KR101085824B1 - 생체적합성 고분자를 이용한 다기능성 조영제 및 이의 제조방법 - Google Patents
생체적합성 고분자를 이용한 다기능성 조영제 및 이의 제조방법 Download PDFInfo
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- KR101085824B1 KR101085824B1 KR1020090020676A KR20090020676A KR101085824B1 KR 101085824 B1 KR101085824 B1 KR 101085824B1 KR 1020090020676 A KR1020090020676 A KR 1020090020676A KR 20090020676 A KR20090020676 A KR 20090020676A KR 101085824 B1 KR101085824 B1 KR 101085824B1
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- Prior art keywords
- contrast agent
- polysuccinimide
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- polymer
- agent
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- ZUUZGQPEQORUEV-UHFFFAOYSA-N tetrahydrate;hydrochloride Chemical compound O.O.O.O.Cl ZUUZGQPEQORUEV-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
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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
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
- C08G73/10—Polyimides; Polyester-imides; Polyamide-imides; Polyamide acids or similar polyimide precursors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0041—Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal
- A61K49/0043—Fluorescein, used in vivo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
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- 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
-
- 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
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
- C08G73/10—Polyimides; Polyester-imides; Polyamide-imides; Polyamide acids or similar polyimide precursors
- C08G73/16—Polyester-imides
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Abstract
Description
Loading amount (mol) |
Particle size distribution (nm) |
Zeta potential range (mv) |
Loading Efficiency (%) |
0.000000444 | 55 ~ 75 | -5 ~ -10 | 70 ~ 80 |
0.000000887 | 55 ~ 75 | -8 ~ -15 | 70 ~ 80 |
0.0000017 | 80 ~ 120 | -8 ~ -15 | 60 ~ 70 |
Loading amount (%) |
Particle size distribution (nm) |
Zeta potential range (mv) |
Loading Efficiency (%) |
5 | 60∼70 | 20∼30 | 85∼90 |
10 | 60∼70 | 20∼30 | 85∼90 |
15 | 60∼70 | 20∼30 | 85∼90 |
20 | 150∼200 | 20∼30 | 70∼80 |
Claims (9)
- 삭제
- 중량평균분자량이 1,000 ~ 100,000 범위인 말레산 무수물로부터 합성된 폴리숙신이미드가 주사슬을 이루고 있고, 곁사슬로는1) 중량평균분자량이 100 ~ 20,000 범위인 폴리에틸렌글리콜, 폴리비닐피롤리돈, 덱스트란, 폴리에틸렌옥사이드, 폴리라이신 또는 폴리비닐알콜로부터 유래된 친수성기,2) 탄소 수 3 ~ 80의 아민 또는 인지질로부터 유래된 소수성기,3) 가돌리늄, 망간, 산화철, 알루미늄, 실리콘, 바륨, 이트륨 및 희토류원소 중에서 선택된 조영제를 포집하는 알칸올아민기, 및4) 말단에 형광물질이 결합된 알킬렌디아민기가 결합되어 있는 것임을 특징으로 하는 폴리숙신이미드계 고분자.
- 제 2 항에 있어서, 상기 말단에 형광물질이 결합된 알킬렌디아민기는 카르복시플루오레세인 디아세테이트 N-석시니미딜 에스테르(carboxyfluorescein diacetate N-succinimidyl ester), CYDyeTM 3.5(mono reactive NHS-에스테르) 및CYDyeTM 5.5(mono reactive NHS-에스테르) 중에서 선택된 N-하이드록시 석시니미딜 에스테르(NHS-ester)로 개질된 형광물질을 알킬렌디아민 말단에 결합반응시켜 제조된 것을 특징으로 하는 폴리숙신이미드계 고분자.
- 제 2 항에 있어서, 상기 폴리숙신이미드계 고분자의 입자 크기가 20 ~ 200 nm인 것을 특징으로 하는 폴리숙신이미드계 고분자.
- 제 2 항 내지 제 4 항 중에서 선택된 어느 한 항의 폴리숙신이미드계 고분자가 포함되어 있는 것을 특징으로 하는 조영제.
- 제 5 항에 있어서, 항암제가 봉입된 것을 특징으로 하는 조영제.
- 제 6 항에 있어서, 상기 항암제는 독소루비신(Doxorubicin), 이피루비신(Epirubicin), 도세탁셀(Docetaxel), 파클리탁셀(Paclitaxel), 발루비신(Valrubicin), 시스플라틴(Cisplatin) 또는 타모시펜(Tamoxifen)인 것을 특징으 로 하는 조영제.
- 제 2 항 내지 제 4 항 중에서 선택된 어느 한 항의 고분자와 조영제를 합성하고, 접선 흐름 분리 모듈을 갖는 투석(Dialysis with Tangential flow separation module) 장치로 조영제를 정제하는 것을 특징으로 하는 다기능성 조영제의 제조방법.
