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1. 发明申请

US20060088584A1 Liposomal formulations of hydrophobic photosensitizer for photodynamic therapy 有权
标题翻译：用于光动力疗法的疏水性光敏剂的脂质体制剂
公开(公告)号：US20060088584A1
公开(公告)日：2006-04-27
申请号：US11298729
申请日：2005-12-09
申请人： Volker Albrecht , Alfred Fahr , Dietrich Scheglmann , Susanna Grafe , Wolfgang Neuberger
发明人： Volker Albrecht , Alfred Fahr , Dietrich Scheglmann , Susanna Grafe , Wolfgang Neuberger
IPC分类号： A61K9/127 , A61K31/70 , A61K31/409
CPC分类号： A61K41/0071 , A61K9/127
摘要： Pharmaceutical liposomal formulations are described for photodynamic therapy comprising a, hydrophobic porphyrin photosensitizer, a monosaccharide and one or more synthetic phospholipids, which are stable in storage especially through freeze-drying process. The liposomal formulations provide therapeutically effective amounts of the photosensitizer for intravenous administration. In particular derivatives of chlorins and bacteriochlorins, such as temoporfin, are, hydrophobic photosensitizers whose efficacy and safety are enhanced by such liposomal formulations. The formulation can be efficiently freeze-dried preserving the size of the liposomal vehicles, and the content of a therapeutically effective amount of the photosensitizer, due to the selection of phospholipids and monosaccharides. The invention also relates to liposome compositions formed upon reconstitution with an aqueous vehicle. The freeze-dried formulation upon reconstitution with a suitable aqueous vehicle forms liposomes that are useful for intravenous administration.
摘要翻译：描述了用于光动力学治疗的药物脂质体制剂，其包括疏水性卟啉光敏剂，单糖和一种或多种合成磷脂，其特别通过冷冻干燥方法在储存中稳定。脂质体制剂提供治疗有效量的用于静脉内给药的光敏剂。特别是二氢卟酚和细菌二氢卟酚的衍生物，如temoporfin，是通过这种脂质体制剂增强其功效和安全性的疏水性光敏剂。由于磷脂和单糖的选择，制剂可以有效地冷冻干燥，保持脂质体载体的大小和治疗有效量的光敏剂的含量。本发明还涉及在用水性载体重建时形成的脂质体组合物。用合适的水性载体重建后的冷冻干燥制剂形成可用于静脉内给药的脂质体。

2. 发明申请

US20060159740A1 Hydrophobic photosensitizer formulations for photodynamic therapy 审中-公开
标题翻译：用于光动力疗法的疏水性光敏剂配方
公开(公告)号：US20060159740A1
公开(公告)日：2006-07-20
申请号：US11384767
申请日：2006-03-20
申请人： Volker Albrecht , Alfred Fahr , Dietrich Scheglmann , Susanna Grafe , Wolfgang Neuberger
发明人： Volker Albrecht , Alfred Fahr , Dietrich Scheglmann , Susanna Grafe , Wolfgang Neuberger
IPC分类号： A61K31/409 , A61K31/555 , A61K9/127
CPC分类号： A61K41/0071 , A61K9/127
摘要： Pharmaceutical liposomal formulations for photodynamic therapy are presented, which are stable in storage as liquid formulations, comprise a hydrophobic photosensitizer and one or more synthetic phospholipids. The liposomal formulations provide therapeutically effective amounts of the photosensitizer for intravenous administration. The formed liposomes contain the hydrophobic photosensitizer within the lipid bilayer membrane. In the present formulation the size of the liposomal vehicles and their content of a therapeutically effective amount of the photosensitizing agent remain unchanged over storage times of a year or more, thus making the liquid formulations commercially viable. Being stable in the liquid state also makes them easy to store, and easier to use for doctors and patients. They can be prepared in a ‘factory setting’ delivered to practitioners in a liquid state and be available for use in PDT related treatments as called for by the practitioners' patient needs.
摘要翻译：提出了用于光动力学治疗的药物脂质体制剂，其作为液体制剂在储存中稳定，包含疏水性光敏剂和一种或多种合成磷脂。脂质体制剂提供治疗有效量的用于静脉内给药的光敏剂。形成的脂质体在脂质双层膜内含有疏水性光敏剂。在本发明的制剂中，脂质体载体的大小及其治疗有效量的光敏剂的含量在一年以上的保存时间内保持不变，从而使液体制剂在商业上可行。在液体状态下稳定也使得它们易于储存，并且更容易用于医生和患者。他们可以在“工厂设置”下准备就绪，以液体状态送达医生，并可根据医生的病人需要进行PDT相关治疗。

