CN102076331B - 具有可控的药物释放速率的前药和药物-大分子轭合物 - Google Patents

具有可控的药物释放速率的前药和药物-大分子轭合物 Download PDF

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CN102076331B
CN102076331B CN2009801238298A CN200980123829A CN102076331B CN 102076331 B CN102076331 B CN 102076331B CN 2009801238298 A CN2009801238298 A CN 2009801238298A CN 200980123829 A CN200980123829 A CN 200980123829A CN 102076331 B CN102076331 B CN 102076331B
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formula
compound
drug
optionally substituted
macromolecule
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CN102076331A (zh
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D·V·桑迪
G·阿什利
B·赫恩
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Prolynx LLC
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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
    • 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
    • A61K47/54—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 compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • 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
    • 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
    • C08G65/333—Polymers modified by chemical after-treatment with organic compounds containing nitrogen
    • C08G65/33303—Polymers modified by chemical after-treatment with organic compounds containing nitrogen containing amino group
    • C08G65/33317—Polymers modified by chemical after-treatment with organic compounds containing nitrogen containing amino group heterocyclic
    • 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
    • C08G65/333—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
    • 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

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
CN2009801238298A 2008-06-26 2009-06-26 具有可控的药物释放速率的前药和药物-大分子轭合物 Active CN102076331B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US13314808P 2008-06-26 2008-06-26
US61/133,148 2008-06-26
US19205008P 2008-09-15 2008-09-15
US61/192,050 2008-09-15
PCT/US2009/048943 WO2009158668A1 (en) 2008-06-26 2009-06-26 Prodrugs and drug-macromolecule conjugates having controlled drug release rates

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CN102076331A CN102076331A (zh) 2011-05-25
CN102076331B true CN102076331B (zh) 2013-12-18

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US (2) US8680315B2 (enExample)
EP (1) EP2306986B1 (enExample)
JP (2) JP6084770B2 (enExample)
CN (1) CN102076331B (enExample)
DK (1) DK2306986T3 (enExample)
ES (1) ES2672526T3 (enExample)
WO (1) WO2009158668A1 (enExample)

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WO2011140393A1 (en) 2010-05-05 2011-11-10 Prolynx Llc Controlled release from macromolecular conjugates
EP2571496A4 (en) * 2010-05-05 2016-03-30 Prolynx Llc CONTROLLED RELEASE OF MEDICINE FROM DENIMERS
EP2729179B1 (en) 2011-06-06 2020-09-23 Starpharma Pty Ltd Macromolecules
WO2013036857A1 (en) * 2011-09-07 2013-03-14 Prolynx Llc Sulfone linkers
AU2012304337B2 (en) 2011-09-07 2015-05-07 Prolynx Llc Hydrogels with biodegradable crosslinking
WO2013059323A1 (en) * 2011-10-18 2013-04-25 Prolynx Llc Peg conjugates of exenatide
EP2850201A4 (en) * 2012-05-11 2016-08-31 Alexander Krantz Site-specific labeling and targeted administration of proteins for the treatment of cancer
CN106232131A (zh) * 2013-10-22 2016-12-14 普洛林克斯有限责任公司 生长抑素和其类似物的结合物
IL290330B2 (en) 2013-12-19 2023-09-01 Seagen Inc Methylene carbamate binders for use with drug-targeting conjugates
WO2016025752A1 (en) * 2014-08-14 2016-02-18 Prolynx Llc Reagents for thiol conjugation and conjugates formed therefrom
MA40524A (fr) 2014-09-26 2021-03-17 Bayer Pharma AG Dérivés d'adrénomédulline stabilisés et leur utilisation
GB201508024D0 (en) * 2015-05-11 2015-06-24 Haemostatix Ltd Haemostatic compositions
CN109414469A (zh) * 2016-03-16 2019-03-01 普罗林科斯有限责任公司 艾塞那肽类似物的缓释偶联物
CN106177977B (zh) * 2016-07-11 2020-09-04 天津科技大学 一种抗肿瘤药物三元偶联物及合成和应用
JOP20190191A1 (ar) 2017-02-22 2019-08-08 Astrazeneca Ab وحدات شجرية علاجية
WO2019140266A1 (en) 2018-01-12 2019-07-18 Prolynx Llc Protocol for minimizing toxicity of combination dosages and imaging agent for verification
US12071517B2 (en) 2018-07-19 2024-08-27 Starpharma Pty Ltd. Therapeutic dendrimer
BR112021000658A2 (pt) 2018-07-19 2021-04-13 Starpharma Pty Ltd Dendrímero, composições, composição farmacêutica, método de tratamento de câncer, uso de dendrímero, método, uso, dendrímero ou composição, processo de produção de dendrímero e intermediários para a produção de dendrímero
JPWO2020050378A1 (ja) * 2018-09-06 2021-08-30 生化学工業株式会社 第３級アミン化合物又はイミン化合物を結合させた、ポリマーコンジュゲートとその製造方法
WO2020067507A1 (ja) * 2018-09-28 2020-04-02 生化学工業株式会社 第１級アミン化合物又は第２級アミン化合物－酸性多糖コンジュゲートとその製造方法
CN114286693A (zh) 2019-04-05 2022-04-05 普罗林科斯有限责任公司 改良偶联接头
CA3143584A1 (en) 2019-06-18 2020-12-24 Bayer Aktiengesellschaft Adrenomedullin-analogues for long-term stabilization and their use
BR112022002308A2 (pt) 2019-08-07 2022-04-26 Prolynx Llc Esterilização a vapor de hidrogéis reticulados por ligantes beta-eliminativos
CN110423355B (zh) * 2019-08-29 2021-09-14 武汉轻工大学 羧甲基化莲藕多糖-曲古霉素a轭合物的制备方法
EP4139340A1 (en) 2020-04-22 2023-03-01 Merck Sharp & Dohme LLC Human interleukin-2 conjugates biased for the interleukin-2 receptor beta gammac dimer and conjugated to a nonpeptidic, water-soluble polymer
US20240261425A1 (en) * 2021-04-09 2024-08-08 Nanjing University Conjugate and the preparing method and use thereof
WO2024235071A1 (en) * 2023-05-16 2024-11-21 Nanjing University Conjugate and the preparation thereof

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US9387254B2 (en) 2016-07-12
JP6084770B2 (ja) 2017-02-22
US8680315B2 (en) 2014-03-25
JP2011528654A (ja) 2011-11-24
CN102076331A (zh) 2011-05-25
EP2306986B1 (en) 2018-03-21
WO2009158668A1 (en) 2009-12-30
ES2672526T3 (es) 2018-06-14
DK2306986T3 (en) 2018-06-18
EP2306986A1 (en) 2011-04-13
US20140296476A1 (en) 2014-10-02
EP2306986A4 (en) 2015-01-28
US20110263502A1 (en) 2011-10-27
JP2015172078A (ja) 2015-10-01

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