JP2006527234A - 4−ヒドロキシタモキシフェンによる過剰瘢痕化の治療及び予防 - Google Patents
4−ヒドロキシタモキシフェンによる過剰瘢痕化の治療及び予防 Download PDFInfo
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Abstract
Description
段階2 段階1とは別に、1,2−ジフェニル−1−ブタノンをヒドロキシル化して1−(4−ヒドロキシフェニル)−2−フェニル−1−ブタノンを形成する;
段階3 段階1と段階2の生成物とを反応させて、1−(4−ジメチルアミノエトキシフェニル)−1−[p−2−テトラヒドロピラニルオキシ)フェニル]−2−フェニルブタン−1−オールを形成する;
段階4 メタノール/塩酸を用いて脱水して、1−[p−(β−ジメチルアミノエトキシ)フェニル]−Z−1−(p−ヒドロキシフェニル)−2−フェニル−1−ブタ−1−エン=4−OH−タモキシフェン、E及びZ異性体混合物を製造する;
段階5 クロマトグラフィー及び結晶化によりE及びZ異性体を分離して、一定の比活性度を得る。
Bronaugh and Maibach,Percutaneous Absorption:Drugs Cosmetics Mechanisms Methodology,Marcel Dekker 1999.
Carthew,P.,P.N.Lee,R.E Edwards,R.T.Heydon,B.M.Nolan,E.A.Martin,Cumulative exposure to tamoxifen:DNA adducts and liver cancer in the rat,Arch Toxicol,75:375−80(2001).
Chetrite,G.,C.Varin,L.Delalonde,J.R.Pasqualini,Effect of promegestone,tamoxifen,4−hydroxytamoxifen and ICT 164,384 on the oestrone sulphatase activity of human breast cancer cells,Anticancer Res,13(4)931−4(Jul−Aug.1993).
Chau,D.,J.S.Mancoll,S.Lee,J.Zhao,L.G.Philips,G.I.Gittes,M.T. Longaker,Tamoxifen downregulates TGB−beta production in keloid fibroblasts,Ann.Plast.Surg.,40(5):490−3(1998).
Dietze,E.C.,L.E.Caldwell,S.L.Grupin,M.Mancini, and V.L.Seewald,Tamoxifen,but not 4−hydroxytamoxifen initiates apoptosis in p53(−)normal human mammary epithelial cells by inducing mitochondrial depolarization,J.Biol.Chem.,276(7):5384−94(Feb.16,2001).
Fentiman,I.S.,Tamoxifen and mastalgia.An emerging indication,Drugs 32:477−80(1986).
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Malet C,A.Gompel,P.Spritzer,N Bricourt,NH Yaneva,I.Mowszowicz,F.Kutten and P Mauvais Jarvis,Tamoxifen and hydroxytamoxifen isomers versus estradiol effects on normal human breast cells in culture,Cancer Research,48:7193−7199(1988).
Mauvais−Jarvis,P.,N.Baudot,D.Castaigne,P.Banzet,and F.Kuttenn,Z−4−hydroxytamoxifen concentration and metabolism after local percutaneous administration to human breast,Cancer Research,46:1521−1525(1986).
Mikulec,A.A., M.M.Hanasono,J.Lum,J.M.Kadleck,M.Kita,R.J.Koch,Effect of tamoxifen on transforming growth factor betal production by keloid and fetal fibroblasts,Arch.Facial Plast.Surg.,3(2):111(2001).
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Claims (19)
- 瘢痕、又は過剰瘢痕に発達する危険を有する創傷又は外科的創を治療又は予防する薬剤組成物の製造における、4−ヒドロキシタモキシフェンの使用。
- 前記瘢痕はケロイド瘢痕である、請求項1記載の使用。
- 前記瘢痕はケロイド瘢痕に発達する危険を有する、請求項1記載の使用。
- 前記瘢痕は肥厚性瘢痕である、請求項1記載の使用。
- 前記瘢痕は肥厚性瘢痕に発達する危険を有する、請求項1記載の使用。
- 前記4−ヒドロキシタモキシフェンは、皮膚適用可能な形態を有する請求項1乃至5のいずれか記載の使用。
- 前記4−ヒドロキシタモキシフェンは、注入投与可能な形態を有する請求項1乃至5のいずれか記載の使用。
- 前記4−ヒドロキシタモキシフェンは、浸透促進剤を含有する輸送手段中に存在する請求項1乃至6のいずれか記載の使用。
- 前記4−ヒドロキシタモキシフェンは、Z異性体及びE異性体の混合物である請求項1乃至8のいずれか記載の使用。
- 前記4−ヒドロキシタモキシフェンの大部分がZ異性体である、請求項1乃至8のいずれか記載の使用。
- 一日につき瘢痕1cm2毎に、約0.25〜3.0μgの前記4−ヒドロキシタモキシフェンが投与される、請求項1乃至10のいずれか記載の使用。
- 前記薬剤組成物は、一日につき瘢痕1cm2毎に、約0.5〜2.5μgの前記4−ヒドロキシタモキシフェンを投与することが可能である、請求項11記載の使用。
- 前記薬剤組成物は、一日につき瘢痕1cm2毎に、約1.0μgの前記4−ヒドロキシタモキシフェンを投与することが可能である、請求項12記載の使用。
- 前記薬剤組成物は、一日につき瘢痕1cm2毎に、約2.0μgの前記4−ヒドロキシタモキシフェンを投与することが可能である、請求項13記載の使用。
- 前記4−ヒドロキシタモキシフェンは、軟膏、クリーム、パッチ、ジェル、乳剤、散剤、及びオイルから選択された経皮投与形態に調製される、請求項1乃至6及び請求項8乃至14のいずれか記載の使用。
- 前記4−ヒドロキシタモキシフェンは、水性アルコールジェルに調製される請求項1乃至6及び請求項8乃至14のいずれか記載の使用。
- 前記水性アルコールジェルは、エチルアルコール、イソプロピルミリステート及びヒドロキシプロピルセルロースを含む請求項16記載の使用。
