JP2018035200A - ドナリエラ属(Dunaliella)の粉末の治療的使用 - Google Patents
ドナリエラ属(Dunaliella)の粉末の治療的使用 Download PDFInfo
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Abstract
Description
本発明は、高いトリグリセリドおよび低い高−密度リポタンパク質(HDL)コレステロールレベル、アテローム硬化症および糖尿病を含む多数の状態の処置における粗製ドナリエラ バーダウィル(Dunaliella bardawil)粉末の使用に関する。
参考文献
以下の参考文献リストは、本発明の背景として直接関係があると考えられる:
1.非特許文献1
2.1980年3月18日に発効された特許文献1
3.1980年4月29日に発効された特許文献2
4.非特許文献2
5.非特許文献3
6.非特許文献4
ドナリエラ属(Dunaliella)の2種であるドナリエラ サリーナ(Dunaliella salina)Teod.およびドナリエラ バーダウィル(Dunaliella bardawil)は、単細胞で2本の鞭毛を持ち(biflagellate)、壁が無い緑藻で、大変大量のβ−カロテンを生産することができる(1)。D.バーダウィル(bardawil)は、β−カロテン含量が約50%の全トランス−β−カロテンから構成され、そして残りのほとんどが9−シスβ−カロテンおよび幾らかの他のβ−カロテン異性体からなる耐塩性の藻である(2)。最高約5重量%のβ−カロテンを含む藻を得るために、D.バーダウィル(bardawil)を培養する方法が記載された(3)。後にこの方法を開発して、この割合が8%以上に増加した。藻であるドナリエラ バーダウィル(Dunaliella bardawil)に蓄積するβ−カロテンの天然の異性体混合物は、合成の全トランス−β−カロテンを与えることにより観察されるよりも約10倍高い程度で、ラットおよびニワトリの脂肪組織に蓄積することが示された(4)。
本発明の目的は糖尿病、低血漿HDLおよび/または高血漿TGおよび/またはアテローム硬化症に罹患している患者の処置法を提供することである。
方法および材料
以下に記載するすべてのヒトの実験には、以下のように調製したドナリエラ属(Dunaliella)の粉末を含むカプセルを使用した。
第1実験の目的は、フィブラートと粗製ドナリエラ属(Dunaliella)の粉末が豊富な食事とを組み合わせた処置が、血漿アポAIおよびHDLコレステロールレベルに及ぼす効果を実験することであった。
ドナリエラ属(Dunaliella)のアテローム発生に及ぼす効果について試験するために、オスのアポ−E欠損マウス(n=10)に、8%の粗製ドナリエラ属(Dunaliella)の粉末を補充した上記のような標準的な餌を6週間与えた。対照群(n=10)は餌のみを受けた。大動脈洞で損傷サイズにより決定されるアテローム硬化症は、対照群のマウスよりも粗製ドナリエラ属(Dunaliella)の粉末で処置したマウスの群で34%低かった(図2)。
ドナリエラ属(Dunaliella)の粉末がアテローム発生に及ぼす効果について試験するために、オスのアポ−E欠損マウス(n=13)に、8%のドナリエラ属(Dunaliella)の粉末を補充した標準的な餌を8週間与えた。第2群(n=12)はβ−カロテンを含まない酸化したドナリエラ属(Dunaliella)の粉末で処置する一方、対照群(n=12)は餌のみを受けた。大動脈洞で損傷サイズにより決定されるアテローム硬化症は、対照群のマウスよりもドナリエラ属(Dunaliella)の処置群で33%低かった、p=0.027(図3)。対照的に、酸化したドナリエラ属(Dunaliella)の粉末はアテローム発生に影響しなかった。
ドナリエラ属(Dunaliella)がアテローム発生に及ぼす効果について試験するために、オスのLDL受容体欠損マウス(n=10)に、8%のドナリエラ属(Dunaliella)の粉末を補充した標準的な餌を3週間与え、続いて西洋食を7週間与えた。第2群は酸化したドナリエラ属(Dunaliella)の粉末で処置し(n=10)、そして対照群(n=10)は餌、続いて西洋食のみを受けた。大動脈洞で損傷サイズにより決定されるアテローム硬化症は、ドナリエラ属(Dunaliella)で処置した群で対照群よりも65%低かった、p=0.004(図4)。対照的に、酸化したドナリエラ属(Dunaliella)の粉末はアテローム発生に影響しなかった。
コレステロール吸収は、14C−コレステロール(これは様々に吸収される)に対する3H−シトステノール(これは吸収されない)の便排出の比率を測定する糞便二重アイソトープ法(fecal dual isotope method)により測定した。アポ−E欠損マウスを2群に分け、ドナリエラ属(Dunaliella)で処置したマウス群は、餌の中に8%の粗製ドナリエラ属(Dunaliella)の粉末を3週間投与して(n=6)、そして対照群(n=6)は餌のみを受けた。粗製ドナリエラ属(Dunaliella)の粉末のアポ−E欠損マウスへの投与は(RXRアゴニストについて前に記載したものに類似して)、コレステロール吸収の阻害をもたらした(図5)。
ヒトの実験の目的は、低HDL(<35mg/dl)および高TGレベル(>250mg/dl)の患者においてフィブラートと粗製ドナリエラ バーダウィル(Dunaliella bardawil)の粉末との組み合わせの効果を実験することであった。
ドナリエラ属(Dunaliella)の糖尿病に及ぼす効果を試験するために、オスのLDLR−/−マウス(n=30)に糖尿病を誘導するために西洋食(脂肪から42%のカロリー)を与えた。西洋食の摂取から4週間後、マウスを6群に分け(各群n=5)、そしてロシグリタゾン(rosiglitazone)(食事の0.02重量/重量%)、粗製ドナリエラ属(Dunaliella)の粉末(食事の8重量/重量%)または9−シスレチノイン酸(24ナノモル/マウスx日)により強化された西洋食を与えた。処置は4週間続けた。
