JP5197355B2 - ポリフェノールとコキシブの組み合わせおよび方法 - Google Patents
ポリフェノールとコキシブの組み合わせおよび方法 Download PDFInfo
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Description
本発明は、ポリフェノールおよび非ポリフェノールであるシクロオキシゲナーゼ−2(COX−2)阻害剤が、最も典型的に、治療的に有効な組み合わせとして提供される組成物および方法を、対象とする。このような組み合わせは、好ましくは、ポリフェノールの抗腫瘍効果が非ポリフェノールであるシクロオキシゲナーゼ−2阻害剤により高められるように配合される(および/または逆)。
本発明者らは、意外にも、COX−2阻害剤の抗腫瘍作用がCOX−2阻害剤と1つまたはそれ以上のポリフェノールとの併用療法により実質的に増大され得ることを発見した。際立ったことに、増大した抗腫瘍効果が腫瘍発生率の低減の点で相乗的であるだけでなく、腫瘍多重度をも実質的に低減することに、注目すべきである。
企図されたポリフェノールの投与
すでに上で論じたように、多くの単離したおよび/または合成したポリフェノールを投与し得るが、しかしながら、特に好ましい態様において、緑茶から単離したポリフェノールの混合物を採用する。最も好ましいポリフェノール混合物は、ポリフェノンEとして三井農林から市販されている。経口投与のための多くの他の用量および配合のなかで、好ましい用量および投与計画がClin.Cancer Res.2003 Aug 15;9(9):3312−9中に記述されており、これを本明細書中に参照により組み込む。
同様に、様々なCOX−2阻害剤を種々の投与量および計画で投与し得ることが、企図される。しかしながら、特に好ましい態様において、COX−2阻害剤は、炎症性疾患の治療において医師が通常処方する用量および計画で投与される(例えば、セレコキシブおよびロフェコキシブを、それぞれ、200から800mgおよび12.5から50mgの1日用量で)。最も好ましくは、そして許容できる場合、用量を最高許容量に調整する。
非小細胞肺癌および小細胞肺癌の患者における続発性肺癌の危険性は、患者1人につき1年あたり、それぞれ1から2%および2から10%であると推定される。シスプラチンは、肺癌治療に広く使用され、実験動物における発癌物質としても公知である。我々は、最近、(−)−エピガロカテキンガレートまたはCOX−2阻害剤であるセレコキシブが、個々の化合物として投与された場合、A/Jマウスにおけるシスプラチン誘発肺腫瘍を部分的に阻害することを、報告した(Carcinogenesis.21(5):915,2000;Proc AACR 44 #4920:981,2003)。しかしながら、これらと他の化合物の組み合わせは、実施/発表していなかった。組み合わせ治療の結果を、以下の実施例1および2のそれぞれの項に提供する。
Claims (17)
- 少なくとも1つのポリフェノールと、非ポリフェノールであるシクロオキシゲナーゼ−2(COX−2)阻害剤とを含む、哺乳動物における腫瘍発生率又は腫瘍多重度を低減するための医薬組成物であって、
前記ポリフェノールがエピガロカテキンガレートであり、
前記非ポリフェノールであるCOX−2阻害剤がセレコキシブである
ことを特徴とする、医薬組成物。 - ポリフェノールが緑茶ポリフェノールである、請求項1に記載の医薬組成物。
- シクロオキシゲナーゼ−2阻害剤が、1日あたり5mg〜500mgの投与に適した用量であり、ならびにポリフェノールが、1日あたり50mg〜1500mgの投与に適した用量である、請求項1または2に記載の医薬組成物。
- 哺乳動物における腫瘍多重度が肺癌多重度である、請求項1〜3のいずれか一項に記載の医薬組成物。
- 少なくとも1つのポリフェノールおよびシクロオキシゲナーゼ−2阻害剤が別々の投与単位で配合されている、請求項1〜4のいずれか一項に記載の医薬組成物。
- 少なくとも1つのポリフェノールが、化学的に異なるポリフェノールの混合物の一部として組成物中に存在している、請求項1〜5のいずれか一項に記載の医薬組成物。
- 化学的に異なるポリフェノールの混合物がポリフェノンEを含む、請求項6に記載の医薬組成物。
- 腫瘍多重度を低減する医薬の製造における組成物の使用であって、
前記組成物は少なくとも1つのポリフェノールと、非ポリフェノールであるCOX−2阻害剤とを含んでなり、
ここで前記ポリフェノールがエピガロカテキンガレートであり、
前記非ポリフェノールであるCOX−2阻害剤がセレコキシブである
ことを特徴とする、使用。 - シクロオキシゲナーゼ−2阻害剤の用量が、1日あたり5mg〜500mgである、請求項8に記載の使用。
- ポリフェノールの用量が、1日あたり50mg〜1500mgである、請求項8または9に記載の使用。
- 医薬がポリフェノールおよびシクロオキシゲナーゼ−2阻害剤を同時投与するように配合されている、請求項8〜10のいずれか一項に記載の使用。
- 腫瘍が肺腫瘍である、請求項8〜11のいずれか一項に記載の使用。
- ポリフェノールおよびシクロオキシゲナーゼ−2阻害剤が単一投与単位で配合されている、請求項8〜12のいずれか一項に記載の使用。
- 緑茶ポリフェノールと、非ポリフェノールであるシクロオキシゲナーゼ−2阻害剤とを含み、さらに栄養補助的に許容できる担体を含んでなる、哺乳動物における腫瘍発生率又は腫瘍多重度を低減するための添加剤であって、
前記ポリフェノールがエピガロカテキンガレートであり、
前記非ポリフェノールであるCOX−2阻害剤がセレコキシブである
ことを特徴とする、添加剤。 - ポリフェノールが、化学的に異なるポリフェノールの混合物の一部として製品中に存在している、請求項14に記載の添加剤。
- 化学的に異なるポリフェノールの混合物がポリフェノンEを含む、請求項14または15に記載の添加剤。
- ロスマリヌス種(Rosmarinus spec.)、ウンカリア・トメントーサ(Uncaria tomentosa)およびハイペリカム種(Hypericum spec.)からなる群から選択される植物の抽出物の少なくとも1つ、またはアスコルビン酸塩、クルクミン、シリマリン、ビタミンE、ガンマリノール酸およびオメガ−3−脂肪酸からなる群から選択される化合物をさらに含む、請求項14〜16のいずれか一項に記載の添加剤。
