公开(公告)号：US20070184114A1

公开(公告)日：2007-08-09

申请号：US11638091

申请日：2006-12-12

申请人： Gregor Cevc

发明人： Gregor Cevc

IPC分类号： A61K38/40 ,  A61K9/14 ,  A61K36/54 ,  A61K36/537 ,  A61K36/906 ,  A61K36/53

CPC分类号： A61K9/1272 ,  A61K31/16 ,  A61K31/573 ,  A61K31/58

摘要： A formulation comprising molecular arrangements capable of penetrating pores in a barrier, owing to penetrant adaptability, despite the fact that the average diameter of said pores is smaller than the average penetrant diameter, provided that the prenetrants can transport agents or else enable agent permeation through the pores after penetrants have entered pores, characterized in that the formulation comprises at least one consistency builder in an amount that increases the formulation to maximally 5 Nm/s so that spreading over, and retention at, the application area is enabled and/or at least one antioxidant in an amount that reduces the increase of oxidation index to less than 100% per 6 months and/or at least one microbiocide in an amount that reduces the bacterial count of 1 million germs added per g of total mass of the formulation to less than 100 in the case of aerobic bacteria, to less than 10 in the case of entero-bacteria, and to less than 1 in the case of Pseudomonas aeruginosa or Staphilococcus aureus, after a period of 4 days.

摘要翻译： 尽管事实上所述孔的平均直径小于平均渗透剂直径，但是由于渗透剂的适应性，包含能够渗透屏障中的孔的分子结构的制剂，条件是预浸料可以输送试剂，或者使试剂渗透通过 渗透剂之后的毛孔已经进入孔隙，其特征在于该制剂包含至少一种使制剂增加至最大5Nm 3 / s的量的稠度助洗剂，从而使施用区域的扩展和保持力达到和/或至少 一种抗氧化剂，其量使氧化指数增加至每6个月小于100％，和/或至少一种杀微生物剂，其量将每千克制剂总量的细菌计数减少到100万 在需氧细菌的情况下为100，在肠细菌的情况下小于10，在绿脓假单胞菌的情况下小于1 nosa或金黄色葡萄球菌，经过4天的时间。

公开(公告)号：US07473432B2

公开(公告)日：2009-01-06

申请号：US10357617

申请日：2003-02-04

申请人： Gregor Cevc ,  Ulrich Vierl

发明人： Gregor Cevc ,  Ulrich Vierl

IPC分类号： A61K9/127

CPC分类号： A61K9/127 ,  A61K9/1272 ,  A61K31/192 ,  A61K31/196 ,  A61K31/405 ,  A61K31/5415 ,  A61K47/10 ,  A61K47/12 ,  A61K47/16 ,  A61K47/20 ,  A61K47/26 ,  A61K47/34 ,  Y10S514/886

摘要： The invention describes novel formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) based on complex aggregates with at least three amphipatic components suspended in a suitable, e.g. pharmaceutically acceptable, polar liquid medium. A suitably ionised NSAID is one of the two, amongst said three, components that tends to destabilise lipid membranes, the other system component with such activity being typically a surfactant. In contrast, the remaining amongst said at least three amphipatic components typically forms a stable lipid membrane on it's own. An essential characteristics of the resulting, relatively large, aggregates is an improved ability to penetrate pores, in a semi-permeable barrier, at least 30%, and often much smaller than the average diameter of the complex aggregate. This enables said aggregates to mediate NSAID transport through semi-permeable barriers including mammalian skin. As a result of the skin penetration by NSAID loaded large aggregates, the drug delivered transcutaneously with such carriers gets deeper into the tissue than the corresponding NSAID from a solution on the skin surface. This is believed to be due to the special ability of suitable large carriers to bypass the local sink of blood capillaries at the epidermal-dermal junction in the skin. The carrier-mediated delivery of locally applied NSAIDs thus allows therapy of deep tissues under the drug administration site, which is medically highly desirable.

