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1. 发明申请

US20140155486A1 Administration of Iloprost as Aerosol Bolus 审中-公开
标题翻译：伊洛前列素作为气溶胶丸的施用
公开(公告)号：US20140155486A1
公开(公告)日：2014-06-05
申请号：US14061525
申请日：2012-04-26
申请人： Tobias Gessler , Thomas Schmehl , Werner Seeger , Robert Voswinckel
发明人： Tobias Gessler , Thomas Schmehl , Werner Seeger , Robert Voswinckel
IPC分类号： A61K31/191 , A61K9/00
CPC分类号： A61K31/5578 , A61K9/0078 , A61K9/08 , A61K31/191 , A61M11/005 , A61M11/06 , A61M15/0021 , A61M15/0085 , A61M15/009 , A61M2016/0024 , A61M2205/50
摘要： The present invention relates to novel methods, compositions and kits useful for the treatment of pulmonary diseases such as pulmonary arterial hypertension. In particular, aerosolisable compositions of iloprost are provided which are for use in inhalation therapy. Their administration is by bolus inhalation, which is patient-friendly, effective, and well tolerated. Bolus inhalation may, for example, be achieved using an efficient nebuliser based on the vibrating mesh technology.
摘要翻译：本发明涉及可用于治疗肺部疾病如肺动脉高压的新方法，组合物和试剂盒。特别地，提供伊洛前列素的气溶胶组合物，其用于吸入治疗。他们的管理是通过快速吸入，其是耐心友好的，有效的和良好耐受的。可以使用基于振动筛网技术的有效雾化器来实现刺激吸入。

2. 发明申请

US20120148493A1 Composite Materials Loaded with Therapeutic and Diagnostic Agents Comprising Polymer Nanoparticles and Polymer Fibers 审中-公开
标题翻译：由聚合物纳米颗粒和聚合物纤维组成的包含治疗和诊断剂的复合材料
公开(公告)号：US20120148493A1
公开(公告)日：2012-06-14
申请号：US13256872
申请日：2010-03-16
申请人： Thomas Schmehl , Juliane Nguyen , Moritz Beck-Broichsitter , Tobias Gessler , Thomas Kissel , Marcel Thieme
发明人： Thomas Schmehl , Juliane Nguyen , Moritz Beck-Broichsitter , Tobias Gessler , Thomas Kissel , Marcel Thieme
IPC分类号： A61K9/70 , A61P9/00 , A61P11/00 , A61P11/06 , A61P35/00 , A61P17/00 , A61P17/02 , D01D5/00 , A61K49/00 , A61P3/00 , B82Y5/00
CPC分类号： A61K9/5153 , A61K9/70
摘要： The invention relates to composite materials comprising polymer nanofibers and polymer nanoparticles, wherein at least one of the two polymer materials is loaded with a substance selected from therapeutic and diagnostic agents. Fibers and nanoparticles can comprise identical or different polymers; the polymer materials are, however, biocompatible in every case. Therapeutic and diagnostic agents can be hydrophilic or lipophilic and the two polymer materials likewise. The at least one polymer material and the substance with which said material is loaded are either both hydrophilic or both lipophilic. The polymer nanoparticles of the composite materials have a diameter of 10 nm to 600 nm. The polymer fibers have diameters of 10 nm to 50 μm and lengths of 1 μm to several meters. The invention further relates to a method for producing said composite materials. Polymer nanoparticles can be produced in different ways, such as through controlled precipitation of a polymer solution that optionally comprises a loading substance. The nanoparticles are then mixed with another polymer and a loading substance as applicable, depending on whether particles, fibers or both are to be loaded with substance. The processing of this solution into composites comprising polymer fibers polymer nanoparticles can occur by means of electrospinning, melt spinning, extruding or template process. Composite materials according to the invention are suitable for the production of pharmaceuticals that release therapeutically or diagnostically effective substances slowly and in a controlled manner.
摘要翻译：本发明涉及包含聚合物纳米纤维和聚合物纳米颗粒的复合材料，其中两种聚合物材料中的至少一种负载有选自治疗剂和诊断剂的物质。纤维和纳米颗粒可以包含相同或不同的聚合物; 然而，聚合物材料在每种情况下都是生物相容的。治疗和诊断剂可以是亲水的或亲脂的，并且两种聚合物材料同样。所述至少一种聚合物材料和所述材料被加载的物质既是亲水的，也是亲油的。复合材料的聚合物纳米颗粒具有10nm至600nm的直径。聚合物纤维的直径为10nm〜50μm，长度为1〜数米。本发明还涉及一种生产所述复合材料的方法。聚合物纳米颗粒可以以不同的方式制备，例如通过可选地包含负载物质的聚合物溶液的可控沉淀。然后将纳米颗粒与另一种聚合物和负载物质混合，这取决于颗粒，纤维或两者是否被装载物质。将该溶液加工成包含聚合物纤维聚合物纳米颗粒的复合材料可以通过静电纺丝，熔融纺丝，挤出或模板方法进行。根据本发明的复合材料适用于缓慢地并以受控方式释放治疗或诊断有效物质的药物。

