JP2021528372A - ニコチンアミドアデニンジヌクレオチド(nad+)前駆体及び少なくとも1種のケトン又はケトン前駆体を使用する組成物及び方法 - Google Patents
ニコチンアミドアデニンジヌクレオチド(nad+)前駆体及び少なくとも1種のケトン又はケトン前駆体を使用する組成物及び方法 Download PDFInfo
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Abstract
【選択図】 なし
Description
[0011]一実施形態では、本開示は、酸化ストレス、酸化ストレスに関連する状態、グルタチオンレベルの低下、グルタチオンレベルの低下に関連する状態、低レドックス比NAD+/NADH、又は低レドックス比NAD+/NADHに関連する状態からなる群から選択される少なくとも1つの身体的状態を処置又は予防する方法を提供する。本方法は、有効量の、ニコチンアミドアデニンジヌクレオチド(NAD+)前駆体と少なくとも1種のケトン又はケトン前駆体との組み合わせを、これらを必要とする個体に投与することを含む。
[0045]以下、いくつかの定義を示す。しかしながら定義が以下の「実施形態」の項にある場合もあり、上記の見出し「定義」は、「実施形態」の項におけるそのような開示が定義ではないことを意味するものではない。
[0063]トリグリセリドの上昇:150mg/dL(1.7mmol/L)超、又はこの脂質異常を対象とする治療;
[0064]HDLコレステロールの低下:男性で40mg/dL(1.03mmol/L)未満、女性で50mg/dL(1.29mmol/L)未満、又はこの脂質異常を対象とする治療;
[0065]血圧の上昇:収縮期BPが130超若しくは拡張期BPが85mmHg超、又は以前に診断された高血圧の治療;及び
[0066]空腹時血漿グルコースの上昇:(FPG)が100mg/dL(5.6mmol/L)超、又は以前に2型糖尿病であると診断されている。
[0074]本開示は、NAD+前駆体と少なくとも1種のケトン又はケトン前駆体(例えば、ケトンエステル)との組み合わせを含む組成物を提供する。一実施形態では、NAD+前駆体は、トリプトファン、ニコチン酸(ナイアシン)、ニコチンアミド(ナイアシンアミド)、ニコチンアミドリボシド(NR)、還元型ニコチンアミドリボシド(NRH)、β−ニコチンアミドモノヌクレオチド(NMN)、トリゴネリン(N−メチルニコチネート)、ニコチン酸モノヌクレオチド、ニコチン酸リボシド、これらの化合物のうちの少なくとも1つを濃縮した食品抽出物、例えば、ニコチンアミドアデニンジヌクレオチド(NAD)を濃縮した食品抽出物、及びこれらの混合物からなる群から選択される。本明細書で使用される場合、「ニコチンアミドリボシド」は、ニコチンアミドリボシドのL−バリン及びL−フェニルアラニンエステルを含む。
[0103]
[0106]分化したヒトiPSC星状細胞は、Cellular Dynamics International(CDI、Madison、WI、USA)から入手した。細胞は、製造元の指示に従って解凍した。iCell星状細胞を、10%ウシ胎仔血清及びN2補体を添加したDMEMで培養した。
[0109]Seahorse装置を使用して、ミトコンドリア機能の指標としてhiPSC由来星状細胞における酸素消費速度を測定した。脱共役剤FCCPを添加することにより、脱共役(=最大)呼吸を決定した。
Claims (19)
- 酸化ストレス、酸化ストレスに関連する状態、グルタチオンレベルの低下、及びグルタチオンレベルの低下に関連する状態からなる群から選択される少なくとも1つの身体的状態を処置又は予防する方法であって、
有効量の、ニコチンアミドアデニンジヌクレオチド(NAD+)前駆体と少なくとも1種のケトン又はケトン前駆体との組み合わせを、当該組み合わせを必要とする個体に投与することを含む、方法。 - 前記少なくとも1つの身体的状態が、老化の有害な影響、筋減少、I型糖尿病、II型糖尿病、糖尿病合併症、インスリン抵抗性、メタボリックシンドローム、脂質異常症、過体重、肥満、コレステロールレベルの上昇、トリグリセリドレベルの上昇、脂肪酸レベルの増加、脂肪性肝疾患、心血管疾患、スタチン誘発性ミオパチーなどのミオパチー、非アルコール性脂肪性肝炎、耳鳴、めまい、アルコールによる二日酔い、難聴、骨粗鬆症、高血圧、アテローム性動脈硬化/冠動脈疾患、ストレス後の心筋障害、外傷性脳損傷、嚢胞性線維症、炎症、がん、HIV感染症、脳卒中、片頭痛、及び脳虚血からなる群から選択される、請求項1に記載の方法。
- 前記NAD+前駆体が、トリプトファン、ニコチン酸、ニコチンアミド、ニコチンアミドリボシド(NR)、還元型ニコチンアミドリボシド(NRH)、β−ニコチンアミドモノヌクレオチド(NMN)、トリゴネリン、ニコチン酸モノヌクレオチド、ニコチン酸リボシド、及びこれらの混合物からなる群から選択される、請求項1に記載の方法。
