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1. 发明授权

US08986731B2 Pegylated liposomal formulations of hydrophobic photosensitizers for photodynamic therapy 有权
标题翻译：用于光动力学治疗的疏水性光敏剂的聚乙二醇化脂质体制剂
公开(公告)号：US08986731B2
公开(公告)日：2015-03-24
申请号：US11349405
申请日：2006-02-07
申请人： Volker Albrecht , Alfred Fahr , Dietrich Scheglmann , Susanna Gräfe , Wolfgang Neuberger
发明人： Volker Albrecht , Alfred Fahr , Dietrich Scheglmann , Susanna Gräfe , Wolfgang Neuberger
IPC分类号： A61K9/127 , A61K31/407 , A61K31/555 , A61K41/00
CPC分类号： A61K9/1271 , A61K31/407 , A61K31/555 , A61K41/0071
摘要： Pharmaceutical pegylated liposomal formulations for photodynamic therapy are presented. The pegylated liposomal formulation provides therapeutically effective amounts of the photosensitizer for intravenous administration. At least one of the phospholipids in the liposomes has been linked with poly ethylene glycol (PEG) as an integral part of the phospholipids. The formed pegylated liposomes contain the hydrophobic photosensitizer within the lipid bilayer membrane. Pegylation of liposomes carrying the hydrophobic photosensitizer helps to maintain the drug level within the therapeutic window for longer time periods and provides the drug a longer circulating half life in vivo. Further the pegylated formulation of hydrophobic photosensitizers shows improved pharmacokinetics over standard non-liposomal formulations thus enhancing the efficacy of PDT with the pegylated liposomal formulations.
摘要翻译：提出了用于光动力学治疗的药物聚乙二醇化脂质体制剂。聚乙二醇化脂质体制剂提供治疗有效量的用于静脉内施用的光敏剂。脂质体中的至少一种磷脂已经与作为磷脂的组成部分的聚乙二醇（PEG）连接。形成的聚乙二醇化脂质体在脂质双层膜内含有疏水性光敏剂。携带疏水性光敏剂的脂质体的聚乙二醇化有助于在治疗窗口内维持更长时间的药物水平，并使药物在体内延长循环半衰期。此外，疏水性光敏剂的聚乙二醇化制剂显示与标准非脂质体制剂相比改善的药物代谢动力学，从而增强PDT与聚乙二醇化脂质体制剂的功效。

2. 发明申请

US20120101427A1 NOVEL PHOTOSENSITIZER FORMULATIONS FOR ORAL ADMINISTRATION 审中-公开
标题翻译：用于口腔管理的新型光敏剂配方
公开(公告)号：US20120101427A1
公开(公告)日：2012-04-26
申请号：US13266056
申请日：2009-04-28
申请人： Gerard Farmer , Gerhard Wieland , Dietrich Scheglmann , Arno Wiehe , Susanna Gräfe , Nikolay E. Nufantiev , Volker Albrecht , Wolfgang Neuberger
发明人： Gerard Farmer , Gerhard Wieland , Dietrich Scheglmann , Arno Wiehe , Susanna Gräfe , Nikolay E. Nufantiev , Volker Albrecht , Wolfgang Neuberger
IPC分类号： A61M37/00 , A61K31/498 , C07D487/22 , C07D241/46 , A61K9/127 , A61K38/02 , A61K31/7056 , A61K31/706 , A61K31/79 , A61P35/00 , A61P17/00 , A61P9/00 , A61P19/02 , A61P31/04 , A61P33/02 , A61P31/12 , A61P31/00 , A61K31/409 , B82Y5/00
CPC分类号： A61K31/122 , A61K31/40 , A61K31/498 , A61K41/0071
摘要： The present invention provides novel drug formulations for oral administration for diverse medical applications including anticancer, antimetastatic, antibacterial, antifungal, antiprotozoic, antiviral, antiprionic and PDT treatments for diagnostic and therapeutic purposes. In a preferred embodiment the oral drug formulation comprises a photosensitizer and suitable excipients and may be administered in multiple doses over an extended period of time with exposure to activating radiation occurring generally between individual doses or in a light-independent manner. In another preferred embodiment PDT methods for treating hyperplasia and neoplasia, for localizing hyperplasic and neoplasic tissues and pathogen bacteria by fluorescence, for treating infections caused by pathogen bacteria in complex body fluids and for fat reduction, skin disorders and vascular diseases are provided.
摘要翻译：本发明提供用于口服给药以用于各种医学应用的新型药物制剂，包括用于诊断和治疗目的的抗癌，抗转移，抗细菌，抗真菌，抗原生动脉，抗病毒，抗细胞和PDT治疗。在优选的实施方案中，口服药物制剂包含光敏剂和合适的赋形剂，并且可以在延长的时间段内以多个剂量施用，暴露于通常在单独剂量之间或以轻轻独立的方式发生的活化辐射。在另一个优选实施方案中，提供了用于治疗增生和瘤形成的PDT方法，用于通过荧光定位超基质和新生组织和病原体细菌，用于治疗复杂体液中由病原体引起的感染和用于减脂，皮肤病和血管疾病。