3. 发明申请

US20080299208A1 Anisometric Particles In The Form Of Nanofibers/Mesofibers,Nanopipes, Nanocables/Mesocables, Nanobands/Mesobands, And The Curved Or Branched Variations Thereof 审中-公开
标题翻译：纳米纤维/中间纤维，纳米管，纳米管/中间体，纳米棒/中间体及其弯曲或分支变异形式的非对称粒子
公开(公告)号：US20080299208A1
公开(公告)日：2008-12-04
申请号：US11666653
申请日：2005-10-22
申请人： Joachim H. Wendorff , Angreas Greiner , Thomas Schmehl , Tobias Gessler
发明人： Joachim H. Wendorff , Angreas Greiner , Thomas Schmehl , Tobias Gessler
IPC分类号： A61K9/14 , B06B1/02 , A61P11/00 , B29C35/08
CPC分类号： D01D5/00 , A61K9/0073 , A61K9/70 , B82Y5/00 , B82Y30/00 , D01D5/26 , D01D10/00
摘要： The invention relates to novel anisometric mesoparticles and nanoparticles in the form of anisometric mesofibers/nanofibers, mesopipes/nanopipes, mesobands/nanobands, mesocables/nanocables, and the curved and branched or superimposed variations thereof as well as a novel method for the production thereof. The invention particularly relates to anisometric mesoparticles and nanoparticles which have an aerodynamic diameter
摘要翻译：本发明涉及新型的各向异性中粒子和各向异性介质/纳米纤维，介孔/纳米管，中间体/纳米棒，介质/纳米线及其弯曲和分支或叠加变化形式的纳米粒子，以及其生产方法。本发明特别涉及空气动力学直径小于5um的不等规中微粒和纳米颗粒，其生产方法，如果不能直接用作活性物质，则加载活性物质，特别是其用于生产抗肺疾病的药物或者如果颗粒不能直接用作没有载体的药物，则在人和动物中的全身性疾病。

4. 发明申请

US20130149535A1 BIODEGRADABLE NANO-, MESO-, AND MICRO-POLYMER PARTICLES FOR MAINTAINING A LOW SURFACE TENSION IN THE LUNG AND FOR PROTECTING THE PULMONARY SURFACTANT 审中-公开
标题翻译：用于维持肺中低表面张力和保护肺部表面活性剂的生物可降解的纳米，MESO和微聚合物颗粒
公开(公告)号：US20130149535A1
公开(公告)日：2013-06-13
申请号：US13809626
申请日：2011-07-18
申请人： Moritz Beck-Broichsitter , Thomas Schmehl , Tobias Gessler
发明人： Moritz Beck-Broichsitter , Thomas Schmehl , Tobias Gessler
IPC分类号： C08F220/34
CPC分类号： C08F220/34 , A61K9/007 , A61K9/0073 , A61K9/1635 , A61K9/5138 , A61K31/78 , A61K31/785 , C08L33/14 , Y10T428/2982
摘要： The present invention provides nano-, meso- and micro-polymer particles which are able to bind pathogenic proteins penetrating into the lining layer of the lung. Known pathogenic proteins in the pulmonary lining layer are negatively charged. These proteins damage the pulmonary surfactant system which is essential to maintain a low surface tension in the lung and thus a functional respiration. Polymer particles of this invention have a diameter between 20 nm and 10 μm, are water-insoluble, have a positive surface charge and a low surface hydrophobicity. The isoelectric point of said particles is greater than 5 to that said particles are present in the lining layer of the lung as positively charged particles, and at the same time higher than the isoelectric point of the pathogenic protein to be bound. Polymer particles of this invention can for example be prepared using the precipitation or emulsion method. Polymer particles of this invention can be utilized for maintaining a low surface tension in the lung and for protecting the pulmonary surfactant.
摘要翻译：本发明提供能够结合穿透到肺内衬层的病原性蛋白质的纳米，中等和微聚合物颗粒。肺内衬层中已知的病原性蛋白质带负电荷。这些蛋白质损害肺表面活性剂体系，这对于保持肺中的低表面张力以及功能性呼吸是至关重要的。本发明的聚合物颗粒的直径在20nm和10μm之间，是不溶于水的，具有正的表面电荷和低的表面疏水性。所述颗粒的等电点大于5，所述颗粒作为带正电荷的颗粒存在于肺内衬层中，并且同时高于待结合的致病性蛋白质的等电点。本发明的聚合物颗粒可以例如使用沉淀或乳液法制备。本发明的聚合物颗粒可用于在肺中保持低表面张力并保护肺表面活性剂。

