DE60315145T2 - Hydrophiles polymerderivat mit y-verzweigung und herstellungsverfahren dafür; obige verbindung enthaltender medizinischer verbundwerkstoff - Google Patents
Hydrophiles polymerderivat mit y-verzweigung und herstellungsverfahren dafür; obige verbindung enthaltender medizinischer verbundwerkstoff Download PDFInfo
- Publication number
- DE60315145T2 DE60315145T2 DE60315145T DE60315145T DE60315145T2 DE 60315145 T2 DE60315145 T2 DE 60315145T2 DE 60315145 T DE60315145 T DE 60315145T DE 60315145 T DE60315145 T DE 60315145T DE 60315145 T2 DE60315145 T2 DE 60315145T2
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- Prior art keywords
- group
- peg
- branched
- derivative according
- polyethylene glycol
- Prior art date
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- Expired - Lifetime
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
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- 238000006243 chemical reaction Methods 0.000 claims description 15
- 125000000524 functional group Chemical group 0.000 claims description 15
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
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Classifications
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- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2203/00—Applications
- C08L2203/02—Applications for biomedical use
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
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- Medicinal Preparation (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Materials For Medical Uses (AREA)
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| PCT/CN2003/000179 WO2003076490A1 (en) | 2002-03-13 | 2003-03-12 | Hydrophilic polymer derivate with y type branch and preparation method of it medical composite comprising above compound |
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| DE10209822A1 (de) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung niedermolekularer Substanzen an ein modifiziertes Polysaccharid |
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| EP1496076B1 (en) * | 2002-03-13 | 2007-07-25 | Beijing Jiankai Technology Co., Ltd. | Hydrophilic polymer derivate with y type branch and preparation method of it medical composite comprising above compound |
| AU2003255406B2 (en) | 2002-09-11 | 2009-09-10 | Fresenius Kabi Deutschland Gmbh | Hydroxyalkyl starch derivatives |
| DE10326303A1 (de) * | 2003-06-11 | 2004-12-30 | Celares Gmbh | Reagenzien zur Modifikation von Biopharmazeutika, deren Herstellung und Anwendung |
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| GB0329825D0 (en) * | 2003-12-23 | 2004-01-28 | Celltech R&D Ltd | Biological products |
| DE202005021885U1 (de) | 2004-03-11 | 2011-03-03 | Fresenius Kabi Deutschland Gmbh | Hydroxyalkylstärke-Protein-Konjugate, durch reduktive Aminierung hergestellt |
| EP1888651B1 (en) * | 2005-05-20 | 2014-07-30 | Agency for Science, Technology and Research | Aldehyde conjugated flavonoid preparations |
| US7858080B2 (en) | 2005-05-20 | 2010-12-28 | Agency For Science, Technology And Research | Aldehyde conjugated flavonoid preparations |