3. 发明申请

US20110142948A1 Nanoparticle Carrier Systems based on Human Serum Albumin for Photodynamic Therapy 有权
标题翻译：基于人血清白蛋白的纳米粒子载体系统用于光动力疗法
公开(公告)号：US20110142948A1
公开(公告)日：2011-06-16
申请号：US12941350
申请日：2010-11-08
申请人： Klaus Langer , Matthias Wacker , Beate Röder , Annegret Preuss , Volker Albrecht , Susanna Gräfe , Arno Wiehe , Hagen von Briesen , Karin Löw , Sylvia Wagner
发明人： Klaus Langer , Matthias Wacker , Beate Röder , Annegret Preuss , Volker Albrecht , Susanna Gräfe , Arno Wiehe , Hagen von Briesen , Karin Löw , Sylvia Wagner
IPC分类号： A61K31/409 , A61K9/00 , A61K9/14 , A61P35/00 , A61P17/00 , A61P27/02 , A61P13/00 , A61P19/02 , A61P29/00 , A61P31/04 , B82Y5/00
CPC分类号： A61K31/409 , A61K9/5169 , A61K41/0071
摘要： Compositions, which are stable in storage, and a method of production of pharmaceutical based nanoparticulate formulations for photodynamic therapy comprising a hydrophobic photosensitizer, human serum albumin (HSA) and stabilizing agent are provided. These nanoparticulate formulations provide therapeutically effective amounts of photosensitizer (PS) for parenteral administration. In particular, tetrapyrrole derivatives can be used as photosensitizers whose efficacy and safety are enhanced by such nanoparticulate formulations. A method of preparing the HSA-based nanoparticles under sterile conditions is also provided. In one of the preferred embodiments of the present invention temoporfin, a hydrophobic PS, is formulated as a nanoparticle for parenteral administration. The formulations are useful for treating hyperplasic and neoplasic conditions, inflammatory problems, and more specifically to target tumor cells.
摘要翻译：提供了在储存中稳定的组合物以及用于光动力疗法的药物基纳米颗粒制剂的制备方法，其包括疏水性光敏剂，人血清白蛋白（HSA）和稳定剂。这些纳米颗粒制剂提供用于胃肠外给药的治疗有效量的光敏剂（PS）。特别地，四吡咯衍生物可以用作光敏剂，其功效和安全性通过这样的纳米颗粒制剂增强。还提供了在无菌条件下制备基于HSA的纳米颗粒的方法。在本发明的一个优选实施方案中，一种疏水性PS被配制成用于肠胃外给药的纳米颗粒。该制剂可用于治疗过度和肿瘤状况，炎症问题，更具体地涉及靶向肿瘤细胞。

4. 发明授权

US09315510B2 Method and application of unsymmetrically meso-substituted porphyrins and chlorins for PDT 有权
标题翻译：用于PDT的不对称内消旋卟啉和二氢卟酚的方法和应用
公开(公告)号：US09315510B2
公开(公告)日：2016-04-19
申请号：US13119907
申请日：2009-09-17
申请人： Arno Wiehe , Daniel Aicher , Christian B. W. Stark , Volker Albrecht , Susanna Gräfe
发明人： Arno Wiehe , Daniel Aicher , Christian B. W. Stark , Volker Albrecht , Susanna Gräfe
IPC分类号： A61K31/409 , C07D487/22 , C07H15/26
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.
摘要翻译：提供了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，感染和其它过度增生性疾病的PDT，荧光诊断和PDT治疗非肿瘤适应症如关节炎，炎性疾病，病毒或细菌感染，皮肤病学，眼科学或泌尿系统疾病，以及提供以药物质量获得它们的方法。一个实施方案由合成具有定义的内消旋取代基排列的卟啉的方法组成，然后通过二羟基化或还原将该卟啉体系转化为二氢卟酚体系，并且如果形成多于一种的异构体，则通过色谱法分离，或者在正常或反向相二氧化硅。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为二氢卟酚，从而选择性地形成某种异构体。另一个实施方案是提供具有更高膜亲和力和增加的PDT功效的两亲化合物。在另一个实施方案中，提供了避免使用气态H 2 S的还原性裂解锇酸酯（VI）酯的方法。在另一个实施方案中，鉴定了取代基，通过它们的空间和/或电子影响直接使二羟基化或还原与二亚胺，使得一种异构体是有利的。另一个实施方案包括将所需的异构体配制成待注射的脂质体制剂，避免不期望的作用，如四吡咯体系的溶解性问题或延迟的药代动力学。

