JP4903569B2 - サイトカインモジュレータ及び関係する使用法 - Google Patents
サイトカインモジュレータ及び関係する使用法 Download PDFInfo
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- JP4903569B2 JP4903569B2 JP2006525993A JP2006525993A JP4903569B2 JP 4903569 B2 JP4903569 B2 JP 4903569B2 JP 2006525993 A JP2006525993 A JP 2006525993A JP 2006525993 A JP2006525993 A JP 2006525993A JP 4903569 B2 JP4903569 B2 JP 4903569B2
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- blackberry
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- elderberry
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Description
本発明の組成物は、ローズヒップ、ブルーベリー、ブラックベリー、エルダーベリー、クランベリー、ローズマリー、クローブ、ナツシロギク、イラクサの根、アーティチョーク、霊芝、オリーブ抽出物、緑茶抽出物(没食子酸エピガロカテキン)、ブドウ種子抽出物、レスベラトロール、アフラモムムメレグエタ(Aframomum melegueta)、ボスウェリアセラータ(boswellia serrata)抽出物、ボスウェリアフォルテ(boswellia forte)、イプリフラボン、トコトリエノール、月見草油、INM−176、ルリヂサオイル、クリルオイル、少なくとも1種類のキサントフィル(例えばアスタキサンチン)、生コーヒー抽出物(クロロゲン酸)、及びフェルラ酸、から選択された少なくとも1つ又はそれ以上の成分を含んでいる。具体的には、本発明の組成物は、ローズヒップと、ブラックベリー、ブルーベリー及びエルダーベリーの内の少なくとも1種類とを含んでいる。組成物はまた、ローズヒップ、レスベラトロール、及びアフラモムムメレグエタ(Aframomum melegueta)を含んでいる。別の組成物は、ローズヒップ、レスベラトロール、及びアスタキサンチンを含んでいる。本組成物は、サイトカインの表出、産生、受容、分泌、及び/又は放出を抑制すると共に、サイトカインの応答を抑制して、それにより免疫調整及び/又は炎症反応の低減又は排除を図るために、ここに引用している何れの投薬量で投与してもよい。
ローズヒップ、ブラックベリー粉末、ブルーベリー粉末、及びエルダーベリー抽出物を含んでいる本発明の代表的な組成物は、以下の製法に従って錠剤形態に製造することができる。他の投与媒体、例えばゲルタブ、カプセル、液体、及び持続放出処方など、製薬産業で周知の製造技法に従って配合及び調合してもよい。
本発明は、特定の健康条件に最適で、且つ必要に応じて組成物に使用することのできる成分を選択するための成分選別操作を含んでいる。例えば、IL−1を調整するための栄養補給剤の場合には、活性成分は独自の選別操作を介して選択される。各種因子として、生物学的、商業的、規制的、及び記述的弁別子が含まれる。幾つかの好適な弁別子とその重み付け値を、表IIに概略的に掲げている。弁別子は、商業又は消費者主導の目的に基づいて重みが指定されることが望ましい。表IIでは、重み3は選別操作における弁別子の重み即ち重要度が高いことを(「因数3弁別子」);2は選別操作における重みはかなり重いが因数3の重みよりも軽いことを(「因数2弁別子」);そして1は弁別子としては重みが最も軽いことを(「因数1弁別子」)、それぞれ意味する。
本組成物の各成分は、少なくとも2種類の異なる生物学的メカニズムを介してサイトカインを調整することができる。第1のメカニズムでは、各成分は、インターロイキンサイトカインの産生即ち合成を抑制する。このメカニズムでは、インターロイキンサイトカインの産生をコード化する遺伝子のmRNA転写を、各成分が防止すると考えられている。従って、遺伝子転写が阻止され、サイトカインは、身体により又は体内で合成できなくなる。第2のメカニズムでは、体内の薬剤及び細胞のインターロイキンサイトカインに対する連鎖反応を各成分が抑制する。より具体的には、各成分は、化合物の中でもとりわけ急性期タンパク質、例えば、C反応性タンパク質(CRP)の産生を阻止する。CRPは、外傷及び/又は炎症の状態下でインターロイキンサイトカイン、例えばIL−1及びIL−6に応答して、肝臓内で肝細胞により合成される。各成分は、細胞、例えば肝臓の細胞のインターロイキンサイトカインに対する応答メカニズムに影響を及ぼして、それら細胞がCRPの産生を低下又は停止させる。
この評価では、白血球に各成分をそれぞれ異なる濃度で投与した。次いで、炎症刺激物であるリポポリサッカライド(lipoplysaccharide(LPS))を、成分と細胞を入れた培養物、並びに処理されていない白血球対照試料に加えた。成分で処理した細胞と処理していない細胞の両方のIL−1サイトカイン産生を比較して、細胞により産生されたIL−1の濃度に50%の変化が起きる成分の濃度を推定した。
