JPH11503456A - 多糖結合ニトリックオキサイド−求核剤付加物 - Google Patents
多糖結合ニトリックオキサイド−求核剤付加物Info
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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- A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
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- A61P35/04—Antineoplastic agents specific for metastasis
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- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B15/00—Preparation of other cellulose derivatives or modified cellulose, e.g. complexes
- C08B15/05—Derivatives containing elements other than carbon, hydrogen, oxygen, halogens or sulfur
- C08B15/06—Derivatives containing elements other than carbon, hydrogen, oxygen, halogens or sulfur containing nitrogen, e.g. carbamates
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/30—Introducing nitrogen atoms or nitrogen-containing groups
Abstract
Description
Claims (1)
- 【特許請求の範囲】 トリックオキサイド放出[N2O2]官能基を含む多糖を含有する、ニトリック 介して当該多糖に結合している)。 2. 当該ニトリックオキサイド放出[N2O2]官能基が、次のI、II、III、I V、V、VI、VIIおよびVIIIからなる群より選ばれる式の化合物からのもので、当 該多糖に含まれている請求の範囲第1項記載の高分子組成物。 〔式中、Jは有機または無機部位であり、好ましくは炭素原子を介して複合体の 残りの部分の窒素と結合していない部位であり、M+xは医薬上許容されるカチオ ン(式中、xはカチオンの原子価である)であり、aは1または2であり、bお よびcは中性化合物を与える最も小さい整数である。〕; (式中、bおよびdは同一または異なって0または1であり、R1、R2、R3、 R4およびR5は同一または異なって水素、C3-8シクロアルキル、C1-12直鎖ま たは分枝鎖アルキル、ベンジル、ベンゾイル、フタロイル、アセチル、トリフル オロアセチル、p−トルイル、t−ブトキシカルボニルまたは2,2,2−トリ クロロ−t−ブトキシカルボニルであり、x、yおよびzは同一または異なって 2〜12の整数である。); (式中、Bは であり、R6およびR7は同一または異なって水素、C3-8シクロアルキル、C1-1 2 直鎖または分枝鎖アルキル、ベンジル、ベンゾイル、フタロイル、アセチル、 トリフルオロアセチル、p−トルイル、t−ブトキシカルボニルまたは2,2, 2−トリクロロ−t−ブトキシカルボニルであり、fは0〜12の整数であり、 ただしBが置換されたピペラジン部位 の場合、fは2〜12の整数である。); (式中、R8は水素、C3-8シクロアルキル、C1-12直鎖または分枝鎖アルキル、 ベンジル、ベンゾイル、フタロイル、アセチル、トリフルオロアセチル、p−ト ルイル、t−ブトキシカルボニルまたは2,2,2−トリクロロ−t−ブトキシ カルボニルであり、R9は水素またはC1−C12直鎖または分枝鎖アルキルであり 、gは2〜6である。); (式中、R1およびR2は独立して直鎖または分枝鎖C1−C12アルキル基および ベンジルからなる群より選ばれ、M+xは医薬上許容されるカチオンであり、xは カチオンの原子価である。); K[(M)x' x(L)y(R1R2N-N2O2)z] (VI) (式中、Mは医薬上許容される金属、またはxが少なくとも2の場合、異なる2 種の医薬上許容される金属の混合物であり、Lは(R1R2N−N2O2)とは異な る配位子であり、少なくとも1つの金属に結合しており、R1およびR2はそれぞ れ有機部位であり、それらは同一または異なっていてよく、xは1〜10の整数 であり、x’は金属Mの形式的な酸化状態を示し、1〜6の整数であり、yは1 〜18の整数であり、yが少なくとも2の場合、配位子Lは同一または異なって いてもよく、zは1〜20の整数であり、Kは化合物を必要な程度まで中性にす る医薬上許容される対イオンである。); [R-N(H)N(NO)O-]yX (VII) (式中、RはC2-8低級アルキル、フェニル、ベンジルまたはC3-8シクロアル キルであり、R基のいかなるものも1〜3個の置換基で置換されていてもよく、 その置換基は同一または異なっていて、ハロゲン、ヒドロキシ、C1-8アルコキ シ、−NH2、−C(O)NH2、−CH(O)、−C(O)OHおよび−NO2 からなる群より選ばれ、Xは医薬上許容されるカチオン、医薬上許容される金属 