5. 发明申请

US20130039847A1 LIPOSOMES FOR PULMONARY ADMINISTRATION 审中-公开
标题翻译：用于脉冲管理的药物
公开(公告)号：US20130039847A1
公开(公告)日：2013-02-14
申请号：US13386006
申请日：2010-06-29
申请人： Tobias Gessler , Thomas Schmehl , Monika Rieger
发明人： Tobias Gessler , Thomas Schmehl , Monika Rieger
IPC分类号： A61K9/127 , A61K49/00 , A61K31/519 , A61K31/192 , A61P9/12 , A61K31/19 , A61K51/04 , A61P11/00
CPC分类号： A61K9/127 , A61K9/0078
摘要： The invention relates to liposomes for pulmonary application, advantageously comprising at least one first and at least one second phospholipid, cholesterol, and at least one active substance and/or colorant, wherein the first phospholipid is a phosphatidylcholine, preferably DSPC, and the second phospholipid is a phosphatidylcholine or an ethanolamine, preferably selected from the group DMPC, DPPC, DPPE. It is thereby advantageous if the first and the second phospholipid are present at a molar ratio of 0.5:1 to 10:1, preferably at a ratio of 6:1 to 2:1, in particular preferably at a ratio of 3:1. It is further advantageous if the molar ratio between phospholipids and cholesterol is between 10:1 and 1:1, preferably between 6:1 and 3:1, in particular preferably 4:1. The second phospholipid is further preferably DMPC or DPPE, in particular preferably DPPE. The size of the liposomes is advantageously between 0.05 μm and 5 μm, preferably between 0.2 μm and 2.0 μm, and the median aerodynamic mass diameter of aerosol particles comprising the liposomes is between 1 μm and 6 μm, preferably between 1.5 μm and 5 μm, in particular preferably between 2 μm and 4.5 μm. It is further in particular advantageous if the liposomes comprise an atomization stability of greater than 50%, preferably greater than 75%, in particular preferably greater than 80%, and if the transition temperature is greater than 37° C., preferably greater than 45° C., in particular preferably greater than 50° C.
摘要翻译：本发明涉及用于肺部施用的脂质体，有利地包含至少一种第一和至少一种第二磷脂，胆固醇和至少一种活性物质和/或着色剂，其中第一种磷脂是磷脂酰胆碱，优选DSPC，第二种磷脂是磷脂酰胆碱或乙醇胺，优选选自DMPC，DPPC，DPPE。因此，如果第一和第二磷脂以0.5:1至10:1的摩尔比，优选以6:1至2:1的比例，特别优选以3:1的比例存在，则是有利的。如果磷脂和胆固醇之间的摩尔比在10:1和1:1之间，优选在6:1和3:1之间，特别优选的是4:1，这是进一步有利的。第二磷脂进一步优选为DMPC或DPPE，特别优选DPPE。脂质体的大小有利地在0.05μm和5μm之间，优选在0.2μm和2.0μm之间，并且包含脂质体的气溶胶颗粒的中值空气动力学质量直径在1μm至6μm之间，优选在1.5μm和5μm之间，特别优选为2μm〜4.5μm。进一步特别有利的是，如果脂质体包含大于50％，优选大于75％，特别优选大于80％的雾化稳定性，并且如果转变温度大于37℃，优选大于45℃ ℃，特别优选大于50℃

