JP7137745B2 - ベータカゼインa2および抗酸化能 - Google Patents
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Description
発明の概要
本発明の第1の態様では、ベータカゼインを含有する組成物を動物に与えることによって、動物において抗酸化能を改善する方法であって、ベータカゼインは、酵素消化でベータカソモルフィン-7を生成することが不可能な1種または複数のベータカゼインを75重量%以上含む、方法が提供される。
本発明のある特定の実施形態では、組成物は、動物の血液または組織中のグルタチオンレベルを増加させるために摂取される。
本発明の好ましい実施形態では、動物はヒトである。あるいは、動物は、酸化ストレスの影響を受けやすい任意の他の動物であってもよく、例えばイヌやネコが挙げられる。
乳は、ヒト、ヤギ、ブタおよびスイギュウを含むいずれの哺乳動物からも得ることができるが、本発明の好ましい実施形態では、乳は牛乳である。
実施例1は、脱脂粉乳食を給餌したウサギの試験である。使用した脱脂粉乳は、ベータカゼインのA1バリアントのみを含有する乳(A1)またはベータカゼインのA2バリアントのみを含有する乳(A2)のいずれか由来のものであった。結果を図1~4に示す。図1および2は、A2を給餌したウサギについて、回腸内および肝臓内でシステインとGSHの両者の取込みが上昇したことを示す。肝臓はGSH恒常性のための主な貯蔵器官であるので、肝臓内GSHの増加は、体内のGSHレベルの全体的な増加を示す。A2食を給餌したウサギから摘出した脳の前頭皮質および海馬領域も、A1食を給餌したウサギから摘出した同一の脳領域と比較して、GSHレベルが上昇していた。前頭皮質におけるGSHの低いレベルは、自閉症、ADHD、ダウン症候群および統合失調症などの障害に関与していることが示されている。海馬における低いレベルは、記憶回復に影響し得る。海馬におけるシステインの低いレベルは、自閉症およびアルツハイマー病に罹患した患者において見出されている。この結果は、A2を給餌したウサギは、A1を給餌したウサギと比べて、様々な体器官を通して、およびとりわけ脳内で、比較的高い抗酸化能を有したことを示している。
合計で10匹の雄性ウサギ(NZW、年齢および/または体重をマッチさせた)を2つの群に無作為に分け、主なタンパク質源としての脱脂粉乳(SMP)でつくられたウサギ飼料を合計で12週間給餌した。総タンパク質含有量は16.8%であり、タンパク質の60%はSMPに由来した、すなわち、食餌の10%が乳タンパク質からなった。使用したSMPは、ベータカゼインのA1バリアントのみを含有する乳(A1)またはベータカゼインのA2バリアントのみを含有する乳(A2)のいずれかに由来した。SMP食は、ウサギが飼料の摂取を拒むことに関した問題を防ぐために、嗜好性について試験した。12週期間の最後に、ウサギを安楽死させた。組織サンプルを入手し、さらに使用するまで-80℃で保存した。溶解バッファー1Xを用いて組織を溶解し、組織溶解物を氷上で15秒間、超音波処理した。タンパク質含有量を測定するのに100μLの超音波処理物を使用した。残りの溶解物を微量遠心管に加え、等量の0.4N過塩素酸を加えた後、氷上で5分間インキュベーションした。サンプルを13,000RPMで遠心分離し、上清を新しい微量遠心管に移した。100μLのサンプルを円錐形微量オートサンプラーバイアルに加え、オートサンプラー冷却トレイ中で4℃で保持した。10μLのこのサンプルをHPLCシステムに注入した。Agilent Eclipse XDB-C8分析カラム(3x150mm;3.5μm)およびAgilent Eclipse XDB-C8(4.6x12.5mm;5μm)ガードカラムを使用して、レドックスおよびメチル化経路の代謝産物の分離を完了した。2種の移動相を使用した。移動相Aは、リン酸でpH2.65に調整した0%アセトニトリル、25mMリン酸ナトリウム、1.4mM 1-オクタンスルホン酸であった。移動相Bは50%アセトニトリルであった。流量は最初は0.6mL/分に設定して、段階的グラジエントを使用した:0~9分 0%B、9~19分 50%B、19~30分 50%B。次いで、次の運転の前に、カラムを5%Bで12分間平衡化した。温度を27℃に維持した。電気化学検出器はBDD Analytical cell Model 5040を有するESA CoulArrayであり、作動電位は1500mVに設定した。標準検量線およびESA供給のHPLCソフトウェアを使用して、代謝産物のピーク面積からサンプル濃度を測定した。サンプル濃度をタンパク質含有量に対して正規化した。チオールレベルが標準曲線の範囲内であることを確保するために、ある場合には、必要に応じてサンプルを移動相に希釈し、または最大50μLのサンプルを注入した。
適格な中国人男性または女性には、不定期に乳を摂取し、市販乳への自己申告の不耐性、乳摂取後の自己申告の軽度から中等度の消化器不快感を有し、安静呼吸時に心電図および血圧が正常な、25~68歳の人が含まれた。平均±標準偏差(SD)年齢が46.6±14.0歳の、合計で21名の男性および24名の女性が登録された。23名は、尿中ガラクトース試験の結果に基づき、ラクトース欠乏症が確認された。