5. 发明授权

US08815931B2 Oral formulations for tetrapyrrole derivatives 有权
标题翻译：四吡咯衍生物的口服制剂
公开(公告)号：US08815931B2
公开(公告)日：2014-08-26
申请号：US12768244
申请日：2010-04-27
申请人： Susanna Gräfe , Nikolay Nifantiev , Albrecht Volker , Wolfgang Neuberger , Gerhard Wieland , Dietrich Scheglmann , Alfred Fahr , Arno Wiehe
发明人： Susanna Gräfe , Nikolay Nifantiev , Albrecht Volker , Wolfgang Neuberger , Gerhard Wieland , Dietrich Scheglmann , Alfred Fahr , Arno Wiehe
IPC分类号： A61K31/40 , A61K9/127 , A61K31/498 , A61K9/00 , A61K31/409
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：提出了在光动力治疗（PDT）和抗微生物光动力疗法（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通过胃肠粘膜进行粘膜粘附和吸收。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，α-铁蛋白（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，使用合适的表面活性剂/增溶剂稳定口服制剂，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。配制药物可以在给予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，因为哺乳动物体内没有已知的可以代谢Temoporfin或类似光敏剂的酶系统。 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。

6. 发明申请

US20100273803A1 Oral Formulations for Tetrapyrrole Derivatives 有权
标题翻译：四吡咯衍生物的口服制剂
公开(公告)号：US20100273803A1
公开(公告)日：2010-10-28
申请号：US12768244
申请日：2010-04-27
申请人： Susanna Gräfe , Nikolay Nifantiev , Albrecht Volker , Wolfgang Neuberger , Gerhard Wieland , Dietrich Scheglmann , Alfred Fahr , Arno Wiehe
发明人： Susanna Gräfe , Nikolay Nifantiev , Albrecht Volker , Wolfgang Neuberger , Gerhard Wieland , Dietrich Scheglmann , Alfred Fahr , Arno Wiehe
IPC分类号： A61K31/498 , C07D241/46 , A61K31/409 , C07D487/22 , A61P35/00 , A61P31/00 , A61K8/49 , A61Q19/00 , A61Q9/00
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：提出了在光动力治疗（PDT）和抗微生物光动力疗法（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通过胃肠粘膜进行粘膜粘附和吸收。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，α-铁蛋白（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，使用合适的表面活性剂/增溶剂稳定口服制剂，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。配制药物可以在给予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，因为哺乳动物体内没有已知的可以代谢Temoporfin或类似光敏剂的酶系统。 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. 发明授权

US06831207B1 DNA sequences encoding for subunit CHLD of plant magnesium chelatases and determining the activity of plant magnesium chelatases 失效
标题翻译：编码植物镁螯合酶亚基CHLD的DNA序列，并确定植物镁螯合酶的活性
公开(公告)号：US06831207B1
公开(公告)日：2004-12-14
申请号：US09403463
申请日：1999-10-21
申请人： Bernhard Grimm , Jutta Papenbrock , Frank Hänel , Susanna Gräfe , Frank Schmidt , Wolfgang Streber
发明人： Bernhard Grimm , Jutta Papenbrock , Frank Hänel , Susanna Gräfe , Frank Schmidt , Wolfgang Streber
IPC分类号： A01H500
CPC分类号： C12N9/00 , C12N15/8269 , C12N15/8274
摘要： The present invention relates to a nucleic acid molecule which encodes a protein with the function of a plant Mg chelatase subunit CHLD or an active fragment thereof; a protein which has the function of a plant Mg chelatase subunit CHLD or an active fragment thereof, preferably a recombinant protein; a method of determining the interaction of plant Mg chelatase subunits, in which a host cell is transformed with a DNA sequence as claimed in one or more of claims 1 to 3 and at least with one DNA sequence encoding a further subunit of Mg chelatase in such a manner that the interaction of the Mg chelatase gene products leads to a directly or indirectly, qualitatively or quantitatively measurable signal, preferably by activating a marker gene, and transgenic plants, transgenic plant cells, transgenic plant organs, transgenic plant seeds, transgenic propagation material comprising an abovementioned nucleic acid molecule.
摘要翻译：本发明涉及编码具有植物Mg螯合酶亚基CHLD或其活性片段的功能的蛋白质的核酸分子; 具有植物Mg螯合酶亚单位CHLD或其活性片段，优选重组蛋白质的功能的蛋白质; 确定植物Mg螯合酶亚基的相互作用的方法，其中宿主细胞用如权利要求1至3中的一项或多项所述的DNA序列转化，并且至少在编码另一个Mg螯合酶亚单位的DNA序列中 Mg螯合酶基因产物的相互作用导致直接或间接，定性或定量可信号的信号，优选通过激活标记基因和转基因植物，转基因植物细胞，转基因植物器官，转基因植物种子，转基因繁殖材料包含上述核酸分子。

