アルコール、ヘキサン、アセトン、酢酸エチル、クロロホルム、及びジエチルエーテルからなる群から選択された1種以上の溶媒であることを特徴とする請求項4に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記有機溶媒は、エタノールであることを特徴とする請求項5に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記米、米ぬか、または籾殻の抽出物は、米、米ぬか、または籾殻の抽出物のオイル分画、米、米ぬか、または籾殻の抽出物の液相分画、及び米、米ぬか、または籾殻の抽出物のワックス分画からなる群から選択された何れか1つ以上を含むことを特徴とする請求項1に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記米ぬかの抽出物のオイル分画は、米ぬか油であることを特徴とする請求項7に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記米、米ぬか、または籾殻の抽出物は、米、米ぬか、または籾殻の有機溶媒抽出物を第2の有機溶媒に再分画した分画物であることを特徴とする請求項1に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記米、米ぬか、または籾殻の抽出物は、米ぬかの低級アルコール抽出物を第2の有機溶媒に再分画した分画物であることを特徴とする請求項1に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 前記米、米ぬか、または籾殻の抽出物は、米ぬかのエタノール抽出物をヘキサンに再分画した分画物であることを特徴とする請求項1に記載のヒスタミン受容体活性阻害用の薬剤学的組成物。
- 米、米ぬか、または籾殻の抽出物を有効成分として含むヒスタミン受容体の活性阻害による睡眠障害、不安またはうつ病の予防または改善用食品組成物。
- 前記睡眠障害の予防または改善は、入眠潜時の減少、睡眠持続時間の増加、またはノンレム睡眠の増加であることを特徴とする請求項12に記載の睡眠障害、不安またはうつ病の予防または改善用食品組成物。
- 前記米、米ぬか、または籾殻の抽出物は、水、有機溶媒、またはこれらの混合物を用いて抽出された、米、米ぬか、または籾殻の抽出物であることを特徴とする請求項12に記載の睡眠障害、不安またはうつ病の予防または改善用食品組成物。
- 前記有機溶媒は、低級アルコール、ヘキサン、アセトン、酢酸エチル、クロロホルム、及びジエチルエーテルからなる群から選択された1種以上の溶媒であることを特徴とする請求項13に記載の睡眠障害、不安またはうつ病の予防または改善用食品組成物。
- 前記有機溶媒は、エタノールであることを特徴とする請求項15に記載の睡眠障害、不安またはうつ病の予防または改善用食品組成物。
- 前記米、米ぬか、または籾殻の抽出物は、米、米ぬか、または籾殻の抽出物のオイル分画、米、米ぬか、または籾殻の抽出物の液相分画、及び米、米ぬか、または籾殻の抽出物のワックス分画からなる群から選択された何れか1つ以上を含むことを特徴とする請求項12に記載の睡眠障害、不安またはうつ病の予防または改善用食品組成物。
- 前記米ぬかの抽出物のオイル分画は、米ぬか油であることを特徴とする請求項17に記載の睡眠障害、不安またはうつ病の予防または改善用食品組成物。
- 前記米、米ぬか、または籾殻の抽出物は、米、米ぬか、または籾殻のエタノール抽出物をヘキサンに再分画した分画物であることを特徴とする請求項12に記載の睡眠障害、不安またはうつ病の予防または改善用食品組成物。
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KR10-2011-0050474 | 2011-05-27 | ||
KR1020110050472A KR101336411B1 (ko) | 2011-05-27 | 2011-05-27 | 쌀 추출물의 수면 장애, 불안 또는 우울증의 개선, 예방 또는 치료를 위한 신규 용도 |
KR1020110050474A KR101336502B1 (ko) | 2011-05-27 | 2011-05-27 | 쌀겨 추출물 또는 쌀겨 분말의 수면 장애, 불안 또는 우울증의 개선, 예방 또는 치료를 위한 신규 용도 |
KR10-2011-0050472 | 2011-05-27 | ||
KR1020110056624A KR101351883B1 (ko) | 2011-06-13 | 2011-06-13 | 왕겨 추출물의 수면 장애, 불안 또는 우울증의 개선, 예방 또는 치료를 위한 신규 용도 |
KR10-2011-0056624 | 2011-06-13 | ||
PCT/KR2011/008374 WO2012165731A1 (ko) | 2011-05-27 | 2011-11-04 | 쌀, 쌀겨 또는 왕겨 추출물의 히스타민 수용체 길항제로서의 신규 용도 |
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Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160165941A1 (en) | 2014-11-21 | 2016-06-16 | Flipn'Sweet, LLC | Sugar substitute compositions comprising digestion resistent soluble fiber |
CN107156842A (zh) * | 2017-05-22 | 2017-09-15 | 辽宁大学 | 含有稻壳黄酮的抗乳腺癌保健品 |
CN106983830A (zh) * | 2017-05-22 | 2017-07-28 | 辽宁大学 | 含有米糠黄酮的抗抑郁保健品 |
CN107184834A (zh) * | 2017-05-22 | 2017-09-22 | 辽宁大学 | 含有稻壳黄酮的抗抑郁保健品 |