1.対照、西洋食のみ(対照)
2.9−シスレチノイン酸(RA)
3.ロシグリタゾン(Rosi)
4.ドナリエラ属(Dunaliella)の粉末8%(Dun)
結果
ドナリエラ属(Dunaliella)の処置は、ロシグリタゾンおよび対照群に比べて血漿グルコースおよびインスリンレベルの両方を下げた(図7および8)。さらにドナリエラ属(Dunaliella)の処置は、ロシグリタゾン群に比べて血漿コレステロールおよびTGレベルの両方を有意に下げた(図9および10)。他方、9−シスレチノイン酸は血漿インスリンおよびグルコースレベルに影響を与えず、そしてドナリエラ属(Dunaliella)群のそれらのレベルは有意に低かった。結果はドナリエラ属(Dunaliella)の粉末が、LDLR−/−マウスモデルにおいて9−シスレチノイン酸またはロシグリタゾンよりも効果的に血漿インスリンおよびグルコースレベルを下げることができることを証明する。
Claims (17)
- 有効量の実質的に粗製のドナリエラ属(Dunaliella)の藻類調製物および核内受容体の1以上のアクチベーターを含んでなる、アテローム硬化症に罹患した対象のHDLコレステロールの血漿レベルの増加および大動脈洞での損傷サイズの低減のうちの少なくとも1つにおける使用のための薬剤。
- アテローム硬化症の処置に使用するための、請求項1に記載の薬剤。
- 核内受容体のアクチベーターがペルオキシソーム増殖因子活性化受容体αまたはγ(PPARαまたはPPARγ)アゴニストである、請求項1または2に記載の薬剤。
- PPARαまたはPPARγアゴニストがフィブラートである、請求項3に記載の薬剤。
- フィブラートがクロフィブラート、フェノフィブラート、ベザフィブラート、シプロフィブラート、ベクロフィブラートおよびゲムフィブロジルから選択される、請求項4に記載の薬剤。
- フィブラートがベザフィブラートおよびシプロフィブラートのうちの少なくとも一つである、請求項5に記載の薬剤。
- 上記の粗製のドナリエラ属(Dunaliella)の粉末が経口的に投与される、請求項1から6のいずれか一項に記載の薬剤。
- 上記藻類がドナリエラ バーダウィル(Dunaliella Bardawil)である請求項1から7のいずれか一項に記載の薬剤。
- 上記粉末がカプセル化されている、請求項1から8のいずれか一項に記載の薬剤。
- アテローム硬化症に罹患した対象のHDLコレステロールの血漿レベルの増加および大動脈洞での損傷サイズの低減のうちの少なくとも1つにおける使用のための製薬学的組成物の調製における、フィブラートと有効量の実質的に粗製のドナリエラ属(Dunaliella)の藻類調製物の使用。
- アテローム硬化症の処置に使用するための、請求項10に記載の使用。
- フィブラートがクロフィブラート、フェノフィブラート、ベザフィブラート、シプロフィブラート、ベクロフィブラートおよびゲムフィブロジルから選択される、請求項10または11に記載の使用。
- フィブラートがベザフィブラートおよびシプロフィブラートのうちの少なくとも一つである、請求項12に記載の使用。
- 上記の粗製のドナリエラ属(Dunaliella)の粉末が経口的に投与される、請求項10から13のいずれか一項に記載の使用。
- 上記藻類がドナリエラ バーダウィル(Dunaliella Bardawil)である、請求項10から14のいずれか一項に記載の使用。
- 上記粉末がカプセル化されている、請求項10から15のいずれか一項に記載の使用。
- アテローム硬化症に罹患した対象の大動脈洞におけるアテローム発生の阻害に使用するための製薬学的組成物の調製における、有効量の粗製のドナリエラ属(Dunaliella)の藻類の使用。
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JP2009187809A Active JP5356946B2 (ja) | 2003-09-24 | 2009-08-13 | ドナリエラ属(Dunaliella)の粉末の治療的使用 |
JP2013126599A Withdrawn JP2013177457A (ja) | 2003-09-24 | 2013-06-17 | ドナリエラ属(Dunaliella)の粉末の治療的使用 |
JP2016104166A Active JP6321074B2 (ja) | 2003-09-24 | 2016-05-25 | ドナリエラ属(Dunaliella)の粉末の治療的使用 |
JP2017235555A Active JP6490782B2 (ja) | 2003-09-24 | 2017-12-07 | ドナリエラ属(Dunaliella)の粉末の治療的使用 |
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JP2004212054A Active JP5020463B2 (ja) | 2003-09-24 | 2004-07-20 | ドナリエラ属(Dunaliella)の粉末の治療的使用 |
JP2009187809A Active JP5356946B2 (ja) | 2003-09-24 | 2009-08-13 | ドナリエラ属(Dunaliella)の粉末の治療的使用 |
JP2013126599A Withdrawn JP2013177457A (ja) | 2003-09-24 | 2013-06-17 | ドナリエラ属(Dunaliella)の粉末の治療的使用 |
