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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

US20110034854A1 PDT ASSISTED VISION CORRECTION AND SCAR PREVENTION 审中-公开
标题翻译： PDT辅助视力矫正和防护
公开(公告)号：US20110034854A1
公开(公告)日：2011-02-10
申请号：US12743515
申请日：2008-11-20
申请人： Wolfgang Neuberger , Volker Albrecht
发明人： Wolfgang Neuberger , Volker Albrecht
IPC分类号： A61M37/00 , A61K31/409 , A61K9/127 , A61P17/02
CPC分类号： A61N5/062 , A61F9/00802 , A61F2009/00872
摘要： A method and formulation are disclosed for improving the results of corneal refractive surgery, and generally reducing post-operative scarring and scarring arising from other traumas. In the vision examples, after completion of a procedure, including Photorefractive Keratotomy (PRK) or Laser-In-Situ Keratomileusis (LASIK), a photosensitizer or photosensitizer precursor is applied to the treatment site. After allowing sufficient time for the photosensitizers to accumulate among proliferating cells that occur as a result of ablation, radiation appropriate to activate the photosensitizers is administered to the treatment site. The photosensitizer is thus activated to destroy only those proliferating cells. In this way, proliferating tissue is eliminated and the cornea maintains the shape created during the surgery. As a result, instances of regression and the need for follow-up treatments, is minimized. This method is also useful for preventing post-surgical scarring that can lead to vision problems such as corneal haze. Likewise the method and formulations, presented here, are suitable for reducing post-operative scarring, and trauma cased scarring in general. For such scars, a photosensitizer or photosensitizer precursor is topically applied to the treatment site. After allowing sufficient time for the photosensitizers to attach to proliferating cells, radiation appropriate to activate the photosensitizers is administered to the treatment site. The photosensitizer is activated to destroy only those proliferating cells.
摘要翻译：公开了用于改善角膜屈光手术结果的方法和制剂，并且通常减少由其他创伤引起的术后瘢痕形成和瘢痕形成。在视觉实例中，在完成包括光折射角膜切开术（PRK）或激光原位角膜磨镶术（LASIK））的手术完成后，将光敏剂或光敏剂前体施用于治疗部位。在允许足够的时间使光敏剂在由于消融引起的增殖细胞之间累积，适当激活光敏剂的辐射被施用于治疗部位。因此，光敏剂被激活以仅破坏那些增殖细胞。以这种方式，消除增殖组织，并且角膜保持手术期间产生的形状。因此，尽可能减少了回归和后续治疗的需要。这种方法也可用于预防术后瘢痕形成，导致视力问题，如角膜混浊。同样地，这里给出的方法和制剂适用于减少手术后瘢痕形成和一般的外伤瘢痕形成。对于这种疤痕，将光敏剂或光敏剂前体局部施用于治疗部位。在允许足够的时间使光敏剂附着于增殖细胞之后，向治疗部位施用适于激活光敏剂的辐射。光敏剂被激活以仅破坏那些增殖细胞。

4. 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。

5. 发明授权

US09409037B2 Enhanced anti-microbial PDT 有权
标题翻译：增强抗微生物PDT
公开(公告)号：US09409037B2
公开(公告)日：2016-08-09
申请号：US13006274
申请日：2011-01-13
申请人： Volker Albrecht , Gerhard Wieland , Burkhard Gitter , Wolfgang Neuberger
发明人： Volker Albrecht , Gerhard Wieland , Burkhard Gitter , Wolfgang Neuberger
IPC分类号： A61N5/06 , A61M1/36 , A61L2/00
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.
摘要翻译：提供了用于消除，减少，破坏和/或抑制诸如病原体微生物和诸如血液，血清和其他体液的复杂环境中的恶化或恶性细胞的不期望的体液物质的方法和装置。在优选的实施方案中，给出了在复合体液中有效灭活，减少和/或破坏革兰氏（ - ）和革兰氏阴性（+）细菌的抗微生物光动力疗法（PDT）治疗。增强抗微生物PDT活性的方法包括在通过通道引导细菌污染的流体与光敏剂停留时间之后，向细菌污染的流体施用光敏剂，优选以间歇方式发射辐射，并将经处理的体液恢复到相应的身体区域。基于治疗参数，电磁辐射优选间歇地以脉冲宽度递送。此外，该方法/装置通过中和致病微生物片段的生物活性并减少和/或除去负责其的病原微生物片段来减少不良宿主的炎症反应。