6. 发明申请

US20090298917A1 Non-Viral Vector System For The Delivery Of Nucleic Acid Into The Lung 审中-公开
标题翻译：非病毒载体系统将核酸递送到肺部
公开(公告)号：US20090298917A1
公开(公告)日：2009-12-03
申请号：US11920500
申请日：2006-05-20
申请人： Thomas Kissel , Elke Kleemann , Michael Neu , Tobias Gessler , Thomas Schmehl
发明人： Thomas Kissel , Elke Kleemann , Michael Neu , Tobias Gessler , Thomas Schmehl
IPC分类号： A61K31/7088 , C12N15/63 , A61P11/00 , A61P35/00
CPC分类号： C08G81/00
摘要： The present invention related to a non-viral vector system for the delivery of nucleic acids which is modified on the basis of polyethylene imine (PEI) with polyethylene glycol (PEG) and which contains a peptide sequence with PTD/CPP-functionality.This vector system is used as gene transfer system for the epithelial cells of the bronchial tubes and alveoli of the lung. The system is highly stable, protects the DNA in the pulmonary environment, has a low zeta-potential and a low aggregation tendency in a medium with a high ionic strength. Furthermore, it is characterized by a low in vitro and in vivo cytotoxicity and allows for a very high transfection efficiency. The vector system according to the present invention is used for a transfection by inhalation in local pulmonary therapy.
摘要翻译：本发明涉及用于递送基于聚乙烯亚胺（PEI）与聚乙二醇（PEG）并且含有具有PTD / CPP-功能的肽序列的核酸的非病毒载体系统。该载体系统用作支气管和肺泡的上皮细胞的基因转移系统。该系统高度稳定，保护了肺部环境中的DNA，在高离子强度的培养基中具有低ζ电位和低聚集倾向。此外，其特征在于体外和体内细胞毒性低，并且可以获得非常高的转染效率。根据本发明的载体系统用于通过吸入在局部肺部治疗中的转染。

7. 发明申请

US20060002992A1 Atomizable liposomes and their use for the pulmonary administration of active substances 有权
标题翻译：可雾化脂质体及其用于肺部给予活性物质的用途
公开(公告)号：US20060002992A1
公开(公告)日：2006-01-05
申请号：US10510040
申请日：2003-04-04
申请人： Thomas Schmehl , Tobias Gessler , Esther Waschkowitz
发明人： Thomas Schmehl , Tobias Gessler , Esther Waschkowitz
IPC分类号： A61K9/127
CPC分类号： A61K9/0078 , A61K9/1271
摘要： The present invention discloses a method to prepare specific liposomal formulations for the pulmonary application of therapeutic substances. The liposomal components, DPPC and cholesterol at a molar ratio of 7:3 and 7:4, respectively, are combined with the non-toxic excipients, sphingomyelin, dimyristoylphophatidylcholine and/or polyethylene glycol, to prepare liposomes that are stabile during nebulization with commercially available nebulizers and exhibit sustained release kinetics of encapsulated drug substances.
摘要翻译：本发明公开了一种制备用于肺部施用治疗物质的特定脂质体制剂的方法。将脂质体成分，DPPC和胆固醇分别以7：3和7：4的摩尔比与无毒赋形剂，鞘磷脂，二肉豆蔻酰磷酰胆碱和/或聚乙二醇组合，以制备在商业雾化期间稳定的脂质体可用的喷雾器并显示包封的药物物质的持续释放动力学。

8. 发明申请

US20060127485A1 Bio-degradable colloid particles, in particular for pulmonary applications 审中-公开
标题翻译：生物降解胶体颗粒，特别是肺部应用
公开(公告)号：US20060127485A1
公开(公告)日：2006-06-15
申请号：US10534885
申请日：2003-11-14
申请人： Werner Seeger , Thomas Schmehl , Tobias Gessler , Lea Dailey , Matthias Wittmar
发明人： Werner Seeger , Thomas Schmehl , Tobias Gessler , Lea Dailey , Matthias Wittmar
IPC分类号： A61K9/14 , A61K31/557
CPC分类号： A61K9/5138 , A61K9/0078 , A61K9/5153 , A61K9/5161 , A61K47/34 , C08F8/44 , C08F283/06 , C08L51/08 , C08L2666/02
摘要： The invention concerns a compound formed from a biologically degradable, water-soluble comb polymer based on a polyol backbone with side chains carrying amino groups, and, as a stabilizer, at least one negatively charged organic base, which can be a Lewis or Bronsted base, or its corresponding acid, which can be a Lewis or Bronsted acid, wherein the acid groups of the stabilizers are available in excess or deficiency in relation to the primary, secondary or tertiary amino groups or the basic groups are available in excess or deficiency in relation to the quaternary amino groups of the comb polymers, so that the colloidal particles feature a positive or negative zeta potential. Such colloidal particles are particularly suitable for pulmonary application of acidic or negatively charged pharmaceutically active ingredients.
摘要翻译：本发明涉及一种由基于具有携带氨基的侧链的多元醇主链的生物降解性水溶性梳形聚合物形成的化合物，以及作为稳定剂的至少一种带负电荷的有机碱，其可以是Lewis或Bronsted碱，或其相应的酸，其可以是路易斯或布朗斯台德酸，其中稳定剂的酸基可以相对于伯，仲或叔氨基或碱基获得过量或缺乏可用于过量或不足与梳状聚合物的季氨基的关系，使得胶体颗粒具有正或负ζ电位。这种胶体颗粒特别适用于肺部施用酸性或带负电荷的药物活性成分。