8. 发明授权

US08956648B2 Calciumphosphate-based nanoparticles as carrier-systems for photodynamic therapy 有权
标题翻译：基于磷酸钙的纳米粒子作为光动力疗法的载体系统
公开(公告)号：US08956648B2
公开(公告)日：2015-02-17
申请号：US13140855
申请日：2009-12-18
申请人： Burkhard Gitter , Susanna Gräfe , Arno Wiehe , Volker Albrecht , Matthias Epple , Janine Schwiertz , Kathirvel Ganesan
发明人： Burkhard Gitter , Susanna Gräfe , Arno Wiehe , Volker Albrecht , Matthias Epple , Janine Schwiertz , Kathirvel Ganesan
IPC分类号： A61P35/00 , A61P31/04 , A61K9/14 , A61K31/5415 , B82Y5/00 , A61K9/51 , A61K41/00 , A61K49/00
CPC分类号： A61K9/5115 , A61K41/0057 , A61K41/0071 , A61K49/0093 , Y10S977/773
摘要： The present invention provides pharmaceutical photosensitizer-loaded nanoparticle formulations and their methods of preparation for photodynamic therapy, comprising a hydrophobic or hydrophilic photosensitizer, nanoparticulate calcium phosphate and in certain cases auxiliary reagents such as stabilizers. The calcium phosphate-based nanoparticle formulations of the present invention provide excellent storage stability and therapeutically effective amounts of photosensitizer for intravenous or topical administration. In a preferred embodiment, tetrapyrrole derivatives such as porphyrins, chlorins and bacteriochlorins, are the preferred hydrophobic photosensitizers to be formulated in calcium phosphate nanoparticle formulations for photodynamic tumor therapy. Additionally, 5,10,15,20-tetrakis(4-phosphonooxyphenyl)porphine (pTPPP) is a preferred hydrophilic photosensitizer for photodynamic tumor therapy. In another preferred embodiment, hydrophilic cationic and anionic photosensitizers, especially those of the phenazinium, phenothiazinium and xanthenes series have been found to inactive pathogen bacteria and are the preferred photosensitizers to be formulated in calcium phosphate nanoparticle formulations for antibacterial photodynamic therapy. In another embodiment, photosensitizing nanoparticle formulations are useful to locate cells, tissues or bacteria by using fluorescence imaging methods.
摘要翻译：本发明提供负载药物的光敏剂纳米颗粒制剂及其制备光动力疗法的方法，其包括疏水或亲水性光敏剂，纳米颗粒磷酸钙，在某些情况下，辅助试剂如稳定剂。本发明的基于磷酸钙的纳米颗粒制剂提供优异的储存稳定性和用于静脉内或局部给药的治疗有效量的光敏剂。在优选的实施方案中，四吡咯衍生物如卟啉，二氢卟酚和细菌二氢卟酚是拟配制在用于光动力学肿瘤治疗的磷酸钙纳米颗粒制剂中的优选的疏水性光敏剂。另外，5,10,15,20-四（4-膦酰氧基苯基）卟吩（pTPPP）是用于光动力学肿瘤治疗的优选亲水性光敏剂。在另一个优选的实施方案中，已经发现亲水性阳离子和阴离子光敏剂，特别是吩嗪鎓，吩噻嗪和呫吨系列的亲水性阳离子和阴离子光敏剂是无活性的病原体细菌，并且是配制在用于抗菌光动力学治疗的磷酸钙纳米颗粒制剂中的优选的光敏剂。在另一个实施方案中，光敏纳米颗粒制剂可用于通过使用荧光成像方法定位细胞，组织或细菌。

