WO2013054525A1 - グルタチオン含有健康飲料 - Google Patents
グルタチオン含有健康飲料 Download PDFInfo
- Publication number
- WO2013054525A1 WO2013054525A1 PCT/JP2012/006525 JP2012006525W WO2013054525A1 WO 2013054525 A1 WO2013054525 A1 WO 2013054525A1 JP 2012006525 W JP2012006525 W JP 2012006525W WO 2013054525 A1 WO2013054525 A1 WO 2013054525A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- glutathione
- vitamin
- beverage
- expression
- chondroitin
- Prior art date
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Abstract
Description
(試験飲料)
以下の3種類の試験飲料を用いて二重盲検試験を行った。a飲料、b飲料、c飲料の処方の概要を以下の表1に示す。
被験者は、健常者の男性60名(年齢53.5±2.5歳、平均BMI22.3kg/m2)であった。事前の健康診断により、非喫煙の被験者で、血糖値(グルコース、HbA1C)、肝機能(GOT、GPT、γ-GTP)、膵機能(アミラーゼ)、尿酸値、腎機能(クレアチニン)が正常であることを確認後、被験者を、a飲料(従来品)を摂取する被験者(A群)と、b飲料(本発明の飲料)を摂取する被験者(B群)と、c飲料(従来品の有効成分を除きグルタチオン含有酵母を添加した飲料)を摂取する被験者(C群)との3群に、20名ずつ無作為に分類し二重盲検試験を行った。被験者は、いずれの飲料を摂取しているかを知らされることなく、上記飲料のいずれかを20mLずつ、朝、昼、晩の一日3回5週間の試験期間中に摂取するよう指示された。なお、試験期間中は、他のサプリメント等の摂取は控えるように指示されたが、特に厳格な食事制限は行わず、通常通りの生活をおくるように指導された。
本発明の飲料が皮膚の老化の予防・改善効果を有しているか否かを確認するために、各群の被験者につき、摂取開始前と摂取5週間後の顔の皮膚の状態を、皮膚画像解析カウンセリングシステムである「VISIA」を用いて、しみ、毛穴、色むら、紫外線しみ、ポルフィリン、しわの6項目について分析した。各項目と6項目の総合的な判定について、統計解析ソフトJMP8を使用し、ウィルコクスンの符号付順位検定により解析した。結果を以下の表2並びに図1(a)及び(b)に示す。
本発明の飲料が総合感情障害における効果を有しているか否かを確認するために、各群の被験者は、摂取開始前と摂取5週間後に、POMS日本版調査票に回答した。ウィルコクスンの符号付順位検定を用いた結果を以下の表3に示す。なお、B群の被験者において、一部の項目の未記入者がいたため、n=19となっている項目がある。
本発明の飲料が自律神経機能やバランスにおいて改善効果を有しているかどうかを確認するために、各群の被験者につき、摂取開始前と摂取5週間後に、「きりつ名人」を用いて評価が行われた。「きりつ名人」の取扱説明書の指示に従い、心拍数の測定のため両手首にクリップを止め、胸に電極を貼り、血圧を測定するために腕にカフを巻き、パルスオキシメータを指に装着した。各被験者は、座位にて安静を3分間維持した後、音声ガイダンスにしたがって起立するよう指示された。起立後約3分30秒測定が継続された。オシロメトリック法による血圧測定は、座位安静1分後から毎分6回測定され、自律神経は30秒後から1拍ごとに解析された。ウィルコクスンの符号付順位検定の下側検定を行った結果、自律神経バランスの項目において、b飲料を摂取した被験者において87.4%の向上がみられ(図3参照)、b飲料の摂取が、日常生活において衰えが問題となる自律神経機能やバランス感覚において、a飲料やc飲料との相加的効果を超える相乗的効果をもたらすことが確認された。
本発明の飲料が被験者の全身的な健康度において改善効果を有しているかどうかを確認するために、各群の被験者につき、摂取開始前と摂取5週間後に、AMSAT(アムサット)-HC(Auto Mastic System for Analysis Therapy - Holistic Concept:全自動皮膚抵抗値測定システム)を用いて解析した。各被験者は額・両手・両足の計6極の電極をつなぎ、22パターンの電流値が17秒で計測された。計測された値は、システムにおけるデータバンク情報と比較され、波形解析を含めた特殊なアルゴリズムで全身の部位や脊髄、神経系にも振り分けられ全身74箇所について、測定結果理想値から逸脱度を最大±100%で表示されたが、甲状腺、直腸、感覚器、咽頭、大腿部、股関節、盲腸において、B群は、A群やC群と比較して有利な効果が見られた。
