JP2005510537A - 化学療法の所望されない効果を改善する方法および組成物 - Google Patents
化学療法の所望されない効果を改善する方法および組成物 Download PDFInfo
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- JP2005510537A JP2005510537A JP2003546839A JP2003546839A JP2005510537A JP 2005510537 A JP2005510537 A JP 2005510537A JP 2003546839 A JP2003546839 A JP 2003546839A JP 2003546839 A JP2003546839 A JP 2003546839A JP 2005510537 A JP2005510537 A JP 2005510537A
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- allopurinol
- methyl
- dimethyl
- chemical
- glutathione
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Abstract
Description
本発明は、化学療法(例えばシスプラチンを使用する化学治療)の所望されない効果を改善する方法および組成物に関する。
癌の処置の1つのアプローチは、化学療法であり、その化学療法において、癌細胞に有毒な、または別の点で有害な1つ以上の化学物質が、癌を罹患した個体に投与される。不運なことに、ほとんどの(全部ではないが)化学治療剤が、患者の健康に悪影響を与える所望されない効果を引き起こす。
一つの局面において、本発明は、本明細書中に開示された少なくとも2つの化学保護剤を各々含む化学保護剤組成物を提供する。本発明の化学保護剤組成物は、例えば、少なくとも1つの化学療法の有害な効果の改善に対して有用である。
(好ましい実施形態の詳細な説明)
本明細書中で使用される場合、用語「化学保護剤」は、化学療法の少なくとも1つの有害な効果を改善し得る化学物質を言う。
群A(グルタチオンまたはグルタチオン前駆体):メチオニン;N−アセチル−DL−メチオニン;S−アデノシルメチオニン;システイン;N−アセチルシステイン;グルタチオン;グルタチオンエチルエステル;グルタチオンジエチルエステル;グルタチオントリエチルエステル;DiNAC;RibCys;ホモシステイン;シスタチオン;シスタミン;OTCAおよびRibCyst。
この実施例は、N−アセチルシステイン、Ebselenおよびアロプリノール(単独で、または組み合わせた)が、MTS細胞生存可能性アッセイを使用して測定された場合、シスプラチンの能力を阻害せず、培養NuTu−19卵巣癌腫瘍細胞を殺すことを示す。
図5は、培養培地中のN−アセチルシステインの濃度に対する生存培養NuTu−19卵巣癌細胞のパーセンテージのプロットを示す。N−アセチルシステインおよびEbselen存在下(47μMの濃度)であるがシスプラチン非存在下で培養されたNuTu−19細胞の生存能力は、上のグラフで示される。N−アセチルシステイン、Ebselen(47μMの濃度)およびシスプラチン(43μMの濃度)存在下で培養されたNuTu−19細胞の生存能力は、下のグラフで示される。図5に示したデータは、N−アセチルシステインおよびEbselenの組み合わせが、シスプラチンの能力を阻害せず、培地中でNuTu−19卵巣癌腫瘍細胞を殺傷することを示している。
(実施例2)
この実施例は、Ebselenが、インビトロにおいてシスプラチンによる損傷から内耳有毛細胞を保護することを示す。
この実施例は、EbselenおよびEbselenとアロプリノールとの組み合わせが、インビボにおいて、シスプラチンによる損傷からラットの内耳有毛細胞を保護することを示す。
Claims (17)
- 化学保護剤組成物であって、該組成物は、メチオニン、N−アセチル−DL−メチオニン、S−アデノシルメチオニン、システイン、ホモシステイン、シスタチオン、シスタミン、N−アセチルシステイン、グルタチオン、グルタチオンエチルエステル、グルタチオンジエチルエステル、グルタチオントリエチルエステル、シスタミン、DiNAC、RibCys、RibCyst、β−LactCys、α−LactCys、MeliCys、MaltCys、CellCys、OTCA、アロプリノール、1−メチルアロプリノール、2−メチルアロプリノール、5−メチルアロプリノール、7−メチルアロプリノール、1,5−ジメチルアロプリノール、2,5−ジメチルアロプリノール、1,7−ジメチルアロプリノール、2,7−ジメチルアロプリノール、5,7−ジメチルアロプリノール、2,5,7−トリメチルアロプリノール、1−エトキシカルボニルアロプリノール、1−エトキシカルボニル−5−メチルアロプリノール,2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オン、および6−ジSeCDから成る群より選択される少なくとも2つの化学保護剤を含む、化学保護剤組成物。
- 請求項1に記載の化学保護剤組成物であって、該組成物は、アロプリノール、2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オン、およびN−アセチルシステインから成る群より選択される少なくとも2つの化学保護剤を含む、化学保護剤組成物。
- アロプリノール、2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オンを含む、請求項1に記載の化学保護剤組成物。
- アロプリノールおよびN−アセチルシステインを含む、請求項1に記載の化学保護剤組成物。
- 2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オン、およびN−アセチルシステインを含む、請求項1に記載の化学保護剤組成物。
