公开(公告)号：US6103751A

公开(公告)日：2000-08-15

申请号：US102417

申请日：1998-06-22

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

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

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

CPC classification number: A61K49/0036 ,  A61K49/0052 ,  C07D487/22 ,  C07D519/00

Abstract: 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--.

Abstract translation: 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-。

公开(公告)号：US5506255A

公开(公告)日：1996-04-09

申请号：US160384

申请日：1993-12-01

Applicant: Kevin M. Smith ,  Ravindra K. Pandey ,  Joseph M. Ryan ,  Nadine Jagerovic ,  Thomas J. Dougherty

Inventor： Kevin M. Smith ,  Ravindra K. Pandey ,  Joseph M. Ryan ,  Nadine Jagerovic ,  Thomas J. Dougherty

IPC: A61K41/00 ,  C07D487/22 ,  A61K31/40

CPC classification number: C07D487/22 ,  A61K41/0071

Abstract: Novel photosensitizers related to rhodoporphyrins and phylloerythrin methyl ester, their preparation and use as photosensitizers for detection and treatment of tumors by photodynamic therapy. The novel photosensitizers accumulate and concentrate preferentially in tumor tissue, have strong light absorption in the 650 to 700 nm region and have reduced skin phototoxicity.

Abstract translation: 与紫罗兰卟啉和叶绿菊酯甲酯相关的新型光敏剂，它们的制备和用作光敏剂用于通过光动力学治疗检测和治疗肿瘤。 新型光敏剂积聚并优先集中在肿瘤组织中，在650〜700nm区域具有强光吸收，降低皮肤光毒性。

公开(公告)号：US5459159A

公开(公告)日：1995-10-17

申请号：US239089

申请日：1994-05-05

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty

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

CPC classification number: C07D487/22 ,  A61K41/0071 ,  A61K51/0485 ,  C07D519/00 ,  A61K2123/00

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20100137396A1

公开(公告)日：2010-06-03

申请号：US12448660

申请日：2007-09-27

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty ,  David A. Bellnier ,  Hector R. Nava

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty ,  David A. Bellnier ,  Hector R. Nava

IPC: A61K31/407 ,  A61P35/00

CPC classification number: A61K31/409

Abstract: A method for treatment of esophageal high grade dysplasia comprising the steps of: injecting HPPH in a physiologically compatible medium into a patient having high grade dysplasia tissue to provide a dose level of 3 through 5 mg/m2 of body surface area, waiting for a time period of 24 through 60 hours to permit preferential absorption of the HPPH into esophageal cancer tissue, and exposing the esophageal cancer tissue to light at a wavelength of about 670±5 nm at an energy of from about 75 to about 200 Joules/cm.

Abstract translation: 一种治疗食管高级别发育不良的方法，包括以下步骤：将HPPH在生理相容性培养基中注入具有高度发育不良组织的患者，以提供3至5mg / m 2的体表面积的剂量水平，等待一段时间 时间为24至60小时，以允许优先吸收HPPH进入食管癌组织，并以约75至约200焦耳/厘米的能量将食管癌组织暴露于波长约670±5nm的光。

公开(公告)号：US07097826B2

公开(公告)日：2006-08-29

申请号：US10177129

申请日：2002-06-21

Applicant: Ravindra K. Pandey ,  Zachary Grossman ,  Peter Kanter ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Zachary Grossman ,  Peter Kanter ,  Thomas J. Dougherty

IPC: A61B5/055

CPC classification number: A61K51/0485 ,  A61K41/0071 ,  A61K49/0002 ,  A61K49/085 ,  A61K49/10 ,  A61K51/0478 ,  C07D471/22 ,  C07D487/22

Abstract: A compound comprising a chemical combination of a photodynamic tetra-pyrrolic compound with a plurality of radionuclide element atoms such that the compound may be used to enhance MR imaging and also be used as a photodynamic compound for use in photodynamic therapy to treat hyperproliferative tissue. The preferred compounds have the structural formula: where R1, R2, R2a R3, R3a R4, R5, R5a R6, R7, R7a, and R8 cumulatively contain at least two functional groups that will complex or combine with an MR imaging enhancing element or ion. The compound is intended to include such complexes and combinations and includes the use of such compounds for MR imaging and photodynamic therapy treatment of tumors and other hyperproliferative tissue.