- 前記4−ヒドロキシタモキシフェンは、水性アルコール溶液に調製される請求項1乃至6及び請求項8乃至14のいずれか記載の使用。
- 前記水性アルコール溶液は、エチルアルコール、イソプロピルミリステート及びヒドロキシプロピルセルロースを含む請求項18記載の使用。
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2009545559A (ja) * | 2006-07-31 | 2009-12-24 | ラボラトワール・ベザン・ザンテルナショナル | 過剰瘢痕化の治療および予防 |
JP2011507860A (ja) * | 2007-12-21 | 2011-03-10 | コーダ セラピューティクス, インコーポレイテッド | 異常瘢痕または過剰瘢痕の治療のための抗コネキシンポリヌクレオチドおよび抗コネキシンペプチドの使用 |
JP2011507862A (ja) * | 2007-12-21 | 2011-03-10 | コーダ セラピューティクス, インコーポレイテッド | 異常瘢痕または過剰瘢痕の治療のための抗コネキシン43ポリヌクレオチドの使用 |
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MXPA05006526A (es) * | 2002-12-18 | 2006-02-17 | Besins Int Lab | Tratamiento de mastalgia con 4-hidroxi tamoxifen. |
EP2050443B1 (en) | 2002-12-18 | 2017-05-24 | Besins Healthcare Luxembourg SARL | Reduction of breast density with 4-hydroxy tamoxifen |
JP5490346B2 (ja) * | 2003-04-01 | 2014-05-14 | ブザン ヘルスケア ルクセンブルグ エスアーエールエル | 4−ヒドロキシタモキシフェンによる乳癌の予防および治療 |
NZ547744A (en) * | 2003-12-15 | 2009-09-25 | Besins Int Lab | Use of 4-hydroxytamoxifen for the preparation of a medicament for the treatment of gynecomastia |
US7968532B2 (en) | 2003-12-15 | 2011-06-28 | Besins Healthcare Luxembourg | Treatment of gynecomastia with 4-hydroxy tamoxifen |
US20050208139A1 (en) * | 2004-03-22 | 2005-09-22 | Ascend Therapeutics, Inc. | Chemically stable compositions of 4-hydroxy tamoxifen |
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- 2004-06-02 JP JP2006515986A patent/JP4682129B2/ja not_active Expired - Lifetime
- 2004-06-02 US US10/858,399 patent/US7767717B2/en active Active
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- 2004-06-02 DK DK04740032T patent/DK1631275T3/da active
- 2004-06-02 AT AT04740032T patent/ATE393625T1/de active
- 2004-06-02 PT PT04740032T patent/PT1631275E/pt unknown
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Cited By (5)
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JP2009545559A (ja) * | 2006-07-31 | 2009-12-24 | ラボラトワール・ベザン・ザンテルナショナル | 過剰瘢痕化の治療および予防 |
JP2011507860A (ja) * | 2007-12-21 | 2011-03-10 | コーダ セラピューティクス, インコーポレイテッド | 異常瘢痕または過剰瘢痕の治療のための抗コネキシンポリヌクレオチドおよび抗コネキシンペプチドの使用 |
JP2011507862A (ja) * | 2007-12-21 | 2011-03-10 | コーダ セラピューティクス, インコーポレイテッド | 異常瘢痕または過剰瘢痕の治療のための抗コネキシン43ポリヌクレオチドの使用 |
JP2015057430A (ja) * | 2007-12-21 | 2015-03-26 | コーダ セラピューティクス, インコーポレイテッド | 異常瘢痕または過剰瘢痕の治療のための抗コネキシンポリヌクレオチドおよび抗コネキシンペプチドの使用 |
JP2015057431A (ja) * | 2007-12-21 | 2015-03-26 | コーダ セラピューティクス, インコーポレイテッド | 異常瘢痕または過剰瘢痕の治療のための抗コネキシン43ポリヌクレオチドの使用 |
Also Published As
Publication number | Publication date |
---|---|
EP1631275A1 (en) | 2006-03-08 |
US7767717B2 (en) | 2010-08-03 |
US20050032910A1 (en) | 2005-02-10 |
AU2004246812B8 (en) | 2010-01-14 |
EP1631275B1 (en) | 2008-04-30 |
AU2004246812B2 (en) | 2009-12-17 |
WO2004110420A8 (en) | 2005-11-24 |
ES2304610T3 (es) | 2008-10-16 |
AU2004246812A1 (en) | 2004-12-23 |
PT1631275E (pt) | 2008-08-04 |
DK1631275T3 (da) | 2008-08-18 |
WO2004110420A1 (en) | 2004-12-23 |
CA2528431A1 (en) | 2004-12-23 |
DE602004013439T2 (de) | 2009-06-04 |
ATE393625T1 (de) | 2008-05-15 |
HK1082203A1 (en) | 2006-06-02 |
CA2528431C (en) | 2012-09-18 |
NZ544031A (en) | 2008-08-29 |
JP4682129B2 (ja) | 2011-05-11 |
DE602004013439D1 (de) | 2008-06-12 |
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