- 少なくとも1つの化学療法の有害効果を改善する方法であって、該方法は、化学治療を受けている被験体に化学保護剤組成物を投与する工程を含み、該化学保護組成物は、少なくとも1つの化学療法の有害効果を改善するために有効であり、該化学保護剤組成物は、L−メチオニン、N−アセチル−DL−メチオニン、S−アデノシルメチオニン、システイン、ホモシステイン、シスタチオン、シスタミン、N−アセチルシステイン、グルタチオン、グルタチオンエチルエステル、グルタチオンジエチルエステル、グルタチオントリエチルエステル、シスタミン、DiNAC、RibCys、RibCyst、β−LactCys、α−LactCys、MeliCys、MaltCys、CellCys、OTCA、アロプリノール、1−メチルアロプリノール、2−メチルアロプリノール、5−メチルアロプリノール、7−メチルアロプリノール、1,5−ジメチルアロプリノール、2,5−ジメチルアロプリノール、1,7−ジメチルアロプリノール、2,7−ジメチルアロプリノール、5,7−ジメチルアロプリノール、2,5,7−トリメチルアロプリノール、1−エトキシカルボニルアロプリノール、1−エトキシカルボニル−5−メチルアロプリノール、2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オン、および6−ジSeCDから成る群より選択される化学保護剤を含む、方法。
- 前記化学保護剤組成物が、アロプリノール、2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オン、およびN−アセチルシステインから成る群より選択される化学保護剤を含む、請求項6に記載の方法。
- 前記化学保護剤組成物が、アロプリノールおよび2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オンを含む、請求項6に記載の方法。
- 前記アロプリノールが、10〜2400mg/日量で投与され、そして前記2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オンが5〜5000mg/日量で投与される、請求項8に記載の方法。
- 前記化学保護剤組成物が、アロプリノールおよびN−アセチルシステインを含む、請求項6に記載の方法。
- 前記アロプリノールが、10〜2400mg/日量で投与され、そして前記N−アセチルシステインが、5〜5000mg/日量で投与される、請求項10に記載の方法。
- 前記化学保護剤組成物が、2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オンおよびN−アセチルシステインを含む、請求項6に記載の方法。
- 前記2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オンが、5〜5000mg/日量で投与され、そして前記N−アセチルシステインが、5〜5000mg/日量で投与される、請求項12に記載の方法。
- 化学保護剤組成物であって、該化学保護剤組成物は、以下:
(a)メチオニン、N−アセチル−DL−メチオニン、S−アデノシルメチオニン、システイン、N−アセチルシステイン、グルタチオン、グルタチオンエチルエステル、グルタチオンジエチルエステル、グルタチオントリエチルエステル、DiNAC、RibCys、ホモシステイン、シスタチオン、シスタミン、OTCAおよびRibCystから成る群より選択される、化学保護剤;
(b)アロプリノール、1−メチルアロプリノール、2−メチルアロプリノール、5−メチルアロプリノール、7−メチルアロプリノール、1,5−ジメチルアロプリノール、2,5−ジメチルアロプリノール、1,7−ジメチルアロプリノール、2,7−ジメチルアロプリノール、5,7−ジメチルアロプリノール、2,5,7−トリメチルアロプリノール、1−エトキシカルボニルアロプリノール、および1−エトキシカルボニル−5−メチルアロプリノールから成る群より選択される、化学保護剤;および
(c)Ebselenおよび6−ジSeCDから成る群より選択される、化学保護剤、
を含む、化学保護剤組成物。 - 薬学的組成物であって、該薬学的組成物は、以下:
(a)メチオニン、N−アセチル−DL−メチオニン、S−アデノシルメチオニン、システイン、ホモシステイン、シスタチオン、シスタミン、N−アセチルシステイン、グルタチオン、グルタチオンエチルエステル、グルタチオンジエチルエステル、グルタチオントリエチルエステル、シスタミン、DiNAC、RibCys、RibCyst、β−LactCys、α−LactCys、MeliCys、MaltCys、CellCys、OTCA、アロプリノール、1−メチルアロプリノール、2−メチルアロプリノール、5−メチルアロプリノール、7−メチルアロプリノール、1,5−ジメチルアロプリノール、2,5−ジメチルアロプリノール、1,7−ジメチルアロプリノール、2,7−ジメチルアロプリノール、5,7−ジメチルアロプリノール、2,5,7−トリメチルアロプリノール、1−エトキシカルボニルアロプリノール、1−エトキシカルボニル−5−メチルアロプリノール、2−フェニル−1,2−ベンゾイソセレナゾール−3(2H)−オン、および6−ジSeCDから成る群より選択される、化学保護剤;および
(b)化学治療剤
を含む、薬学的組成物。 - 前記化学治療剤が白金を含む、請求項15に記載の薬学的組成物。
- 前記化学治療剤がシスプラチンを含む、請求項16に記載の薬学的組成物。
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KR20170138527A (ko) * | 2015-04-22 | 2017-12-15 | 신-낫 프로덕츠 엔터프라이즈 엘엘씨 | 공결정 조성물 및 그의 약제학적 용도 |
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US20030157191A1 (en) | 2003-08-21 |
US20110065729A1 (en) | 2011-03-17 |
AU2002352982B2 (en) | 2008-03-06 |
US20060089313A1 (en) | 2006-04-27 |
CA2466869C (en) | 2010-01-19 |
EP1461033A4 (en) | 2007-07-04 |
CA2466869A1 (en) | 2003-06-05 |
WO2003045334A3 (en) | 2004-02-26 |
KR20040063977A (ko) | 2004-07-15 |
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US8309560B2 (en) | 2012-11-13 |
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