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    Adduct of fluorescent dye and tumor avid tetrapyrrole
    31.
    发明授权
    Adduct of fluorescent dye and tumor avid tetrapyrrole 有权
    荧光染料和肿瘤病毒四吡咯的加合物

    公开(公告)号：US07947729B2

    公开(公告)日：2011-05-24

    申请号：US11632433

    申请日：2005-07-13

    Applicant: Ravindra K. Pandey ,  Yihui Chen ,  William Potter ,  Allan Oseroff

    Inventor： Ravindra K. Pandey ,  Yihui Chen ,  William Potter ,  Allan Oseroff

    IPC: C07B47/00 ,  C07D487/22

    CPC classification number: A61K49/0032 ,  A61K41/0057 ,  A61K41/0071 ,  A61K49/0052 ,  C07D487/22 ,  Y10S514/912

    Abstract: A compound having preferential localization in tumor tissue relative to normal tissue, a preferential electromagnetic absorption at a wavelength between about 660 and 900 nm, and a fluorescence at a wavelength shifted from the preferential absorption by at least +30 nm and preferably at least +50 nm. The compound further preferably destroys tumor tissue in which it is absorbed when exposed to light at its preferential absorption wavelength. In a preferred embodiment of the invention, the compound is a conjugate of a tumor avid tetrapyrrole compound with a fluorescent dye, and more preferably the fluorescent dye is an indocyanine dye such as indocyanine green. The tumor avid tetrapyrrole compound is preferably a porphyrin derivative selected from the group consisting of chlorins, bacteriochlorins, purpurins and derivatives thereof.

    Abstract translation: 相对于正常组织在肿瘤组织中优先定位的化合物，在约660和900nm之间的波长处的优先电磁吸收以及波长从优选吸收偏移至少±30nm，优选至少+50nm的荧光 nm。 该化合物进一步优选地破坏在其优先吸收波长下暴露于光时被吸收的肿瘤组织。 在本发明的一个优选实施方案中，化合物是肿瘤病毒四吡咯化合物与荧光染料的缀合物，更优选荧光染料是吲哚菁染料，如吲哚菁绿。 肿瘤病毒四吡咯化合物优选为选自二卟啉，细菌二氢卟酚，紫草素及其衍生物的卟啉衍生物。

    ADDUCT OF FLUORESCENT DYE AND TUMOR AVID TETRAPYRROLE
    32.
    发明申请
    ADDUCT OF FLUORESCENT DYE AND TUMOR AVID TETRAPYRROLE 有权
    荧光染色和肿瘤血小板衍生物的添加

    公开(公告)号：US20090043090A1

    公开(公告)日：2009-02-12

    申请号：US11632433

    申请日：2005-07-13

    Applicant: Ravindra K. Pandey ,  Yihui Chen ,  William Potter ,  Allan Oseroff

    Inventor： Ravindra K. Pandey ,  Yihui Chen ,  William Potter ,  Allan Oseroff

    IPC: C09B47/00 ,  C09B47/04

    CPC classification number: A61K49/0032 ,  A61K41/0057 ,  A61K41/0071 ,  A61K49/0052 ,  C07D487/22 ,  Y10S514/912

    Abstract: A compound having preferential localization in tumor tissue relative to normal tissue, a preferential electromagnetic absorption at a wavelength between about 660 and 900 nm, and a fluorescence at a wavelength shifted from the preferential absorption by at least +30 nm and preferably at least +50 nm. The compound further preferably destroys tumor tissue in which it is absorbed when exposed to light at its preferential absorption wavelength. In a preferred embodiment of the invention, the compound is a conjugate of a tumor avid tetrapyrrole compound with a fluorescent dye, and more preferably the fluorescent dye is an indocyanine dye such as indocyanine green. The tumor avid tetrapyrrole compound is preferably a porphyrin derivative selected from the group consisting of chlorins, bacteriochlorins, purpurins and derivatives thereof.