- 제 8 항에 있어서, 상기 조영제 정제 후, 디메틸설폭사이드 또는 디메틸포름이미드의 용매에 녹인 혼합 용액과 항암제를 고강도 초음파 발생기(Ultra-sonicator)로 100분 이하 조사하여 항암제를 봉입시키는 것을 특징으로 하는 다기능성 조영제의 제조방법.
Priority Applications (5)
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KR1020090020676A KR101085824B1 (ko) | 2009-03-11 | 2009-03-11 | 생체적합성 고분자를 이용한 다기능성 조영제 및 이의 제조방법 |
JP2011553928A JP2012520372A (ja) | 2009-03-11 | 2009-09-28 | 生体適合性高分子を用いた多機能性造影剤及びその製造方法 |
US13/255,074 US20110318275A1 (en) | 2009-03-11 | 2009-09-28 | Multifunctional contrast agent using biocompatible polymer and preparation method |
PCT/KR2009/005533 WO2010104253A1 (en) | 2009-03-11 | 2009-09-28 | Multifunctional contrast agent using biocompatible polymer and preparation method |
EP09841566A EP2406302A1 (en) | 2009-03-11 | 2009-09-28 | Multifunctional contrast agent using biocompatible polymer and preparation method |
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KR1020090020676A KR101085824B1 (ko) | 2009-03-11 | 2009-03-11 | 생체적합성 고분자를 이용한 다기능성 조영제 및 이의 제조방법 |
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US (1) | US20110318275A1 (ko) |
EP (1) | EP2406302A1 (ko) |
JP (1) | JP2012520372A (ko) |
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WO (1) | WO2010104253A1 (ko) |
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WO2016028636A1 (en) * | 2014-08-16 | 2016-02-25 | Memorial Sloan Kettering Cancer Center | Helical polycarbodiimide polymers and associated imaging, diagnostic, and therapeutic methods |
KR101952297B1 (ko) | 2017-09-21 | 2019-02-26 | 한국화학연구원 | 항암제의 탑재율을 조절하여 조영 성능의 제어가 가능한 항암조영제를 이용한 암 진단 효율 향상 방법 |
KR102205795B1 (ko) * | 2019-04-03 | 2021-01-20 | 채창훈 | 백금 항암제인 카보플라틴을 폴리숙신이미드에 결합시킨 개량 항암제 |
WO2021230388A1 (ko) * | 2020-05-11 | 2021-11-18 | 채창훈 | 백금 항암제인 카보플라틴을 폴리숙신이미드에 결합시킨 개량 항암제 |
CN112940157B (zh) * | 2021-03-22 | 2023-01-10 | 南方医科大学 | 一种钆螯合物及其制备方法和应用 |
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KR100560107B1 (ko) | 2004-10-14 | 2006-03-13 | 한국화학연구원 | 주사제용 다기능성 폴리숙신이미드계 고분자 |
KR100634381B1 (ko) | 2005-11-23 | 2006-10-16 | 한국화학연구원 | 다기능성 폴리숙신이미드계 고분자 및 이를 이용한 조영제 |
US20070036729A1 (en) * | 2005-06-29 | 2007-02-15 | Andreas Briel | Compositions containing magnetic iron oxide particles, and use of said compositions in imaging methods |
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US5610255A (en) * | 1993-02-22 | 1997-03-11 | Bayer Ag | Process for preparing polysuccinimide and polyaspartic acid |
DE19958586A1 (de) * | 1999-12-06 | 2001-06-07 | Aventis Res & Tech Gmbh & Co | Mikropartikel auf Basis von Asparaginsäure und deren Verwendung als MRI-Kontrastmittel |
TWI235066B (en) * | 2001-10-03 | 2005-07-01 | Celator Technologies Inc | Liposome loading with metal ions |
EP2015784A4 (en) * | 2006-05-03 | 2012-12-26 | Wisconsin Alumni Res Found | USING RING OPENING METATHESISPOLYMERIZATION SYNTHETIZED MAGNETIC RESONANCE GRAIN |
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- 2009-09-28 WO PCT/KR2009/005533 patent/WO2010104253A1/en active Application Filing
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KR100560107B1 (ko) | 2004-10-14 | 2006-03-13 | 한국화학연구원 | 주사제용 다기능성 폴리숙신이미드계 고분자 |
US20070036729A1 (en) * | 2005-06-29 | 2007-02-15 | Andreas Briel | Compositions containing magnetic iron oxide particles, and use of said compositions in imaging methods |
KR100634381B1 (ko) | 2005-11-23 | 2006-10-16 | 한국화학연구원 | 다기능성 폴리숙신이미드계 고분자 및 이를 이용한 조영제 |
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Macromol. Biosci. Vol.4 pp.1028~1038.(2004)* |
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WO2010104253A1 (en) | 2010-09-16 |
US20110318275A1 (en) | 2011-12-29 |
JP2012520372A (ja) | 2012-09-06 |
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