3. 发明申请

US20050048109A1 Non-polar photosensitizer formulations for photodynamic therapy 审中-公开
标题翻译：用于光动力疗法的非极性光敏剂配方
公开(公告)号：US20050048109A1
公开(公告)日：2005-03-03
申请号：US10648168
申请日：2003-08-26
申请人： Volker Albrecht , Alfred Fahr , Dietrich Scheglmann , Susanna Grafe , Wolfgang Neuberger
发明人： Volker Albrecht , Alfred Fahr , Dietrich Scheglmann , Susanna Grafe , Wolfgang Neuberger
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 non-polar photosensitizer and a second polar substance. When a formulation includes the presence of monosaccharides or polyalcohols, it can be efficiently freeze-dried preserving the size of the liposomal vehicles and the content of a therapeutically effective amount of the photosensitizing agent. 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：描述了一种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在不需要冷冻干燥的情况下在储存中稳定的磷脂。脂质体制剂提供治疗有效量的用于静脉内施用的光敏剂。可以通过聚乙二醇化来改变磷脂，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。当制剂包含单糖或多元醇的存在时，可有效地冷冻干燥保存脂质体载体的大小和治疗有效量的光敏剂的含量。本发明还涉及在与水性载体重建时形成的脂质体组合物。用合适的水性载体重构后的冷冻干燥制剂形成也可用于静脉内施用的脂质体。

4. 发明申请

US20060127471A1 Pegylated liposomal formulations of hydrophobic photosensitizers for photodynamic therapy 有权
公开(公告)号：US20060127471A1
公开(公告)日：2006-06-15
申请号：US11349405
申请日：2006-02-07
申请人： Volker Albrecht , Alfred Fahr , Dietrich Schegimann , Susanna Grafe , Wolfgang Neuberger
发明人： Volker Albrecht , Alfred Fahr , Dietrich Schegimann , Susanna Grafe , Wolfgang Neuberger
IPC分类号： A61K31/555 , A61K9/127 , A61K31/407
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.

5. 发明申请

US20090162423A1 Formulations for cosmetic and wound care treatments with photosensitizes as fluorescent markers 审中-公开
标题翻译：用于化妆品和伤口护理治疗的制剂，作为荧光标记物进行光敏化
公开(公告)号：US20090162423A1
公开(公告)日：2009-06-25
申请号：US12004325
申请日：2007-12-20
申请人： Wolfgang Neuberger , Susanna Grafe , Nikolay E. Nifantiev
发明人： Wolfgang Neuberger , Susanna Grafe , Nikolay E. Nifantiev
IPC分类号： A61K9/127 , A61K38/00 , A61P17/00 , A61K31/715
CPC分类号： A61K31/715 , A61K9/0019 , A61K9/06 , 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射的填充材料的分布。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。

6. 发明申请

US20080214460A1 Formulations for cosmetic and wound care treatments with photosensitizers as fluorescent markers 审中-公开
标题翻译：用光敏剂作为荧光标记的化妆品和伤口护理治疗的配方
公开(公告)号：US20080214460A1
公开(公告)日：2008-09-04
申请号：US12006911
申请日：2008-01-07
申请人： Wolfgang Neuberger , Susanna Grafe , Nikolay E. Nifantiev
发明人： Wolfgang Neuberger , Susanna Grafe , Nikolay E. Nifantiev
IPC分类号： A61K38/00
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射的填充材料的分布。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，配制的光敏剂与填料偶联，使得可以在更长的时间内进行跟踪。将脂质体配制的光敏剂与填料一起注入处理区域，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。