本発明の飲料が血液成分についていかなる作用を及ぼしているかを確認するために、血液検査を行った。RIA法により血中DHEA-S濃度を測定したところ、b飲料を摂取した被験者の血中DHEA-S濃度に変化がみられため、詳しく検討した。B群は、A群、C群と比較してb飲料を摂取することでt検定により有意に血中DHEA-S濃度が増加していた(p=0.0001)(図4参照)。なお、各被験者の血中DHEA-S濃度は50代男性の正常範囲内である53~342μg/dLであった。また、各群の被験者の血中DHEA-S濃度の各飲料摂取前に対する摂取後のDHEA-S濃度の平均増加率(縦軸)を図5に示す。b飲料の摂取が、DHEA-S濃度の増加を顕著にもたらすことが確認された。
A群、B群、C群の各被験者の血液試料を用い、統計解析による発現変動遺伝子(プローブ)の抽出を行った。マイクロアレイアッセイを使用して検出されたデータを用い、正規化済みの発現データを対象に有意差検定によるP値の算出と発現比に基づくカットオフを実施した。2群間の有意差検定は、マイクロアレイデータにおける2群間検定に用いられるSAM t-testを使用した。飲料の摂取前後の比較の組合せにおいてそれぞれ算出されたP値が、0.05未満となったプローブについて、2群間の対数発現比がlog ratioで0.263以上(発現比として、1.2倍以上)を示すプローブを有意な発現上昇プローブとし、2群間の対数発現比がlog ratio で-0.263以下(発現比として、0.8333倍以下)を示すプローブを有意な発現低下プローブとしてカットオフ通過プローブとした。
b飲料を摂取したB群の被験者において、皮膚の状態、総合感情障害、自律神経バランス、全身的な健康度における試験において、また、DHEA-Sの血中濃度、臭嗅受容体遺伝子発現等の生化学的指標において、a飲料の効果とc飲料の効果との相加効果にとどまらず、相乗的な改善効果が被験者にもたらされることが確認された。
一卵性双子の女性2人[姉](the first twin sister:FTS)と[妹](the second twin sister:STS)(姉BMI34.9、妹BMI33.6)が被験者となり試験を行った。[姉]は、上記実施例1で使用したa飲料を20mLずつ、朝、昼、晩の一日3回5週間摂取し、31日の休止期間後、上記実施例1で使用したb飲料を20mLずつ、朝、昼、晩の一日3回5週間摂取するよう指示された。[妹]は、b飲料を20mLずつ、朝、昼、晩の一日3回5週間摂取し、31日間の休止期間後、a飲料を20mLずつ、朝、昼、晩の一日3回5週間摂取するよう指示された。前期5週間+31日の休止期間+後期5週間の合計101日間を試験期間とした。
上記一卵性双子の[姉]と[妹]は、試験期間中に左と右の頬それぞれについてスキングリップメーターAS-GP1(朝日バイオメッド社製)を用い、製造者作成の取扱い説明書に基づき、複数回の肌弾力試験を行った。その結果を図9((a)及び(b))に示す。[姉]はa飲料を摂取している期間及びその後の31日間の休止期間中には、肌弾力性の増加はみられなかったが、休止期間後にb飲料を摂取した後期5週間において左頬(実線)、右頬(点線)ともに肌弾力性が顕著に増加した(図9(a)参照)。[妹]は、b飲料を摂取した前期5週間において肌弾力性が増加したが、31日間の休止期間において弾力性は減少し、a飲料を摂取した5週間においてはほとんど変化がみられなかった(図9(b)参照)。
上記[姉]と[妹]は、試験期間中に血中クレアチニン濃度(mg/dL)を酵素法(クレアチナーゼ-サルコシンオキシダーゼ-ペルオキシダーゼ法)(三菱化学メディエンスにて委託測定)により複数回測定した。その結果を図10に示す。[姉]は点線、[妹]は実線で示される。[姉]はa飲料を摂取した前期5週間及びその後の31日間の休止期間中には、血中クレアチニン濃度の減少はみられなかったが、休止期間後にb飲料を摂取した後期5週間において血中クレアチニン濃度が顕著に減少した(図10点線→部分参照)。[妹]は、b飲料を摂取した前期5週間において血中クレアチニン濃度が減少したが(図10実線→部分参照)、31日間の休止期間において増加し、a飲料を摂取した後期5週間においては変化がみられなかった(図10実線参照)。慢性腎臓病や高血圧患者においてクレアチニンが高濃度であることが知られており(Annals of Internal Medicine,Vol. 141 No. 12,929-937 及びArch. Intern. Med. Vol 161,2001, 1207-1216)、本発明の飲料が、高血圧の改善や慢性腎臓病の改善に効果があることが示唆された。