    Abstract translation: 相对于正常组织在肿瘤组织中优先定位的化合物，在约660和900nm之间的波长处的优先电磁吸收以及波长从优选吸收偏移至少±30nm，优选至少+50nm的荧光 nm。 该化合物进一步优选地破坏在其优先吸收波长下暴露于光时被吸收的肿瘤组织。 在本发明的一个优选实施方案中，化合物是肿瘤病毒四吡咯化合物与荧光染料的缀合物，更优选荧光染料是吲哚菁染料，如吲哚菁绿。 肿瘤病毒四吡咯化合物优选为选自二卟啉，细菌二氢卟酚，紫草素及其衍生物的卟啉衍生物。

    Metallation enhancements in tumor-imaging and PDT therapy
    33.
    发明授权
    Metallation enhancements in tumor-imaging and PDT therapy 有权
    肿瘤成像和PDT治疗中的金属化增强

    公开(公告)号：US08609837B2

    公开(公告)日：2013-12-17

    申请号：US13168421

    申请日：2011-06-24

    Applicant: Ravindra K. Pandey ,  Heinz Baumann ,  Yihui Chen ,  Penny Joshi ,  Nayan Patel

    Inventor： Ravindra K. Pandey ,  Heinz Baumann ,  Yihui Chen ,  Penny Joshi ,  Nayan Patel

    IPC: C07D487/22 ,  G01N33/559

    CPC classification number: A61K41/0076 ,  A61K41/0071 ,  A61K49/0036 ,  A61K49/0052 ,  C07D487/22 ,  C09B23/0033 ,  C09B23/0066 ,  C09B47/00

    Abstract: A compound in the form of a metallized tetrpyrollic photosensizer linked to a fluorescent dye where the photosensitizer (PS), is linked by a structure that does not have detrimental radiation emmitance or absorbing characteristics, to a fluorophore, usually a cyanine dye (CD). The photosensitizer in accordance the invention is a metallized analog of porphyrins, chlorins, purpurinimides, bacterio pupurinimides, phthalocyanines, expanded porphyrins, benzoporphyrin derivatives and purpurins. The fluorophore is usually a cyanine dye with variable substituents. And, A method for determining effectiveness of PDT by comparing proportion of STAT-3 monomer with crosslinked STAT-3 dimer after PDT where the relative proportion of STAT-3 monomer to crosslinked STAT-3 directly correlates to efficacy of the PDT.

    Abstract translation: 与荧光染料连接的金属化四层光敏剂形式的化合物，其中光敏剂（PS）通过不具有有害辐射发射或吸收特性的结构连接到荧光团，通常为花青染料（CD）。 根据本发明的光敏剂是卟啉，二氢卟酚，紫嘌呤酰胺，细菌栀子酰胺，酞菁，膨胀卟啉，苯并卟啉衍生物和紫杉醇的金属化类似物。 荧光团通常是具有可变取代基的花青染料。 另外，通过比较PDT后STAT-3单体与交联的STAT-3二聚体的比例，其中STAT-3单体与交联的STAT-3的相对比例与PDT的功效直接相关，从而确定PDT有效性的方法。

    MULTIMODALITY AGENTS FOR TUMOR IMAGING AND THERAPY
    34.
    发明申请
    MULTIMODALITY AGENTS FOR TUMOR IMAGING AND THERAPY 审中-公开
    用于肿瘤成像和治疗的多功能剂

    公开(公告)号：US20110223102A1

    公开(公告)日：2011-09-15

    申请号：US12677381

    申请日：2008-09-11

    Applicant: Ravindra K. Pandey ,  Suresh Pandey ,  Lalit Goswami ,  Allan Oseroff ,  Shipra Dubey ,  Munawwar Sajjad ,  Stephanie Pincus

    Inventor： Ravindra K. Pandey ,  Suresh Pandey ,  Lalit Goswami ,  Allan Oseroff ,  Shipra Dubey ,  Munawwar Sajjad ,  Stephanie Pincus

