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    Nanoparticles for two-photon activated photodynamic therapy and imaging
    1.
    发明申请
    Nanoparticles for two-photon activated photodynamic therapy and imaging 审中-公开
    纳米粒子用于双光子激活光动力治疗和成像

    公开(公告)号：US20090035576A1

    公开(公告)日：2009-02-05

    申请号：US11900334

    申请日：2007-09-10

    申请人： Paras N. Prasad ,  Sehoon Kim ,  Tymish Y. Ohulchanskyy ,  Ravindra K. Pandey

    发明人： Paras N. Prasad ,  Sehoon Kim ,  Tymish Y. Ohulchanskyy ,  Ravindra K. Pandey

    IPC分类号： B32B5/16

    CPC分类号： A61K41/0071 ,  A61K41/008 ,  A61K49/0021 ,  A61K49/0093 ,  C01B33/141 ,  G01N33/582 ,  G01N33/585 ,  Y10T428/2982

    摘要： The present invention provides organically modified silica (ORMOSIL) nanoparticles into which have been incorporated two-photon absorption dye molecules. The two photon absorption dye displays a unique aggregation induced fluorescence enhancement behavior. As a result ORMOSIL nanoparticles with high amounts of the dye can be prepared. These particles can be used for imaging. In one embodiment, the nanoparticles can additionally have incorporated therein a photosensitizer. The photosensitzer can be activated by intraparticle fluorescence resonance energy transfer (FRET) from the dye aggregates resulting in enhanced fluorescence and singlet oxygen generation from photosensitizer under two-photon excitation conditions. Such nanoparticles can be used for photodynamic therapy applications.

    摘要翻译： 本发明提供了已经掺入双光子吸收染料分子的有机改性二氧化硅（ORMOSIL）纳米颗粒。 两个光子吸收染料显示出独特的聚集诱导的荧光增强行为。 因此，可以制备具有大量染料的ORMOSIL纳米颗粒。 这些颗粒可用于成像。 在一个实施方案中，纳米颗粒另外可以掺入光敏剂。 光敏剂可以通过来自染料聚集体的颗粒内荧光共振能量转移（FRET）来激活，从而在双光子激发条件下从光敏剂产生增强的荧光和单线态氧产生。 这种纳米颗粒可用于光动力疗法应用。

    Nanoparticles for two-photon activated photodynamic therapy and imaging
    2.
    发明申请
    Nanoparticles for two-photon activated photodynamic therapy and imaging 审中-公开
    纳米粒子用于双光子激活光动力治疗和成像

    公开(公告)号：US20080233051A1

    公开(公告)日：2008-09-25

    申请号：US11983845

    申请日：2007-11-13

    申请人： Paras N. Prasad ,  Sehoon Kim ,  Tymish Y. Ohulchanskyy ,  Ravindra K. Pandey

    发明人： Paras N. Prasad ,  Sehoon Kim ,  Tymish Y. Ohulchanskyy ,  Ravindra K. Pandey

    IPC分类号： A61K9/14 ,  A61K31/695 ,  A61K49/00

    CPC分类号： A61K31/695 ,  A61K41/0071 ,  A61K41/008 ,  A61K49/0021 ,  A61K49/0093

    摘要： The present invention provides organically modified silica (ORMOSIL) nanoparticles into which have been incorporated two-photon absorption dye molecules. The two photon absorption dye displays a unique aggregation induced fluorescence enhancement behavior. As a result ORMOSIL nanoparticles with high amounts of the dye can be prepared. These particles can be used for imaging. In one embodiment, the nanoparticles can additionally have incorporated therein a photosensitizer. The photosensitizer can be activated by intraparticle fluorescence resonance energy transfer (FRET) from the dye aggregates resulting in enhanced fluorescence and singlet oxygen generation from photosensitizer under two-photon excitation conditions. Such nanoparticles can be used for photodynamic therapy applications.

