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1. 发明授权

US07488794B2 High yield S-nitrosylation process 有权
公开(公告)号：US07488794B2
公开(公告)日：2009-02-10
申请号：US10881713
申请日：2004-06-30
申请人： Robert A. Herrmann , David Knapp
发明人： Robert A. Herrmann , David Knapp
IPC分类号： C07K1/113 , C08B37/16
CPC分类号： C07C381/00 , C08B37/00 , C08B37/0012
摘要： A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation. The S-nitrosylated species can be isolated, for example, by a process in which the precipitate is removed from the solution (e.g., by centrifugation) and the aqueous solvent remaining in the precipitate is sublimated (e.g., by freezing the precipitate and subjecting it to a vacuum). The isolated S-nitrosylated product is preferably protected from heat, light, moisture and oxygen.

2. 发明授权

US06706274B2 Differential delivery of nitric oxide 有权
标题翻译：差异递送一氧化氮
公开(公告)号：US06706274B2
公开(公告)日：2004-03-16
申请号：US09765131
申请日：2001-01-18
申请人： Robert A. Herrmann , David Knapp
发明人： Robert A. Herrmann , David Knapp
IPC分类号： A61F200
CPC分类号： A61K9/0024 , A61K31/21 , A61K31/53 , A61K45/06 , A61L27/54 , A61L29/16 , A61L31/16 , A61L2300/114 , A61L2300/45 , A61L2300/602
摘要： This invention relates to devices and methods for the local, differential delivery of nitric oxide within the body. The devices include devices having at least two differing nitric oxide donor compounds, such as nitric oxide donor compounds having differing half-lives and nitric oxide donor compounds having different release mechanisms. The devices also include devices having at least two chemically distinct compositions to which nitric oxide donor compounds are adsorbed or attached or within which the donor compounds are disposed. The devices are typically used to increase local nitric oxide concentration in the body upon placement of the medical article at a delivery position on or within a patient. The methods of the present invention include a method of treating an atherosclerotic lesion which comprises: exposing the lesion to a first higher concentration of nitric oxide effective to reduce the number of cells within the lesion; and subsequently exposing the lesion to a second lower concentration of nitric oxide effective to inhibit restenosis. The methods of the present invention also include methods for preferentially providing differing nitric oxide donor compounds within different tissues to effect therapy.
摘要翻译：本发明涉及用于局部，差异地递送体内一氧化氮的装置和方法。所述装置包括具有至少两种不同一氧化氮供体化合物的装置，例如具有不同半衰期的一氧化二氮供体化合物和具有不同释放机制的一氧化氮供体化合物。所述装置还包括具有至少两种化学上不同的组合物的装置，其中一氧化氮供体化合物被吸附或附着，其中配置施主化合物。该装置通常用于在将医疗用品放置在患者身上或患者内的输送位置时增加身体中的局部一氧化氮浓度。本发明的方法包括治疗动脉粥样硬化病变的方法，其包括：将病变暴露于第一高浓度的一氧化氮，有效减少损伤内的细胞数; 并随后将病变暴露于有效抑制再狭窄的第二较低浓度的一氧化氮。本发明的方法还包括优先在不同组织内提供不同的一氧化氮供体化合物以实现治疗的方法。

3. 发明授权

US06417347B1 High yield S-nitrosylation process 失效
标题翻译：高产率的S-亚硝基化工艺
公开(公告)号：US06417347B1
公开(公告)日：2002-07-09
申请号：US09645171
申请日：2000-08-24
申请人： Robert A. Herrmann , David Knapp
发明人： Robert A. Herrmann , David Knapp
IPC分类号： C08B3702
CPC分类号： C07C381/00 , C08B37/00 , C08B37/0012
摘要： A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation. The S-nitrosylated species can be isolated, for example, by a process in which the precipitate is removed from the solution (e.g., by centrifugation) and the aqueous solvent remaining in the precipitate is sublimated (e.g., by freezing the precipitate and subjecting it to a vacuum). The isolated S-nitrosylated product is preferably protected from heat, light, moisture and oxygen.
摘要翻译：提供了生产S-亚硝基化物质的方法。该方法包括：（a）提供包含硫醇和含亚硝酸盐的物质的脱氧碱性水溶液; （b）通过向溶液中加入酸来酸化溶液，同时混合溶液（例如通过剧烈搅拌该溶液）以产生S-亚硝基化物质; 和（c）分离S-亚硝基化物质。含有亚硝酸盐的物质可以是例如无机亚硝酸盐，例如碱金属亚硝酸盐或有机亚硝酸盐，例如亚硝酸烷基酯（例如亚硝酸亚乙酯，亚硝酸戊酯，亚硝酸异丁酯或亚硝酸叔丁酯）。硫醇优选为含硫醇的多糖，含硫醇的脂蛋白，含巯基的氨基酸或含硫醇的蛋白质，更优选含硫醇的多糖如硫醇化环糊精。在许多优选实施方案中，S-亚硝基化物质不溶于酸化溶液，在形成时沉淀。 S-亚硝基化物质可以例如通过其中从溶液中除去沉淀物（例如通过离心）并且残留在沉淀物中的水性溶剂升华的方法分离（例如，通过冷冻沉淀物并使其沉淀到真空）。分离的S-亚硝基化产物优选保护免受热，光，水分和氧气的影响。