| US20070092486A1 (en) * | 2005-10-21 | 2007-04-26 | Avigenics, Inc. | Glycolated and glycosylated poultry derived therapeutic proteins |
| US20080171696A1 (en) * | 2005-10-21 | 2008-07-17 | Avigenics, Inc. | Pharmacodynamically enhanced therapeutic proteins |
| WO2007140282A1 (en) * | 2006-05-24 | 2007-12-06 | Peg Biosciences | Peg linker compounds and biologically active conjugates thereof |
| CN101168594B (zh) * | 2006-10-24 | 2011-07-27 | 北京键凯科技有限公司 | 寡肽为骨架的聚乙二醇活性衍生物、其制备方法及与药物分子的结合物 |
| CN102827284B (zh) * | 2006-11-14 | 2015-07-29 | 上海仁会生物制药股份有限公司 | 带有聚乙二醇基团的Exendin或其类似物及其制剂和用途 |
| WO2009025669A1 (en) * | 2007-08-20 | 2009-02-26 | Enzon Pharmaceuticals, Inc. | Polymeric linkers containing pyridyl disulfide moieties |
| KR101502645B1 (ko) * | 2007-09-04 | 2015-03-13 | 바이오스티드 진 익스프레션 테크. 컴파니 리미티드 | 폴리에틸렌 글리콜에 의해 변형된 인터페론 알파 2ｂ, 이의 제조 방법 및 용도 |
| PT2196475E (pt) * | 2007-09-04 | 2012-09-07 | Biosteed Gene Expression Tech Co Ltd | Interferão alfa-2a modificado por polietilenoglicol, seu processo de síntese e aplicação |
| EP2070950A1 (en) | 2007-12-14 | 2009-06-17 | Fresenius Kabi Deutschland GmbH | Hydroxyalkyl starch derivatives and process for their preparation |
| AU2007363326B2 (en) * | 2007-12-29 | 2014-01-30 | Biosteed Gene Expression Tech. Co., Ltd. | Y-type polyethylene glycol modified G-CSF and preparation method and use thereof |
| JP5458416B2 (ja) * | 2008-04-03 | 2014-04-02 | バイオスティード ジーン エクスプレッション テック． カンパニー リミテッド | 二本鎖ポリエチレングリコール化成長ホルモン、その製造方法およびその使用 |
| CN101701068B (zh) * | 2009-10-30 | 2011-09-21 | 北京化工大学 | 一种pH响应性的Y型药物输送材料及其制备方法 |
| JP2011105792A (ja) * | 2009-11-12 | 2011-06-02 | Japan Science & Technology Agency | ブロックコポリマー、ブロックコポリマー−金属錯体複合体、及びそれを用いた中空構造体キャリア |
| FR2953720B1 (fr) * | 2009-12-11 | 2012-05-11 | Oreal | Utilisation de derives de benzyloxy-ethylamines comme conservateur, |
| EP2591008A1 (en) | 2010-07-09 | 2013-05-15 | Fresenius Kabi Deutschland GmbH | Conjugates comprising hydroxyalkyl starch and a cytotoxic agent and process for their preparation |
| US20130217871A1 (en) | 2010-07-09 | 2013-08-22 | Helmut Knoller | Conjugates comprising hydroxyalkyl starch and a cytotoxic agent and process for their preparation |
| EP2590680A1 (en) | 2010-07-09 | 2013-05-15 | Fresenius Kabi Deutschland GmbH | Conjugates comprising hydroxyalkyl starch and a cytotoxic agent and process for their preparation |
| EP2590681A1 (en) | 2010-07-09 | 2013-05-15 | Fresenius Kabi Deutschland GmbH | Conjugates comprising hydroxyalkyl starch and a cytotoxic agent and process for their preparation |
| EP2633053A1 (en) | 2010-10-29 | 2013-09-04 | Noxxon Pharma AG | Use of hepcidin binding nucleic acids for depletion of hepcidin from the body |
| CN103083680B (zh) * | 2011-11-07 | 2014-12-24 | 北京键凯科技有限公司 | 聚乙二醇-氨基酸寡肽-依诺替康药物结合物及其药物组合物 |
| WO2013089182A1 (ja) * | 2011-12-14 | 2013-06-20 | 国立大学法人筑波大学 | 新規分岐ポリエチレングリコール及びその用途 |
| WO2014114262A1 (zh) * | 2013-01-28 | 2014-07-31 | 天津键凯科技有限公司 | 水溶性聚合物-氨基酸寡肽-药物结合物及其制备方法和用途 |
| US9700633B2 (en) | 2013-01-28 | 2017-07-11 | Jenkem Technology Co., Ltd., Tianjin Branch | Conjugates of water soluble polymer-amino acid oligopeptide-drug, preparation method and use thereof |