9. 发明授权

US08709449B2 Methods and compositions for improving photodynamic therapy through administration of lipids 有权
标题翻译：通过施用脂质改善光动力疗法的方法和组合物
公开(公告)号：US08709449B2
公开(公告)日：2014-04-29
申请号：US11055923
申请日：2005-02-10
申请人： Volker Albrecht , Susanna Gräfe
发明人： Volker Albrecht , Susanna Gräfe
IPC分类号： B32B27/30 , C08K5/04 , C08K5/09
CPC分类号： A61K9/0019 , A61K9/107 , A61K31/409 , A61K31/555 , A61K31/685 , A61K41/0071 , A61K47/24 , A61K47/44 , A61K2300/00 , A61K41/00
摘要： The present invention provides methods and compositions for increasing the effectiveness of photodynamic therapy (“PDT”) and for reducing the duration of skin phototoxicity associated with PDT treatment. The disclosed methods generally include the administration of a lipid composition before, during, or after the administration of photosensitizers used in the PDT treatment protocol. The lipids are preferably phospholipids. It was discovered that the disclosed methods resulted in a more rapid clearance of photosensitizers from the skin and other tissue of patients, which results in a shorter period of skin phototoxicity after PDT treatment. The present invention also provides a composition which is preferably comprised of non-polar photosensitizers and phospholipids.
摘要翻译：本发明提供用于增加光动力疗法（“PDT”）的有效性并减少与PDT治疗相关的皮肤光毒性持续时间的方法和组合物。所公开的方法通常包括在给予PDT治疗方案中使用的光敏剂之前，期间或之后施用脂质组合物。脂质优选为磷脂。发现所公开的方法导致光敏剂从皮肤和患者的其他组织更快速地清除，这导致PDT治疗后皮肤光毒性的时间更短。本发明还提供了优选由非极性光敏剂和磷脂组成的组合物。

10. 发明申请

US20110021973A1 FORMULATIONS FOR COSMETIC AND WOUND CARE TREATMENTS WITH PHOTOSENSITIZERS AS FLUORESCENT MARKERS 审中-公开
标题翻译：使用光敏剂作为荧光标记的化妆和治疗护理品的配方
公开(公告)号：US20110021973A1
公开(公告)日：2011-01-27
申请号：US12896614
申请日：2010-10-01
申请人： Wolfgang Neuberger , Susanna Gräfe , Nikolay E. Nifantiev
发明人： Wolfgang Neuberger , Susanna Gräfe , Nikolay E. Nifantiev
IPC分类号： A61M37/00
CPC分类号： A61L27/50
摘要： Photoactive materials, such as photosensitizers, are used as fluorescent markers for in vivo detection of the distribution of the injected filler material during cosmetic treatments. In one preferred embodiment, liposomal formulated temoporfin is used, as the photoactive component, in very small concentrations along with fillers for cosmetic and wound healing applications. Fillers, which can be used in the invention, include collagen, hyaluronic acids and other synthetic or natural products which are generally used in wound healing, scar reduction and other such medical applications. In a preferred embodiment, the formulated photosensitizer is coupled to the filler so that tracking is possible over longer periods of time A liposomal formulated photosensitizer is injected with the fillers into the treatment area, and is irradiated with laser light shortly after injection. The emitted fluorescence is measured by a special non-invasive device. Thereby it is possible to monitor the injection site and the distribution of the injected solution around the injection site. When irradiated with laser or other light source, the fluorescence of the photosensitizer is detected using a fluorescence detector, which permits tracking the filler at injection site and in the injection volume.
摘要翻译：光敏剂如光敏剂被用作荧光标记物，用于在化妆品处理期间体内检测注入的填充材料的分布。在一个优选的实施方案中，作为光活性成分的脂质体配制的temoporfin以非常小的浓度与用于化妆品和伤口愈合应用的填充剂一起使用。可用于本发明的填充剂包括胶原蛋白，透明质酸和通常用于伤口愈合，瘢痕减少等医学应用中的其它合成或天然产物。在优选的实施方案中，将配制的光敏剂偶联到填料，使得可以在更长时间内进行跟踪。将脂质体配制的光敏剂注射到处理区域中，并在注射后不久用激光照射。发射的荧光通过特殊的非侵入性装置测量。因此，可以监测注射部位和注射部位周围注射溶液的分布情况。当用激光或其他光源照射时，使用荧光检测器检测光敏剂的荧光，其允许在注射部位和注射体积中追踪填料。

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