JP2001511768A - 活性型ビタミンd類似体を使用した前立腺疾患の治療方法 - Google Patents
活性型ビタミンd類似体を使用した前立腺疾患の治療方法Info
- Publication number
- JP2001511768A JP2001511768A JP53002898A JP53002898A JP2001511768A JP 2001511768 A JP2001511768 A JP 2001511768A JP 53002898 A JP53002898 A JP 53002898A JP 53002898 A JP53002898 A JP 53002898A JP 2001511768 A JP2001511768 A JP 2001511768A
- Authority
- JP
- Japan
- Prior art keywords
- alkenyl
- dihydroxyvitamin
- compound
- hydrogen
- prostate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.C-24位で置換された炭化水素部位を有する1α-ヒドロキシビタミンD化合 物の有効量で細胞を処理することを特徴とするヒトの前立腺の腫瘍性又は過形成 性細胞の過剰増殖活性を阻害する方法。 2.前記1α-ヒドロキシビタミンD化合物が、式(I) [式中、B及びCは、それぞれ水素又は炭素−炭素結合で、C-22とC-23の間に二 重結合を形成し;R1及びR2は、同一又は異なり、水素、ヒドロキシル、低,級ア ルキル、低級フルオロアルキル、O-低級アルキル、低級アルケニル、低級フルオ ロアルケニル、O-低級アルケニル、O-低級アシル、O-芳香族アシル、低級シクロ アルキルであり、R1及びR2の両方がアルケニル基ではなく、又はそれらが結合し ている炭素と一緒になってC3〜C8シクロカーボン環を形成している;R3は、低級 アルキル、低級級アルケニル、低級フルオロアルキル、低級フルオロアルケニル 、O-低級アルキル、O-低級アルケニル、O-低級アシル、O-芳香族アシルシクロア ルキル;X1は、水素或いはヒドロキシルであるか、又はR3がアルケニル基の場合 はR3と一緒になって結合を形成し、及びX2は水素或いはヒドロキシルであるか、 又はR1或いはR2と一緒になって二重結合を形成し ている。] で示される請求の範囲第1項に記載の方法。 3.式(I)の化合物が、1α,24-ジヒドロキシビタミンD2、1α,24-ジヒドロキ シビタミンD4、1α,25-ジヒドロキシビタミンD2、1α,25-ジヒドロキシビタミン D4、1α-ヒドロキシビタミンD2又は1α-ヒドロキシビタミンD4である請求の範囲 第2項に記載の方法。 4.前記処理段階が、前記前立腺細胞の増殖を阻害し、その細胞の分化を誘導 及び増強することを包含する請求の範囲第1項に記載の方法。 5.異常な細胞分化又は細胞増殖で特徴づけられる前立腺疾患の治療方法であ って、そのような治療が必要なオスのヒト又は動物に、増殖阻害に有効な量の式 [式中、B及びCは、それそれ水素又は炭素−炭素結合で、C-22とC-23の間に二 重結合を形成し;R1及びR2は、同一又は異なり、水素、ヒドロキシル、低級アル キル、低級フルオロアルキル、O-低級アルキル、低級アルケニル、低級フルオロ アルケニル、O-低級アルケニル、O-低級アシル、O-芳香族アシル、低級シクロア ルキルであり、R1及びR2の両方がアルケニル基ではなく、又はそれらが結合して いる炭素と一緒になってC3〜C8シクロカーボン環を形成してい る;R3は、低級アルキル、低級アルケニル、低級フルオロアルキル、低級フルオ ロアルケニル、O-低級アルキル、O-低級アルケニル、O-低級アシル、O-芳香族ア シルシクロアルキル;X1は、水素或いはヒドロキシルであるか、又はR3がアルケ ニル基の場合はR3と一緒になって結合を形成し、及びX2は水素或いはヒドロキシ ルであるか、又はR1或いはR2と一緒になって二重結合を形成している。] の化合物を投与することを特徴とする方法。 6.前記治療的量が、0.01μg/kg/日〜2.0μg/kg/日である請求の範囲第5項 に記載の方法。 7.前立腺癌を有するオスの被験者に、癌の細胞異常増殖活性を減少させ又は 安定化する活性型ビタミンD化合物である第1抗癌剤の有効量を投与するヒトの 前立腺癌の治療方法であって、前記化合物又はそのインビボ代謝物が、1α,25- ジヒドロキシビタミンD3の結合親和性と実質的に等価なVDR結合親和性を有し、1 α,25-ジヒドロキシビタミンD3よりも実質的に高カルシウム血症の危険性が少な いことを特徴とする方法。 8.前記活性型ビタミンDが、エストラムスチンホスフェート、プレドニムス チン、シスプラチン、5-フルオロ-ウラシル、メルファラン、ヒドロキシウレア 、マイトマイシン、イダルビシン、メトトレキセート、アドリアマイシン及びダ ウノマイシンからなる群より選択される第2抗癌剤を含有する混合物で投与され る請求の範囲第7項に記載の方法。 9.(a)活性型ビタミンD化合物である第1抗癌剤、及び (b)(i)第2抗癌剤、(ii)骨剤、(iii)アンドロゲン抑制剤及び(iv)5α-レ ダクターゼ阻害剤及びそれらの組合せからなる群より選択される薬剤、 を包含することを特徴とする薬剤組成物。 10.