JP4733126B2 - 蛍光色素と腫瘍親和性テトラピロールの付加物 - Google Patents
蛍光色素と腫瘍親和性テトラピロールの付加物 Download PDFInfo
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- 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
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
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- 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
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- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
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Description
1. 正常組織と相対して腫瘍組織が優先的に局在し、
2. 蛍光効率が高く、
3. 毒性、光毒性、発癌性又は催奇形性であってはならず、
4. 合成が容易でなければならず、
5. 化学的に純粋でなければならず、
6. 深在腫瘍が検出され得るように600〜800nmの範囲にある長波長吸収を有しなければならず、
7. 活性化によって局在する腫瘍を破壊しなければならず、
8.腫瘍が生体内蛍光分光法によって簡単に検出され得るように発光波長が優先的吸収波長から充分に分けられ(移動され)て重大な妨害を防止しなければならない、
生理的に適合する化合物が望ましい。
ここで、本発明の種類と操作方式を、添付の図面と用いられる以下の発明の詳細な説明においてより充分に記載する。
上記構造の好ましい色素においては、R7dは、
本発明に従って用いられるタイプの色素の個々の例は以下の通り: インドシアニングリーン(ジインドール、即ち、トリカルボシアニン、色素); インドシアニングリーン820nm類似体CAS172616-80-7 (R7dは
腫瘍親和性テトラピロール化合物は、通常はクロリン、バクテリオクロリン及びバクテリオプルプリンからなる群より選ばれる、好ましくはポルフィリン誘導体(実際にポルフィリンから誘導されてもされなくてもポルフィリン関連化合物を含む)である。好ましいポルフィリン誘導体は、通常は下記一般式:
本発明の多くの結合体の一般式は、
である。
本発明の好ましい化合物は、以下の式:
で表すことができる。
前述したように、本発明による HPPHとインドシアニングリーン820nm類似体(1)を用いた好ましい化合物の調製を示す概略図の一例は、以下の通りであり、ここで、炭素原子a-d、f-g、m-oについての置換基は通常水素であるが、低級アルキルであってもよい。
本発明の一般的に多くの好ましい化合物は、以下の通り簡単に表すことができる。
R = 可変炭素単位をもつ炭素鎖を含有するアルキル基、スルホン酸基又はカルボキシル基
R2 = フッ素化置換基をもった又はもっていない種々の芳香族系
本発明の他の好ましい光感作性化合物は、以下の通り表すことができる。
R1 = CONH-(CH2)n-光感受性物質
R = R1 = CONH-(CH2)n-光感受性物質
光感受性物質: ポルフィリン、クロリン、バクテリオクロリン、フタロシアニン、拡張ポルフィリン
R2 = ハロゲン
R3 = 可変炭素単位をもつ炭素鎖を含有するアルキル基、スルホン酸基又はカルボキシル基
R = CONH(CH2)nNH-葉酸
以下の実施例は、本発明の化合物の合成のための好ましい方法を具体的に説明するものである。
市販の色素1(60mg)と4-アミノチオフェノール2(60mg)を乾燥DMFに溶解し、一晩撹拌した。溶媒を除去した後、残留物を溶離溶媒としてMeOH/CH2Cl2(1:3)を用いるシリカカラムクロマトグラフィによって精製し、中間体3を〜60%収量で得た。UV-vis: 830nm (MeOH中)(ε= 207,000). 1H NMR (CHCl3), δ (ppm) 9.0 (d, 2H, H-a), 8.2 (d, 2H, H-b), 8.0 (t, 4H, H-c), 7.62 (d, 4H, H-d), 7.48 (三重項に重なった2d, 2H, H-e), 7.12 (d, 2H, H-f), 6.70 (d, 2H, H-g), 6.35 (d, 2H, H-h), 4.30 (t, 4H, H-i), 2.95 (t, 4H, H-j), 2.80 (m, 4H, H-k), 2.00 (m, 10H, H-1の4H ), m, n, oの6H), 1.90 (s, 12H, H-p), 1.30 (s, H-q)。3(C52H56N3NaO6S3)のMS分析: 937, 実測値: 938
HPPH-ICG結合体5の合成:
Claims (2)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US58887604P | 2004-07-16 | 2004-07-16 | |
US60/588,876 | 2004-07-16 | ||
PCT/US2005/024782 WO2006019775A1 (en) | 2004-07-16 | 2005-07-13 | Adduct of fluorescent dye and tumor avid tetrapyrrole |
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JP2008506694A JP2008506694A (ja) | 2008-03-06 |
JP4733126B2 true JP4733126B2 (ja) | 2011-07-27 |
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US (1) | US7947729B2 (ja) |
EP (1) | EP1781170B1 (ja) |
JP (1) | JP4733126B2 (ja) |
KR (1) | KR101194486B1 (ja) |
CN (1) | CN1984915B (ja) |
AU (1) | AU2005275220B2 (ja) |
HK (1) | HK1109391A1 (ja) |
WO (1) | WO2006019775A1 (ja) |
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US8017104B2 (en) | 2007-02-28 | 2011-09-13 | Carestream Health, Inc. | Large stoke shift dye used for optical imaging |
US8906354B2 (en) | 2007-02-28 | 2014-12-09 | Bruker Biospin Corporation | Loaded latex optical molecular imaging probes containing lipophilic large stokes shift dyes |
US10568963B2 (en) * | 2009-10-21 | 2020-02-25 | Health Research, Inc. | Multifunctional nanoplatforms for fluorescence imaging and photodynamic therapy developed by post-loading photosensitizer and fluorophore to polyacrylamide nanoparticles |