上記[姉]と[妹]は、試験期間中に血中総コレステロール濃度(mg/dL)を酵素法(三菱化学メディエンスにて委託測定)により複数回測定した。その結果を図11に示す。[姉]はa飲料を摂取している期間及びその後の31日間の休止期間中には、血中総コレステロール濃度の減少はみられなかったが、休止期間後にb飲料を摂取した後期5週間において総コレステロール濃度が顕著に減少した(図11点線→部分参照)。[妹]は、b飲料を摂取した前期5週間において総コレステロール濃度が減少し(図11実線→部分参照)、31日間の休止期間においても増加せず、a飲料を摂取した後期5週間においても減少傾向がみられた。
上記[姉]と[妹]は、試験期間中に血中LDLコレステロール濃度(mg/dL)を酵素法(三菱化学メディエンスにて委託測定)により複数回測定した。その結果を図12に示す。[姉]はa飲料を摂取している期間及びその後の31日間の休止期間中には、血中LDLコレステロール濃度の減少はみられなかったが、休止期間後にb飲料を摂取した後期5週間においてLDLコレステロール濃度が減少した(図12点線→部分参照)。[妹]は、b飲料を摂取した前期5週間においてLDLコレステロール濃度が減少し(図12実線→部分参照)、31日間の休止期間においても増加しなかったが、a飲料を摂取した後期5週間においてはわずかに増加傾向がみられた。上記総コレステロール濃度の結果をあわせ、本発明の飲料は、いわゆるメタボリック症状に対して効果を有することが示唆された。
上記[妹]に睡眠状況について問診したところ、[妹]がb飲料を摂取した際に、[妹]のみが元々持っていた睡眠状況の問題が改善された。具体的には、夜間に咳が出たり、大きないびきをかいたりすることが少なくなったとの回答を得た。この問題は、一卵性双子でありながら妹に特異的であったが、a飲料を摂取した際には改善が認められなかった。
本発明の飲料が被験者の全身的な健康度において改善効果を有しているかどうかを確認するために、上記[姉]と[妹]につき、摂取開始前と摂取5週間後に、AMSATを用いて上記実施例1に記載されている手順と同様の手順にて解析した。a飲料を摂取した前と後に解析を行った場合、[姉]と[妹]いずれにおいても顕著な数値の変化は見られなかったが(図13(a)及び(b)参照)、b飲料を摂取した前と期間後に解析を行った場合、[姉]と[妹]いずれにおいても74の検査項目のほとんどにおいて摂取後に顕著な数値の減少を示し、理想状態とされる0に近い数字となった(図14(a)及び(b)参照)。このことは、AMSATを用いた全身的な健康度の評価において、細胞間質の軟化が抑制され炎症性の改善効果がみられたことを示している。
b飲料を摂取した上記双子の[姉]と[妹]及び、実施例1においてb飲料を摂取したB群の被検者男性群の血液試料を用い、実施例1の遺伝子発現調査において行ったのと同様の手順で統計解析による発現変動遺伝子(プローブ)の抽出を行った。b飲料の摂取前後で発現変動が1.2倍以上増加又は1.2倍以上減少がみとめられたプローブについて、被験者の属する群においてどのようにプローブの発現変動が重複しているかを、発現増加と減少のそれぞれについてベン図として表記した(図15(a)(b)参照)。双子の被験者と男性の被験者の両方において発現が増加していたプローブ数は9であった。有意に増加している9種類のプローブには(図15(中央重なり部分)参照)、臭嗅受容体(olfactory receptor)タンパク質をコードする遺伝子OR14I1が含まれており、臭嗅受容体に関する遺伝子が活性化されていたことは、上記AMSATを用いた全身的な健康度の評価において、感覚器における数値も含めて有利な効果がみられたこととも一致する。
肥満傾向にある双子のa飲料とb飲料の摂取量は、体重1kgあたり姉0.63mL/kg/日、妹0.68mL/kg/日であって、実施例1における男子の摂取量よりも少なくなっている。少ない摂取量であっても、5週間本発明のb飲料を摂取することで、血中クレアチニン濃度の減少、総コレステロールの減少、LDLコレステロールの減少、睡眠状況の改善等、老化やストレスの予防・改善効果がもたらされることが確認された。また、発現遺伝子解析においても、b飲料の摂取は健康状態の向上に寄与することがわかった。b飲料の摂取は、肥満傾向の体質で起こる炎症反応を抑制することで細胞のストレスを軽減し、基礎代謝を活発にすることで肥満傾向の改善に効果がある。
