JPH11503911A - 動静脈及び静脈の移植治療:方法及び組成物 - Google Patents
動静脈及び静脈の移植治療:方法及び組成物Info
- Publication number
- JPH11503911A JPH11503911A JP8531889A JP53188996A JPH11503911A JP H11503911 A JPH11503911 A JP H11503911A JP 8531889 A JP8531889 A JP 8531889A JP 53188996 A JP53188996 A JP 53188996A JP H11503911 A JPH11503911 A JP H11503911A
- Authority
- JP
- Japan
- Prior art keywords
- oligonucleotide
- vein
- antisense
- myc
- tissue
- 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.)
- Granted
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.血液透析患者の血液透析アクセス部位の失敗を防ぐための方法であって、 前記血液透析アクセス部位を、核プロトオンコジーンmRNAに相補的なオリゴヌ クレオチドに接触させることを含むことを特徴とする方法。 2.前記血液透析アクセス部位が、ブレーシャーチミーノフィステル、スノフ ボックス(snuffbox)フィステル、短頭(brachiocephalic)フィステル、PTFE血 液透析移植物、及びウシ頸動脈移植物及び自己移植物からなる群から選択される ことを特徴とする請求項1に記載の方法。 3.前記接触が、注入、カテーテル挿入又は注射を含むことを特徴とする請求 項1に記載の方法。 4.前記接触が、インプラントからの拡散又は脈管周囲組織中に位置したリザ ーバーからの拡散を含むことを特徴とする請求項1に記載の方法。 5.前記接触が、外科部位を閉じる前の脈管周囲注射又は外科部位を閉じた後 の皮下注射のいずれかによる脈管周囲組織内への注射を含むことを特徴とする請 求項1に記載の方法。 6.前記接触が、前記血液透析アクセス部位の形成後に繰り返されることを特 徴とする請求項5に記載の方法。 7.脈管移植物を処理するための方法であって、 前記脈管移植物を、核プロトオンコジーンmRNAに相補的なオリゴヌクレオチド に接触させることを含むことを特徴とする方法。 8.前記接触が、インプラントからの拡散又は脈管周囲組織中に位置したリザ ーバーからの拡散を含むことを特徴とする請求項7に 記載の方法。 9.前記接触が、外科部位を閉じる前の脈管周囲注射又は外科部位を閉じた後 の皮下注射のいずれかによる脈管周囲組織内への注射を含むことを特徴とする請 求項7に記載の方法。 10.静脈から作られた脈管移植物の失敗を防ぐための生体外での方法であって 、 生体外で、前記静脈を、核プロトオンコジーンmRNAに相補的なオリゴヌクレオ チドに接触させることを特徴とする方法。 11.前記接触が、滅菌及び生理的に許容される緩衝液中で少くとも10分間、前 記静脈を前記オリゴヌクレオチドと共にインキュベートすることを含むことを特 徴とする請求項10に記載の方法。 12.前記生理的に許容される緩衝液が20〜37℃であることを特徴とする請求項 11に記載の方法。 13.前記オリゴヌクレオチドが10〜200μMの濃度を有することを特徴とする 請求項12に記載の方法。 14.前記静脈が、伏在静脈、橈側静脈、尺側皮静脈、上腕静脈、及び大腿静脈 からなる群から選択されることを特徴とする請求項13に記載の方法。 15.血液透析アクセス部位と、 前記血液透析アクセス部位の少くとも1の層に位置した核プロトオンコジーン mRNAに相補的なオリゴヌクレオチドと、 を含むことを特徴とする組成物。 16.前記血液透析アクセス部位が、ブレーシャーチミーノフィステル、スノフ ボックス(snuffbox)フィステル、短頭(brachiocephalic)フィステル、PTFE血 液透析移植物、及びウシ頸動脈移植物及び自己移植物からなる群から選択される ことを特徴とする請求項15に記載の組成物。 17.前記層が、内皮層、中膜、外膜及び脈管周囲組織からなる群から選択され ることを特徴とする請求項15に記載の組成物。 18.前記部分が、PTFE移植片、再充填可能リザーバー、ステント、ゲル及び移 植可能具からなる群から選択されることを特徴とする請求項17に記載の組成物。 19.前記オリゴヌクレオチドがリザーバー内に位置することを特徴とする請求 項15に記載の組成物。 20.前記リザーバーが0.5〜10mgの間の前記オリゴヌクレオチドを含むことを 特徴とする請求項19に記載の組成物。 21.前記リザーバーが前記血液透析アクセス部位の静脈側にあることを特徴と する請求項20に記載の組成物。 22.脈管移植物と、 該脈管移植物の少くとも1の層に位置した該プロトオンコジーンmRNAに相補的 なオリゴヌクレオチドと、 を含むことを特徴とする組成物。 23.前記移植物が、プロテーゼフィステル、動静脈シャント、ネイティブ静脈 フィステル、静脈移植物、免疫抑制同種移植物、免疫抑制異種移植物、及び静脈 自己移植物であることを特徴とする請求項22に記載の組成物。 