中心、またはC1-8低級アルキル、−C(O)CH3および−C(O)NH2から なる群より選ばれる医薬上許容される有機基であり、yは1〜3であり、Xの原 子価と一致する。);および 〔式中、R1およびR2は独立して、C1-12直鎖アルキル、アルコキシまたはアシ ルオキシで置換されたC1-12直鎖アルキル、ヒドロキシまたはハロゲン置換され たC2-12直鎖アルキル、C3-12分枝鎖アルキル、ヒドロキシ、ハロゲン、アルコ キシまたはアシルオキシで置換されたC3-12分枝鎖アルキル、置換されていない か、またはヒドロキシ、アルコキシ、アシルオキシ、ハロゲンまたはベンジルで 置換されているC3-12直鎖およびC3-12分枝鎖オレフィンから選ばれるか、ある いはR1およびR2がそれらが結合している窒素原子と共に複素環基、好ましくは ピロリジノ、ピペリジノ、ピペラジノまたはモルホリノ基を形成し、R3は、置 換されていないか、またはヒドロキシ、ハロゲン、アシルオキシまたはアルコキ シで置換されているC1-12直鎖およびC3-12分枝鎖アルキル、置換されていない か、またはハロゲン、アルコキシ、アシルオキシまたはヒドロキシで置換されて いるC2-12直鎖またはC3-12分枝鎖オレフィン、置換されていないかまたは置換 されているC1-12アシル、スルホニルおよびカルボキサミドから選ばれる基、あ るいはR3は式−(CH2)n−ON=N(O)NR1R2(式中、nは2〜8の整 数であり、R1およびR2は上記に定義した通り)である。〕 3. 当該[N2O2]官能基が、式IIIの化合物からのもので、Bは置換された ピペラジン部位 である請求の範囲第2項記載の高分子組成物。 4. 当該[N2O2]官能基が、式Vの化合物からのもので、R1およびR2がそ れらが結合している窒素原子と共に複素環基を形成するようにR1およびR2が選 ばれる請求の範囲第2項記載の高分子組成物。 5. 複素環基がピロリジノ、ピペリジノ、ピペラジノおよびモルホリノからな る群より選ばれる請求の範囲第4項記載の高分子組成物。 6. 当該[N2O2]官能基が、式VIIIの化合物からのもので、複素環基がピロ リジノ、ピペリジノ、ピペラジノおよびモルホリノからなる群より選ばれる請求 の範囲第2項記載の高分子組成物。 7. 当該官能基の部位Xが多糖鎖のペンダント基の一部である請求の範囲第1 項記載の高分子組成物。 る群より選ばれるニトリックオキサイド放出[N2O2]官能基を含む化合物との 共沈生成物を含有する、ニトリックオキサイド放出が可能な高分子組成物。 9. 当該[N2O2 -]官能基が、次のI、II、III、IV、V、VI、VIIおよびVII Iからなる群より選ばれる式の化合物に含まれている請求の範囲第8項記載の高 分子組成物。 〔式中、Jは有機または無機部位であり、M+xは医薬上許容されるカチオン(式 中、xはカチオンの原子価である)であり、aは1または2であり、bおよびc は中性化合物を与える最も小さい整数である。〕; (式中、bおよびdは同一または異なって0または1であり、R1、R2、R3、 R4およびR5は同一または異なって水素、C3-8シクロアルキル、C1-12直鎖ま たは分枝鎖アルキル、ベンジル、ベンゾイル、フタロイル、アセチル、トリフル オロアセチル、p−トルイル、t−ブトキシカルボニルまたは2,2,2−トリ クロロ−t−ブトキシカルボニルであり、x、yおよびzは同一または異なって 2〜12の整数である。); (式中、Bは であり、R6およびR7は同一または異なって水素、C3-8シクロアルキル、C1-1 2 直鎖または分枝鎖アルキル、ベンジル、ベンゾイル、フタロイル、アセチル、 トリフルオロアセチル、p−トルイル、t−ブトキシカルボニルまたは2,2, 2−トリクロロ−t−ブトキシカルボニルであり、fは0〜12の整数であ り、ただしBが置換されたピペラジン部位 の場合、fは2〜12の整数である。); (式中、R8は水素、C3-8シクロアルキル、C1-12直鎖または分枝鎖アルキル、 ベンジル、ベンゾイル、フタロイル、アセチル、トリフルオロアセチル、p−ト ルイル、t−ブトキシカルボニルまたは2,2,2−トリクロロ−t−ブトキシ カルボニルであり、R9は水素またはC1−C12直鎖または分枝鎖アルキルであり 、gは2〜6である。); (式中、R1およびR2は独立してC1−C12直鎖または分枝鎖アルキルおよびベ ンジルからなる群より選ばれ、M+xは医薬上許容されるカチオンであり、xはカ チオンの原子価である。); K[(M)x'x(L)y(R1R2N-N2O2)z] (VI) (式中、Mは医薬上許容される金属、またはxが少なくとも2の場合、異なる2 種の医薬上許容される金属の混合物であり、Lは(R1R2N−N2O2)とは異な る配位子であり、少なくとも1つの金属に結合しており、R1およびR2はそれぞ れ有機部位であり、それらは同一または異なっていてよく、xは1〜10の整数 であり、x’は金属Mの形式的な酸化状態を示し、1〜6の整数であり、yは1 〜18の整数であり、ただし、yが少なくとも2の場合、配位子Lは同一または 異なっていてもよく、zは1〜20の整数であり、Kは化合物を必要な程度まで 中性にする医薬上許容される対イオンである。); [R-N(H)N(NO)O-]yX (VII) (式中、RはC2-8低級アルキル、フェニル、ベンジルまたはC3-8シクロアルキ ルであり、R基のいかなるものも1〜3個の置換基で置換されていてもよく、そ の置換基は同一または異なっていて、ハロゲン、ヒドロキシ、C1-8アルコキシ 