WO2018229779A1 (en) | 2017-06-15 | 2018-12-20 | Better Than Sweet Ltd. | Cane-sugar substitute |
CN107259308B (zh) * | 2017-06-23 | 2020-07-03 | 贺州学院 | 一种植物源鲜切荸荠黄化抑制剂及其制备和应用方法 |
KR101912814B1 (ko) | 2018-08-31 | 2018-10-29 | 한국식품연구원 | 쌀겨 추출물 분말의 제조방법 |
WO2020087012A1 (en) * | 2018-10-25 | 2020-04-30 | Ori Hofmekler | Natural sweetening flavor composition |
CN109907319A (zh) * | 2019-03-12 | 2019-06-21 | 中南林业科技大学 | 一种米糠提取物及其制备方法和在保健食品中的应用 |
KR102422965B1 (ko) | 2022-04-21 | 2022-07-20 | 재단법인 전남바이오산업진흥원 | 감탕나무(Ilex integra Thunb.) 잎 추출물을 포함하는 수면장애 예방 또는 개선용 조성물 |
CN116392554A (zh) * | 2023-04-23 | 2023-07-07 | 昆明理工大学 | 红米种皮活性成分在制备防治溃疡性结肠炎药物中的应用 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06298658A (ja) * | 1993-02-16 | 1994-10-25 | Soken Kk | 抗潰瘍剤 |
JP2000119681A (ja) * | 1998-10-16 | 2000-04-25 | Agency Of Ind Science & Technol | 生理活性米糠油の増収法 |
JP2001238653A (ja) * | 1999-12-20 | 2001-09-04 | Snow Brand Food Co Ltd | 食品の抗酸化能を増強させる方法及び食品用の抗酸化能増強剤 |
JP2001240859A (ja) * | 2000-02-28 | 2001-09-04 | Snow Brand Food Co Ltd | 肉から得られる抗酸化性物質及びその使用方法 |
JP2005272388A (ja) * | 2004-03-25 | 2005-10-06 | Ss Pharmaceut Co Ltd | 睡眠改善医薬組成物 |
JP2005530866A (ja) * | 2002-05-10 | 2005-10-13 | 雲清 劉 | 有機医薬とβ−シクロデキストリン誘導体との複合体、およびその調製方法 |
JP2007272388A (ja) * | 2006-03-30 | 2007-10-18 | Namco Bandai Games Inc | プログラム、情報記録媒体および画像生成システム |
JP2007291071A (ja) * | 2006-03-31 | 2007-11-08 | Daiichi Sankyo Healthcare Co Ltd | 催眠用医薬組成物 |
JP2009046471A (ja) * | 2007-07-24 | 2009-03-05 | Taisho Pharmaceutical Co Ltd | 睡眠改善剤 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1534082A4 (en) * | 2002-08-14 | 2006-05-10 | Bionutrigen Co Ltd | POWDER OR EXTRACTS FROM PLANT BLOOMS WITH EFFECTS OF GRAVITY AND COMPREHENSIVE GRAVITY OF ELASTIC FOOD |
US20050249823A1 (en) * | 2003-11-04 | 2005-11-10 | Murphy Tanya K | Methods for the prevention or amelioration of neuropsychiatric and related diseases |
EP2010162A4 (en) * | 2006-04-03 | 2013-01-09 | Isa Odidi | COMPOSITION FOR DISPOSING A MEDICINAL PRODUCT |
JP2008295380A (ja) * | 2007-05-31 | 2008-12-11 | Ikari Super Market:Kk | ギャバ含有食品素材およびその製造方法 |
KR100905747B1 (ko) * | 2007-07-13 | 2009-07-01 | 고려대학교 산학협력단 | 안토시아닌을 함유하는 비스테로이드성 항염증제에 의해유발된 위염 및 위궤양 치료용 조성물 |
KR100963339B1 (ko) * | 2008-04-02 | 2010-06-14 | 다산엠앤에프(주) | 쌀 프롤라민을 포함하는 항소화성궤양 조성물 |
CN101608156A (zh) * | 2008-06-17 | 2009-12-23 | 王茂芝 | 一种养生保健酒 |
KR101041044B1 (ko) * | 2008-09-10 | 2011-06-13 | 우석대학교 산학협력단 | 불면 증상의 예방 및 개선용 조성물과 그의 제조방법 |
CN101538519B (zh) * | 2009-04-29 | 2012-10-03 | 湛江师范学院 | 纯天然双蛹保健米酒及其制备方法 |
CN101869237A (zh) * | 2010-06-04 | 2010-10-27 | 刘小松 | 一种带有原花青素和花青素的米面淀粉食品 |
CN101884640B (zh) * | 2010-07-01 | 2012-04-18 | 北京世纪博康医药科技有限公司 | 谷维素的用途 |
CN101912115B (zh) * | 2010-08-04 | 2012-05-02 | 安徽燕之坊食品有限公司 | 一种改善睡眠的营养米及其加工方法 |