前記活性型ビタミンD化合物が、式(I) [式中、B及びCは、それそれ水素又は炭素−炭素結合で、C-22とC-23の間に二 重結合を形成し;R1及びR2は、同一又は異なり、水素、ヒドロキシル、低級アル キル、低級フルオロアルキル、O-低級アルキル、低級アルケニル、低級フルオロ アルケニル、O-低級アルケニル、O-低級アシル、O-芳香族アシル、低級シクロア ルキルであり、但し、R1及びR2はの両方がアルケニル基ではなく、又はそれらが 結合している炭素と一緒になってC3〜C8シクロカーボン環を形成している;R3は 、低級アルキル、低級級アルケニル、低級フルオロアルキル、低級フルオロアル ケニル、O-低級アルキル、 O-低級アルケニル、O-低級アシル、O-芳香族アシル シクロアルキルである;X1は、水素或いはヒドロキシルであるか、又はR3がアル ケニル基の場合はR3と一緒になって結合を形成し、及びX2は水素或いはヒドロキ シルであるか、又はR1或いはR2と一緒になって二重結合を形成している。] で示される請求の範囲第9項に記載の薬剤組成物。 11.活性型ビタミンD化合物が、1α,24-ジヒドロキシビタミンD2、1α,24-ジ ヒドロキシビタミンD4、1α,25-ジヒドロキシビタミンD2、1α,25-ジヒドロ キシビタミンD4、1α-ヒドロキシビタミンD2又は1α-ヒドロキシビタミンD4から なる群より選択される請求の範囲第9項に記載の薬剤組成物。 12.前記第2抗癌剤が、エストラムスチンホスフェート、プレドニムスチン、 シスプラチン、5-フルオロ-ウラシル、メルファラン、ヒドロキシウレア、マイ トマイシン、イダルビシン、メトトレキセート、アドリアマイシン及びダウノマ イシンからなる群より選択される請求の範囲第9項に記載の薬剤組成物。 13.前記活性型ビタミンD化合物が、約0.01μg/kg/日〜約2.0μg/kg/日の投 与量範囲で存在する請求の範囲第9項に記載の薬剤組成物。 14.さらに薬学的に許容されるキャリヤーを包含する請求の範囲第10項に記載 の薬剤組成物。 15.前記アンドロゲン抑制剤が、エストロゲン、LHRH類似体、抗エストロゲン 剤及び抗アンドロゲン剤からなる群より選択される請求の範囲第9項に記載の薬 剤組成物。 16.前記5α-レダクターゼ酵素阻害剤が、フィナステライドである請求の範囲 第9項に記載の薬剤組成物。 17.前記骨剤が、複合化エストロゲン又はその等価物、カルシトニン、ビスホ スホネート、カルシウム補充剤、コバラミン、百日咳毒素及びホウ素からなる群 より選択される請求の範囲第9項に記載の薬剤組成物。 18.前立腺癌又は前立腺肥大の過剰増殖性細胞活性を軽減するヒトの治療方法 であって、その治療が必要なヒトに、C-24位で置換された炭化水素部位を有する 活性型ビタミンD化合物を治療に効果的な量で投与することを特徴とする治療方 法。
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US08/781,910 US5763429A (en) | 1993-09-10 | 1996-12-30 | Method of treating prostatic diseases using active vitamin D analogues |
PCT/US1997/022450 WO1998029123A1 (en) | 1996-12-30 | 1997-12-10 | Method of treating prostatic diseases using active vitamin d analogues |
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Also Published As
Publication number | Publication date |
---|---|
CN1158081C (zh) | 2004-07-21 |
MX9906989A (es) | 2003-02-27 |
HUP0000558A3 (en) | 2000-12-28 |
DE69737066D1 (de) | 2007-01-18 |
CN1554351A (zh) | 2004-12-15 |
CA2276606C (en) | 2008-11-25 |
DE69737066T2 (de) | 2007-06-21 |
WO1998029123A1 (en) | 1998-07-09 |
ATE347366T1 (de) | 2006-12-15 |
BR9713663A (pt) | 2000-04-04 |
AU5595698A (en) | 1998-07-31 |
HUP0000558A2 (hu) | 2000-10-28 |
NZ336508A (en) | 2001-08-31 |
KR20000062403A (ko) | 2000-10-25 |
CN1248917A (zh) | 2000-03-29 |
AU723835B2 (en) | 2000-09-07 |
EP0948334A1 (en) | 1999-10-13 |
US20040023934A1 (en) | 2004-02-05 |
PL334393A1 (en) | 2000-02-28 |
US5763429A (en) | 1998-06-09 |
CA2276606A1 (en) | 1998-07-09 |
EP0948334B1 (en) | 2006-12-06 |
US6537982B1 (en) | 2003-03-25 |
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