- 前記少なくとも1種のケトン又はケトン前駆体が、中鎖トリグリセリド(MCTs)、MCT誘導体、モノエステル、アセトアセテートジエステルなどのケトンエステル、ケトン塩、BHB(β−ヒドロキシブチレート)、D−BHB塩、β−ヒドロキシペンタノエート、β−ケトペンタノエート、アセトアセテート(AcA)、及びこれらの混合物からなる群から選択される、請求項1に記載の方法。
- 前記組み合わせが経腸的に投与される、請求項1に記載の方法。
- 前記組み合わせが、食品製品、栄養補助食品、経口栄養補助食品(ONS)、メディカルフード、及びこれらの組み合わせからなる群から選択される組成物として投与される、請求項1に記載の方法。
- 前記NAD+前駆体の少なくとも一部が、前記少なくとも1種のケトン又はケトン前駆体の少なくとも一部と同じ組成物で投与される、請求項1に記載の方法。
- 前記NAD+前駆体の少なくとも一部が、前記少なくとも1種のケトン又はケトン前駆体の少なくとも一部と異なる組成物で投与される、請求項1に記載の方法。
- 健康な中高年者において、代謝低下の最初を遅らせる、筋肉量を維持する、酸化ストレスを減少させる、及び/又は免疫機能を維持する方法であって、
有効量の、ニコチンアミドアデニンジヌクレオチド(NAD+)前駆体と少なくとも1種のケトン又はケトン前駆体との組み合わせを、前記健康な中高年者に投与することを含む、方法。 - 前記健康な中高年者が高齢者である、請求項9に記載の方法。
- 肥満又は糖尿病のうちの少なくとも1つを有する個体において、活性酸素種の代謝を増強する、グルコース調節を改善する、及び/又は筋機能を改善する方法であって、
有効量の、ニコチンアミドアデニンジヌクレオチド(NAD+)前駆体と少なくとも1種のケトン又はケトン前駆体との組み合わせを、前記個体に投与することを含む、方法。 - サルコペニアを有する個体においてミトコンドリア機能を改善する方法であって、
有効量の、ニコチンアミドアデニンジヌクレオチド(NAD+)前駆体と少なくとも1種のケトン又はケトン前駆体との組み合わせを、前記個体に投与することを含む、方法。 - 前記サルコペニアを有する個体が、サルコペニアを有すること以外は健康である、請求項12に記載の方法。
- 肥満及び/若しくは糖尿病の将来の発症を予防するための胎児代謝プログラミング、妊娠糖尿病中の母体及び胎児の健康、運動能力及び身体機能、生活の質、長寿、外傷後の回復及び生存、又は外傷及び手術からの回復のうちの1つ以上を改善する方法であって、
有効量の、ニコチンアミドアデニンジヌクレオチド(NAD+)前駆体と少なくとも1種のケトン又はケトン前駆体との組み合わせを、個体に投与することを含む、方法。 - 前記個体が、認知機能障害又は認知障害でなく、前記組成物が、認知を改善するのに有効な量の前記組み合わせを含む、請求項14に記載の方法。
- 筋パフォーマンス又は運動後の筋肉回復のうちの少なくとも1つを改善する方法であって、
前記運動前、前記運動中、及び前記運動後からなる群から選択される少なくとも1つの期間中に、有効量の、ニコチンアミドアデニンジヌクレオチド(NAD+)前駆体と少なくとも1種のケトン又はケトン前駆体との組み合わせを、前記運動を行う個体に投与することを含む、方法。 - ニコチンアミドアデニンジヌクレオチド(NAD+)前駆体と少なくとも1種のケトン又はケトン前駆体との組み合わせを含む組成物であって、
(i)酸化ストレス、酸化ストレスに関連する状態、グルタチオンレベルの低下、グルタチオンレベルの低下に関連する状態からなる群から選択される少なくとも1つの身体的状態の処置又は予防、あるいは(ii)肥満及び/若しくは糖尿病の将来の発症を予防するための胎児代謝プログラミング、妊娠糖尿病中の母体及び胎児の健康、運動能力及び身体機能、生活の質、長寿、外傷後の回復及び生存、又は外傷及び手術からの回復のうちの1つ以上の改善、のうちの少なくとも1つに有効な量の前記組み合わせを含む、組成物。 - 前記組み合わせの前記量が、老化の有害な影響、筋減少、I型糖尿病、II型糖尿病、糖尿病合併症、インスリン抵抗性、メタボリックシンドローム、脂質異常症、過体重、肥満、コレステロールレベルの上昇、トリグリセリドレベルの上昇、脂肪酸レベルの増加、脂肪性肝疾患、心血管疾患、スタチン誘発性ミオパチーなどのミオパチー、非アルコール性脂肪性肝炎、耳鳴、めまい、アルコールによる二日酔い、難聴、骨粗鬆症、高血圧、アテローム性動脈硬化/冠動脈疾患、ストレス後の心筋障害、外傷性脳損傷、嚢胞性線維症、炎症、がん、及びHIV感染症からなる群から選択される少なくとも1つの身体的状態を処置又は予防するのに有効である、請求項17に記載の組成物。
- 食品製品、栄養補助食品、経口栄養補助食品(ONS)、メディカルフード、及びこれらの組み合わせからなる群から選択される、請求項18に記載の組成物。
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