7. 发明申请

US20090028926A1 Method and mixture for in vivo photochemical cross-linking of collagen 审中-公开
标题翻译：胶原蛋白体内光化学交联的方法和混合物
公开(公告)号：US20090028926A1
公开(公告)日：2009-01-29
申请号：US11880973
申请日：2007-07-25
申请人： Susanna Grafe , Wolfgang Neuberger , Danilo Castro
发明人： Susanna Grafe , Wolfgang Neuberger , Danilo Castro
IPC分类号： A61K38/00 , A61K31/33 , A61K9/70 , A61L15/00 , A61P17/00
CPC分类号： A61K31/33 , A61K9/0019 , A61K9/127 , A61K47/24
摘要： A method and a composition for photochemical cross linking of collagen by photoactive agent in-vivo are presented. The method includes a non-toxic photoactive formulation of the composition with collagen, which is administered to treatment area locally; followed by irradiation with suitable wavelength. In one of the embodiment liposomal formulated mTHPC is added to the collagen and is irradiated with a 652 nm laser, resulting in producing efficient collagen scaffolds with strengthen and stabilized microstructure, thus improving the physiochemical properties of the collagen scaffold. It improves the thermostability, mechanical property and swelling ratio of newly formed scaffold. Photochemical cross-linked collagens shows antimicrobial effect, when irradiated with suitable wavelength it disinfects the treatment site and curbs microbial growth.
摘要翻译：提出了通过光活性剂在体内对胶原蛋白的光化学交联的方法和组合物。该方法包括具有胶原蛋白的组合物的无毒光活性制剂，其局部施用于治疗区域; 然后用合适的波长照射。在其中一个实施方案中，将脂质体配制的mTHPC加入到胶原中并用652nm激光照射，从而产生具有强化和稳定的微结构的有效的胶原支架，从而改善胶原支架的物理化学性质。提高新型脚手架的热稳定性，机械性能和溶胀比。光化学交联胶原显示抗菌效果，当用合适的波长照射时，其消毒处理部位并抑制微生物生长。

8. 发明申请

US20110257586A1 CALCIUMPHOSPHATE-BASED NANOPARTICLES AS CARRIER-SYSTEMS FOR PHOTODYNAMIC THERAPY 审中-公开
标题翻译：基于钙磷酸盐的纳米颗粒作为光化学治疗的载体系统
公开(公告)号：US20110257586A1
公开(公告)日：2011-10-20
申请号：US13140855
申请日：2009-12-18
申请人： Burkhatd Gitter , Susanna Grafe , Arno Wiehe , Volker Albrecht , Matthias Epple , Janine Schwiertz , Kathirvel Ganesan
发明人： Burkhatd Gitter , Susanna Grafe , Arno Wiehe , Volker Albrecht , Matthias Epple , Janine Schwiertz , Kathirvel Ganesan
IPC分类号： A61M37/00 , A61K31/409 , A61K31/675 , A61P35/00 , A61P31/04 , A61K9/14 , A61K31/5415 , B82Y5/00
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. 发明申请

US20050102712A1 DNA sequences encoding the subunit CHLD of plant magnesium chelatases, and determining the activity of plant magnesium chelatases 审中-公开
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：US20050102712A1
公开(公告)日：2005-05-12
申请号：US10637763
申请日：2003-08-08
申请人： Bernhard Grimm , Jutta Papenbrock , Frank Hanel , Susanna Grafe , Frank Schmidt , Wolfgang Streber
发明人： Bernhard Grimm , Jutta Papenbrock , Frank Hanel , Susanna Grafe , Frank Schmidt , Wolfgang Streber
IPC分类号： A01H5/00 , C07K16/16 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/00 , C12N15/09 , C12N15/82 , C12Q1/68 , A01H1/00 , C12Q1/48
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，并且至少编码一种编码其中的Mg螯合酶亚单位的DNA序列 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。

10. 发明申请

US20060270617A1 HkI10311129, novel antibiotic, method for producting the same and the use thereof 失效
标题翻译： HkI10311129，新型抗生素，其制备方法及其用途
公开(公告)号：US20060270617A1
公开(公告)日：2006-11-30
申请号：US11497953
申请日：2006-08-02
申请人： Ute Mollmann , Kerstin Herold , Martin Roth , Ingrid Groth , Friedrich Gollmick , Udo Grafe , Karin Grafe , Andrea Grafe , Susanna Grafe
发明人： Ute Mollmann , Kerstin Herold , Martin Roth , Ingrid Groth , Friedrich Gollmick , Udo Grafe , Karin Grafe , Andrea Grafe , Susanna Grafe
IPC分类号： A61K31/704 , C07H15/24
CPC分类号： C07D309/10
摘要： The invention relates to the novel antibiotic HKI10311129 which has a molecular weight of 1113 and the summation formula C56H75NO22. The invention also relates to a method for producing said antibiotic using the microorganism Streptomyces spec. DSM 13059, and to the use thereof as an antibacterial substance which is especially effective against infections with Gram positive bacteria, especially antibiotic-resistant germs.
摘要翻译：本发明涉及新型抗生素HKI10311129，其分子量为1113，总和式为C 56 H 22 NO 22。本发明还涉及使用微生物链霉菌属（Streptomyces spec）生产所述抗生素的方法。 DSM 13059，以及其作为抗菌物质的用途，其特别有效地抵抗革兰氏阳性菌，特别是抗生素抗性细菌的感染。

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