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    APPLICATION OF ß-FUNCTIONALIZED DIHYDROXY-CHLORINS FOR PDT
    1.
    发明公开
    APPLICATION OF ß-FUNCTIONALIZED DIHYDROXY-CHLORINS FOR PDT 有权
    应用BETA功能化二羟基氯气PDT

    公开(公告)号：EP2870159A2

    公开(公告)日：2015-05-13

    申请号：EP11810524.6

    申请日：2011-08-12

    申请人： CeramOptec GmbH ,  Biolitec Pharma Marketing Ltd.

    发明人： AICHER, Daniel ,  WIEHE, Arno ,  STARK, Christian, B., W. ,  ALBRECHT, Volker ,  GRAFE, Susanna

    IPC分类号： C07D487/22 ,  A61K31/409 ,  A61P35/00 ,  A61P17/00

    CPC分类号： A61K31/409 ,  C07D487/22

    摘要： The present invention provides methods to obtain biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders. An embodiment of the present invention consists of a method to synthesize diketo-chlorins as precursors. In yet another embodiment these precursors are converted to
    β -unctionalized hydroxy- and dihydroxy-chlorins. Another embodiment is to provide amphiphilic compounds with a higher membrane affinity and increased PDT-efficacy. Another embodiment consists of the formulation of the desired isomer into a liposomal formulation to be injected avoiding undesirable effects like precipitation at the injection site or delayed pharmacokinetics of the tetrapyrrole systems.

    ENHANCED ANTI-MICROBIAL PDT
    5.
    发明公开
    ENHANCED ANTI-MICROBIAL PDT 审中-公开
    增强抗微生物PDT

    公开(公告)号：EP2542305A2

    公开(公告)日：2013-01-09

    申请号：EP11735020.7

    申请日：2011-01-13

    申请人： CeramOptec GmbH

    发明人： ALBRECHT, Volker ,  WIELAND, Gerhard ,  GITTER, Burkhard ,  NEUBERGER, Wolfgang

    IPC分类号： A61N5/00 ,  A61N5/06 ,  A61K31/407 ,  A61P31/04

    CPC分类号： A61N5/062 ,  A61L2/0029 ,  A61L2/0052 ,  A61L2202/21 ,  A61M1/3681 ,  A61M1/3686 ,  A61N5/0624 ,  A61N2005/063 ,  A61N2005/0652

    摘要： Present invention provides enhanced methods and improved devices to eliminate, reduce, destroy and/or inhibit undesired body fluid species, such as pathogen microbes and deteriorated or malignant cells in complex environments like blood, serum and other body fluids. In preferred embodiments, present invention provides an antimicrobial PDT treatment that effectively inactivates, reduces and/or destroys both Gram (−) and Gram (+) bacteria in complex body fluids. Methods to enhance antimicrobial PDT activity includes the steps of administering a photosensitizer to bacteria-contaminated fluid, after a dwell time guiding bacteria-contaminated fluid with photosensitizer through a channel, emitting radiation preferably in an intermittent manner, and restoring treated body fluids to corresponding body regions. Electromagnetic radiation is preferably delivered intermittently with pulse width based on treatment parameters. Preferred device embodiments comprise guiding channels and at least one electromagnetic radiation source, arranged separately or in sequence. Preferably, laser device or LED-panels are used to deliver electromagnetic radiation to activate the photosensitizer. When used with preferred photosensitizer composition based on Safranin O, preferred laser radiation wavelength is in the range of 500-580 nm. Additionally, present invention diminishes adverse host's inflammatory responses by neutralizing the biological activity of pathogenic microorganism fragments and reducing and/or removing pathogenic microorganism fragments responsible for it.

    摘要翻译： 本发明提供了增强的方法和改进的装置，以消除，减少，破坏和/或抑制诸如血液，血清和其他体液等复杂环境中的病原体微生物和恶化或恶性细胞等不希望的体液物质。 在优选实施方案中，本发明提供了一种抗微生物PDT治疗，其有效地灭活，减少和/或破坏复杂体液中的革兰氏阴性细菌和革兰氏阳性细菌。 增强抗微生物PDT活性的方法包括以下步骤：在用光敏剂引导细菌污染的流体通过通道，优选以间歇方式发射辐射并将经处理的体液恢复至相应的身体的驻留时间之后，将光敏剂施用于细菌污染的流体 区域。 电磁辐射优选基于治疗参数以脉冲宽度间歇地传递。 优选的设备实施例包括分开或依次布置的引导通道和至少一个电磁辐射源。 优选地，使用激光装置或LED面板来传递电磁辐射以激活光敏剂。 当与基于番红O的优选光敏剂组合物一起使用时，优选的激光辐射波长在500-580nm的范围内。 此外，本发明通过中和致病微生物片段的生物学活性并减少和/或去除对其有害的致病微生物片段来减少不利的宿主炎症反应。

    Non-polar photosensitizer formulations for photodynamic therapy
    8.
    发明公开
    Non-polar photosensitizer formulations for photodynamic therapy 有权
    用于光动力疗法的非极性光敏剂制剂

    公开(公告)号：EP2471512A3

    公开(公告)日：2012-07-11

    申请号：EP12161556.1

    申请日：2004-06-23

    申请人： CeramOptec GmbH

    发明人： Albrecht, Volker ,  Fahr, Alfred ,  Scheglmann, Dietrich ,  Gräfe, Susanna ,  Neuberger, Wolfgang