Abstract translation: 包括光动力四吡咯化合物与多个放射性核素元素原子的化学组合的化合物，使得该化合物可用于增强MR成像，并且还可用作光动力学化合物用于光动力学治疗以治疗过度增生组织。 优选的化合物具有以下结构式：其中R 1，R 2，R 2，R 3，R 3， R 5，R 5，R 5a，R 6，R 5，R 5，R 5， R 7，R 7a和R 8累积含有至少两个将与MR成像增强元件或离子复合或组合的官能团。 该化合物旨在包括这种复合物和组合，并且包括使用这些化合物用于肿瘤和其它过度增生组织的MR成像和光动力治疗治疗。

公开(公告)号：US06534040B2

公开(公告)日：2003-03-18

申请号：US09739155

申请日：2000-12-18

Applicant: Ravindra K. Pandey ,  Zachary Grossman ,  Peter Kanter ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Zachary Grossman ,  Peter Kanter ,  Thomas J. Dougherty

IPC: C07D48722

CPC classification number: A61K51/0478 ,  A61K41/0071 ,  A61K49/085 ,  A61K51/0485 ,  C07D471/22 ,  C07D487/22

Abstract: Compositions that are a chemical combination of porphyrins, chlorins, bacteriochlorins, and related tetra-pyrrolic compounds with radioactive elements such as Technetium99, Gadolinium, Indium111 and radioactive iodine. When the element can form cations, the compound is usually a chelate with the porphyrin or chlorin structure. When the element forms anions, the compound is usually a direct chemical combination of the radioactive element into the porphyrin or chlorin structure. The invention further includes the method of using the compounds of the invention for diagnostic imaging of hyperproliferative tissue such as tumors and new blood vessel growth as is associated with the wet form of age related macular degeneration and methods of making the compounds. Compounds for MRI contrast imaging of the invention are usually Tc99, In111 or Gd(III) complexes of compounds of the formula:

Abstract translation: 组合物是卟啉，二氢卟酚，细菌色素和与放射性元素相关的四吡咯化合物如锝99，钆，铟111和放射性碘的化学组合。 当元素可以形成阳离子时，化合物通常是具有卟啉或二氢卟酚结构的螯合物。 当元素形成阴离子时，化合物通常是放射性元素与卟啉或二氢卟酚结构的直接化学组合。 本发明还包括使用本发明的化合物用于诊断超增殖组织如肿瘤和新血管生长的成像的方法，其与湿性形式的年龄相关性黄斑变性相关联，以及制备该化合物的方法。 本发明的MRI造影成像的化合物通常是下式化合物的Tc99，In111或Gd（III）络合物：

公开(公告)号：US5498710A

公开(公告)日：1996-03-12

申请号：US231113

申请日：1994-04-22

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty ,  Kevin M. Smith ,  Isabelle Meunier

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty ,  Kevin M. Smith ,  Isabelle Meunier

IPC: C07D487/22

CPC classification number: C07D487/22

Abstract: Compounds having properties superior to known photosensitizers defined by the following chemical formula: ##STR1## including R groups R.sup.1, R.sup.2, R.sup.3, and R.sup.4, wherein R.sup.1 and R.sup.2 are methyl or --CH(O--(CH.sub.2).sub.n CH.sub.3)CH.sub.3 or are joined together to form the group D and wherein R.sup.3 and R.sup.4 are methyl or --CH(O--(CH.sub.2).sub.n CH.sub.3)CH.sub.3 or are joined together to form the group D; provided that one of R.sup.1 and R.sup.2 or R.sup.3 and R.sup.4 are joined together to form the group D wherein one of the remaining R groups is methyl and one of the remaining R groups is --CH(O--(CH.sub.2).sub.n CH.sub.3)CH.sub.3, where n is an integer of 5 through 7 and group D is: ##STR2## and R.sub.5 is independently at each occurrence --OR.sub.6 where R.sub.6 is lower alkyl of 1 through 7 carbon atoms or R.sub.6 is an amino acid residue.