    摘要翻译： 本发明提供了已经掺入双光子吸收染料分子的有机改性二氧化硅（ORMOSIL）纳米颗粒。 两个光子吸收染料显示出独特的聚集诱导的荧光增强行为。 因此，可以制备具有大量染料的ORMOSIL纳米颗粒。 这些颗粒可用于成像。 在一个实施方案中，纳米颗粒另外可以掺入光敏剂。 可以通过来自染料聚集体的颗粒内荧光共振能量转移（FRET）来激活光敏剂，从而在双光子激发条件下从光敏剂产生增强的荧光和单线态氧产生。 这种纳米颗粒可用于光动力疗法应用。

    Adduct of fluorescent dye and tumor avid tetrapyrrole
    5.
    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

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

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

    IPC分类号： C07B47/00 ,  C07D487/22

    CPC分类号： A61K49/0032 ,  A61K41/0057 ,  A61K41/0071 ,  A61K49/0052 ,  C07D487/22 ,  Y10S514/912

    摘要： 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.

    摘要翻译： 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
    6.
    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

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

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

    IPC分类号： C09B47/00 ,  C09B47/04

    CPC分类号： A61K49/0032 ,  A61K41/0057 ,  A61K41/0071 ,  A61K49/0052 ,  C07D487/22 ,  Y10S514/912

    摘要： 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.

    摘要翻译： 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。

    Carotene analogs of porphyrins, chlorins and bacteriochlorins as therapeutic and diagnostic agents
    7.
    发明授权
    Carotene analogs of porphyrins, chlorins and bacteriochlorins as therapeutic and diagnostic agents 失效
    卟啉类胡萝卜素类似物，二氢卟酚和细菌毒素作为治疗和诊断剂

    公开(公告)号：US6103751A

    公开(公告)日：2000-08-15

    申请号：US102417

    申请日：1998-06-22

    申请人： Ravindra K. Pandey ,  William R. Potter ,  Thomas J. Dougherty

    发明人： Ravindra K. Pandey ,  William R. Potter ,  Thomas J. Dougherty

    IPC分类号： A61K49/00 ,  C07D487/22 ,  C07D519/00 ,  A61K31/40

    CPC分类号： A61K49/0036 ,  A61K49/0052 ,  C07D487/22 ,  C07D519/00

    摘要： A carotene conjugate of the formula: ##STR1## where R.sup.1 is hydrogen or methyl; R.sup.2 is: ##STR2## R.sup.3, R.sup.4 and R.sup.5 are independently, hydrogen, methyl or ethyl; R.sup.6 and R.sup.7 are independently --R.sup.13, --OR , --C(R.sup.6)(O), --C(R.sup.16).sub.2 OR.sup.13, --CH.dbd.CHR.sup.13, or --(CH.sub.2)R.sup.14 ; R.sup.8 is --R.sup.13, --OR.sup.13, --C(R.sup.16)(O), --C(R.sup.16).sub.2 OR.sup.13, --CH.dbd.CHR.sup.13, or --(CH.sub.2)R.sup.14 or taken with R.sup.10 is .dbd.O; R.sup.9 is --R.sup.13, --OR.sup.13, --C(R.sup.16)(O), --C(R.sup.16).sub.2 OR.sup.13, --CH.dbd.CHR.sup.13, or --(CH.sub.2)R.sup.14 or taken with R.sup.10 is a chemical bond; R.sup.10 is --R.sup.13, --OR.sup.13, --C(R.sup.16)(O) , --C(R.sup.16).sub.2 OR.sup.13, --CH.dbd.CHR.sup.13, or --(CH.sub.2)R.sup.14 or taken together with R.sup.9 is a chemical bond or taken with R.sup.8 is .dbd.O; R.sup.11 is R.sup.13, or --OR.sup.13 ; R.sup.12 is --C(R.sup.13).sub.2 C(Y)--, --C(O)O(O)C--, --C(NR.sup.13)O(O)C--, or --C(O)N(R.sup.15)--C(O)--; R.sup.13 is, independently at each occurrence, hydrogen or lower alkyl of from 1 through about 10 carbon atoms; R.sup.14 is an amino acid residue, R.sup.15 is --R.sup.13, --R.sup.14, or --C(O)NHR.sup.13 ; R.sup.16 is, independently at each occurrence, hydrogen or lower alkyl of 1 to about 4 carbon atoms and Y is .dbd.O, .dbd.S, or 2H--.

