JPH09504299A - 非抗原性分枝ポリマー複合体 - Google Patents
非抗原性分枝ポリマー複合体Info
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- JPH09504299A JPH09504299A JP7512785A JP51278595A JPH09504299A JP H09504299 A JPH09504299 A JP H09504299A JP 7512785 A JP7512785 A JP 7512785A JP 51278595 A JP51278595 A JP 51278595A JP H09504299 A JPH09504299 A JP H09504299A
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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
- A61K47/56—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
- A61K47/59—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 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/332—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof
- C08G65/3322—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof acyclic
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/333—Polymers modified by chemical after-treatment with organic compounds containing nitrogen
- C08G65/33396—Polymers modified by chemical after-treatment with organic compounds containing nitrogen having oxygen in addition to nitrogen
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- C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
- C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
- C12N11/08—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer
- C12N11/089—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- General Engineering & Computer Science (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.式: (R)nL−A (I) [式中、(R)は水溶性で実質的に非抗原性のポリマー; (n)=2または3; (L)は各(R)に共有結合している脂肪族連結分子部分;そして (A)は生物活性求核物質と結合し得る官能基またはこうした求核物質と 反 応するために官能基化し得る分子部分である。] を含む実質的に非抗原性の分枝ポリマー。 2.(R)の少なくとも1つが直鎖ポリマーである、請求項1記載のポリマー。 3.(R)の少なくとも1つがポリ(アルキレンオキサイド)である、請求項1 記載のポリマー。 4.ポリ(アルキレンオキサイド)がα−置換ポリ(アルキレンオキサイド)で ある、請求項3記載のポリマー。 5.ポリ(アルキレンオキサイド)がポリ(エチレングリコール)ホモポリマー 、アルキル末端基付加ポリ(エチレンオキサイド)、およびポリ(アルキレンオ キサイド)ブロックコポリマーのコポリマーからなる基から選択される、請 求 項3記載のポリマー。 6.ポリ(アルキレンオキサイド)が約 200〜約20,000の分子量を有する、請求 項5記載のポリマー。 7.ポリ(アルキレンオキサイド)が約 2,000〜約10,000の分子量を有する、請 求項6記載のポリマー。 8.ポリ(エチレングリコール)ホモポリマーが約 5,000の分子量を有する、請 求項7記載のポリマー。 9.各(R)がポリ(エチレングリコール)ホモポリマーである、請求項2記載 のポリマー。 10.(R)の少なくとも1つが分枝ポリマーである、請求項1記載のポリマー。 11.(L)が脂肪族分子部分である、請求項1記載のポリマー。 12.脂肪族分子部分が置換アルキルジアミンおよびトリアミン、リジンエステル 、マロン酸エステル誘導体からなる基から選択される、請求項11記載のポリマー 。 13.(n)が2である、請求項1記載の活性化分枝ポリマー。 14.(A)がヒドロキシル、アミノ、カルボキシル、カルボニル、チオールおよ びメチレン水 素分子部分からなる基から選択される分子部分である、請求項1 記載のポリマー。 15.