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1. 发明申请

WO2012012809A3 APPLICATION OF ß-FUNCTIONALIZED DIHYDROXY-CHLORINS FOR PDT 审中-公开
标题翻译： ß-功能化二羟基氯在PDT中的应用
公开(公告)号：WO2012012809A3
公开(公告)日：2012-05-18
申请号：PCT/US2011047576
申请日：2011-08-12
申请人： CERAMOPTEC GMBH , CERAMOPTEC IND INC , AICHER DANIEL , WIEHE ARNO , STARK CHRISTIAN B W , ALBRECHT VOLKER , GRAFE SUSANNA
发明人： AICHER DANIEL , WIEHE ARNO , STARK CHRISTIAN B W , ALBRECHT VOLKER , GRAFE SUSANNA
IPC分类号： C07D487/22 , A61K31/409 , A61P17/00 , A61P35/00
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 ß-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.
摘要翻译：本发明提供了获得可用作光敏剂的生物活性化合物的方法，所述光敏剂用于诊断和治疗应用，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，炎症的荧光诊断和PDT治疗疾病，病毒或细菌感染，皮肤病，眼科或泌尿系统疾病。本发明的一个实施方案由合成作为前体的二酮 - 二氢卟酚的方法组成。在又一个实施方案中，将这些前体转化成β-官能化羟基 - 和二羟基 - 二氢卟酚。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。另一个实施方案包括将期望的异构体配制成待注射的脂质体制剂，避免不希望的效应，如注射部位的沉淀或四吡咯系统的延迟的药代动力学。

2. 发明专利

BR112013001576A2 composto tetrapirrólico e composição farmacêutica derivado farmacêuticamente aceitável da mesma e respectivos usos e métodos de terapia fotodinâmica e de diagnóstico e tratamento da artrite e de doenças inflamatórias semelhantes. 未知
公开(公告)号：BR112013001576A2
公开(公告)日：2016-07-19
申请号：BR112013001576
申请日：2011-08-12
申请人： CERAMOPTEC GMBH , CERAMOPTEC IND INC
发明人： WIEHE ARNO , STARK CHRISTIAN B W , AICHER DANIEL , GRAFE SUSANNA , ALBRECHT VOLKER
IPC分类号： C07D487/22 , A61K31/409 , A61P17/00 , A61P35/00
摘要： composto tetrapirrólico e composição farmacêutica derivado farmacêuticamente aceitável da mesma e respectivos usos e métodos de terapia fotodinâmica e de diagnóstico e tratamento da artrite e de doenças inflamatórias semelhantes. a presente invenção proporciona métodos para obtenção de compostos biologicamente ativos que podem ser utilizados como fotossensibilizadores para aplicações de diagnóstico e terapêuticas, em particular para pdt de câncer, infecções e outras doenças hiperproliferativas, diagnóstico e tratamento de pdt de fluorescência de uma indicação não tumoral, tal como artrite, doenças inflamatórias, doenças virais ou infecções bacterianas, doenças dermatológicas, oftalmológicas ou urológicas. uma forma de realização da presente invenção consiste num método para sintetizar diceto-clorinas como precursores. ainda noutra modalidade, estes precursores são convertidos em clorinas -hidroxi e di-hidroxi funcionalizadas. outra forma de realização é proprocionar os compostos anfifílicos com uma afinidade mais elevada da membrana e um aumento da eficácia pdt. outra forma de realização consiste na formulação do isômero desejado em uma formulação de lopossomas no local da injeção ou farmacocinética retardada dos sistemas de tetrapirrol.

3. 发明公开

EP2616065A4 GLYCO-SUBSTITUTED DIHYDROXY-CHLORINS AND B-FUNCTIONALIZED CHLORINS FOR ANTI-MICROBIAL PHOTODYNAMIC THERAPY 有权转让
标题翻译：糖的取代的二羟基CHLORE和B-官能CHLORE相片动力疗法抗菌
公开(公告)号：EP2616065A4
公开(公告)日：2014-05-14
申请号：EP11869827
申请日：2011-07-22
申请人： BIOLITEC PHARMA MARKETING LTD , CERAMOPTEC GMBH
发明人： AICHER DANIEL , ALBRECHT VOLKER , GITTER BURKHARD , STARK CHRISTIAN B W , WIEHE ARNO
IPC分类号： A61K31/409 , A61K31/185 , A61K31/19 , A61K31/7004 , A61K31/7056 , A61K41/00 , A61P31/00 , A61P31/04 , C07H15/26
CPC分类号： A61K31/185 , A61K31/19 , A61K31/409 , A61K31/7056 , A61K41/0071 , A61K47/48092 , A61K47/549 , C07H15/26
摘要： Antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals are provided. The conjugates are of the class of compounds of dihydroxychlorins or &bgr;-functionalized chlorins connected to carbohydrate moieties and having the general formula