    IPC分类号： A61K9/127 ,  A61K41/00

    CPC分类号： A61K41/0071 ,  A61K9/127

    摘要： A pharmaceutical liposomal formulation for photodynamic therapy comprising a non-polar porphyrin photosensitizer and one or more phospholipids, which are stable in storage without requiring freeze-drying is described. The liposomal formulation provides therapeutically effective amounts of the photosensitizer for intravenous administration. The phospholipids may be modified by pegylation, i.e. they contain poly ethylene glycol as an integral part of the phospholipids. The formed liposomes contain the non-polar photosensitizer within the membrane and are useful for the combined targeting of a nonpolar photosensitizer and a second polar substance. The invention also relates to the liposome composition formed upon reconstitution with an aqueous vehicle. The freeze-dried formulation upon reconstitution with a suitable aqueous vehicle forms liposomes that are also useful for intravenous administration.

    摘要翻译： 描述了用于光动力疗法的药物脂质体制剂，其包含非极性卟啉光敏剂和一种或多种磷脂，其在储存时稳定而不需要冷冻干燥。 脂质体制剂提供治疗有效量的用于静脉内给药的光敏剂。 磷脂可以通过聚乙二醇化修饰，即它们含有聚乙二醇作为磷脂的组成部分。 形成的脂质体在膜内含有非极性光敏剂，并且可用于非极性光敏剂和第二极性物质的组合靶向。 本发明还涉及用含水载体重构时形成的脂质体组合物。 用合适的含水载体重构后的冻干制剂形成也可用于静脉内给药的脂质体。

    IMPROVED PHOTOSENSITIZERS APPLICATION PROTOCOLS
    9.
    发明授权
    IMPROVED PHOTOSENSITIZERS APPLICATION PROTOCOLS 有权
    改进的应用程序协议光敏剂

    公开(公告)号：EP1626772B1

    公开(公告)日：2011-10-05

    申请号：EP04759670.5

    申请日：2004-03-19

    申请人： CeramOptec GmbH

    发明人： BODE, Hans-Peter ,  ALBRECHT, Volker

    IPC分类号： A61N5/06

    CPC分类号： A61N5/062 ,  A61N5/0601

    摘要： A safer, improved method of photodynamic therapy is provided for treating diseased, hyperproliferative tissue, including cancer, psoriasis, and arthritis, using multiple, sequential administrations of a photosensitizer (PS) prior to irradiation. Preferred photosensitizers are characterized by being retained in the diseased tissue for a longer time than in normal tissue. The interval between administrations is chosen to be of sufficient duration to allow the PS content of normal tissues to drop to a basal or negligible level before the next administration and before irradiation. At that time, the PS content of the diseased tissue is still high, not less than half of the initial content after the last PS administration. In this way, PDT with better selectivity for the diseased tissue is achieved. With sequential PS administrations, the PS burden on normal tissue can be kept low, so that side effects can be reduced, for example damage of the skin by sunlight or bright indoors artificial lighting. The precise durations between PS administrations and eventual irradiation vary between treatments, and are determined on an individual basis. Preferred PS for use with the present invention have a high and extended localization in tumor tissue. A preferred PS with these qualities is pheophorbide a.

    NOVEL METHOD AND APPLICATION OF UNSYMMETRICALLY MESO-SUBSTITUTED PORPHYRINS AND CHLORINS FOR PDT
    10.
    发明公开
    NOVEL METHOD AND APPLICATION OF UNSYMMETRICALLY MESO-SUBSTITUTED PORPHYRINS AND CHLORINS FOR PDT 审中-公开
    新的方法和使用非平衡细观取代的卟啉和氯气PDT

    公开(公告)号：EP2350058A2

    公开(公告)日：2011-08-03

    申请号：EP09815180.6

    申请日：2009-09-17

    申请人： CeramOptec GmbH

    发明人： WIEHE, Arno ,  AICHER, Daniel ,  STARK, Christian, B., W. ,  GRAFE, Susanna

    IPC分类号： C07D403/14 ,  C07D403/06 ,  A61K31/40 ,  A61K31/409 ,  A61P35/00

    CPC分类号： C07D487/22 ,  C07H15/26

    摘要： Biologically active compounds are provided that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders as well as providing methods to obtain them in pharmaceutical quality. One embodiment consists of a method to synthesize a porphyrin with a defined arrangement of meso-substituents and then converting this porphyrin system to a chlorin system by dihydroxylation or reduction, and if more than one isomer is formed separate them by chromatography either on normal or reversed phase silica. In another embodiment the substituents on the porphyrin are selected to direct the reduction or dihydroxylation to the chlorin so that a certain isomer is selectively formed. Another embodiment is to provide amphiphilic compounds with a higher membrane affinity and increased PDT-efficacy. In another embodiment a method to reductively cleave the osmate(VI)ester avoiding the use of gaseous H2S is provided. In another embodiment substituents are identified that via their steric and/or electronic influence direct the dihydroxylation or reduction with diimine so that one isomer is favored. Another embodiment consists of formulate the desired isomer into a liposomal formulation to be injected avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.