WO2019218960A1 - 一种含有聚多巴氨基酸螯合三价铁离子的两亲性聚合物纳米胶束及应用 - Google Patents

一种含有聚多巴氨基酸螯合三价铁离子的两亲性聚合物纳米胶束及应用 Download PDF

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Publication number
WO2019218960A1
WO2019218960A1 PCT/CN2019/086586 CN2019086586W WO2019218960A1 WO 2019218960 A1 WO2019218960 A1 WO 2019218960A1 CN 2019086586 W CN2019086586 W CN 2019086586W WO 2019218960 A1 WO2019218960 A1 WO 2019218960A1
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WIPO (PCT)
Prior art keywords
amino acid
amphiphilic polymer
block
ferric ion
polydopamine
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Ceased
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PCT/CN2019/086586
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English (en)
French (fr)
Chinese (zh)
Inventor
孙继红
凌君
岑佳宇
苗岳栋
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Zhejiang University ZJU
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Zhejiang University ZJU
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Priority to JP2020564078A priority Critical patent/JP7125725B2/ja
Publication of WO2019218960A1 publication Critical patent/WO2019218960A1/zh
Priority to US17/088,566 priority patent/US20210052749A1/en
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/12—Macromolecular compounds
    • A61K49/124—Macromolecular compounds dendrimers, dendrons, hyperbranched compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/12—Macromolecular compounds
    • A61K49/126—Linear polymers, e.g. dextran, inulin, PEG
    • A61K49/128—Linear polymers, e.g. dextran, inulin, PEG comprising multiple complex or complex-forming groups, being either part of the linear polymeric backbone or being pending groups covalently linked to the linear polymeric backbone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1806—Suspensions, emulsions, colloids, dispersions
    • A61K49/1809—Micelles, e.g. phospholipidic or polymeric micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
    • A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
    • A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
    • A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
    • A61K49/1851—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
    • A61K49/1857—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA
    • 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
    • C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites

Definitions

  • amphiphilic polymer nanomicelle containing a polydoba amino acid chelated ferric ion, and the hydrophobic block in the amphiphilic polymer forming the nanomicelle is a biodegradable poly The amino acid block; the amphiphilic polymer nanomicelle containing polydop amino acid chelate the ferric ion with the catechol functional group of the side chain of the polydopa amino acid block, and the chelate bond is represented by the following formula Show:
  • Example 1 is a nuclear magnetic resonance spectrum of polydop amino acid-polysarcosine block copolymer (A) and polysarcosine (B) prepared in Example 1 of the present invention.
  • the hydrodynamic diameter of the polymer nanomicelles in solution was measured by a Zetasizer Nano Series (Malvern Instruments) detector at a wavelength of 657 nm, a fixed angle of 90°, and each sample was tested in parallel three times.
  • the TEM image of the micelle is shown in Figure 2; the DLS test results are shown in Figure 3. 2 and 3, the prepared micelles had an average particle diameter of 20 nm.
  • the cytotoxicity of the micelles was determined by the MTT method, and five parallel samples were set for each sample.
  • the results of cytotoxicity assay are shown in Figure 6, indicating that all samples showed little cytotoxicity at concentrations of 5-500 ⁇ g/mL.
  • concentration was greater than 50 ⁇ g/mL
  • the cell viability decreased slightly with increasing concentration. The decline, but remained above 85%, indicating that this Fe 3+ magnetic resonance contrast agent is low in biotoxicity and has good biocompatibility.
  • POEGMA-g-PDOPA polydoba amino acid-poly(ethylene glycol acrylate) graft polymer
  • Example 2 Other performance test conditions were the same as in Example 1, and the micelle average particle diameter was 35 nm, which had an MRI in vitro reinforcing effect.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Nanotechnology (AREA)
  • Dispersion Chemistry (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Surgery (AREA)
  • Medical Informatics (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)
  • Polyamides (AREA)
PCT/CN2019/086586 2018-05-16 2019-05-13 一种含有聚多巴氨基酸螯合三价铁离子的两亲性聚合物纳米胶束及应用 Ceased WO2019218960A1 (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2020564078A JP7125725B2 (ja) 2018-05-16 2019-05-13 ポリ３，４－ジヒドロキシ－ｌ－フェニルアラニンキレート第二鉄イオンを含有する両親媒性ポリマーナノミセル及びその使用
US17/088,566 US20210052749A1 (en) 2018-05-16 2020-11-03 Amphiphilic polymer nano micelle containing poly-3,4-dihydroxyphenylalanine chelated ferric ions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201810468018.2A CN110496231B (zh) 2018-05-16 2018-05-16 一种含有聚多巴氨基酸螯合三价铁离子的两亲性聚合物纳米胶束及应用
CN201810468018.2 2018-05-16

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US17/088,566 Continuation US20210052749A1 (en) 2018-05-16 2020-11-03 Amphiphilic polymer nano micelle containing poly-3,4-dihydroxyphenylalanine chelated ferric ions

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US (1) US20210052749A1 (enExample)
JP (1) JP7125725B2 (enExample)
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CN114306650B (zh) * 2022-01-21 2022-12-06 南方医科大学 一种磁性四氧化三铁纳米粒及其制备方法和应用
CN118987284A (zh) * 2024-10-25 2024-11-22 杭州奥赛瑞生物医药科技有限责任公司 一种聚合物纳米胶束及其在增强ct成像中的应用
CN118987283A (zh) * 2024-10-25 2024-11-22 杭州奥赛瑞生物医药科技有限责任公司 基于聚氨基酸纳米胶束的多模态对比剂及制备方法和应用
CN119033973A (zh) * 2024-10-30 2024-11-29 杭州奥赛瑞生物医药科技有限责任公司 一种透明质酸修饰的铁基聚多巴氨基酸纳米探针及其制备方法与应用

Citations (2)

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EP2161020A1 (en) * 2008-09-09 2010-03-10 Koninklijke Philips Electronics N.V. Chelating amphiphilic polymers
CN104140546A (zh) * 2014-06-27 2014-11-12 江南大学 一种类碳纳米管状可降解聚合物的制备方法

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KR101721570B1 (ko) * 2011-06-22 2017-03-30 한화케미칼 주식회사 산화철 나노입자 기반 림프절 이미징용 ｍｒｉ 조영제 및 이를 이용하여 림프절을 조영하는 방법
KR101765335B1 (ko) * 2014-09-26 2017-08-22 서울대학교산학협력단 암 세포 조영용 ｍｒｉ 조영제 조성물
CN105524271B (zh) * 2014-10-24 2018-07-03 江苏师范大学 胆酸修饰的聚氨基酸嵌段共聚物的合成及应用
CN106916301A (zh) * 2017-04-14 2017-07-04 四川大学 高载铁量聚多巴胺纳米粒子的制备方法

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EP2161020A1 (en) * 2008-09-09 2010-03-10 Koninklijke Philips Electronics N.V. Chelating amphiphilic polymers
CN104140546A (zh) * 2014-06-27 2014-11-12 江南大学 一种类碳纳米管状可降解聚合物的制备方法

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CN110496231A (zh) 2019-11-26
US20210052749A1 (en) 2021-02-25
JP2021518479A (ja) 2021-08-02
JP7125725B2 (ja) 2022-08-25
CN110496231B (zh) 2020-09-18

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