(A)がスクシンイミジルまたはp−ニトロフェニルカーボネート活性エス テルである、請求項14記載のポリマー。 16.(A)が脂肪族連結分子部分(L)に近接したスペーサー分子部分を含有す る、請求項1記載のポリマー。 17.スペーサー分子部分が炭素原子数18までのアルキル若しくはシクロアルキル 基またはポリマーを含有する、請求項16記載のポリマー。 18.(R)の少なくとも1つが求核物質と共有結合し得る官能基をさらに含有す る、請求項1記載のポリマー。 19.式: (R)nL−A [式中、(R)は水溶性で実質的に非抗原性のポリマー; (n)=2または3; (L)は非抗原性ポリマーのそれぞれに共有結合している脂肪族連結分子部分 ;そして (A)は生物活性求核物質と共有結合し得る官能基である] で示される構造を有する活性化した非抗原性の分枝ポリマーを生物活性求核物 質に接触させること含む、生物活性複合体の形成方法。 20.式: [(R)nL−A1]z-(求核物質) [式中、(R)は水溶性で実質的に非抗原性のポリマー; (n)=2または3; (L)は脂肪族連結分子部分 ;そして (A1)は(L)と生物活性求核物質との間の共有結合を表し;そして、 (z)は求核物質に付着したポリマーの数を表す] で示される構造を含有する、ポリマー複合体。 21.(R)の少なくとも1つがポリ(アルキレンオキサイド)である、請求項20 の複合体。 22.ポリ(アルキレンオキサイド)がα−置換ポリ(アルキレンオキサイド)で ある、請求項21の複合体。 23.ポリ(アルキレンオキサイド)がポリ(エチレングリコール)ホモポリマー 、アルキル末端基付加ポリ(エチレンオキサイド)、およびポリ(アルキレンオ キサイド)ブロックコポリマーのコポリマーからなる基から選択される、請求項 21記載の複合体。 24.ポリ(アルキレンオキサイド)が約 200〜約20,000の分子量を有する、請求 項23記載の複合体。 25.ポリ(アルキレンオキサイド)が約 2,000〜約10,000の分子量を有する、請 求項24記載の複合体。 26.ポリ(エチレングリコール)ホモポリマーが約 5,000の分子量を有する、請 求項25記載の複合体。 27.各(R)がポリ(エチレングリコール)ホモポリマーである、請求項21記載 の複合体。 28.(R)の少なくとも1つが分枝ポリマーである、請求項20記載の複合体。 29.(L)が非平面的分子部分である、請求項20記載のポリマー。 30.求核物質がタンパク質、ペプチドおよびポリペプチドからなる物質から選択 される、請求項20記載の複合体。 31.タンパク質が抗体、モノクローナル抗体、抗体断片および一本鎖結合抗原か らなる群から選択される、請求項30記載の複合体。 32.ペプチドおよびポリペプチドが生物活性ペプチドおよびポリペプチドからな る群から選択される、請求項30記載の複合体。 33.求核物質が、抗新生物薬、抗感染薬、抗不安薬、胃腸薬、中枢神経系−活性 薬、鎮痛薬、妊娠促進薬、避妊薬、抗炎症薬、ステロイド薬、抗尿毒症薬、心臓 血管薬、血管拡張薬、血管収縮薬からなる群の物質の1つである、請求項20 記載の複合体。 34.抗新生物薬が、タキソール(taxol )、タキサン(taxan )、タキソイド( taxoid)分子、アントラサイクリン(anthracyclin)およびメトトレキセート( methotrexate)からなる群から選択される、請求項33記載の複合体。 35.請求項20記載の分枝ポリマー複合体の治療上有効な量を、この治療を必要と する哺乳動物に投与することからなる、治療方法。 36.i) 式: (R)nL−A [式中、(R)はそれぞれ独立した水溶性で実質的に非抗原性のポリマー; (n)=2または3; (L)は非抗原性ポリマーのそれぞれに共有結合している脂肪族連結分子部分 ;そして (A)は求核物質と共有結合を形成し得る官能基である] で示される構造を有する非抗原性の分枝ポリマーをp−ニトロフェニルクロロ ホルメートに接触させること;および ii) i)のp−ニトロフェニルカーボネート活性エステルにN−ヒドロキ シスクシンイミドを反応させること; を含む、非抗原性分枝ポリマーのスクシンイミジルカーボネート活性エステル の製造方法。 37.(A)が脂肪族連結基(L)に近接したスペーサー分枝部分を含有する、請 求項36記載の方法。 38.i) 式: (R)nL−A [式中、(R)はそれぞれ独立した水溶性で実質的に非抗原性のポリマー; (n)=2または3; (L)は非抗原性ポリマーのそれぞれに共有結合している脂肪族連結分子部分 ;そして (A)は求核物質と共有結合を形成し得る官能基である] で示される構造を有する非抗原性の分枝ポリマーをビス−スクシンイミジルカ ーボネートに接触させること; を含む、非抗原性分枝ポリマーのスクシンイミジルカーボネート活性エステル の製造方法。 39.(A)が脂肪族連結基(L)に近接したスペーサー分枝部分を含有する、請 求項38記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US08/143,403 | 1993-10-27 | ||
US08/143,403 US5643575A (en) | 1993-10-27 | 1993-10-27 | Non-antigenic branched polymer conjugates |