4. 发明专利

MX2013000876A DIHIDROXI-CLORINAS GLICO-SUSTITUIDAS Y CLORINAS BETA-FUNCIONALIZADAS PARA TERAPIA FOTODINAMICA ANTI-MICROBIANA. 未知
公开(公告)号：MX2013000876A
公开(公告)日：2013-04-30
申请号：MX2013000876
申请日：2011-07-22
申请人： CERAMOPTEC GMBH
发明人： AICHER DANIEL , ALBRECHT VOLKER , GITTER BURKHARD , STARK CHRISTIAN B W , WIEHE ARNO
IPC分类号： A61K31/185 , A61K31/19 , A61K31/409 , A61P31/00 , A61P31/04
摘要： Se proporcionan conjugados moleculares antimicrobianos para el tratamiento y prevención de enfermedades infecciosas provocadas por microrganismos patogénicos en humanos y animales. La clave para estos conjugados es conectar dihidroxiclorinas o clorinas B-funcionalizadas con fracciones de carbohidrato. Estos conjugados resultan ser muy efectivos en el combate de las infecciones bacterianas provocadas por bacterias gram-positivas y gram-negativas, incluyendo sus cepas resistentes. De manera importante, también son efectivos en entornos complejos, incluyendo sangre, suero y otros fluidos corporales que están presentes en el cuerpo de un paciente. También se proporciona un método de uso para controlar los microrganismos patogénicos en humanos y animales.

5. 发明公开

EP1660041A4 NON-POLAR PHOTOSENSITIZER FORMULATIONS FOR PHOTODYNAMIC THERAPY 有权转让
标题翻译：不是两极的光敏剂制剂的光动力疗法
公开(公告)号：EP1660041A4
公开(公告)日：2010-01-27
申请号：EP04776989
申请日：2004-06-23
申请人： CERAMOPTEC GMBH
发明人： ALBRECHT VOLKER , FAHR ALFRED , SCHEGLMANN DIETRICH , GRAEFE SUSANNA , NEUBERGER WOLFGANG
IPC分类号： A61K9/127 , A61K41/00
CPC分类号： A61K41/0071 , A61K9/127

6. 发明公开

EP2429498A4 NEW ORAL FORMULATIONS FOR TETRAPYRROLE DERIVATIVES 审中-公开
标题翻译： NEUE ORALE FORMULIERUNGENFÜRTETRAPYRROL-DERIVATE
公开(公告)号：EP2429498A4
公开(公告)日：2013-02-06
申请号：EP10772566
申请日：2010-04-28
申请人： CERAMOPTEC GMBH , BIOLITEC RES GMBH
发明人： GRAEFE SUSANNA , NIFANTIEV NIKOLAY , ALBRECHT VOLKER , NEUBERGER WOLFGANG , SCHEGLMANN DIETRICH , GERHARD WIELAND , WIEHE ARNO , FAHR ALBERT
IPC分类号： A61K9/16 , A61K9/127 , A61K9/20 , A61K31/122 , A61K31/409 , A61K31/495 , A61P31/04 , A61P35/00
CPC分类号： A61K31/409 , A61K9/0065 , A61K9/127 , A61K9/1271 , A61K31/498
摘要： Oral formulations and method of formulating photosensitive agents for oral administration during photodynamic therapy (PDT) and Antimicrobial photodynamic therapy (APDT) treatment are presented. The oral formulated photosensitizers show increased solubility and permeability, thus improving the bioavailability of photosensitizers at the treatment site. An orally administered photosensitizer is suitably formulated for mucosal adhesion and absorption via gastrointestinal mucosal membranes. Oral formulation provided herein use lipids and known proteins as carriers for photosensitizers by oral route. Carriers for encapsulating preselected photosensitizers include conventional liposomes, pegylated liposomes, nanoemulsions, nanocrystrals, nanoparticles, fatty emulsions, lipidic formulations, hydrosols, SMEDDS, Alpha-Feto protein (AFP), and Bovine-Serum-Albumin (BSA), fatty emulsions, hot-melt-extrudates and nanoparticles. The oral formulation, in case of a hydrophobic photosensitizer in the present invention, is stabilized using suitable surfactants/solubilizers thus preventing aggregation of the drug in the stomach and until it is absorbed in the duodenum and the small intestine. Oral formulations can be administered in the form of liquid, capsule, tablet, powder, paste or gel. Formulated drugs can be administered orally as one single dose or in multiple doses before administering PDT. In one embodiment Temoporfin (m-THPC) is used as a photosensitizer in the oral formulations. Temoporfin like many hydrophobic photosensitizers are especially suitable to be administered orally because there is no known enzyme system in the mammalian body which can metabolize Temoporfin or similar photosensitizers. Temoporfin can reach the blood system unchanged and fully active after absorption of the formulation in the gastrointestinal tract.
摘要翻译：提出了光动力治疗（PDT）和抗微生物光动力治疗（APDT）治疗中配制口服光敏剂的口服制剂和方法。口服配制的光敏剂显示增加的溶解度和渗透性，从而提高光敏剂在治疗部位的生物利用度。口服给药的光敏剂适于配制用于粘膜粘附和通过胃肠粘膜吸收。本文提供的口服制剂通过口服途径使用脂质和已知蛋白质作为光敏剂的载体。用于封装预选光敏剂的载体包括常规脂质体，聚乙二醇化脂质体，纳米乳剂，纳米胶体，纳米颗粒，脂肪乳剂，脂质制剂，水溶胶，SMEDDS，Alpha-Feto蛋白（AFP）和牛血清白蛋白（BSA），脂肪乳剂，热熔融挤出物和纳米颗粒。在本发明的疏水性光敏剂的情况下，口服制剂使用合适的表面活性剂/增溶剂稳定，从而防止药物在胃中的聚集，直到其被吸收到十二指肠和小肠中。口服制剂可以以液体，胶囊，片剂，粉末，糊剂或凝胶的形式施用。配制药物可以在施用PDT之前以一次剂量或多次剂量口服给药。在一个实施方案中，Temoporfin（m-THPC）用作口服制剂中的光敏剂。类似于许多疏水性光敏剂的Temoporfin特别适合于口服给药，因为在哺乳动物体内没有可以代谢Temoporfin或类似光敏剂的已知的酶系统。 Temoporfin可以在胃肠道吸收制剂后达到血液系统不变和充分活性。