    IPC: A61K51/04 ,  A61K49/00 ,  A61K31/30 ,  A61K31/409 ,  A61K38/12 ,  A61K31/437 ,  A61K31/506 ,  A61P35/00 ,  A61P43/00

    CPC classification number: C07K7/06 ,  A61B5/02007 ,  A61B5/416 ,  A61K41/0071 ,  A61K47/54 ,  A61K47/64 ,  A61K49/0032 ,  A61K49/0036 ,  A61K49/0056 ,  A61K51/082 ,  A61K51/088

    Abstract: A compound that is a conjugate of an antagonist to an integrin expressed by a tumor cell and at least one of a tumor avid tetrapyrollic photosensitizer, a fluorescent dye, and a radioisotope labeled moiety wherein the radioisotope is 11C, 18F, 64Cu, 124I, 99Tc, 111In or GdIII and its method of use for diagnosing, imaging and/or treating hyperproliferative tissue such as tumors. Preferably the photosensitizer is a tumor avid tetrapyrollic photosensitizer, e.g. a porphyrin, chlorin or bacteriochlorin, e.g. pheophorbides and pyropheophorbides. Such conjugates have extreme tumor avidity and can be used to inhibit or completely destroy the tumor by light absoption. The integrin is usually αvβ3, α5β1, αvβ5, α4β1, or α2β1. Preferably, the antagonist is an RGD peptide or another antagonist that may be synthetic such as a 4-{2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)ethyloxy}-benzoyl]amino-2-(S)-amino-ethyl-sulfonylamino group. Such compounds provide tumor avidity and imaging ability thus permitting selective and clear tumor imaging.

    Abstract translation: 作为拮抗剂与由肿瘤细胞表达的整联蛋白结合的化合物，以及至少一种肿瘤病毒四级光敏剂，荧光染料和放射性同位素标记部分，其中放射性同位素为11C，18F，64Cu，124I，99Tc ，111In或GdIII及其用于诊断，成像和/或治疗过度增生组织如肿瘤的方法。 优选地，光敏剂是肿瘤急性四分光敏光敏剂，例如。 卟啉，二氢卟酚或细菌二氢卟酚。 脱镁叶绿素和焦偏镁偏磷酸盐。 这种缀合物具有极端的肿瘤亲合力，可用于通过光吸收抑制或完全破坏肿瘤。 整合素通常为αv＆bgr; 3，α5和bgr; 1，αv＆bgr; 5，α4和bgr; 1或α2和bgr; 1。 优选地，拮抗剂是可以是合成的RGD肽或另一种拮抗剂，例如4- {2-（3,4,5,6-四 - 嘧啶-2-基氨基）乙氧基} - 苯甲酰基]氨基-2-（ S） - 氨基 - 乙基 - 磺酰基氨基。 这样的化合物提供了肿瘤亲合力和成像能力，从而允许选择性和清晰的肿瘤成像。

    Water soluble tetrapyrollic photosensitizers for photodynamic therapy
    35.
    发明授权
    Water soluble tetrapyrollic photosensitizers for photodynamic therapy 有权
    用于光动力疗法的水溶性四光镜光敏剂

    公开(公告)号：US07820143B2

    公开(公告)日：2010-10-26

    申请号：US12378751

    申请日：2009-02-19

    Applicant: Ravindra K. Pandey ,  Amy Gryshuk ,  Lalit Goswami ,  William Potter ,  Allan Oseroff

    Inventor： Ravindra K. Pandey ,  Amy Gryshuk ,  Lalit Goswami ,  William Potter ,  Allan Oseroff

    IPC: A61B5/055

    CPC classification number: C07D471/22 ,  A61K41/0071 ,  A61K41/0076 ,  C09B47/00 ,  C09B69/108