-
2011
- 2011-05-27 KR KR1020110050472A patent/KR101336411B1/ko active IP Right Grant
- 2011-11-04 CN CN201180071169.0A patent/CN103561755A/zh active Pending
- 2011-11-04 EP EP11866924.1A patent/EP2716296B1/en active Active
- 2011-11-04 CA CA2837046A patent/CA2837046A1/en not_active Abandoned
- 2011-11-04 JP JP2014512744A patent/JP6076335B2/ja active Active
- 2011-11-04 AU AU2011369552A patent/AU2011369552A1/en not_active Abandoned
- 2011-11-04 WO PCT/KR2011/008374 patent/WO2012165731A1/ko active Application Filing
- 2011-11-07 US US13/290,357 patent/US20130171280A1/en not_active Abandoned
-
2015
- 2015-07-21 US US14/804,598 patent/US20150320823A1/en not_active Abandoned
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06298658A (ja) * | 1993-02-16 | 1994-10-25 | Soken Kk | 抗潰瘍剤 |
JP2000119681A (ja) * | 1998-10-16 | 2000-04-25 | Agency Of Ind Science & Technol | 生理活性米糠油の増収法 |
JP2001238653A (ja) * | 1999-12-20 | 2001-09-04 | Snow Brand Food Co Ltd | 食品の抗酸化能を増強させる方法及び食品用の抗酸化能増強剤 |
JP2001240859A (ja) * | 2000-02-28 | 2001-09-04 | Snow Brand Food Co Ltd | 肉から得られる抗酸化性物質及びその使用方法 |
JP2005530866A (ja) * | 2002-05-10 | 2005-10-13 | 雲清 劉 | 有機医薬とβ−シクロデキストリン誘導体との複合体、およびその調製方法 |
JP2005272388A (ja) * | 2004-03-25 | 2005-10-06 | Ss Pharmaceut Co Ltd | 睡眠改善医薬組成物 |
JP2007272388A (ja) * | 2006-03-30 | 2007-10-18 | Namco Bandai Games Inc | プログラム、情報記録媒体および画像生成システム |
JP2007291071A (ja) * | 2006-03-31 | 2007-11-08 | Daiichi Sankyo Healthcare Co Ltd | 催眠用医薬組成物 |
JP2009046471A (ja) * | 2007-07-24 | 2009-03-05 | Taisho Pharmaceutical Co Ltd | 睡眠改善剤 |
Non-Patent Citations (6)
Title |
---|
BIOLOGICAL AND PHARMACEUTICAL BULLETIN, vol. 29, no. 6, JPN6014048358, 2006, pages 1148 - 1153, ISSN: 0002941346 * |
EUR J NUTR, vol. 44, no. 8, JPN6014048363, 2005, pages 509 - 516, ISSN: 0002941348 * |
JOURNAL OF THE KOREAN SOCIETY OF FOOD SCIENCE AND NUTRITION, vol. 35, no. 10, JPN6014048361, 2006, pages 1297 - 1303, ISSN: 0002941347 * |
PHARMACOLOGICAL RESEARCH, vol. 40, no. 1, JPN6014048355, 1999, pages 31 - 36, ISSN: 0002941345 * |
ビタミン, vol. 84, no. 8, JPN6014048365, 2010, pages 390 - 391, ISSN: 0002941349 * |
日本薬理学雑誌, vol. 74(2), JPN6014048367, 1978, pages 285 - 295, ISSN: 0002941350 * |
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EP2716296A1 (en) | 2014-04-09 |
EP2716296B1 (en) | 2017-04-26 |
CA2837046A1 (en) | 2012-12-06 |
JP6076335B2 (ja) | 2017-02-08 |
US20130171280A1 (en) | 2013-07-04 |
KR20120132652A (ko) | 2012-12-07 |
AU2011369552A1 (en) | 2013-12-12 |
WO2012165731A1 (ko) | 2012-12-06 |
CN103561755A (zh) | 2014-02-05 |
KR101336411B1 (ko) | 2013-12-04 |
US20150320823A1 (en) | 2015-11-12 |
EP2716296A4 (en) | 2014-10-29 |
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