7. 发明公开

EP1626772A4 IMPROVED PHOTOSENSITIZERS APPLICATION PROTOCOLS 有权
标题翻译：改进的应用程序协议光敏剂
公开(公告)号：EP1626772A4
公开(公告)日：2010-03-10
申请号：EP04759670
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

8. 发明公开

EP1701726A4 ANTIMICROBIAL PHOTODYNAMIC THERAPY COMPOUND AND METHOD OF USE 有权转让
标题翻译：抗菌光动力疗法及相关应用工艺
公开(公告)号：EP1701726A4
公开(公告)日：2007-01-03
申请号：EP04782618
申请日：2004-08-30
申请人： CERAMOPTEC GMBH
发明人： ALBRECHT VOLKER , GITTER BURKHARD
IPC分类号： A61K31/495 , A61K31/50 , A61K41/00 , A61N5/06 , A61P31/04
CPC分类号： A61K41/0019 , A61K41/0057 , A61N5/062
摘要： A method and composition for destroying microbes, especially bacteria, in the body utilizing Safranin O in conjunction with electromagnetic radiation is disclosed. In a preferred method, a composition comprising Safranin O is introduced to a treatment area. After a sufficient period of time has elapsed, radiation of a suitable wavelength is applied to the area to activate the Safranin O and by a photodynamic reaction to destroy the bacteria. Preferred radiation has a wavelength around 530 nm. This method is effective for destroying both Gram-positive and Gram-negative bacteria, and is particularly effective in areas where complex media such as blood serum, blood or saliva are also present.

9. 发明公开

EP2542305A4 ENHANCED ANTI-MICROBIAL PDT 审中-实审转让
标题翻译：高级抗菌PDT
公开(公告)号：EP2542305A4
公开(公告)日：2013-10-02
申请号：EP11735020
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 , A61K31/407 , A61L2/24 , A61N5/06 , 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： Methods and 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 are provided. In preferred embodiments, an antimicrobial photodynamic therapy (PDT) treatment is given that effectively inactivates, reduces and/or destroys both Gram (−) and Gram (+) bacteria in complex body fluids. Methods to enhance antimicrobial PDT activity include 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. Additionally, the method/device 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.

10. 发明公开

EP2034963A4 GEL-FORMULATIONS OF HYDROPHOBIC PHOTOSENSITIZERS FOR MUCOSAL APPLICATIONS 有权转让
标题翻译： GELFORMULIERUNGEN HYDROPHOBER光敏纤维素ZUM AUFTRAGEN AUF DIE SCHLEIMHAUT
公开(公告)号：EP2034963A4
公开(公告)日：2013-03-27
申请号：EP07794902
申请日：2007-05-16
申请人： CERAMOPTEC GMBH
发明人： ALBRECHT VOLKER , SCHEGLMANN DIETRICH
IPC分类号： A61K9/127 , A01N43/04 , A61K9/00 , A61K9/06 , A61K41/00 , A61K47/34
CPC分类号： A61K9/006 , A61K9/0014 , A61K9/06 , A61K9/127 , A61K41/0038 , A61K47/34
摘要： The present invention relates to improved methods of formulations of hydrophobic photosensitizers, and their precursors, for mucosal administration. The formulation of the invention comprises of hydrophobic photosensitizers which have been incorporated into suitably sized liposomes. Additionally, these formulations include the incorporation of PS-loaded liposomes into a copolymer matrix. The liposome of the present invention allows the hydrophobic photosensitizers to be incorporated into the thermogel matrix and thus promoting intimate contact between the formulation and the mucosal layer for enhanced drug absorption.
摘要翻译：本发明涉及用于粘膜给药的疏水性光敏剂及其前体制剂的改进方法。本发明的制剂包含已经掺入适当大小的脂质体中的疏水性光敏剂。此外，这些制剂包括将PS负载的脂质体并入共聚物基质中。本发明的脂质体允许将疏水性光敏剂掺入热凝胶基质中，从而促进制剂与粘膜层之间的紧密接触，以增强药物吸收。

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