    摘要翻译： 下式的胡萝卜素缀合物：其中R1是氢或甲基; R2是：R3，R4和R5独立地是氢，甲基或乙基; R6和R7独立地是-R13，-OR，-C（R6）（O），-C（R16）2OR13，-CH = CHR13或 - （CH2）R14; R8是-R13，-OR13，-C（R16）（O），-C（R16）2OR13，-CH = CHR13或 - （CH2）R14，或R10为= R9为-R13，-OR13，-C（R16）（O），-C（R16）2OR13，-CH = CHR13或 - （CH2）R14或R10为化学键; R 10为-R 13，-OR 13，-C（R 16）（O），-C（R 16）2 OR 13，-CH = CHR 13或 - （CH 2）R 14或与R 9一起为化学键， O; R11是R13或-OR13; R 12是-C（R 13）2 C（Y） - ， - C（O）O（O）C - ， - C（NR 13）O（O）C-或-C（O）N（R 15） O） - ; R 13在每次出现时独立地为氢或1至约10个碳原子的低级烷基; R14是氨基酸残基，R15是-R13，-R14或-C（O）NHR13; R 16在每次出现时独立地为氢或1至约4个碳原子的低级烷基，Y为= O，= S或2H-。

    Pyropheophorbides and their use in photodynamic therapy
    9.
    发明授权
    Pyropheophorbides and their use in photodynamic therapy 失效
    偏焦异构体及其在光动力疗法中的应用

    公开(公告)号：US5459159A

    公开(公告)日：1995-10-17

    申请号：US239089

    申请日：1994-05-05

    申请人： Ravindra K. Pandey ,  Thomas J. Dougherty

    发明人： Ravindra K. Pandey ,  Thomas J. Dougherty

    IPC分类号： A61K31/40 ,  A61K41/00 ,  A61K51/04 ,  A61P31/12 ,  A61P35/00 ,  C07D487/22 ,  C07D519/00

    CPC分类号： C07D487/22 ,  A61K41/0071 ,  A61K51/0485 ,  C07D519/00 ,  A61K2123/00

    摘要： Pyropheophorbide compounds are injected into a host and accumulate in tumor tissue to a higher degree than surrounding normal tissues. When the pyropheophorbide compounds are exposed to a particular wavelength of light the compounds become cytotoxic and destroy the tumor or diseased tissue without causing irreversible normal tissue damage. The pyropheophorbide compounds have shown improved results as compared to drugs currently used in photodynamic therapy. Further, they absorb light further in the red, optimizing tissue penetration and are retained in the skin for short time periods relative to other drugs used in photodynamic therapy.

    摘要翻译： 将焦磷偏磷酸酯化合物注射到宿主中并在肿瘤组织中积聚到比周围正常组织更高的程度。 当焦偏磷酸酯化合物暴露于特定波长的光时，化合物变成细胞毒性并破坏肿瘤或患病组织而不引起不可逆的正常组织损伤。 与目前在光动力疗法中使用的药物相比，焦偏镁离子化合物显示出改善的结果。 此外，它们进一步吸收红色的光，优化组织穿透，并相对于光动力疗法中使用的其他药物，在短时间内保留在皮肤中。

    Metallation enhancements in tumor-imaging and PDT therapy
    10.
    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

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

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

    IPC分类号： C07D487/22 ,  G01N33/559

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

    摘要： 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.

    摘要翻译： 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。