24.前記層が、内皮層、中膜、外膜及び脈管周囲組織からなる群から選択され ることを特徴とする請求項22に記載の組成物。 25.前記オリゴヌクレオチドが、少くとも1の前記層中に少くとも10μMの濃 度を有することを特徴とする請求項24に記載の組成物。 26.前記オリゴヌクレオチドが、前記層の細胞内で少くとも1μMの濃度を有 することを特徴とする請求項25に記載の組成物。 27.前記細胞が平滑筋細胞、筋繊維芽細胞又は繊維芽細胞のいず れかであることを特徴とする請求項26に記載の組成物。 28.切除されたヒト適合性静脈と、 該ヒト適合性静脈の脈管壁中に位置した核プロトオンコジーンmRNAに相補的な オリゴヌクレオチドと、 を含むことを特徴とする組成物。 29.前記切除した適合性静脈が、伏在静脈、橈側静脈、尺側皮静脈、上腕静脈 、及び大腿静脈からなる群から選択されることを特徴とする請求項28に記載の組 成物。 30.前記オリゴヌクレオチドが、内皮層、中膜及び外膜からなる群から選択さ れる前記脈管壁の層内に位置することを特徴とする請求項28に記載の組成物。 31.前記オリゴヌクレオチドが、少くとも1の前記層内で少くとも10μMの濃 度を有することを特徴とする請求項30に記載の組成物。 32.ヒト組織中の細胞外マトリックスタンパク質の合成を阻害する方法であっ て、治療に有効な量の核プロトオンコジーンに各々特異的な1又は複数のアンチ センスオリゴヌクレオチドを前記組織に投与することを含むことを特徴とする方 法。 33.前記核プロトオンコジーンが、c−myc,c−myb,c−Fos,N−myc,L −myc ,p53,c−rel,c−ski,c−ets−1、及びc−ets−2からなる群か ら選択されることを特徴とする請求項32に記載の方法。 34.前記核プロトオンコジーンがc−myc 及びc−myb からなる群から選択さ れ、そして前記細胞外マトリックスタンパク質がコラーゲンからなる群から選択 されることを特徴とする請求項33に記載の方法。 35.前記組織が動脈壁であることを特徴とする請求項34に記載の 方法。 36.前記投与するステップが、カテーテル又はコートされたステントで前記ア ンチセンスオリゴヌクレオチドを局所的に投与することを含むことを特徴とする 請求項35に記載の方法。 37.前記1又は複数のアンチセンスオリゴヌクレオチドが、c−myc に特異的 なアンチセンスオリゴヌクレオチド及びc−myb に特異的なアンチセンスオリゴ ヌクレオチドからなることを特徴とする請求項36に記載の方法。 38.前記核プロトオンコジーンに特異的な前記1又は複数のアンチセンスオリ ゴヌクレオチドがホスホロチオエートオリゴヌクレオチドであることを特徴とす る請求項37に記載の方法。 39.前記組織が皮膚繊維芽細胞を含むことを特徴とする請求項37に記載の方法 。 40.前記アンチセンス化合物が局所的に投与されることを特徴とする請求項34 に記載の方法。 41.前記組織が平滑筋細胞又は繊維芽細胞を含む内部器官を含むことを特徴と する請求項40に記載の方法。 42.前記細胞外マトリックスタンパク質の合成が、細胞外マトリックスタンパ ク質の分泌であることを特徴とする請求項32に記載の方法。 43.前記ヒト組織が結合組織であることを特徴とする請求項32に記載の方法。 44.前記核オンコジーンがc−myc であることを特徴とする請求項35に記載の 方法。 45.前記細胞外マトリックスタンパク質がI型プロコラーゲン又はIII型プロ コラーゲンのいずれかであることを特徴とする請求項44に記載の方法。 46.前記組織がヒト繊維芽細胞を含むことを特徴とする請求項45に記載の方法 。 47.前記組織がヒト平滑筋細胞を含むことを特徴とする請求項45に記載の方法 。 48.前記投与がカテーテルを用いる局所的デリバリーを含むことを特徴とする 請求項38に記載の方法。 49.前記合成の阻害が、細胞外マトリックスI型プロコラーゲン及びIII型プ ロコラーゲンをコードする遺伝子の転写の下降制御、細胞外マトリックスI型プ ロコラーゲン及びIII型プロコラーゲンのmRNA翻訳の下降制御、細胞外マトリッ クスI型プロコラーゲン及びIII型プロコラーゲン前駆体のためのデグラデーシ ョン細胞内経路の上昇制御、並びに細胞外マトリックスI型プロコラーゲン及び III型プロコラーゲンのデグラデーションの上昇制御からなる群から選択される 生物過程の欠如下でおこることを特徴とする請求項48に記載の方法。 50.硬化症を治療する方法であって、有効量のc−myc に特異的なアンチセン スオリゴヌクレオチドを投与するステップを含むことを特徴とする方法。 51.再狭窄におけるコラーゲン合成を阻害する方法であって、有効量のc−my c に特異的なアンチセンスオリゴヌクレオチドを局所的に投与するステップを含 むことを特徴とする方法。 52.前記瘢痕形成の減少が細胞外マトリックスタンパク質形成の進行を減少さ せることを含むことを特徴とする請求項51に記載の方法。 53.前記局所的に投与するステップが、カテーテル又はコートされたステント で投与することを含むことを特徴とする請求項52に記載の方法。 54.