Claims (12)
- 水溶性核タンパク質、オリゴRNA、亜鉛、コラーゲン、コンドロイチン、ヒアルロン酸、ビタミン類、及びグルタチオンを含むことを特徴とする健康飲料。
- ビタミン類が、ビタミンB1、ビタミンB2、ビタミンB6、ビタミンB12から選ばれる1又は2種類以上のビタミンB群と、ビタミンCとを含むことを特徴とする請求項1記載の健康飲料。
- グルタチオンとして、グルタチオン含有酵母抽出物を用いることを特徴とする請求項1又は2記載の健康飲料。
- グルタチオン含有酵母抽出物が、還元型グルタチオンよりも酸化型グルタチオンを多く含むことを特徴とする請求項3記載の健康飲料。
- グルタチオンとして、1000mLあたり6~60mgを添加することを特徴とする請求項1~4のいずれか記載の健康飲料。
- 水溶性核タンパク質、オリゴRNA、亜鉛、コラーゲン、コンドロイチン、ヒアルロン酸、ビタミン類、及びグルタチオンを含むことを特徴とする血中デヒドロエピアンドロステロンサルフェート(DHEA-S)濃度を増加させるための組成物。
- 水溶性核タンパク質、オリゴRNA、亜鉛、コラーゲン、コンドロイチン、ヒアルロン酸、ビタミン類、及びグルタチオンを含むことを特徴とする臭嗅受容体遺伝子の発現を促進するための組成物。
- 水溶性核タンパク質、オリゴRNA、亜鉛、コラーゲン、コンドロイチン、ヒアルロン酸、ビタミン類、及びグルタチオンを含むことを特徴とするTNFRSF10C遺伝子又はTNFSF14遺伝子の発現を抑制するための組成物。
- 水溶性核タンパク質、オリゴRNA、亜鉛、コラーゲン、コンドロイチン、ヒアルロン酸、ビタミン類、及びグルタチオンを含むことを特徴とする老化若しくはストレスを改善又は予防するための組成物。
- ビタミン類が、ビタミンB1、ビタミンB2、ビタミンB6、ビタミンB12から選ばれる1又は2種類以上のビタミンB群と、ビタミンCとを含むことを特徴とする請求項6~9のいずれか記載の組成物。
- グルタチオンとして、グルタチオン含有酵母抽出物を用いることを特徴とする請求項6~10のいずれか記載の組成物。
- グルタチオン含有酵母抽出物が、還元型グルタチオンよりも酸化型グルタチオンを多く含むことを特徴とする請求項11記載の組成物。
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JP2019001766A (ja) * | 2017-06-20 | 2019-01-10 | 国立大学法人北海道大学 | 脂質吸収抑制用剤 |
JP2019131517A (ja) * | 2018-02-01 | 2019-08-08 | エスエス製薬株式会社 | 内服液 |
JP7057150B2 (ja) | 2018-02-01 | 2022-04-19 | エスエス製薬株式会社 | 内服液 |
WO2020027012A1 (ja) * | 2018-07-30 | 2020-02-06 | 味の素株式会社 | 大豆蛋白質飲料 |
WO2021182534A1 (ja) * | 2020-03-12 | 2021-09-16 | フォーデイズ株式会社 | 水溶性核タンパクを含有する健康飲料 |
JP7180935B1 (ja) | 2021-09-14 | 2022-11-30 | プラス・レイ株式会社 | 液状飲料組成物 |
JP2023042506A (ja) * | 2021-09-14 | 2023-03-27 | プラス・レイ株式会社 | 液状飲料組成物 |
WO2023157802A1 (ja) * | 2021-09-14 | 2023-08-24 | プラス・レイ株式会社 | 液状飲料組成物及びその製造方法 |
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KR20140051446A (ko) | 2014-04-30 |
JPWO2013054525A1 (ja) | 2015-03-30 |
US20140302171A1 (en) | 2014-10-09 |
US20180344874A1 (en) | 2018-12-06 |
CN108354102A (zh) | 2018-08-03 |
JP6138048B2 (ja) | 2017-06-07 |
CN103874431A (zh) | 2014-06-18 |
HK1254518A1 (zh) | 2019-07-19 |
KR101656224B1 (ko) | 2016-09-09 |
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