US8609837B2 (en) * | 2010-07-06 | 2013-12-17 | Health Research, Inc. | Metallation enhancements in tumor-imaging and PDT therapy |
WO2014022742A1 (en) * | 2012-08-03 | 2014-02-06 | Health Research, Inc. | Paa nanoplatforms containing fluorophores and targeted moieties covalently linked and photosensitizer post-loaded |
CN103911017B (zh) * | 2012-12-28 | 2017-09-15 | 浙江海正药业股份有限公司 | 菁染料化合物及其制备方法、用于光动力学疗法的双重功能剂及其制备方法 |
TWI650137B (zh) * | 2017-09-01 | 2019-02-11 | 行政院原子能委員會核能硏究所 | 多功能探針及其用途 |
US20200289676A1 (en) * | 2019-03-15 | 2020-09-17 | Lahjavida, Llc | Near-Infrared Dyes And Conjugates For Targeting Tumors |
Citations (2)
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US5707986A (en) * | 1994-03-14 | 1998-01-13 | Miller; Joan W. | Angiographic method using green porphyrins in primate eyes |
WO2003065888A1 (en) * | 2002-02-07 | 2003-08-14 | Mallinckrodt Inc. | Dye-bioconjugates for simultaneous optical diagnostic and therapeutic applications |
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US4649151A (en) | 1982-09-27 | 1987-03-10 | Health Research, Inc. | Drugs comprising porphyrins |
US4968715A (en) | 1988-07-06 | 1990-11-06 | Health Research, Inc. | Use of purified hematoporphyrin trimers in photodynamic therapy |
US5002962A (en) | 1988-07-20 | 1991-03-26 | Health Research, Inc. | Photosensitizing agents |
US5198460A (en) | 1988-07-20 | 1993-03-30 | Health Research Inc. | Pyropheophorbides and their use in photodynamic therapy |
US5498710A (en) | 1994-04-22 | 1996-03-12 | Health Research, Inc. | Alkyl ether analogues of benzoporphyrin derivatives |
US5591847A (en) | 1994-05-23 | 1997-01-07 | Health Research, Inc. | Long wavelength absorbing photosensitizers related to purpurin-18, bacteriopurpurin-18 and related compounds with imide linkages |
US6103751A (en) | 1998-06-22 | 2000-08-15 | Health Research, Inc. | Carotene analogs of porphyrins, chlorins and bacteriochlorins as therapeutic and diagnostic agents |
US6761878B2 (en) * | 2001-10-17 | 2004-07-13 | Mallinckrodt, Inc. | Pathological tissue detection and treatment employing targeted benzoindole optical agents |
US20030105299A1 (en) * | 2001-10-17 | 2003-06-05 | Mallinckrodt Inc. | Carbocyanine dyes for tandem, photodiagnostic and therapeutic applications |
US20030105300A1 (en) * | 2001-10-17 | 2003-06-05 | Mallinckrodt Inc. | Tumor targeted photodiagnostic-phototherapeutic agents |
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US5707986A (en) * | 1994-03-14 | 1998-01-13 | Miller; Joan W. | Angiographic method using green porphyrins in primate eyes |
WO2003065888A1 (en) * | 2002-02-07 | 2003-08-14 | Mallinckrodt Inc. | Dye-bioconjugates for simultaneous optical diagnostic and therapeutic applications |
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AU2005275220B2 (en) | 2012-02-02 |
US7947729B2 (en) | 2011-05-24 |
EP1781170A4 (en) | 2011-01-05 |
EP1781170A1 (en) | 2007-05-09 |
EP1781170B1 (en) | 2014-04-30 |
AU2005275220A1 (en) | 2006-02-23 |
CN1984915B (zh) | 2012-12-19 |
JP2008506694A (ja) | 2008-03-06 |
WO2006019775A1 (en) | 2006-02-23 |
HK1109391A1 (en) | 2008-06-06 |
KR101194486B1 (ko) | 2012-10-24 |
KR20070036152A (ko) | 2007-04-02 |
US20090043090A1 (en) | 2009-02-12 |
CN1984915A (zh) | 2007-06-20 |
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