Abstract translation: 具有优于以下化学式定义的已知光敏剂的性质的化合物：包括R基团R 1，R 2，R 3和R 4的其中R 1和R 2是甲基或-CH（O-（CH 2）n CH 3） 一起形成基团D，其中R 3和R 4是甲基或-CH（O-（CH 2）n CH 3）CH 3或连接在一起形成基团D; 条件是R 1和R 2或R 3和R 4中的一个连接在一起形成基团D，其中剩余的R基团之一是甲基，其余的R基团之一是-CH（O-（CH 2）n CH 3）CH 3，其中n 是5〜7的整数，D为：＆lt; IMAGE＆gt; R5各自独立地为-OR 6，其中R 6为1〜7个碳原子的低级烷基或者R6为氨基酸残基。

公开(公告)号：US4968715A

公开(公告)日：1990-11-06

申请号：US343865

申请日：1989-04-26

Applicant: Thomas J. Dougherty ,  Ravindra K. Pandey

Inventor： Thomas J. Dougherty ,  Ravindra K. Pandey

IPC: C07D487/22 ,  A61K31/40 ,  A61K39/44 ,  A61K41/00 ,  A61P35/00 ,  C07D519/00

CPC classification number: C07D519/00 ,  A61K31/40 ,  A61K41/0071

Abstract: Pure dimer and trimer compounds of hematoporphyrin are prepared and shown to be effective agents in photodynamic therapy. The compounds of the invention are of the formula ##STR1## wherein each X is independently 1-hydroxyethyl or vinyl and wherein R is H or lower alkyl. The compounds of the invention can be conjugated to targeting substances such as immunoglobulins or to labels.

Abstract translation: 制备血卟啉的纯二聚体和三聚体化合物，并显示为光动力学治疗中的有效试剂。 本发明的化合物具有下式：其中每个X独立地为1-（4-羟基苯基） 羟乙基或乙烯基，其中R为H或低级烷基。 本发明的化合物可以与靶向物质例如免疫球蛋白缀合，或与标记缀合。

公开(公告)号：USRE43274E1

公开(公告)日：2012-03-27

申请号：US12321729

申请日：2009-01-23

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

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

IPC: C09B47/04

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

Abstract: Provided herein are compounds for detection, diagnosis and treatment of target tissues or target compositions, including hyperproliferative tissues such as tumors, using photodynamic methods. In particular, photosensitizer compounds that collect in hyperproliferative tissue are provided. In another embodiment, compounds that absorb light at a wavelength of from about 700 to about 850 nm are provided. In a further embodiment, compounds that are detectable by magnetic resonance imaging are provided.

Abstract translation: 本文提供了使用光动力学方法检测，诊断和治疗靶组织或靶组合物的化合物，包括过度增殖组织如肿瘤。 特别地，提供了在过度增殖组织中收集的光敏剂化合物。 在另一个实施方案中，提供了吸收波长为约700至约850nm的光的化合物。 在另一个实施方案中，提供了可通过磁共振成像检测的化合物。

公开(公告)号：USRE38994E1

公开(公告)日：2006-02-28

申请号：US10385378

申请日：2003-03-07

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty

IPC: A61K31/409 ,  C07D487/22

CPC classification number: A61K51/0485 ,  A61K41/0057 ,  A61K41/0076 ,  A61K2123/00 ,  C07D487/22 ,  C07D519/00

Abstract: Conjugate are formed by covalently linking a target-specific compound to pyropheophorbide compound which conjugated are injected into a host and accumulate in tumor tissue to a higher degree than surrounding normal tissues. When the pyropheophorbide compound component of the conjugate is exposed to a particular wavelength of light the compound becomes cytotoxic destroying the tumor or diseased tissue without causing irreversible normal tissue damage. The pyropheophorbide compounds have been shown to have a variety of characteristics when used in photodynamic therapy. These characteristics are further improved when the compounds are bound to a target specific component such as a ligand capable of binding to a specific cellular receptor (e.g. growth hormones and growth factors) or an antibody capable of binding to a particular antigen.

Abstract translation: 共轭体通过将靶特异性化合物与焦磷酸脱氢化合物共价连接而形成，所述化合物与缀合物注射入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。 当缀合物的焦偏心复合物组分暴露于特定波长的光时，该化合物变得细胞毒性破坏肿瘤或患病组织而不引起不可逆的正常组织损伤。 已经显示焦磷酸脱氢化合物在用于光动力疗法中具有多种特征。 当化合物结合到靶特异性组分如能够结合特定细胞受体的配体（例如生长激素和生长因子）或能够结合特定抗原的抗体时，这些特征进一步改善。