摘要翻译： 本发明描述了基于复合聚集体的非甾体抗炎药（NSAID）的新型制剂，其中至少三种两亲成分悬浮在合适的例如血浆中。 药学上可接受的极性液体培养基。 合适的电离的NSAID是趋向于使脂质膜不稳定的所述三种组分中的两种之一，具有这种活性的其它体系组分通常是表面活性剂。 相比之下，所述至少三种两亲成分中的剩余部分通常在其自身上形成稳定的脂质膜。 所得到的相对大的聚集体的基本特征是在半渗透性屏障中渗透孔的改进能力，至少30％，并且通常远小于复合物聚集体的平均直径。 这使得所述聚集体能够通过包括哺乳动物皮肤的半渗透屏障介导NSAID转运。 由于通过NSAID装载的大聚集体的皮肤渗透，与这种载体经皮递送的药物比来自皮肤表面上的溶液的相应NSAID更深入组织中。 这被认为是由于合适的大载体绕过皮肤上表皮 - 真皮连接处的毛细血管的局部水槽的特殊能力。 载体介导的局部施用的NSAID的递送因此允许治疗药物施用部位下的深层组织，其在医学上是非常需要的。

公开(公告)号：US20080095722A1

公开(公告)日：2008-04-24

申请号：US11667325

申请日：2005-11-09

申请人： Gregor Cevc ,  Matthias Rother

发明人： Gregor Cevc ,  Matthias Rother

IPC分类号： A61K8/18 ,  A61P17/00

CPC分类号： A61K9/127 ,  A61K8/14 ,  A61K8/365 ,  A61K9/0014 ,  A61K31/192 ,  A61K2800/75 ,  A61Q19/00 ,  A61Q19/02

摘要： The invention relates to the use of extended surface aggregates (ESAs) comprising at least one first amphipathic component, which is a basic aggregate-forming component, and at least one second amphipathic component, which decreases aggregate sensitivity to physical stress, including stress created by enforced passage of said ESAs through pores with an average pore diameter at least 50% smaller than the average diameter of the ESAs before said passage, such that the average ESA diameter change induced by such physical stress is reduced by 10% or more, compared to the diameter change induced by such stress in a reference system comprising just the first or just the second aggregate component, in the manufacture of a pharmaceutical preparation for enduring treatment of pathological mammalian skin conditions, including skin irritation, skin inflammation and/or skin damage after topical application, for modifying skin pigmentation and/or for treatment of skin itch.

摘要翻译： 本发明涉及使用包含至少一种作为碱性聚集体形成组分的第一两亲性组分的延长表面聚集体（ESAs）和至少一种第二两亲性组分，其降低对物理应力的聚集敏感性，包括由 所述ESAs通过孔，平均孔径比所述通道前的ESAs的平均直径小至少50％，使得由这种物理应力引起的平均ESA直径变化减少10％以上，与 在制备用于持续治疗病理性哺乳动物皮肤病症的药物制剂（包括皮肤刺激，皮肤炎症和/或皮肤损伤）后，在仅包含第一或仅第二聚集体组分的参考系统中由这种应力引起的直径变化 局部应用，用于改善皮肤色素沉着和/或治疗皮肤瘙痒。

公开(公告)号：US07175850B2

公开(公告)日：2007-02-13

申请号：US09887493

申请日：2001-06-22

申请人： Gregor Cevc

发明人： Gregor Cevc

IPC分类号： A61K8/02

CPC分类号： A61K9/1272 ,  A61K31/16 ,  A61K31/573 ,  A61K31/58

摘要： A formulation comprising molecular arrangements capable of penetrating pores in a barrier, owing to penetrant adaptability, despite the fact that the average diameter of said pores is smaller than the average penetrant diameter, provided that the penetrants can transport agents or else enable agent permeation through the pores after penetrants have entered pores, characterized in that the formulation comprises at least one consistency builder in an amount that increases the formulation to maximally 5 Nm/s so that spreading over, and retention at, the application area is enabled and/or at least one antioxidant in an amount that reduces the increase of oxidation index to less than 100% per 6 months and/or at least one microbicide in an amount that reduces the bacterial count of 1 million germs added per g of total mass of the formulation to less than 100 in the case of aerobic bacteria, to less than 10 in the case of entero-bacteria, and to less than 1 in the case of Pseudomonas aeruginosa or Staphilococcus aureus, after a period of 4 days.