6. 发明申请

US20110160642A1 PEGYLATED LIPOSOMAL FORMULATIONS FOR PHOTODYNAMIC TREATMENT OF INFLAMMATORY DISEASES 审中-公开
标题翻译：用于荧光动力治疗炎性疾病的聚乙二醇脂质体制剂
公开(公告)号：US20110160642A1
公开(公告)日：2011-06-30
申请号：US12742336
申请日：2008-11-14
申请人： Wolfgang Neuberger , Volker Albrecht
发明人： Wolfgang Neuberger , Volker Albrecht
IPC分类号： A61M37/00 , A61K9/127 , A61K31/409 , A61P29/00 , A61P19/02
CPC分类号： A61K9/1271 , A61K41/0071 , A61K47/6911
摘要： A PDT treatment system designed to treat all types of human inflammatory disorders. A suitable drug delivery system is developed to target proliferating cells, at inflamed sites, populated with macrophages and other inflammatory mediators. The hydrophobic photosensitizer is loaded into the liposomal bilayer formed of synthetic phospholipids; at least one of the synthetic phospholipids is conjugated to polyethylene glycol (PEG) molecules, to prevent accumulation in the liver and spleen. Further, (PEG) formulated photosensitizer increases the circulatory half-life of the drug, enhances solubility, and modifies pharmacokinetic and pharmacodynamic properties. The formulation, thus, leads to a higher amount of delivered drug to the diseased target synovial tissue, increasing clinical effectiveness. In one embodiment, pegylated liposomes loaded with mTHPC are administered to diseased synovial joints, followed by light irradiation. Activated photosensitizer induces cytotoxic effect in the diseased synovial cells, thus preventing further inflammation and joint erosion and minimizing joint damage.
摘要翻译：设计用于治疗所有类型的人类炎症性疾病的PDT治疗系统。开发合适的药物递送系统以靶向增殖细胞，在发炎部位，富含巨噬细胞和其他炎症介质。将疏水性光敏剂加载到由合成磷脂形成的脂质体双层中; 至少一种合成磷脂与聚乙二醇（PEG）分子缀合，以防止在肝脏和脾脏中积累。此外，（PEG）配制的光敏剂可增加药物的循环半衰期，增强溶解性，并改变药代动力学和药效学性质。因此，该制剂导致更高量的递送药物到患病的目标滑液组织，增加临床有效性。在一个实施方案中，将装载有mTHPC的聚乙二醇化脂质体施用于患病的滑膜关节，随后进行光照射。活化的光敏剂在患病的滑膜细胞中诱导细胞毒性作用，从而防止进一步的炎症和关节侵蚀并最小化关节损伤。

7. 发明申请

US20070154538A1 Removal of fat cells by PDT 审中-公开
标题翻译：通过PDT去除脂肪细胞
公开(公告)号：US20070154538A1
公开(公告)日：2007-07-05
申请号：US11321105
申请日：2005-12-29
申请人： Wolfgang Neuberger , Volker Albrecht
发明人： Wolfgang Neuberger , Volker Albrecht
IPC分类号： A61K31/409 , A61K31/555 , A61K9/127
CPC分类号： A61K9/0019 , A61K9/127 , A61K31/409 , A61K31/555
摘要： A non-surgical, minimally invasive PhotoDynamic Therapy (PDT) method for destruction of undesirable fat cells in the body, which cause obesity, obesity related health problems, and undesirable body contours. In this method photosensitizing agents are formulated into a liposomal formulation or into other delivery means for administering the drug systemically, directly by injection and/or topical application. The photosensitizing formulation is selectively targeted at adipose tissue in the subcutaneous layer. Photosensitized adipose cells are illuminated with a predetermined wavelength of light energy known to initiate a photo cytotoxic effect. The light energy for photoactivation of the photosensitizing agent may be applied interstitially through optical fibers with or without a diffuser tip. Alternatively, a photosensitizing agent is selected to have an activating wavelength which permits external irradiation through the skin. The method ensures safe and permanent fat reduction, minimizes trauma to the area of treatment and also hastens the healing process. A lasting and permanent effect is provided in regions of fat accumulation as the adipose cells are permanently destroyed. This approach is also effective for fat deposits which do not respond to other treatments.
摘要翻译：用于破坏身体中不需要的脂肪细胞的非手术，微创光动力治疗（PDT）方法，其导致肥胖，肥胖相关的健康问题和不期望的身体轮廓。在该方法中，将光敏剂配制成脂质体制剂或其它递送装置，以直接通过注射和/或局部施用全身施用药物。光敏制剂选择性地靶向皮下层中的脂肪组织。用已知的预定波长的光能照射光敏脂肪细胞以引发光细胞毒作用。用于光敏剂的光活化的光能可以通过具有或不具有扩散器尖端的光纤在空隙中施加。或者，选择光敏剂以具有允许通过皮肤的外部照射的激活波长。该方法可确保安全和永久的脂肪减少，减少对治疗领域的创伤，并加快愈合过程。由于脂肪细胞被永久破坏，脂肪堆积区域的持久和永久效应。这种方法对于不响应其他处理的脂肪沉积物也是有效的。