ヒト組織における瘢痕形成を減少させる方法であって、前記ヒト組織に、 治療に有効な量のプロトオンコジーンアンチセンスオリゴヌクレオチドを投与す ることを含むことを特徴とする方法。 55.前記局所的に投与するステップが、c−myc に特異的なアンチセンスオリ ゴヌクレオチド及びc−myb に特異的なアンチセンスオリゴヌクレオチドを、組 み合わせて局所的に投与することを含むことを特徴とする請求項54に記載の方法 。 56.ヒトにおける繊維状結合組織の形成を阻害する方法であって、 前記ヒトに、治療に有効な量のプロトオンコジーンアンチセンスオリゴヌクレ オチドを投与することを含むことを特徴とする方法。 57.細胞外マトリックスタンパク質の合成を阻害するために役立つ医薬組成物 であって、医薬として許容される賦形剤と、必要な患者に投与した時に細胞外マ トリックスタンパク質の合成を阻害するのに十分な量で存在する核プロトオンコ ジーンに特異的なアンチセンスオリゴヌクレオチドと、を含むことを特徴とする 医薬組成物。 58.前記アンチセンスオリゴヌクレオチドが配列番号:1,5,6及び7から なるヌクレオチドの群から選択されることを特徴とする請求項57に記載の組成物 。 59.前記アンチセンスオリゴヌクレオチドが配列番号:1,5,6及び7から なるヌクレオチドの群から選択されることを特徴とする請求項58に記載の方法。
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US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
SE462364B (sv) | 1988-09-30 | 1990-06-18 | Goeran Hansson | Anvaendning av gamma-interferon foer beredning av ett preparat foer behandling av vaskulaer stenos |
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DE69432413T2 (de) | 1993-06-11 | 2004-05-13 | The Board Of Trustees Of The Leland Stanford Junior University, Stanford | Behandlung degenerativer gefaesserkrankungen durch modulation der endogenen stickoxidproduktion oder-aktivitaet |
AU8019694A (en) | 1993-10-15 | 1995-05-04 | Thomas Jefferson University | Inhibition of extracellular matrix synthesis by antisense compounds directed to nuclear proto-oncogenes |
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- 1996-04-19 CA CA002215631A patent/CA2215631A1/en not_active Abandoned
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CA2215631A1 (en) | 1996-10-24 |
EP0871496B1 (en) | 2008-07-09 |
ATE400301T1 (de) | 2008-07-15 |
AU714658B2 (en) | 2000-01-06 |
HUP9800729A2 (hu) | 1998-07-28 |
CN1181706A (zh) | 1998-05-13 |
AU5553296A (en) | 1996-11-07 |
NO974824L (no) | 1997-12-16 |
US6323184B1 (en) | 2001-11-27 |
CN1177615C (zh) | 2004-12-01 |
KR19990007864A (ko) | 1999-01-25 |
WO1996032966A1 (en) | 1996-10-24 |
BR9608454A (pt) | 2002-02-05 |
NO974824D0 (no) | 1997-10-17 |
PL323046A1 (en) | 1998-03-02 |
EP0871496A4 (ja) | 1998-10-21 |
PL188628B1 (pl) | 2005-03-31 |
EP0871496A1 (en) | 1998-10-21 |
DE69637593D1 (de) | 2008-08-21 |
CZ330297A3 (cs) | 1998-03-18 |
JP3958362B2 (ja) | 2007-08-15 |
HU225244B1 (en) | 2006-08-28 |
CZ295039B6 (cs) | 2005-05-18 |
HUP9800729A3 (en) | 2000-07-28 |
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