| CN103965458B (zh) * | 2013-01-28 | 2017-02-15 | 天津键凯科技有限公司 | 聚乙二醇‑氨基酸寡肽‑达沙替尼结合物及其药物组合物 |
| CN104109235B (zh) * | 2014-05-30 | 2017-07-18 | 厦门赛诺邦格生物科技股份有限公司 | 一种具有氮原子支化中心的单一官能化聚乙二醇、制备方法及其生物相关物质 |
| CN106146325B (zh) * | 2015-04-24 | 2019-01-29 | 北京键凯科技股份有限公司 | 一种y型多缩乙二醇衍生物及其制备方法 |
| CN107446908A (zh) * | 2016-06-01 | 2017-12-08 | 湖南华腾制药有限公司 | 分支型聚乙二醇修饰的l‑门冬酰胺酶及其制备方法 |
| CN106750250B (zh) * | 2016-12-21 | 2019-04-23 | 沈阳化工大学 | 以氨基酸作为连接臂的聚乙二醇齐墩果酸衍生物及其制备方法和应用 |
| CN108530637B (zh) * | 2017-03-05 | 2021-03-30 | 厦门赛诺邦格生物科技股份有限公司 | 一种单一功能化支化聚乙二醇的制备方法 |
| CN108659227B (zh) * | 2017-03-30 | 2020-11-06 | 北京键凯科技股份有限公司 | 一种y型分支的亲水性聚合物羧酸衍生物的制备方法 |
| WO2018177055A1 (zh) * | 2017-03-30 | 2018-10-04 | 北京键凯科技股份有限公司 | 一种y型分支的亲水性聚合物羧酸衍生物的制备方法 |
| CN108530642B (zh) * | 2017-11-24 | 2021-01-15 | 四川大学 | 可生物降解的三嵌段杂臂星形双亲性高分子材料及其制备方法 |
| CN109400868B (zh) * | 2018-11-30 | 2021-01-15 | 吉林化工学院 | 一种聚乙二醇单苯甲醚化合物的合成方法 |
| JP2023541816A (ja) | 2020-08-27 | 2023-10-04 | イノージ・セラピューティクス・コーポレイション | 自己免疫性疾患および癌を治療するための方法および組成物 |
| CN112898561A (zh) * | 2021-01-27 | 2021-06-04 | 大连理工大学 | 马来酰亚胺封端聚苯醚及其制备方法 |
| US20250152512A1 (en) | 2022-04-12 | 2025-05-15 | Xiamen Sinopeg Biotech Co., Ltd. | Nitrogen-branched non-linear pegylated lipid containing a tertiary amine and application thereof |
| CN117510828A (zh) | 2022-07-28 | 2024-02-06 | 厦门赛诺邦格生物科技股份有限公司 | 一种含氨基酸残基的三臂聚乙二醇衍生物 |
| WO2024164213A1 (zh) | 2023-02-09 | 2024-08-15 | 谢彦晖 | 聚乙二醇修饰的白介素2、糖皮质激素和透明质酸用于治疗特应性皮炎 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE756285A (fr) * | 1969-09-17 | 1971-03-17 | Hoechst Ag | Produits de polyoxethylation fluores utilisables pour l'appretage de textiles |
| GB1361627A (en) * | 1970-08-04 | 1974-07-30 | Marumo H | Detergent composition |
| IT956228B (it) * | 1972-04-15 | 1973-10-10 | Snia Viscosa | Metodo ed additivi per conferire proprieta antistatiche a composi zioni poliammidiche e prodotti poliammidici ottenuti secondo tale metodo e con l impiego di tali additivi |
| US4520145A (en) * | 1982-07-21 | 1985-05-28 | The Boots Company Plc | Modified thermosetting imide resins with improved fracture toughness |
| DE3730797A1 (de) | 1987-09-14 | 1989-03-23 | Siegel Rolf | Materialien mit nicht-thrombogener oberflaeche |
| GB2215806B (en) | 1988-02-15 | 1992-02-05 | Hakko Co | Method of applying a lining to a pipeline |
| US5122614A (en) | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| JPH0362814A (ja) * | 1989-07-29 | 1991-03-18 | Nisshinbo Ind Inc | 親水性ポリカルボジイミドポリマー、該親水性ポリカルボジイミドポリマーによるパルプ状物及びそれらの製造方法 |
| JP2902201B2 (ja) * | 1991-03-18 | 1999-06-07 | ストックハウゼン ルイジアナ リミティド | 超吸収性ポリマーの残留アクリル酸含量を低下させる方法 |
| US5382657A (en) * | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
| US5349001A (en) | 1993-01-19 | 1994-09-20 | Enzon, Inc. | Cyclic imide thione activated polyalkylene oxides |
| US5840900A (en) | 1993-10-20 | 1998-11-24 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
| US5824701A (en) * | 1993-10-20 | 1998-10-20 | Enzon, Inc. | Taxane-based prodrugs |
| US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5919455A (en) * | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5879923A (en) | 1995-06-26 | 1999-03-09 | Daiichi Pure Chemicals Co., Ltd. | Stable plasmin solution |
