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：US20120177698A1

公开(公告)日：2012-07-12

申请号：US13315236

申请日：2011-12-08

申请人： Gregor Cevc ,  Ulrich Vierl

发明人： Gregor Cevc ,  Ulrich Vierl

IPC分类号： A61K9/00

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 combinations of at least three amphipatic substances forming aggregate suspensions in a polar liquid. Judicious choice of system components ensures said aggregates to have extended, unusually adaptable surfaces. This is probably due to simultaneous action on said aggregates of at least two more soluble substances amongst said three system components, at least one of which is an active ingredient and preferably a drug; the third component alternatively, can take the role of a drug. The disclosure further deals with the use of said combinations in pharmaceutical preparations capable of transporting drugs into the body of warm blood creatures. This is made possible by the drug loading capability of said aggregates with the highly flexible and deformable coating, which renders the resulting drug carriers highly adaptable. The disclosure also provides methods and favourable conditions for carrier manufacturing and application.

摘要翻译： 本发明描述了在极性液体中形成聚集体悬浮液的至少三种两亲物质的组合。 系统组件的可靠选择可确保所述聚合体具有扩展的，异常适应性的表面。 这可能是由于所述三种体系组分中至少两种可溶性物质对所述聚集体的同时作用，其中至少一种是活性成分，优选药物; 替代的第三个组分可以起到药物的作用。 本公开进一步涉及在能够将药物输送到温血生物体内的药物制剂中使用所述组合。 这可以通过所述聚集体与高度柔性和可变形的涂层的药物加载能力而实现，这使得所得到的药物载体高度适应。 本公开还提供了载体制造和应用的方法和有利条件。

公开(公告)号：US07867480B1

公开(公告)日：2011-01-11

申请号：US09890335

申请日：2000-01-26

申请人： Gregor Cevc ,  Amla Chopra

发明人： Gregor Cevc ,  Amla Chopra

IPC分类号： A61K9/113

CPC分类号： A61K38/19 ,  A61K9/1272 ,  A61K39/39 ,  A61K2039/55522 ,  Y02A50/407

摘要： The present invention relates to novel vaccines for the non-invasive, transcutaneous administration of antigens associated with ultradeformable carriers, for the purpose of prophylactic or therapeutic vaccination. The vaccines comprise (a) a transdermal carrier which is a penetrant, (b) a compound which specifically releases or specifically induces cytokine or anticytokine activity or exerts such an activity itself, (c) an antigen, an allergen, a mixture of antigens andlor a mixture of allergens, and (d) a chemical irritant. The invention further relates to methods for the vaccination of mammals for obtaining a protective or therapeutic immune response.

摘要翻译： 本发明涉及用于非侵入性，经皮给予与超可形成载体相关的抗原的新型疫苗，用于预防性或治疗性疫苗接种。 疫苗包含（a）透皮载体，其为渗透剂，（b）特异性释放或特异性诱导细胞因子或抗细胞因子活性或发挥此类活性的化合物，（c）抗原，变应原，抗原和抗体混合物 过敏原的混合物，（d）化学刺激物。 本发明还涉及用于疫苗接种哺乳动物以获得保护性或治疗性免疫应答的方法。

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：US07591949B2

公开(公告)日：2009-09-22

申请号：US10984450

申请日：2004-11-08

申请人： Gregor Cevc ,  Holger Richardsen ,  Andrea Weiland-Waibel

发明人： Gregor Cevc ,  Holger Richardsen ,  Andrea Weiland-Waibel

IPC分类号： B01D61/00 ,  A61K9/127

CPC分类号： A61K9/7023 ,  A61K9/1272

摘要： The invention relates to a method, a kit and a device for controlling the flux of penetrants across an adaptable semi-permeable porous barrier, the method comprising the steps of: preparing a formulation by suspending or dispersing said penetrants in a polar liquid in the form of fluid droplets surrounded by a membrane-like coating of one or several layers, said coating comprising at least two kinds of forms of amphiphilic substances with a tendency to aggregate, said penetrants being able to transport agents through the pores of said barrier or to enable agent permeation through the pores of said barrier after penetrants have entered the pores, selecting a dose amount of said penetrants to be applied on a predetermined area of said barrier to control the flux of said penetrants across said barrier, and applying the selected dose amount of said formulation containing said penetrants onto said area of said porous barrier.