摘要翻译： 尽管所述孔的平均直径小于平均渗透剂直径，但是由于渗透剂的适应性，尽管渗透剂可以输送试剂或使试剂渗透通过 渗透剂之后的毛孔已经进入孔隙，其特征在于该制剂包含至少一种使制剂增加至最大5Nm 3 / s的量的稠度助洗剂，从而使施用区域的扩展和保持力达到和/或至少 一种抗氧化剂，其量使氧化指数增加至每6个月小于100％，和/或至少一种杀微生物剂，其用量将每公斤制剂总量的细菌计数减少到100万 在有氧细菌的情况下，超过100，在肠细菌的情况下小于10，在绿脓假单胞菌的情况下小于1 sa或金黄色葡萄球菌，经过4天的时间。

公开(公告)号：US20090060990A1

公开(公告)日：2009-03-05

申请号：US12250980

申请日：2008-10-14

申请人： Gregor Cevc ,  Ulrich Vierl

发明人： Gregor Cevc ,  Ulrich Vierl

IPC分类号： A61K9/127 ,  A61P29/00

CPC分类号： A61K9/127 ,  A61K9/1272 ,  A61K31/192 ,  A61K31/196 ,  A61K31/405 ,  A61K31/5415 ,  A61K47/10 ,  A61K47/12 ,  A61K47/16 ,  A61K47/20 ,  A61K47/26 ,  A61K47/34 ,  Y10S514/886

摘要： The invention describes novel formulations of nonsteroidal anti-inflammatory drugs (NSAIDS) based on complex aggregates with at least three amphipatic components suspended in a suitable, e.g. pharmaceutically acceptable, polar liquid medium. A suitably ionised NSAID is one of the two, amongst said three, components that tends to destabilise lipid membranes, the other system component with such activity being typically a surfactant. In contrast, the remaining amongst said at least three amphipatic components typically forms a stable lipid membrane on it's own. An essential characteristics of the resulting, relatively large, aggregates is an improved ability to penetrate pores, in a semi-permeable barrier, at least 30%, and often much smaller than the average diameter of the complex aggregate. This enables said aggregates to mediate NSAID transport through semi-permeable barriers including mammalian skin. As a result of the skin penetration by NSAID loaded large aggregates, the drug delivered transcutaneously with such carriers gets deeper into the tissue than the corresponding NSAID from a solution on the skin surface. This is believed to be due to the special ability of suitable large carriers to bypass the local sink of blood capillaries at the epidermal-dermal junction in the skin. The carrier-mediated delivery of locally applied NSAIDs thus allows therapy of deep tissues under the drug administration site, which is medically highly desirable.

公开(公告)号：US20090042989A1

公开(公告)日：2009-02-12

申请号：US12250823

申请日：2008-10-14

申请人： Gregor Cevc ,  Ulrich Vierl

发明人： Gregor Cevc ,  Ulrich Vierl

IPC分类号： A61K31/196 ,  A61K31/192

CPC分类号： A61K9/127 ,  A61K9/1272 ,  A61K31/192 ,  A61K31/196 ,  A61K31/405 ,  A61K31/5415 ,  A61K47/10 ,  A61K47/12 ,  A61K47/16 ,  A61K47/20 ,  A61K47/26 ,  A61K47/34 ,  Y10S514/886

摘要： The invention describes novel formulations of nonsteroidal anti-inflammatory drugs (NSAIDS) based on complex aggregates with at least three amphipatic components suspended in a suitable, e.g. pharmaceutically acceptable, polar liquid medium. A suitably ionised NSAID is one of the two, amongst said three, components that tends to destabilise lipid membranes, the other system component with such activity being typically a surfactant. In contrast, the remaining amongst said at least three amphipatic components typically forms a stable lipid membrane on it's own. An essential characteristics of the resulting, relatively large, aggregates is an improved ability to penetrate pores, in a semi-permeable barrier, at least 30%, and often much smaller than the average diameter of the complex aggregate. This enables said aggregates to mediate NSAID transport through semi-permeable barriers including mammalian skin. As a result of the skin penetration by NSAID loaded large aggregates, the drug delivered transcutaneously with such carriers gets deeper into the tissue than the corresponding NSAID from a solution on the skin surface. This is believed to be due to the special ability of suitable large carriers to bypass the local sink of blood capillaries at the epidermal-dermal junction in the skin. The carrier-mediated delivery of locally applied NSAIDs thus allows therapy of deep tissues under the drug administration site, which is medically highly desirable.