発明の態様
[態様1]ベータカゼインを含有する組成物を動物に与えることによって、動物において抗酸化能を改善する方法であって、ベータカゼインが、酵素消化でベータカソモルフィン-7を生成することが不可能な1種または複数のベータカゼインを75重量%以上含む、方法。
[態様2]1種または複数のベータカゼインがA2型ベータカゼインから選択される、態様1に記載の方法。
[態様3]組成物の摂取が、動物の血液または組織中のグルタチオンレベルを増加させる、態様1または2に記載の方法。
[態様4]組成物の摂取が、酸化ストレスと関連する疾患または障害のリスクを回避または低減させる、態様1から3のいずれかに記載の方法。
[態様5]酸化ストレスと関連する疾患または障害が、がん、炎症、クワシオルコル(タンパク質欠乏症)、発作、自閉症、ダウン症候群、慢性疲労症候群、アルツハイマー病、パーキンソン病、鎌状赤血球貧血症、肝疾患、嚢胞性線維症、HIV、AIDS、感染症、心臓発作、脳卒中、および糖尿病を含む群から選択される、態様4に記載の方法。
[態様6]組成物の摂取が、加齢の作用を回避もしくは低減させる、身体運動後の組織の回復を促進する、または妊孕性を増進させる、態様1から3のいずれかに記載の方法。
[態様7]動物がヒト、イヌ、またはネコである、態様1から6のいずれかに記載の方法。
[態様8]ベータカゼインが90重量%以上のA2ベータカゼインを含む、態様1から7のいずれかに記載の方法。
[態様9]ベータカゼインが100%のA2ベータカゼインを含む、態様1から8のいずれかに記載の方法。
[態様10]組成物が乳または乳製品である、態様1から9のいずれかに記載の方法。
[態様11]乳が、生乳、粉乳、粉末から再構成された液乳、脱脂乳、均質化乳、練乳、無糖練乳、低温殺菌乳、または非低温殺菌乳である、態様10に記載の方法。
[態様12]乳製品が、クリーム、ヨーグルト、クワルク、チーズ、バター、アイスクリーム、乳児用調製粉乳、成人用栄養製品、タンパク質サプリメント、またはペットフードである、態様10に記載の方法。
[態様13]ウシの遺伝子型試験または表現型試験を行い、乳中にA2型のベータカゼインのみを生成すると決定されたウシのみを搾乳することによって、乳が得られる、態様10または11に記載の方法。
[態様14]乳中にA2型のベータカゼインA2のみを生成すると決定されたウシのみを含むウシ群を形成し、次いで、当該群の1頭または複数のウシを搾乳する、態様13に記載の方法。
Claims (11)
- ベータカゼインを含有する、ヒトの血液または組織中のグルタチオンレベルを増加させることによるヒトにおける抗酸化能の改善剤であって、ベータカゼインが、75重量%以上のA2ベータカゼインを含む、前記剤。
- 酸化ストレスと関連する疾患または障害のリスクを回避または低減させるための、請求項1に記載の剤。
- 酸化ストレスと関連する疾患または障害が、がん、炎症、クワシオルコル(タンパク質欠乏症)、発作、自閉症、ダウン症候群、慢性疲労症候群、アルツハイマー病、パーキンソン病、鎌状赤血球貧血症、肝疾患、嚢胞性線維症、HIV、AIDS、感染症、心臓発作、脳卒中、および糖尿病を含む群から選択される、請求項2に記載の剤。
- 加齢の作用を回避もしくは低減させる、身体運動後の組織の回復を促進する、または妊孕性を増進させるための、請求項1から3のいずれか一項に記載の剤。
- ベータカゼインが90重量%以上のA2ベータカゼインを含む、請求項1から4のいずれか一項に記載の剤。
- ベータカゼインが100%のA2ベータカゼインを含む、請求項1から5のいずれか一項に記載の剤。
- 乳または乳製品である、請求項1から6のいずれか一項に記載の剤。
- 乳が、生乳、粉乳、粉末から再構成された液乳、脱脂乳、均質化乳、練乳、無糖練乳、低温殺菌乳、または非低温殺菌乳である、請求項7に記載の剤。
- 乳製品が、クリーム、ヨーグルト、クワルク、チーズ、バター、アイスクリーム、乳児用調製粉乳、成人用栄養製品、またはタンパク質サプリメントである、請求項7に記載の剤。
- ウシの遺伝子型試験または表現型試験を行い、乳中にA2型のベータカゼインのみを生成すると決定されたウシのみを搾乳することによって、乳が得られる、請求項7または8に記載の剤。
- 乳中にA2型のベータカゼインのみを生成すると決定されたウシのみを含むウシ群を形成し、次いで、当該群の1頭または複数のウシを搾乳する、請求項10に記載の剤。
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RU2280448C2 (ru) * | 2002-11-10 | 2006-07-27 | Институт биофизики клетки РАН | Композиция с антиоксидантными свойствами и способ лечения болезней млекопитающих |
CN1917772A (zh) * | 2004-02-23 | 2007-02-21 | 得克萨斯A&M大学系统 | 抗氧化组合物及其使用方法 |
