公开(公告)号：EP3521295B1

公开(公告)日：2021-04-07

申请号：EP19155178.7

申请日：2019-02-02

发明人： GUTSCHE, Claudia Simone ,  WIEHE, Arno ,  HOHLFELD, Benjamin Florian ,  GITTER, Burkhard ,  ALBRECHT, Volker

IPC分类号： C07F15/04 ,  A61P35/00 ,  A61K31/28 ,  A61K31/295 ,  A61K31/315 ,  C07F15/00 ,  C07F15/02 ,  C07F1/08 ,  C07F3/06 ,  C07F5/00 ,  G01N33/574

公开(公告)号：EP2658465B1

公开(公告)日：2019-05-22

申请号：EP11852256.4

申请日：2011-12-29

申请人： biolitec Unternehmensbeteiligungs II AG

发明人： FEMOPASE, Gabriel

IPC分类号： A61B18/22

公开(公告)号：EP2350058B1

公开(公告)日：2018-10-24

申请号：EP09815180.6

申请日：2009-09-17

申请人： biolitec Unternehmensbeteiligungs II AG

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

IPC分类号： C07D487/22 ,  C07H15/26 ,  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.

公开(公告)号：EP2051699B1

公开(公告)日：2018-09-26

申请号：EP07776843.0

申请日：2007-05-08

申请人： biolitec Unternehmensbeteiligungs II AG

发明人： FARMER, Gerard ,  SCHEGLMANN, Dietrich ,  ALBRECHT, Volker ,  NIFANTIEV, Nikolay, E.

IPC分类号： A61K9/127 ,  A61K41/00 ,  A61K9/00

CPC分类号： A61K9/127 ,  A61K9/0014 ,  A61K41/0071

摘要： Highly flexible penetrating liposomal carrier systems are formulated with enhanced skin penetration properties. These specialized formulations of highly flexible penetrating liposomal delivery systems comprise one or more phospholipids, lysophosphatides and hydrophobic photosensitizer. This new formulations can squeeze liposomal particles through intercellular regions of stratum corneum as intact structures, and, in this way, deliver encapsulated photosensitizer to the epidermis, dermis, hypodermis and surroundings. The penetrating liposomal formulation provides therapeutically effective amounts of the hydrophobic photosensitizer through topical application with better skin penetration thus improving drug targeting and the efficacy of photodynamic therapy (PDT).

公开(公告)号：EP3217908A1

公开(公告)日：2017-09-20

申请号：EP15798240.6

申请日：2015-11-09

申请人： biolitec unternehmensbeteiligungs II AG

发明人： NEUBERGER, Wolfgang ,  SCHNITKER, Kai

IPC分类号： A61B18/22 ,  A61B18/12 ,  A61B18/00 ,  A61B17/00

CPC分类号： H04L67/12 ,  A61B18/12 ,  A61B18/1492 ,  A61B18/1815 ,  A61B18/22 ,  A61B90/98 ,  A61B2017/00199 ,  A61B2017/00221 ,  A61B2017/00482 ,  A61B2017/00973 ,  A61B2018/00636 ,  A61B2018/00916 ,  A61B2018/225 ,  A61B2018/2266 ,  G16H40/67

摘要： Medical systems, comprising at least one eletromagnetic radiation emitting device for medical applications, at least one mobile electronic device, and at least one attachable/detachable transmission medium, are provided. The electromagnetic radiation emitting device comprises a radiation source such as a laser source, a radiofrequency source, or a microwave source and required safety features/controls. The mobile electronic device has advanced computing capability and connectivity, and is capable of wirelessly accessing a network, such as a smart phone, a tablet personal computer, and the like. The transmission mediums are optical fibers, handpieces, fiber-optic systems, radiofrequency catheters and electrodes, microwave transmission media, having differently shaped distal tips, differently shaped support tubes, and lens assemblies with different focal distances. This makes the system versatile, as it can be easily adapted to a large number of diverse medical applications.

摘要翻译： 提供了包括用于医疗应用的至少一个电磁辐射发射装置的医疗系统，至少一个移动电子装置以及至少一个可附接/可拆卸的传输介质。 电磁辐射装置包括诸如激光源，射频源或微波源的辐射源以及所需的安全特征/控件。 该移动电子设备具有先进的计算能力和连接性，能够无线接入网络，如智能手机，平板电脑等。 传输介质是光纤，手持件，光纤系统，射频导管和电极，微波传输介质，具有不同形状的远端，不同形状的支撑管和具有不同焦距的透镜组件。 这使得系统功能多样化，因为它可以很容易地适应大量不同的医疗应用。

公开(公告)号：EP3201201A1

公开(公告)日：2017-08-09

申请号：EP15778052.9

申请日：2015-09-30

申请人： biolitec unternehmensbeteiligungs II AG ,  Freie Universität Berlin

发明人： GOLF, Hartwig Richard Arthur ,  WIEHE, Arno ,  GRÄFE, Susanna ,  ALBRECHT, Volker ,  REISSIG, Hans-ulrich

IPC分类号： C07D487/22 ,  C07F5/02 ,  A61K31/409 ,  A61P35/00

CPC分类号： A61K31/409 ,  A61K31/03 ,  C07D487/22 ,  C07F5/02

摘要： 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, opthamological or urological disorders are provided 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 other embodiments the nucleophilic substitution on pentafluorophenyl-substituted tetrapyrroles is used to obtain compounds with a high PDT-efficacy. 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 formulating the desired tetrapyrrole photosensitizer into a pharmaceutical formulation to be injected into the body avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.

摘要翻译： 可用作诊断和治疗应用的光敏剂的生物活性化合物，特别是用于癌症的PDT，感染和其他过度增殖性疾病，非肿瘤性适应症如关节炎，炎性疾病，病毒或细菌感染的荧光诊断和PDT治疗， 提供皮肤病，眼科或泌尿系统疾病以及提供获得药物质量的方法。 一个实施方案由合成具有确定的中位取代基的卟啉并随后通过二羟基化或还原将该卟啉体系转化为二氢卟吩体系的方法组成，并且如果形成多于一种异构体，则通过色谱法将其分离为正常或反转 相二氧化硅。 在另一个实施方案中，选择卟啉上的取代基以指导还原或二羟基化成二氢卟酚，从而选择性形成某种异构体。 另一个实施方案是提供具有较高膜亲和性和增加的PDT-功效的两亲化合物。 在其他实施方案中，使用五氟苯基取代的四吡咯上的亲核取代来获得具有高PDT效力的化合物。 在另一个实施方案中，鉴定取代基是通过它们的空间和/或电子影响直接用二亚胺进行二羟基化或还原，以使一种异构体受到青睐。 另一个实施方案包括将所需的四吡咯光敏剂配制成药物制剂以注射到体内，避免不希望的效应，例如四吡咯系统的溶解度问题或延迟的药代动力学。