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US66051105P | 2005-03-08 | 2005-03-08 | |
US60/660,511 | 2005-03-08 | ||
PCT/US2006/008284 WO2006096778A2 (en) | 2005-03-08 | 2006-03-08 | Polyphenol coxib combinations and methods |
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JP2008533023A JP2008533023A (ja) | 2008-08-21 |
JP2008533023A5 JP2008533023A5 (ja) | 2009-02-05 |
JP5197355B2 true JP5197355B2 (ja) | 2013-05-15 |
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US (1) | US8128967B2 (ja) |
EP (1) | EP1858507B1 (ja) |
JP (1) | JP5197355B2 (ja) |
CN (1) | CN101237863A (ja) |
CA (1) | CA2600276C (ja) |
ES (1) | ES2397085T3 (ja) |
WO (1) | WO2006096778A2 (ja) |
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GB0615781D0 (en) * | 2006-08-09 | 2006-09-20 | Coressence Ltd | Prebiotic composition |
US8734867B2 (en) | 2007-12-28 | 2014-05-27 | Liveleaf, Inc. | Antibacterial having an extract of pomegranate combined with hydrogen peroxide |
JP5744512B2 (ja) * | 2010-12-28 | 2015-07-08 | 花王株式会社 | 容器詰飲料 |
US8722040B2 (en) | 2011-06-24 | 2014-05-13 | Liveleaf, Inc. | Site-activated binding systems that selectively increase the bioactivity of phenolic compounds at target sites |
US9192635B2 (en) | 2011-06-24 | 2015-11-24 | Liveleaf, Inc. | Method of treating damaged mucosal or gastrointestinal tissue by administering a composition comprising a mixture of pomegranate and green tea extracts and releasably bound hydrogen peroxide |
US8716351B1 (en) | 2012-12-23 | 2014-05-06 | Liveleaf, Inc. | Methods of treating gastrointestinal spasms |
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NZ506515A (en) | 1996-10-15 | 2002-05-31 | G | COX-2 inhibitor (4-[5-(4-chlorophenyl)-3(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide) for treating neoplasia |
US6326507B1 (en) * | 1998-06-19 | 2001-12-04 | Trustees Of Dartmouth College | Therapeutic compounds and methods of use |
US20040053900A1 (en) * | 1998-12-23 | 2004-03-18 | Pharmacia Corporation | Method of using a COX-2 inhibitor and an aromatase inhibitor as a combination therapy |
US6649645B1 (en) * | 1998-12-23 | 2003-11-18 | Pharmacia Corporation | Combination therapy of radiation and a COX-2 inhibitor for treatment of neoplasia |
US6428818B1 (en) | 1999-03-30 | 2002-08-06 | Purdue Research Foundation | Tea catechin formulations and processes for making same |
WO2000057875A1 (en) * | 1999-03-30 | 2000-10-05 | Purdue Research Foundation | Compositions containing tea catechins as cancer specific proliferation inhibitors |
AU5140300A (en) * | 1999-05-17 | 2000-12-05 | Ilex Oncology, Inc. | Dfmo and celecoxib in combination for cancer chemoprevention and therapy |