US20060105972A1 (en) * | 2004-11-17 | 2006-05-18 | Nagasawa Herbert T | Method to enhance delivery of glutathione and ATP levels in cells |
EP2448958A4 (en) * | 2009-06-01 | 2013-11-06 | Kenneth James Friel | PEPTIDES OF HUMAN MILK |
WO2013133727A1 (en) * | 2012-03-09 | 2013-09-12 | Fanning Aaron Calvin | Uses of casein compositions |
EP3004071A1 (en) * | 2013-05-31 | 2016-04-13 | Edison Pharmaceuticals, Inc. | Carboxylic acid derivatives for treatment of oxidative stress disorders |
SG10201801156RA (en) * | 2013-08-23 | 2018-03-28 | A2 Milk Co Ltd | Beta-casein a2 and blood glucose levels |
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Patent Citations (2)
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WO2014193248A1 (en) | 2013-05-31 | 2014-12-04 | The A2 Milk Company Limited | Beta-casein a2 and prevention of inflammation of the bowel |
WO2015005804A1 (en) | 2013-07-12 | 2015-01-15 | The A2 Milk Company Limited | Beta-casein a2 and reducing or preventing symptoms of lactose intolerance |
Non-Patent Citations (1)
Title |
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J.Dairy Sci.,2015 Jan.,vol.98,no.1,pp.15-26 |
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Publication number | Publication date |
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KR102374024B1 (ko) | 2022-03-11 |
RU2017142002A (ru) | 2019-06-24 |
WO2016190750A1 (en) | 2016-12-01 |
MX2017014991A (es) | 2018-04-10 |
RU2751945C9 (ru) | 2021-12-21 |
PH12017550132A1 (en) | 2018-05-07 |
BR112017024975A2 (pt) | 2018-08-07 |
BR112017024975B1 (pt) | 2022-03-15 |
JP2018514236A (ja) | 2018-06-07 |
US20180169186A1 (en) | 2018-06-21 |
CL2017002967A1 (es) | 2018-06-01 |
CN107708711A (zh) | 2018-02-16 |
RU2751945C2 (ru) | 2021-07-21 |
KR20180010251A (ko) | 2018-01-30 |
IL255725A (en) | 2018-01-31 |
IL255725B (en) | 2021-10-31 |
EP3297643A4 (en) | 2019-02-06 |
AU2022204759A1 (en) | 2022-07-28 |
AU2016267960A1 (en) | 2017-12-14 |
CA2986889C (en) | 2023-08-29 |
ZA201707968B (en) | 2019-10-30 |
AU2016267960B2 (en) | 2022-04-07 |
CA2986889A1 (en) | 2016-12-01 |
EP3297643A1 (en) | 2018-03-28 |
US10702580B2 (en) | 2020-07-07 |
HK1250631A1 (zh) | 2019-01-11 |
RU2017142002A3 (ja) | 2019-11-21 |
MY190600A (en) | 2022-04-27 |
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