JP2007182447A - 非バイパス侵襲性介入の結果として起こる介入を伴う狭窄症の予防法 - Google Patents
非バイパス侵襲性介入の結果として起こる介入を伴う狭窄症の予防法 Download PDFInfo
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Abstract
【解決手段】本発明は、非バイパス侵襲性介入後の再狭窄に関する。本発明はまた、非バイパス侵襲性介入の結果として起こる徴候的な胸部痛の回復法に関する。この方法は、所定時間でのドーパミン増強/プロラクチン抑制化合物の毎日の量の投与と、血管の傷害を治癒することを可能にするのに少なくとも効果的である期間、投与を継続することを含む。
【選択図】図1
Description
米国では、心筋梗塞(MI)が死のリーディングケースとなっている。ほとんどすべての心筋梗塞が、完全にアテローム性動脈硬化症に帰する。アテローム性動脈硬化症は、幼児期に始まるが、その病気が、主として心臓や脳といった影響されやすい器官への損害と結びつく臨床の徴候に帰着する、人生の末期まで顕在化しないゆっくりとした進行性の病気である。
本発明者らとその共同研究者らは、一定のドーパミン増強化合物、および/または、プロラクチン抑制化合物(例えば、ブロモクリプチンのようなドーパミン作用剤)、および/または、プロラクチン促進剤(例えば、メトクロプラミドのようなドーパミン拮抗剤;5-ヒドロキシトリプトファンのようなセロトニン作用剤と前駆体)の投与と、特にそのような物質の所定時間での投与が、体脂肪貯蔵、肥満症、血漿トリグリセリドそしてコレステロールを減少し、高インスリン血症とインスリン抵抗性と同様に、アテローム性動脈硬化症を予防し緩和することができることを見出した。(米国特許第4,659,715号;第4,749,709号;第4,783,469号;第5,006,526号;第5,344,832号;そしてPCT出願 US92/11166参照)
共に係属している特許出願出願番号07/919,685では、プロラクチンの一日のリズムの神経性の位相振幅を修正しリセットするのに足りる期間、量において頃合いの一日の基準で、動物またはヒトの血流中に、プロラクチン(またはプロラクチンとグルココルチコステロイド("GC")の両方)を投与することによる、脂質代謝障害の調整法を開示する。この調整はインスリンの感受性を増大することに見出される。プロラクチンの投入は、インスリン感受性を増大し体脂肪貯蔵を減らすために、脂肪のないインスリン感受性のヒトのプロラクチン分泌ピーク(またはプロラクチンとグルココルチコステロイドのピーク、それぞれに)と時間において一致する、被験者の毎日のプロラクチン(またはプロラクチンとGC)の分泌プロフィールのピークをつくるように、時機を合わせる。出願番号07/719,745でも、ドーパミン作用剤とプロラクチン促進剤による治療を受けている被験者、特に慢性的あるいは周期的に甲状腺機能低下性である被験者に対する、甲状腺ホルモンの更なる投与を開示し請求している。
ラット平滑筋細胞(5×103)のin vitro調製物を、胎児子ウシ血清(2%)を加え、そしてプロラクチン、PDGF、またはプロラクチンプラスPDGFのいずれかを加えたDMEMで培養した。これらの培地調製物のそれぞれを、ブロモクリプチンの存在化と非存在化でインキュベートした。
被験者SC(42歳、180ポンド)は、徴候と心電図に基づいて診断された急性下壁心筋梗塞を被っていた。彼はTPAを用いて治療を受け、八日後、血管造影図が実施され、それにより左回旋動脈に99%の狭窄、左冠状動脈に50%の狭窄を伴う並みからひどいアテローム性動脈硬化症が示された。
Claims (18)
- (i)経皮経管冠状動脈形成術、(ii)アテローム切除術、(iii)動脈内膜切除術から成るグループより選択された非バイパス侵襲性介入を受けた、哺乳動物における再狭窄の予防または制限のための、プロラクチン抑制化合物を含む試薬であって、
第一の所定時間に上記哺乳動物に毎日投与し、上記試薬の投与時間及び量が昼間の時間07:00-22:00の全部か一部の間の上記哺乳動物の血液プロラクチン濃度を抑制するために選択される、試薬。 - 侵襲性介入に起こりやすい血管の傷害を治癒することを可能にするのに少なくとも十分な期間投与される、請求項1に記載の試薬。
- 一年以上に亘る期間で投与される、請求項1または2に記載の試薬。
- 一回の投与で投与される、請求項1から3のいずれか一項に記載の試薬。
- 複数回の投与で投与される、請求項1から3のいずれか一項に記載の試薬。
- 上記プロラクチン抑制化合物がブロモクリプチンである、請求項1から5のいずれか一項に記載の試薬。
- ブロモクリプチンの量が0.2から15mgの範囲である、請求項6に記載の試薬。
- ブロモクリプチンの量が0.8から8.0mgの範囲である、請求項7に記載の試薬。
- プロラクチン促進化合物を含む別の試薬を更に含む、請求項1から8のいずれか一項に記載の試薬を含むキット。
- 上記プロラクチン促進化合物がメトクロプラミドである、請求項9に記載のキット。
- メトクロプラミドの量が0.5から5.0mgの範囲である、請求項10に記載のキット。
- メトクロプラミドの量が0.5から2.0mgの範囲である、請求項11に記載のキット。
- (i)経皮経管冠状動脈形成術、(ii)アテローム切除術、(iii)動脈内膜切除術から成るグループより選択された非バイパス侵襲性介入を受けた、哺乳動物内の狭心症または一過性黒内障の抑制または除去のための、プロラクチン抑制化合物を含む試薬であって、
第一の所定時間に上記哺乳動物に毎日投与し、上記試薬の投与時間及び量が昼間の時間07:00-22:00の全部か一部の間の上記哺乳動物の血液プロラクチン濃度を抑制するために選択される、試薬。 - 上記プロラクチン抑制化合物が、2-ブロモ-アルファ-エルゴクリプチン;6-メチル-8-ベータ-カルボベンジロキシ-アミノエチル-10-アルファ-エルゴリン;8-アシルアミノエルゴリン類、6-メチル-8-アルファ-(N-アシル)アミノ-9-エルゴリン;6-メチル-8-アルファ-(N-フェニル-アセチル)アミノ-9-エルゴリン;エルゴコルニン;9,10-ジヒドロエルゴコルニン;及びD-2-ハロ-6-アルキル-8-置換エルゴリン類から必須に成るグループから選択される請求項1から5及び13のいずれか一項に記載の試薬。
- 上記プロラクチン抑制化合物が、エルゴット関連D2ドーパミン作用剤である請求項1から5及び13のいずれか一項に記載の試薬。
- 上記プロラクチン促進化合物が、プロラクチン;メラトニン;ドーパミン拮抗剤;セロトニン作用剤;制吐剤;及びエストロゲンから必須に成るグループから選択される請求項9に記載のキット。
- 上記ドーパミン拮抗剤が、メトクロプラミド、ハロペリドール、ピモジド、フェノチアジン、ドンペリドン、スルピリド、またはクロルプロマジンである請求項16に記載のキット。
- 前記セロトニン作用剤が、パルギリン、合成モルフィネ類似体、メタドン、トリプトファン、5-ヒドロキシトリプトファン(5-HTP)、フルオキシタン、またはデクスフェンフルラミンである請求項16に記載のキット。
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BE890369A (fr) * | 1980-09-18 | 1982-03-16 | Sandoz Sa | Nouveaux medicaments a base d'inhibiteurs de la secretion de la prolactine pour le traitement de l'arteriosclerose |