摘要翻译： 本发明涉及一种方法，试剂盒和用于控制穿过适应性半透性多孔屏障的渗透剂通量的装置，所述方法包括以下步骤：通过将所述渗透剂悬浮或分散在极性液体中形式 由一层或几层的膜状涂层包围的流体液滴，所述涂层包含至少两种具有聚集倾向的两亲物质形式，所述渗透剂能够将物质输送通过所述屏障的孔或使得能够 在渗透剂进入孔之后，试剂通过所述阻挡层的孔渗透，选择施用在所述屏障的预定区域上的所述渗透剂的剂量，以控制穿过所述屏障的所述渗透剂的通量，并施加所选择的剂量 所述制剂含有所述渗透剂到所述多孔屏障的所述区域上。

公开(公告)号：US20090060989A1

公开(公告)日：2009-03-05

申请号：US12244703

申请日：2008-10-02

申请人： Gregor Cevc ,  Ulrich Vierl

发明人： Gregor Cevc ,  Ulrich Vierl

IPC分类号： A61K9/127 ,  A61K31/192 ,  A61K31/196 ,  A61P29/00 ,  A61K31/405

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：US20050123897A1

公开(公告)日：2005-06-09

申请号：US10984450

申请日：2004-11-08

申请人： Gregor Cevc ,  Holger Richardsen ,  Andrea Weiland-Waibel

发明人： Gregor Cevc ,  Holger Richardsen ,  Andrea Weiland-Waibel

IPC分类号： A61F2/28 ,  A61F2/02 ,  A61K9/127 ,  A61K9/70 ,  A61K31/045 ,  A61K31/05 ,  A61K31/055 ,  A61K31/14 ,  A61K31/19 ,  A61K31/192 ,  A61K31/305 ,  A61K31/452 ,  A61K45/00 ,  A61K47/02 ,  A61K47/08 ,  A61K47/10 ,  A61K47/12 ,  A61K47/14 ,  A61K47/18 ,  A61K47/22 ,  A61K47/26 ,  A61K47/28 ,  A61K47/32 ,  A61K47/34 ,  A61K47/36 ,  A61K47/38 ,  A61K47/42 ,  A61K47/46 ,  A61L27/22 ,  A61L27/26 ,  A61L27/34 ,  A61L27/48 ,  A61P1/00 ,  A61P1/16 ,  A61P1/18 ,  A61P3/14 ,  A61P7/00 ,  A61P11/00 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P19/00 ,  A61P21/04 ,  A61P25/02 ,  A61P25/08 ,  A61P27/02 ,  A61P27/16 ,  A61P29/00 ,  A61P31/00 ,  A61P31/04 ,  C12Q1/00 ,  C12Q1/18

CPC分类号： A61K9/7023 ,  A61K9/1272

摘要： The invention relates to a method, a kit and a device for controlling the flux of penetrants across an adaptable semi-permeable porous barrier the method comprising the steps of: preparing a formulation by suspending or dispersing said penetrants in a polar liquid in the form of fluid droplets surrounded by a membrane-like coating of one or several layers, said coating comprising at least two kinds of forms of amphiphilic substances with a tendency to aggregate, said penetrants being able to transport agents through the pores of said barrier or to enable agent permeation through the pores of said barrier after penetrants have entered the pores, selecting a dose amount of said penetrants to be applied on a predetermined area of said barrier to control the flux of said penetrants across said barrier, and applying the selected dose amount of said formulation containing said penetrants onto said area of said porous barrier.

摘要翻译： 本发明涉及一种用于控制穿过适应性半渗透性多孔屏障的渗透剂通量的方法，试剂盒和装置，该方法包括以下步骤：通过将所述渗透剂悬浮或分散在极性液体中，形式为 由一层或几层的膜状涂层包围的流体液滴，所述涂层包含至少两种倾向于聚集的两亲物质的形式，所述渗透剂能够通过所述屏障的孔运输试剂或使能剂 在渗透剂进入孔之后通过所述屏障的孔渗透，选择要施用在所述屏障的预定区域上的所述渗透剂的剂量，以控制穿过所述屏障的所述渗透剂的通量，并施加所选择的剂量 将所述渗透剂包含在所述多孔屏障的所述区域上。

公开(公告)号：US20100086504A1

公开(公告)日：2010-04-08

申请号：US12508537

申请日：2009-07-23

申请人： Gregor Cevc ,  Ulrich Vierl

发明人： Gregor Cevc ,  Ulrich Vierl

IPC分类号： A61K8/40 ,  A61K31/135

CPC分类号： A61K31/137 ,  A61K9/0014 ,  A61K9/06 ,  A61K47/24 ,  A61K47/26

摘要： The present invention relates to topical antifungal formulations comprising one or more antifungal (e.g., terbinafine), a lipid and a surfactant, and uses thereof for the treatment of skin and nail fungal infections.

摘要翻译： 本发明涉及包含一种或多种抗真菌剂（例如特比萘芬），脂质和表面活性剂的局部抗真菌制剂及其用于治疗皮肤和指甲真菌感染的用途。