| US5672662A (en) * | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
| AU735900B2 (en) | 1996-03-12 | 2001-07-19 | Pg-Txl Company, L.P. | Water soluble paclitaxel prodrugs |
| US6258351B1 (en) * | 1996-11-06 | 2001-07-10 | Shearwater Corporation | Delivery of poly(ethylene glycol)-modified molecules from degradable hydrogels |
| CN1164533A (zh) | 1997-01-09 | 1997-11-12 | 云南汉德技术发展有限公司 | 一种水溶性抗癌化合物-聚氨基酸紫杉醇酯 |
| US6824766B2 (en) | 1998-04-17 | 2004-11-30 | Enzon, Inc. | Biodegradable high molecular weight polymeric linkers and their conjugates |
| US6153655A (en) | 1998-04-17 | 2000-11-28 | Enzon, Inc. | Terminally-branched polymeric linkers and polymeric conjugates containing the same |
| US7060708B2 (en) | 1999-03-10 | 2006-06-13 | New River Pharmaceuticals Inc. | Active agent delivery systems and methods for protecting and administering active agents |
| US6733755B2 (en) | 2000-02-04 | 2004-05-11 | Supratek Pharma, Inc. | Ligand for vascular endothelial growth factor receptor |
| CN1125097C (zh) | 2000-07-05 | 2003-10-22 | 天津大学 | 聚乙二醇支载的紫杉醇或多烯紫杉醇的前药 |
| CN100475269C (zh) | 2002-03-05 | 2009-04-08 | 北京键凯科技有限公司 | 亲水性聚合物-谷氨酸寡肽与药物分子的结合物、包含该结合物的组合物及用途 |
| EP1496076B1 (en) | 2002-03-13 | 2007-07-25 | Beijing Jiankai Technology Co., Ltd. | Hydrophilic polymer derivate with y type branch and preparation method of it medical composite comprising above compound |
| US7495099B2 (en) | 2002-10-31 | 2009-02-24 | Nippon Kayaku Kabushiki Kaisha | High-molecular weight derivatives of camptothecins |
-
2003
- 2003-03-12 EP EP03709581A patent/EP1496076B1/en not_active Expired - Lifetime
- 2003-03-12 JP JP2003574704A patent/JP4272537B2/ja not_active Expired - Fee Related
- 2003-03-12 AT AT03709581T patent/ATE368066T1/de active
- 2003-03-12 WO PCT/CN2003/000179 patent/WO2003076490A1/zh not_active Ceased
- 2003-03-12 ES ES03709581T patent/ES2291620T3/es not_active Expired - Lifetime
- 2003-03-12 DE DE60315145T patent/DE60315145T2/de not_active Expired - Lifetime
- 2003-03-12 CN CNB038011050A patent/CN1243779C/zh not_active Expired - Lifetime
- 2003-03-12 US US10/507,452 patent/US8003089B2/en active Active
- 2003-03-12 AU AU2003221291A patent/AU2003221291A1/en not_active Abandoned
-
2010
- 2010-05-17 US US12/781,173 patent/US20100221213A1/en not_active Abandoned
-
2011
- 2011-06-17 US US13/163,080 patent/US20110243892A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DE60315145D1 (de) | 2007-09-06 |
| US20050180946A1 (en) | 2005-08-18 |
| CN1243779C (zh) | 2006-03-01 |
| US20100221213A1 (en) | 2010-09-02 |
| JP4272537B2 (ja) | 2009-06-03 |
| ATE368066T1 (de) | 2007-08-15 |
| JP2005520006A (ja) | 2005-07-07 |
| WO2003076490A8 (en) | 2004-10-28 |
| WO2003076490A1 (en) | 2003-09-18 |
| US20110243892A1 (en) | 2011-10-06 |
| ES2291620T3 (es) | 2008-03-01 |
| EP1496076A1 (en) | 2005-01-12 |
| EP1496076B1 (en) | 2007-07-25 |
| US8003089B2 (en) | 2011-08-23 |
| AU2003221291A1 (en) | 2003-09-22 |
| CN1556828A (zh) | 2004-12-22 |
| EP1496076A4 (en) | 2006-06-21 |
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| 8364 | No opposition during term of opposition |