8. 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.

9. 发明授权

US08999933B2 Photodynamic cosmetic procedure and healing method 有权
标题翻译：光动力美容手术和治疗方法
公开(公告)号：US08999933B2
公开(公告)日：2015-04-07
申请号：US11650207
申请日：2007-01-05
申请人： Wolfgang Neuberger , Volker Albrecht , Danilo Castro
发明人： Wolfgang Neuberger , Volker Albrecht , Danilo Castro
IPC分类号： A61K9/127 , A61K8/65 , A61K8/49 , A61K31/407 , A61K31/555 , A61L27/24 , A61L27/54 , A61Q19/06 , A61Q19/08 , A61K41/00 , A61K38/00
CPC分类号： A61K8/65 , A61K8/4946 , A61K9/1271 , A61K31/407 , A61K31/555 , A61K41/0071 , A61K2800/434 , A61K2800/81 , A61L27/24 , A61L27/54 , A61L2300/414 , A61L2300/604 , A61Q19/06 , A61Q19/08
摘要： Innovative non-surgical methods and compositions are provided for administering PDT to promote tissue regeneration or augmentation while minimizing scarring and risk of infection. Among several areas of application, is the treatment of acute and chronic wounds which have afflicted epidermal and connective tissue layers of the body. Another application area is as cosmetic surgery/treatments, including: reducing wrinkles, sulcus, scars (acne or traumatic caused), sequelae cellulite, as well as for other skin irregularities, to give a smoother skin surface. This invention consists of a collagen based or other suitable biodegradable supporting matrix which is embedded with a liposomal loaded photosensitizer. In one embodiment of this invention a liposomal formulated photosensitizer is first injected at the site followed by collagen implantation and PDT treatment. In another embodiment a liposomal formulated photosensitizer is incorporated in the collagen. Generally 30 minutes after collagen is mixed with photosensitizer the light activation is done. The matrix may also carry important growth factors and cytokines, which promote fibroblast cell migration and proliferation, to the wound site. Microbial infection at the wound site can also be controlled by antibacterial PDT.
摘要翻译：提供创新的非手术方法和组合物用于施用PDT以促进组织再生或增强，同时最小化瘢痕形成和感染风险。在几个应用领域中，治疗急性和慢性伤害已经影响了身体的表皮和结缔组织层。另一个应用领域是整容手术/治疗，包括：减少皱纹，沟，疤痕（引起痤疮或创伤），后遗症，以及其他皮肤不规则，使皮肤表面光滑。本发明由胶原基或其它合适的可生物降解的支撑基质组成，其中嵌有脂质体加载的光敏剂。在本发明的一个实施方案中，首先在该部位注射脂质体配制的光敏剂，随后进行胶原植入和PDT处理。在另一个实施方案中，脂质体配制的光敏剂掺入胶原蛋白。一般30分钟后，胶原与光敏剂混合，光激活完成。基质还可以携带重要的生长因子和促进成纤维细胞迁移和增殖的细胞因子到伤口部位。伤口部位的微生物感染也可以通过抗菌PDT来控制。

10. 发明授权

US07354599B2 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：US07354599B2
公开(公告)日：2008-04-08
申请号：US11298729
申请日：2005-12-09
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
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。

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