    Abstract: A tetrapyrollic photosensitizer compound having at least one pendant —CH2CH2CON(CH2CON(CH2COOH)2)2 or —N(CH2COOH)2 group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula: or a pharmaceutically acceptable derivative thereof, wherein R1-R8 and R10 are various substituents and R9 is substituted or unsubstituted —CH2CH2CON(CH2CON(CH2COOH)2)2; or —N(CH2COOH)2. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

    Abstract translation: 具有至少一个-CH 2 CH 2 CON（CH 2 CON（CH 2 COOH）2）2或-N（CH 2 COOH）2基团的四酯类光敏剂化合物或其酯，所述四元醇化合物是二氢卟酚，细菌二氢卟酚，卟啉，焦脱镁叶绿素，嘌呤酰亚胺或细菌嘌呤酰亚胺。 理想地，化合物具有下式：或其药学上可接受的衍生物，其中R 1 -R 8和R 10是各种取代基，R 9是取代或未取代的-CH 2 CH 2 CON（CH 2 CON（CH 2 COOH）2）2; 或-N（CH 2 COOH）2。 本发明还包括通过光注射化合物后用光处理的光动力学治疗方法和注射化合物后通过荧光成像的方法。

    Oxo-bacteriopyropheophorbide-a carboxylic acid and esters thereof
    36.
    发明授权
    Oxo-bacteriopyropheophorbide-a carboxylic acid and esters thereof 失效
    氧化 - 抑菌精 - 一种羧酸及其酯

    公开(公告)号：US07147840B2

    公开(公告)日：2006-12-12

    申请号：US11066511

    申请日：2005-02-25

    Applicant: Ravindra K. Pandey ,  Andrei Kozyrev ,  Xiang Zheng

    Inventor： Ravindra K. Pandey ,  Andrei Kozyrev ,  Xiang Zheng

    IPC: A61B5/055

    CPC classification number: C07D487/22

    Abstract: A compound having the structural formula: where R is H or lower alkyl of 1 through 12 carbon atoms. In general, the compounds of the invention are 132-Oxo-bacteriopyropheophorbide—a carboxylic acid and C1–C12 alkyl esters thereof. A method for the preparation of the carboxylic acid compounds of the invention includes the step of reacting bacteriopyropheophorbide—a alkyl ester with lithium hydroxide tetrahydrofuran and water. A method of the invention for the preparation of the C1–C12 alkyl ester compounds of the invention includes the steps of reacting bacteriopyropheophorbide—a alkyl, especially methyl, ester with lithium hydroxide in tetrahydrofuran and water to obtain 132-Oxo-bacterio-pyropheophobide-a carboxylic acid followed by reacting the carboxylic acid with an acid chloride producing reagent to obtain the 132-Oxo-bacterio pyropheophobide-a acid chloride (compound 5) and reacting the 132-Oxo-bacterio pyropheophobide-a acid chloride with a C1–C12 alcohol to obtain a 132-Oxo-bacterio-pyropheophobide-a carboxylic acid C1–C12 alkyl ester (compound 6). The compounds of the invention may be used as long wavelength absorbing photosensitizers for photodynamic therapy.

    Abstract translation: 具有以下结构式的化合物：其中R是H或1至12个碳原子的低级烷基。 一般而言，本发明的化合物是其中一个羧酸和一个C 1 -C 12烷基酯的十二烷基氧杂菌素。 制备本发明的羧酸化合物的方法包括使烷基酯与氢氧化锂四氢呋喃和水反应的步骤。 本发明的制备本发明的C 12 -C 12烷基酯化合物的方法包括以下步骤：使抑制甜菜碱 - 烷基，特别是甲基酯与 氢氧化锂在四氢呋喃和水中的溶液，得到13β-氧代 - 焦磷酸酯 - 羧酸，随后将羧酸与产生酰基氯的试剂反应，得到13重量％ > - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - > 12醇，得到13β-氧代 - 焦磷酸酯 - 羧酸C 1 -C 12烷基酯 （化合物6）。 本发明的化合物可用作光动力疗法的长波吸收光敏剂。

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