摘要翻译： 本发明描述了基于复合聚集体的非甾体抗炎药（NSAIDS）的新制剂，其中至少有三个两亲成分悬浮在合适的例如， 药学上可接受的极性液体培养基。 合适的电离的NSAID是趋向于使脂质膜不稳定的所述三种组分中的两种之一，具有这种活性的其它体系组分通常是表面活性剂。 相比之下，所述至少三种两亲成分中的剩余部分通常在其自身上形成稳定的脂质膜。 所得到的相对大的聚集体的基本特征是在半渗透性屏障中渗透孔的改进能力，至少30％，并且通常远小于复合物聚集体的平均直径。 这使得所述聚集体能够通过包括哺乳动物皮肤的半渗透屏障介导NSAID转运。 由于通过NSAID装载的大聚集体的皮肤渗透，与这种载体经皮递送的药物比来自皮肤表面上的溶液的相应NSAID更深入组织中。 这被认为是由于合适的大载体绕过皮肤上表皮 - 真皮连接处的毛细血管的局部水槽的特殊能力。 载体介导的局部施用的NSAID的递送因此允许治疗药物施用部位下的深层组织，其在医学上是非常需要的。

公开(公告)号：US20080311184A1

公开(公告)日：2008-12-18

申请号：US11929544

申请日：2007-10-30

申请人： Gregor Cevc

发明人： Gregor Cevc

IPC分类号： A61K9/127 ,  A61K38/00 ,  A61K45/00 ,  A61K38/21 ,  A61K39/395 ,  A61K31/7088 ,  A61K31/70 ,  A61K38/43 ,  A61P43/00

CPC分类号： A61K9/127 ,  A61K9/1271 ,  A61K9/1272

摘要： This invention describes the principles and procedures suitable for developing, testing, manufacturing, and using combinations of various amphipatic, if necessary modified, macromolecules (such as polypeptides, proteins, etc.) or other chain molecules (such as suitable, e.g. partly hydrophobised, polynucleotides or polysaccharides) with the aggregates which comprise a mixture of polar and/or charged amphipats and form extended surfaces that can be freely suspended or supported. The described methods can be utilised for the optimisation of aggregates that, after association with chain molecules exerting some activity or a useful function, are suitable for the application in vitro or in vivo, for example, in the fields of drug delivery, diagnostics or bio/catalysis. As special examples, mixtures of vesicular droplets consisting of lipids loaded (associated) with insulin, interferon, interleukin, nerve growth factor, calcitonin, and an immunoglobulin, etc., are described.

摘要翻译： 本发明描述了适用于开发，测试，制造和使用各种两性的，如果需要的修饰的大分子（例如多肽，蛋白质等）或其它链分子（例如合适的，例如部分疏水化的， 多核苷酸或多糖），其聚集体包含极性和/或带电两亲的混合物并形成可以自由悬浮或支持的延伸表面。 所描述的方法可以用于聚合物的优化，所述聚集体在与施加某种活性或有用功能的链分子缔合之后适用于体外或体内的应用，例如在药物递送，诊断或生物学领域 /催化。 作为特例，描述了由与胰岛素，干扰素，白细胞介素，神经生长因子，降钙素和免疫球蛋白等负载（相关联）的脂质组成的囊泡液的混合物。

公开(公告)号：US20080279815A1

公开(公告)日：2008-11-13

申请号：US11929480

申请日：2007-10-30

申请人： Gregor Cevc

发明人： Gregor Cevc

IPC分类号： A61K38/21 ,  A61K31/715 ,  A61K38/20 ,  A61K39/395 ,  A61K38/28

CPC分类号： A61K9/127 ,  A61K9/1271 ,  A61K9/1272

摘要： This invention describes the principles and procedures suitable for developing, testing, manufacturing, and using combinations of various amphipatic, if necessary modified, macromolecules (such as polypeptides, proteins, etc.) or other chain molecules (such as suitable, e.g. partly hydrophobised, polynucleotides or polysaccharides) with the aggregates which comprise a mixture of polar and/or charged amphipats and form extended surfaces that can be freely suspended or supported. The described methods can be utilised for the optimisation of aggregates that, after association with chain molecules exerting some activity or a useful function, are suitable for the application in vitro or in vivo, for example, in the fields of drug delivery, diagnostics or bio/catalysis. As special examples, mixtures of vesicular droplets consisting of lipids loaded (associated) with insulin, interferon, interleukin, nerve growth factor, calcitonin, and an immunoglobulin, etc., are described.