PCT/US1994/012237 WO1995011924A1 (en) | 1993-10-27 | 1994-10-24 | Non-antigenic branched polymer conjugates |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH09504299A true JPH09504299A (ja) | 1997-04-28 |
JP3626494B2 JP3626494B2 (ja) | 2005-03-09 |
Family
ID=22503911
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP51278595A Expired - Lifetime JP3626494B2 (ja) | 1993-10-27 | 1994-10-24 | 非抗原性分枝ポリマー複合体 |
Country Status (8)
Country | Link |
---|---|
US (1) | US5643575A (ja) |
EP (2) | EP1055685B1 (ja) |
JP (1) | JP3626494B2 (ja) |
AU (1) | AU8090294A (ja) |
CA (1) | CA2174325C (ja) |
DE (2) | DE69427045T2 (ja) |
DK (2) | DK1055685T3 (ja) |
WO (1) | WO1995011924A1 (ja) |
Cited By (14)
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WO2001048052A1 (fr) | 1999-12-24 | 2001-07-05 | Kyowa Hakko Kogyo Co., Ltd. | Glycols de polyalkylene ramifies |
WO2002032957A1 (fr) | 2000-10-16 | 2002-04-25 | Chugai Seiyaku Kabushiki Kaisha | Erythropoietine modifiee par peg |
JP2006526569A (ja) * | 2003-05-30 | 2006-11-24 | エンゾン インコーポレイテッド | 脂肪族生物分解性リンカーに基づく放出可能なポリマー複合体 |
JP2008530271A (ja) * | 2005-02-04 | 2008-08-07 | エンゾン ファーマスーティカルズ インコーポレイテッド | ポリマー複合体の調製方法 |
JP2009532330A (ja) * | 2006-02-28 | 2009-09-10 | オリガシス コーポレイション | アクリロイルオキシエチルホスホリルコリン含有ポリマー抱合体及びその製法 |
JP2010536788A (ja) * | 2007-08-16 | 2010-12-02 | ファーマエッセンティア コーポレイション | タンパク質−高分子結合体 |
WO2011034105A1 (ja) | 2009-09-15 | 2011-03-24 | 株式会社カネカ | 水溶性長鎖分子を付加した修飾エリスロポエチン |
JP4758608B2 (ja) * | 2001-11-07 | 2011-08-31 | ネクター セラピューティックス | 分枝ポリマーおよびそれらの結合体 |
WO2014157117A1 (ja) | 2013-03-27 | 2014-10-02 | 日油株式会社 | アミノ基を一つ有するポリエチレングリコールの精製方法 |
JP2015521667A (ja) * | 2012-06-18 | 2015-07-30 | ポリセリックス・リミテッド | 複合体化試薬 |
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Also Published As
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DK0788515T3 (da) | 2001-07-16 |
DE69427045D1 (de) | 2001-05-10 |
EP0788515A4 (en) | 1998-07-01 |
EP0788515B1 (en) | 2001-04-04 |
AU8090294A (en) | 1995-05-22 |
EP1055685A1 (en) | 2000-11-29 |
CA2174325A1 (en) | 1995-05-04 |
DE69427045T2 (de) | 2001-10-25 |
DE69434046D1 (de) | 2004-11-04 |
DK1055685T3 (da) | 2005-01-03 |
US5643575A (en) | 1997-07-01 |
CA2174325C (en) | 2009-05-26 |
DE69434046T2 (de) | 2005-10-06 |
EP1055685B1 (en) | 2004-09-29 |
WO1995011924A1 (en) | 1995-05-04 |
EP0788515A1 (en) | 1997-08-13 |
JP3626494B2 (ja) | 2005-03-09 |
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