JP2016104166A Active JP6321074B2 (ja) | 2003-09-24 | 2016-05-25 | ドナリエラ属(Dunaliella)の粉末の治療的使用 |
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EP (2) | EP1522310B1 (ja) |
JP (5) | JP5020463B2 (ja) |
AT (1) | ATE548046T1 (ja) |
HK (1) | HK1071845A1 (ja) |
IL (1) | IL162987A (ja) |
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JP2007210917A (ja) * | 2006-02-08 | 2007-08-23 | Kochi Univ | 脂肪細胞縮小化剤、医薬品及び飲食品 |
AU2006341188A1 (en) * | 2006-03-24 | 2007-10-04 | Ian Simon Tracton | Stable packaged dosage form and process therefor |
JP2008222555A (ja) * | 2007-03-08 | 2008-09-25 | Nagasakiken Koritsu Daigaku Hojin | アディポネクチン受容体発現増加剤 |
WO2009105048A2 (fr) * | 2008-02-19 | 2009-08-27 | Rached Smida | Nouvelles applications du hdl reconstitué |
JP5443470B2 (ja) | 2008-04-29 | 2014-03-19 | 株式会社日健総本社 | 眼障害の治療方法 |
JP5733592B2 (ja) * | 2008-10-20 | 2015-06-10 | 株式会社日健総本社 | 脂質異常治療薬の副作用防止物質 |
US8747834B2 (en) | 2009-03-03 | 2014-06-10 | Solazyme, Inc. | Methods of treating impaired glucose metabolism via administration of algal biomass |
US9180152B2 (en) | 2009-12-10 | 2015-11-10 | Nikken Sohonsha Corporation | Method for treating psoriasis |
US9577089B2 (en) | 2010-03-02 | 2017-02-21 | Vishay-Siliconix | Structures and methods of fabricating dual gate devices |
US10098371B2 (en) | 2013-01-28 | 2018-10-16 | Solazyme Roquette Nutritionals, LLC | Microalgal flour |
FR3009619B1 (fr) | 2013-08-07 | 2017-12-29 | Roquette Freres | Compositions de biomasse de microalgues riches en proteines de qualite sensorielle optimisee |
GB201718822D0 (en) | 2017-11-14 | 2017-12-27 | Univ Greenwich | Production of dunaliella |
JP6947665B2 (ja) * | 2018-03-13 | 2021-10-13 | アイカ工業株式会社 | 光硬化性粘着樹脂組成物 |
CN113905750A (zh) * | 2019-04-01 | 2022-01-07 | 戴尔哈修墨医学研究内结构和服务有限公司 | 用于预防及/或治疗神经退行性疾病、与蛋白质错误折叠关联的疾病及认知能力下降的杜氏藻属藻类制剂 |
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US20080019997A1 (en) | 2008-01-24 |
US8343549B2 (en) | 2013-01-01 |
JP6321074B2 (ja) | 2018-05-09 |
JP2016147916A (ja) | 2016-08-18 |
EP1522310A1 (en) | 2005-04-13 |
US20100221348A1 (en) | 2010-09-02 |
EP1522310B1 (en) | 2012-03-07 |
JP2013177457A (ja) | 2013-09-09 |
JP5356946B2 (ja) | 2013-12-04 |
JP2009256392A (ja) | 2009-11-05 |
HK1071845A1 (en) | 2005-08-05 |
EP2269620A1 (en) | 2011-01-05 |
US7763255B2 (en) | 2010-07-27 |
US20050063991A1 (en) | 2005-03-24 |
JP2005097255A (ja) | 2005-04-14 |
ATE548046T1 (de) | 2012-03-15 |
IL162987A (en) | 2013-06-27 |
US7264813B2 (en) | 2007-09-04 |
JP5020463B2 (ja) | 2012-09-05 |
JP6490782B2 (ja) | 2019-03-27 |
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