9. 发明授权

US06779521B1 Combination mouthpiece for inhalation therapy devices used by oxygen dependent patients 失效
标题翻译：用于氧依赖患者的吸入治疗装置的组合口
公开(公告)号：US06779521B1
公开(公告)日：2004-08-24
申请号：US10088156
申请日：2002-07-23
申请人： Thomas Schmehl , Tobias Gessler , Werner Seeger
发明人： Thomas Schmehl , Tobias Gessler , Werner Seeger
IPC分类号： A61M1500
CPC分类号： A61M11/06 , A61M11/002 , A61M15/00 , A61M15/0021 , A61M15/009 , A61M16/0493 , A61M16/12 , A61M16/125 , A61M16/14 , A61M2202/0208
摘要： A combination mouthpiece for inhalation therapy devices, having a body (1) defining an aerosol duct (2) through which, in use, a stream of air carrying an aerosolized drug is supplied to a patient during inspiration, an inlet hole (4) through the body for receiving in a releasable and secure manner an oxygen tube adapter (5), characterised by at least one partition (6) within the body (1) defining at least one oxygen duct (3), the oxygen duct being in a form such that it extends generally parallel with the aerosol duct (2) and has a flow cross-section sized in order to guide a suitably large oxygen stream from the oxygen tube adapter (5) through the inlet hole (4) to the patient.
摘要翻译：一种用于吸入治疗装置的组合喉舌，具有限定气溶胶通道（2）的主体（1），在使用中，携带雾化药物的空气流在吸气期间被提供给患者，入口孔（4）穿过所述主体以可释放和安全的方式接收氧管适配器（5），其特征在于，所述主体（1）内的至少一个分隔件（6）限定至少一个氧气管道（3），所述氧气管道为使得其大致平行于气溶胶管道（2）延伸，并且具有流动横截面尺寸，以便将适当大的氧气流从氧气管接头（5）引导通过入口孔（4）到患者。

10. 发明授权

US10258570B2 Liposomes for pulmonary administration 有权
公开(公告)号：US10258570B2
公开(公告)日：2019-04-16
申请号：US13386006
申请日：2010-06-29
申请人： Tobias Gessler , Thomas Schmehl , Monika Rieger
发明人： Tobias Gessler , Thomas Schmehl , Monika Rieger
IPC分类号： A61K9/127 , A61K9/00
摘要： The invention relates to liposomes for pulmonary application, advantageously comprising at least one first and at least one second phospholipid, cholesterol, and at least one active substance and/or colorant, wherein the first phospholipid is a phosphatidylcholine, preferably DSPC, and the second phospholipid is a phosphatidylcholine or an ethanolamine, preferably selected from the group DMPC, DPPC, DPPE. It is thereby advantageous if the first and the second phospholipid are present at a molar ratio of 0.5:1 to 10:1, preferably at a ratio of 6:1 to 2:1, in particular preferably at a ratio of 3:1. It is further advantageous if the molar ratio between phospholipids and cholesterol is between 10:1 and 1:1, preferably between 6:1 and 3:1, in particular preferably 4:1. The second phospholipid is further preferably DMPC or DPPE, in particular preferably DPPE. The size of the liposomes is advantageously between 0.05 μm and 5 μm, preferably between 0.2 μm and 2.0 μm, and the median aerodynamic mass diameter of aerosol particles comprising the liposomes is between 1 μm and 6 μm, preferably between 1.5 μm and 5 μm, in particular preferably between 2 μm and 4.5 μm. It is further in particular advantageous if the liposomes comprise an atomization stability of greater than 50%, preferably greater than 75%, in particular preferably greater than 80%, and if the transition temperature is greater than 37° C., preferably greater than 45° C., in particular preferably greater than 50° C.

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