US6630160B1 (en) * | 1999-09-07 | 2003-10-07 | Genetic Services Management, Inc. | Process to modulate disease risk with doses of a nutraceutical |
US6775951B2 (en) * | 2000-01-28 | 2004-08-17 | Larry Gumpert | Metal roofing light transmitting panel |
CA2396593A1 (en) * | 2000-01-28 | 2001-08-02 | Merck & Co., Inc. | Treatment or prevention of prostate cancer with a cox-2 selective inhibiting drug |
US6713506B2 (en) * | 2000-10-11 | 2004-03-30 | University Of South Florida | Tea polyphenol esters and analogs thereof for cancer prevention and treatment |
US6902739B2 (en) * | 2001-07-23 | 2005-06-07 | Nutracea | Methods for treating joint inflammation, pain, and loss of mobility |
US6953786B2 (en) * | 2002-10-01 | 2005-10-11 | The Regents Of The University Of California | Compositions comprising plant-derived polyphenolic compounds and inhibitors of reactive oxygen species and methods of using thereof |
US6821536B2 (en) | 2002-11-22 | 2004-11-23 | Quercegen Holdings Llc | Antioxidative compositions |
EP1633208A1 (en) | 2003-05-27 | 2006-03-15 | DSM IP Assets B.V. | Novel nutraceutical compositions and use thereof |
WO2005013902A2 (en) * | 2003-08-04 | 2005-02-17 | Mayo Foundation For Medical Education And Research | Methods and compositions for inhibiting the proliferation of prostate cancer cells |
DE20316876U1 (de) * | 2003-11-03 | 2004-02-05 | China Vital Med E.K. | Nahrungsergänzungsmittel |
US7067159B2 (en) * | 2003-12-05 | 2006-06-27 | New Chapter, Inc. | Methods for treating prostate cancer with herbal compositions |
WO2005072760A1 (en) * | 2004-01-23 | 2005-08-11 | The Medical College Of Ohio | Polyphenols as an intravesical agent for the prevention of transitional cell tumor implantation |
-
2006
- 2006-03-08 US US11/817,999 patent/US8128967B2/en not_active Expired - Fee Related
- 2006-03-08 CA CA2600276A patent/CA2600276C/en not_active Expired - Fee Related
- 2006-03-08 WO PCT/US2006/008284 patent/WO2006096778A2/en active Application Filing
- 2006-03-08 EP EP06737455A patent/EP1858507B1/en not_active Not-in-force
- 2006-03-08 CN CNA2006800157514A patent/CN101237863A/zh active Pending
- 2006-03-08 JP JP2008500877A patent/JP5197355B2/ja not_active Expired - Fee Related
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Also Published As
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CN101237863A (zh) | 2008-08-06 |
US8128967B2 (en) | 2012-03-06 |
EP1858507A2 (en) | 2007-11-28 |
JP2008533023A (ja) | 2008-08-21 |
US20090028963A1 (en) | 2009-01-29 |
EP1858507B1 (en) | 2012-11-28 |
WO2006096778A3 (en) | 2006-11-09 |
ES2397085T3 (es) | 2013-03-04 |
WO2006096778A2 (en) | 2006-09-14 |
CA2600276A1 (en) | 2006-09-14 |
CA2600276C (en) | 2013-01-08 |
EP1858507A4 (en) | 2008-09-10 |
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