US4783469A (en) * | 1986-03-07 | 1988-11-08 | Meier Albert H | Method of inhibiting body fat stores |
US4659715A (en) * | 1986-03-07 | 1987-04-21 | Louisiana State University And Agricultural And Mechanical College | Method of inhibiting body fat stores |
US4749709A (en) * | 1986-03-07 | 1988-06-07 | Louisiana State University And Agricultural And Mechanical College | Method of inhibiting body fat stores |
DE3728695A1 (de) * | 1987-08-25 | 1989-03-09 | Schering Ag | Neue benzimidazol-derivate |
US5344832A (en) * | 1990-01-10 | 1994-09-06 | The Board Of Supervisors Of Louisiana University And Agricultural And Mechanical College | Method for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia and hyperglycemia in vertebrates |
US5468755A (en) * | 1988-05-10 | 1995-11-21 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Therapeutic process for the treatment of the pathologies of Type II diabetes |
US5006526A (en) * | 1988-10-17 | 1991-04-09 | Louisiana State University | Method of treating a vertebrate animal to reduce plasma triglycerides and cholesterol levels and to alleviate and prevent atherosclerosis |
CA2117075A1 (en) * | 1991-09-06 | 1993-03-18 | Norihiko Shimazaki | Quinazoline derivatives and their preparation |
DE4315349A1 (de) * | 1992-10-06 | 1994-11-10 | Thomae Gmbh Dr K | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
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1995
- 1995-05-31 US US08/455,354 patent/US5565454A/en not_active Expired - Lifetime
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1996
- 1996-05-30 DK DK96921645T patent/DK0828492T3/da active
- 1996-05-30 EP EP96921645A patent/EP0828492B1/en not_active Expired - Lifetime
- 1996-05-30 CA CA002219452A patent/CA2219452A1/en not_active Abandoned
- 1996-05-30 DE DE69635754T patent/DE69635754T9/de active Active
- 1996-05-30 AT AT96921645T patent/ATE315936T1/de active
- 1996-05-30 ES ES96921645T patent/ES2255080T3/es not_active Expired - Lifetime
- 1996-05-30 WO PCT/US1996/010443 patent/WO1996038148A1/en active IP Right Grant
- 1996-05-30 EP EP06000956A patent/EP1661571A3/en not_active Withdrawn
- 1996-05-30 JP JP53682796A patent/JP4480799B2/ja not_active Expired - Lifetime
- 1996-10-15 US US08/732,660 patent/US5902811A/en not_active Expired - Lifetime
-
2007
- 2007-02-20 JP JP2007039648A patent/JP2007182447A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH11507334A (ja) * | 1995-05-31 | 1999-06-29 | エルゴ サイエンス インコーポレイティド | 非バイパス侵襲性介入の結果として起こる介入を伴う狭窄症の予防法 |
Also Published As
Publication number | Publication date |
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DE69635754T2 (de) | 2006-07-27 |
DE69635754T9 (de) | 2007-03-08 |
EP0828492A1 (en) | 1998-03-18 |
EP0828492B1 (en) | 2006-01-18 |
WO1996038148A1 (en) | 1996-12-05 |
MX9709163A (es) | 1998-03-31 |
CA2219452A1 (en) | 1996-12-05 |
US5565454A (en) | 1996-10-15 |
ATE315936T1 (de) | 2006-02-15 |
ES2255080T3 (es) | 2006-06-16 |
EP0828492A4 (en) | 1999-07-07 |
US5902811A (en) | 1999-05-11 |
JP4480799B2 (ja) | 2010-06-16 |
JPH11507334A (ja) | 1999-06-29 |
EP1661571A2 (en) | 2006-05-31 |
DK0828492T3 (da) | 2006-03-06 |
EP1661571A3 (en) | 2006-08-02 |
DE69635754D1 (de) | 2006-04-06 |
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