JP2015147773A - Hmb組成物及びその使用 - Google Patents
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Abstract
Description
タンパク質キナーゼCは、カルシウム及び脂質により活性化されるセリン−スレオニンキナーゼのファミリーであり、多くの細胞内シグナル伝達カスケードにおいて重要な役割を担う。少なくとも12個の異なるPKCアイソタイプがあり、それらはその一次構造及び生化学的特性に基づいて3つのクラスへ分類される(CA Carter:“Protein kinase C as a drug target:Implications for drug or diet prevention and treatmento of cancer.”Current Drug Targets 1: 163−183 (2000))。これらは、活性化のためにジアシルグリセロール、ホスファチジルセリン及びカルシウムを要する従来型(cPKCα、βI、βII及びγ)、ジアシルグリセロール及びホスファチジルセリンを要するがカルシウムとは無関係の新規型(nPKCδ、ε、η、θ及びμ)、並びにカルシウム及びジアシルグリセロールとは無関係の非定型(aPKCλ、τ及びζ)である。
核因子κB(NFκB)は、哺乳類細胞の幅広い種類で見られる転写因子のファミリーである。成熟分子は、次の5つの遺伝子産物(RelA (p65)、p50、RelB、c−Rel及びp52)の1つ又は2つから生成されるホモ二量体又はヘテロ二量体であり、そのもっとも共通のものはRelA及びp50の二量体である。非活性化条件下で、NFκBは、阻害性タンパク質IκBαとの会合によって、サイトゾルに局在化する。上流のシグナル伝達はIκBキナーゼを包含し、結合したIκBαのリン酸化はNFκBからのその放出を生じ、後者を核へと転移させ、特異的遺伝子転写を活性化させる。リン酸化したIκBαはユビキチン−プロテオソーム経路によって分解される。
Claims (21)
- HMB、HMBの塩、これらの代謝産物又は誘導体を投与することを含む、タンパク質キナーゼC、核因子κB、ユビキチン連結酵素及び26Sプロテアソームの構成要素からなる群から選択される構成要素の発現及び/又は活性を下方制御することによる、患者における疾病状態の予防又は治療のための方法。
- HMB、HMBの塩、これらの代謝産物又は誘導体の投与がタンパク質キナーゼCの発現及び/又は活性を下方制御する、請求項1に記載の方法。
- HMB、HMBの塩、これらの代謝産物又は誘導体の投与が核因子κBの発現及び/又は活性を下方制御する、請求項1に記載の方法。
- HMB、HMBの塩、これらの代謝産物又は誘導体の投与がユビキチン連結酵素の発現及び/又は活性を下方制御する、請求項1に記載の方法。
- HMB、HMBの塩、これらの代謝産物又は誘導体の投与が26Sプロテアソームの構成要素の発現及び/又は活性を下方制御する、請求項1に記載の方法。
- L−カルニチン、遊離アミノ酸を実質的に欠如する大型中性アミノ酸で強化されたアミノ窒素源、ω−3脂肪酸及び難消化性オリゴ糖からなる群から選択される構成要素の少なくとも1つがHMB又はHMBの塩との組み合わせで投与される、請求項1に記載の方法。
- 疾病状態が癌、カヘキシー、年齢関連消耗、長期入院と関連した消耗、HIV/エイズ、関節炎、外傷、肝疾患、クローン病、IBD、腎不全及びCOPDからなる群から選択される、請求項1に記載の方法。
- 疾病がカヘキシーである、請求項7に記載の方法。
- a.HMB、HMBの塩、これらの代謝産物又は誘導体、
b.カルニチン、
c.大型中性アミノ酸で強化されたアミノ窒素源
を含み、遊離アミノ酸を実質的に欠如する組成物。 - HMBがHMBナトリウム、HMBカリウム、HMBマグネシウム、HMBクロム、HMBカルシウム、HMBアルカリ金属、HMBアルカリ土類金属及びHMBラクトンからなる群から選択される、請求項9に記載の組成物。
- ω−3脂肪酸をさらに含む、請求項9に記載の組成物。
- 前記ω−3脂肪酸がエイコサペンタエン酸及びドコサヘキサエン酸からなる群から選択される、請求項11に記載の組成物。
- 前記大型中性アミノ酸がアミノ窒素源の少なくとも10%である、請求項9に記載の組成物。
- 前記遊離アミノ酸が組成物の0.4g/回未満である、請求項9に記載の組成物。
- カルニチンの2g未満/回をさらに含む、請求項9に記載の組成物。
- FOSの少なくとも1g/回をさらに含む、請求項9に記載の組成物。
- ビタミン、ミネラル及び微量ミネラルからなる群から選択される栄養素をさらに含む、請求項9に記載の組成物。
- a.HMBカルシウムの約2g/lから10g/lまで、
b.ω−3脂肪酸の少なくとも1g/l、
c.カルニチンの約1g/lから約8g/lまで、
d.FOSの約1g/lから約25g/lまで、
大型中性アミノ酸で強化されたアミノ窒素源を含む組成物であり、前記アミノ窒素源が大型中性アミノ酸の約10重量%から60重量%までを含み、及び前記組成物が遊離アミノ酸を実質的に欠如する組成物。 - 組成物がヒト又は動物へ投与される、請求項9に記載の組成物。
- 組成物が食事性サプリメント、食事置換物、栄養バー、咀嚼物又は咬合物及び飲料からなる群から選択される、請求項9に記載の組成物。
- 請求項9に記載の組成物を患者へ投与することを含む、患者の疾病関連消耗を治療する方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/810,762 | 2004-03-26 | ||
US10/810,762 US20050215640A1 (en) | 2004-03-26 | 2004-03-26 | HMB compositions and uses thereof |
Related Parent Applications (1)
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JP2012139422A Division JP5732437B2 (ja) | 2004-03-26 | 2012-06-21 | Hmb組成物及びその使用 |
Publications (2)
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JP2015147773A true JP2015147773A (ja) | 2015-08-20 |
JP2015147773A5 JP2015147773A5 (ja) | 2015-10-08 |
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JP2007504991A Active JP5145033B2 (ja) | 2004-03-26 | 2005-03-14 | Hmb組成物及びその使用 |
JP2012139422A Active JP5732437B2 (ja) | 2004-03-26 | 2012-06-21 | Hmb組成物及びその使用 |
JP2015045519A Pending JP2015147773A (ja) | 2004-03-26 | 2015-03-09 | Hmb組成物及びその使用 |
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JP2007504991A Active JP5145033B2 (ja) | 2004-03-26 | 2005-03-14 | Hmb組成物及びその使用 |
JP2012139422A Active JP5732437B2 (ja) | 2004-03-26 | 2012-06-21 | Hmb組成物及びその使用 |
Country Status (15)
Country | Link |
---|---|
US (9) | US20050215640A1 (ja) |
EP (3) | EP2444082B1 (ja) |
JP (3) | JP5145033B2 (ja) |
KR (2) | KR101253063B1 (ja) |
CN (1) | CN101212961A (ja) |
AU (1) | AU2005235133B2 (ja) |
BR (1) | BRPI0509017A (ja) |
CA (2) | CA2807787C (ja) |
EC (1) | ECSP066873A (ja) |
ES (2) | ES2586402T3 (ja) |
HK (1) | HK1155972A1 (ja) |
IL (1) | IL178039A0 (ja) |
MX (1) | MXPA06010922A (ja) |
TW (1) | TWI369981B (ja) |
WO (1) | WO2005102301A2 (ja) |
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