、−NH2、−C(O)NH2、−CH(O)、−C(O)OHおよび−NO2か らなる群より選ばれ、Xは医薬上許容されるカチオン、医薬上許容される金属中 心、またはC1-8低級アルキル、−C(O)CH3および−C(O)NH2からな る群より選ばれる医薬上許容される有機基であり、yは1〜3の整数であり、X の原子価と一致する。);および 〔式中、R1およびR2は独立して、C1-12直鎖アルキル、アルコキシまたはアシ ルオキシで置換されたC1-12直鎖アルキル、ヒドロキシまたはハロゲン置換され たC2-12直鎖アルキル、C3-12分枝鎖アルキル、ヒドロキシ、ハロゲン、アルコ キシまたはアシルオキシで置換されたC3-12分枝鎖アルキル、置換されていな いか、またはヒドロキシ、アルコキシ、アシルオキシ、ハロゲンまたはベンジル で置換されているC3-12直鎖または分枝鎖オレフィンから選ばれるか、あるいは R1およびR2がそれらが結合している窒素原子と共に複素環基を形成し、R3は 、置換されていないか、またはヒドロキシ、ハロゲン、アシルオキシまたはアル コキシで置換されているC1-12直鎖およびC3-12分枝鎖アルキル、置換されてい ないか、またはハロゲン、アルコキシ、アシルオキシまたはヒドロキシで置換さ れているC2-12直鎖またはC3-12分枝鎖オレフィン、置換されていないかまたは 置換されているC1-12アシル、スルホニルおよびカルボキサミドから選ばれる基 、あるいはR3は式−(CH2)n−ON=N(O)NR1R2(式中、nは2〜8 の整数であり、R1およびR2は上記に定義した通り)である。〕 10. 当該化合物が式IIIの化合物であり、Bは置換されたピペラジン部位 である請求の範囲第9項記載の高分子組成物。 11. 当該化合物が式Vの化合物であり、R1およびR2がそれらが結合してい る窒素原子と共に複素環基を形成するようにR1およびR2が選ばれる請求の範囲 第9項記載の高分子組成物。 12. 複素環基がピロリジノ、ピペリジノ、ピペラジノおよびモルホリノから なる群より選ばれる請求の範囲第11項記載の高分子組成物。 13. 当該化合物が式VIIIの化合物であり、複素環基がピロリジノ、ピペリジ ノ、ピペラジノおよびモルホリノからなる群より選ばれる請求の範囲第9項記載 の高分子組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US08/419,424 | 1995-04-10 | ||
US08/419,424 US5691423A (en) | 1992-08-24 | 1995-04-10 | Polysaccharide-bound nitric oxide-nucleophile adducts |
PCT/US1996/004899 WO1996032136A1 (en) | 1995-04-10 | 1996-04-10 | Polysaccharide-bound nitric oxide-nucleophile adducts |
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JP2009281020A Division JP2010111675A (ja) | 1995-04-10 | 2009-12-10 | 多糖結合ニトリックオキサイド−求核剤付加物 |
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JP2009281020A Pending JP2010111675A (ja) | 1995-04-10 | 2009-12-10 | 多糖結合ニトリックオキサイド−求核剤付加物 |
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JP2009281020A Pending JP2010111675A (ja) | 1995-04-10 | 2009-12-10 | 多糖結合ニトリックオキサイド−求核剤付加物 |
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Also Published As
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JP2010111675A (ja) | 2010-05-20 |
AU5448396A (en) | 1996-10-30 |
AU695579B2 (en) | 1998-08-13 |
WO1996032136A1 (en) | 1996-10-17 |
CA2216696C (en) | 2009-01-06 |
EP0822833A1 (en) | 1998-02-11 |
US5691423A (en) | 1997-11-25 |
CA2216696A1 (en) | 1996-10-17 |
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A912 | Re-examination (zenchi) completed and case transferred to appeal board |
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A761 | Written withdrawal of application |
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