摘要翻译： 本发明描述了适用于开发，测试，制造和使用各种两性的，如果需要的修饰的大分子（例如多肽，蛋白质等）或其它链分子（例如合适的，例如部分疏水化的， 多核苷酸或多糖），其聚集体包含极性和/或带电两亲的混合物并形成可以自由悬浮或支持的延伸表面。 所描述的方法可以用于聚合物的优化，所述聚集体在与施加某种活性或有用功能的链分子缔合之后适用于体外或体内的应用，例如在药物递送，诊断或生物学领域 /催化。 作为特例，描述了由与胰岛素，干扰素，白细胞介素，神经生长因子，降钙素和免疫球蛋白等负载（相关联）的脂质组成的囊泡液的混合物。

公开(公告)号：US20070042030A1

公开(公告)日：2007-02-22

申请号：US11481804

申请日：2006-07-05

申请人： Gregor Cevc

发明人： Gregor Cevc

IPC分类号： A61K9/127

CPC分类号： A61K9/127 ,  A61K9/0019 ,  A61K9/1272

摘要： The invention relates to a preparation for the application of agents in the form of minuscule droplets of fluid, in particular provided with membrane-like structures consisting of one or several layers of amphiphilic molecules, or an amphiphilic carrier substance, in particular for transporting the agent into and through natural barriers such as skin and similar materials. The preparation contains a concentration of edge active substances which amounts to up to 99 mol-% of the agent concentration which is required for the induction of droplet solubilization. Such preparations are suitable, for example, for the non-invasive applications of antidiabetics, in particular of insulin. The invention, moreover, relates to the methods for the preparation of such formulations.

摘要翻译： 本发明涉及一种用于以微小液滴形式施用试剂的制剂，特别是提供了由一层或多层两亲分子组成的膜状结构或两亲性载体物质，特别是用于运送该试剂 进入和穿过天然屏障，如皮肤和类似材料。 该制剂含有浓度高达诱导液滴溶解所需的试剂浓度的99mol％的边缘活性物质的浓度。 这样的制剂例如适用于抗糖尿病药物，特别是胰岛素的非侵入性应用。 此外，本发明涉及制备这些制剂的方法。

公开(公告)号：US6165500A

公开(公告)日：2000-12-26

申请号：US844664

申请日：1992-04-08

申请人： Gregor Cevc

发明人： Gregor Cevc

IPC分类号： A61K9/127

CPC分类号： A61K9/127 ,  A61K9/1272 ,  Y10T428/2984

摘要： The invention relates to a preparation for the application of agents in the form of minuscule droplets of fluid, in particular provided with membrane-like structures consisting of one or several layers of amphiphilic molecules, or an amphiphilic carrier substance, in particular for transporting the agent into and through natural barriers such as skin and similar materials. The preparation contains a concentration of edge active substances which amounts to up to 99 mol-% of the agent concentration which is required for the induction of droplet solubilization. Such preparations are suitable, for example, for the non-invasive applications of antidiabetics, in particular of insulin. The invention, moreover, relates to the methods for the preparation of such formulations.

摘要翻译： 本发明涉及一种用于以微小液滴形式施用试剂的制剂，特别是提供了由一个或几个两层的两亲分子组成的膜状结构或两亲性载体物质，特别是用于运输该试剂 进入和穿过天然屏障，如皮肤和类似材料。 该制剂含有浓度高达诱导液滴溶解所需的试剂浓度的99mol％的边缘活性物质的浓度。 这样的制剂例如适用于抗糖尿病药物，特别是胰岛素的非侵入性应用。 此外，本发明涉及制备这些制剂的方法。