本実施例のインターロイキン合成抑制評価を実施するために、ヒトの白血球、具体的にはバージニア州マナッサスのATCCから得たTHP−1細胞を、加湿した37℃の培養器に5%の二酸化炭素を供給してATCCの推奨条件下で成長させた。各種化合物のIL−1抑制能力を試験するため、複数のTHP−1細胞の群を96ウェルプレート(well plates)で培養した。具体的には5x105THP−1細胞を、10%ウシ胎仔血清と、ペニシリン及びストレプトマイシンのような抗生物質を加えたRPMI1640に入れた。これら細胞試料を入れた状態で、各成分を投与した。
本実施例では、本発明の組成物に含むことのできる他の成分を試験し、(a)これらの成分の、サイトカイン、例えばIL−1の分泌又は産生を低減及び/又は抑制する効果を評価し、(b)これら他の成分と随意の主要成分(ローズヒップ、アーティチョーク抽出物、オリーブ抽出物、及びイラクサの根)との相互作用を評価し、及び(c)肝細胞によるC反応性タンパク質(CRP)を測定することにより、これら他の成分の、肝細胞のインターロイキンサイトカイン、例えばIL−1応答に対する効果を評価した。
約150から200人の被験者に対して本発明の組成物を20週間に亘って毎日投与することにより、生体試験が行われる。より具体的には、(a)IL−1合成の抑制効果をパターン1個体群で評価し、(b)CRPレベルによって測定されるIL−1応答の抑制効果を、CRPレベルが3mgCRP/Lより上の血液を有するパターン2個体群で評価するため、組成物を試験する。
被験者50人に投与されることになる本発明の別の成分には、ローズヒップ、ブラックベリー、ブルーベリー、及びアフラモムムメレグエタ(Aframomum melegueta)が含まれ、一日の量としては、ローズヒップが1200mg、ブラックベリーが165mg、ブルーベリーが330mg、アフラモムムメレグエタ(Aframomum melegueta)が300mgである。これらの成分は錠剤の形態をしている。
上記実施例1から3の本発明の組成物に含まれる成分の試験結果に基づけば、上記成分を含む組成物は、被験者に投与されると、インターロイキンサイトカインを調整し、具体的には、インターロイキンサイトカインの合成を抑制し、C反応性タンパク質の合成を低減し、及び/又は被験者の体内におけるインターロイキンサイトカインに対する応答を抑制することが明らかである。
Claims (14)
- 被験者の炎症反応を治療するための組成物において、
50−5000mgの一日投薬量のローズヒップ、および40−2000mgの一日投薬量のブルーベリーを提供する、ローズヒップおよびブルーベリー、並びに
ブラックベリー、エルダーベリー、レスベラトロル、アフラモムメレゲータおよびそれらの混合物の少なくとも1つの治療上有効な量が含まれ、
前記被験者内で少なくともIL−1合成を抑制する組成物。 - 前記炎症反応は、炎症状態、疾病、及び症状の内の少なくとも1つによって発生する、請求項1に記載の組成物。
- 該組成物が、ローズヒップ、ブルーベリー、およびブラックベリーを含む、請求項1記載の組成物。
- 該組成物が、ローズヒップ、ブルーベリー、およびエルダーベリーを含む、請求項1記載の組成物。
- 該組成物が、ローズヒップ、ブルーベリー、ブラックベリー、およびエルダーベリーを含む、請求項1記載の組成物。
- 前記ブラックベリーの治療上有効な量は、一日投薬量当たり100mgである、請求項1、2、3または5に記載の組成物。
- 前記エルダーベリーの治療上有効な量は、一日投薬量当たり200mgである、請求項1、2、4または5に記載の組成物。
- レスベラトロールを、一日投薬量当たり200mgである治療上有効な量で含む、請求項1、3または4記載の組成物。
- アフラモムメレゲータを一日投薬量当たり150−1500mgである治療上有効な量で含む、請求項1、3、4または8記載の組成物。
- 前記被験者内のインターロイキンサイトカインおよび炎症のバイオマーカーの少なくとも1つの合成を抑制するに有効な治療上有効な量でアスタキサンチンをさらに含む、請求項1記載の組成物。
- 前記ブラックベリーは、前記被験者内の炎症のバイオマーカーの合成を低減する、請求項1に記載の組成物。
- 前記炎症のバイオマーカーはC反応性タンパク質である、請求項11に記載の組成物。
- 前記組成物は、炎症状態、疾病、及び硬直の内の少なくとも1つを低減する、請求項1、3、4または5に記載の組成物。
- 前記組成物は、少なくとも50mgのローズヒップと、少なくとも200mgのブルーベリーと、少なくとも100mgのブラックベリーと、少なくとも200mgのエルダーベリーと、を含んでいる、請求項1に記載の組成物。
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US7838050B2 (en) | 2010-11-23 |
TWI358300B (en) | 2012-02-21 |
KR20070028276A (ko) | 2007-03-12 |
WO2005025586A1 (en) | 2005-03-24 |
CN1882354A (zh) | 2006-12-20 |
CN102309573B (zh) | 2013-11-20 |
KR101245440B1 (ko) | 2013-03-19 |
JP2007513868A (ja) | 2007-05-31 |
US20050058728A1 (en) | 2005-03-17 |
CN102309573A (zh) | 2012-01-11 |
WO2005025586B1 (en) | 2005-05-06 |
CN1882354B (zh) | 2012-07-04 |
TW201206455A (en) | 2012-02-16 |
TW200518765A (en) | 2005-06-16 |
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