4. 发明授权

US07799335B2 Differential delivery of nitric oxide 有权
标题翻译：差异递送一氧化氮
公开(公告)号：US07799335B2
公开(公告)日：2010-09-21
申请号：US10798592
申请日：2004-03-11
申请人： Robert A. Herrmann , David Knapp
发明人： Robert A. Herrmann , David Knapp
IPC分类号： A61F2/00 , A61F13/00
CPC分类号： A61K9/0024 , A61K31/21 , A61K31/53 , A61K45/06 , A61L27/54 , A61L29/16 , A61L31/16 , A61L2300/114 , A61L2300/45 , A61L2300/602
摘要： This invention relates to devices and methods for the local, differential delivery of nitric oxide within the body. The devices include devices having at least two differing nitric oxide donor compounds, such as nitric oxide donor compounds having differing half-lives and nitric oxide donor compounds having different release mechanisms. The devices also include devices having at least two chemically distinct compositions to which nitric oxide donor compounds are adsorbed or attached or within which the donor compounds are disposed. The devices are typically used to increase local nitric oxide concentration in the body upon placement of the medical article at a delivery position on or within a patient. The methods of the present invention include a method of treating an atherosclerotic lesion which comprises: exposing the lesion to a first higher concentration of nitric oxide effective to reduce the number of cells within the lesion; and subsequently exposing the lesion to a second lower concentration of nitric oxide effective to inhibit restenosis. The methods of the present invention also include methods for preferentially providing differing nitric oxide donor compounds within different tissues to effect therapy.
摘要翻译：本发明涉及用于局部，差异地递送体内一氧化氮的装置和方法。所述装置包括具有至少两种不同一氧化氮供体化合物的装置，例如具有不同半衰期的一氧化二氮供体化合物和具有不同释放机制的一氧化氮供体化合物。所述装置还包括具有至少两种化学上不同的组合物的装置，其中一氧化氮供体化合物被吸附或附着，其中配置施主化合物。该装置通常用于在将医疗用品放置在患者身上或患者内的输送位置时增加身体中的局部一氧化氮浓度。本发明的方法包括治疗动脉粥样硬化病变的方法，其包括：将病变暴露于第一高浓度的一氧化氮，有效减少损伤内的细胞数; 并随后将病变暴露于有效抑制再狭窄的第二较低浓度的一氧化氮。本发明的方法还包括优先在不同组织内提供不同的一氧化氮供体化合物以实现治疗的方法。

5. 发明授权

US06762282B2 High yield S-nitrosylation process 有权
标题翻译：高产率的S-亚硝基化工艺
公开(公告)号：US06762282B2
公开(公告)日：2004-07-13
申请号：US10436965
申请日：2003-05-13
申请人： Robert A. Herrmann , David Knapp
发明人： Robert A. Herrmann , David Knapp
IPC分类号： C07K1113
CPC分类号： C07C381/00 , C08B37/00 , C08B37/0012
摘要： A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation. The S-nitrosylated species can be isolated, for example, by a process in which the precipitate is removed from the solution (e.g., by centrifugation) and the aqueous solvent remaining in the precipitate is sublimated (e.g., by freezing the precipitate and subjecting it to a vacuum). The isolated S-nitrosylated product is preferably protected from heat, light, moisture and oxygen.
摘要翻译：提供了生产S-亚硝基化物质的方法。该方法包括：（a）提供包含硫醇和含亚硝酸盐的物质的脱氧碱性水溶液; （b）通过向溶液中加入酸来酸化溶液，同时混合溶液（例如通过剧烈搅拌该溶液）以产生S-亚硝基化物质; 和（c）分离S-亚硝基化物质。含有亚硝酸盐的物质可以是例如无机亚硝酸盐，例如碱金属亚硝酸盐或有机亚硝酸盐，例如亚硝酸烷基酯（例如亚硝酸亚乙酯，亚硝酸戊酯，亚硝酸异丁酯或亚硝酸叔丁酯）。硫醇优选为含硫醇的多糖，含硫醇的脂蛋白，含巯基的氨基酸或含硫醇的蛋白质，更优选含硫醇的多糖如硫醇化环糊精。在许多优选实施方案中，S-亚硝基化物质不溶于酸化溶液，在形成时沉淀。 S-亚硝基化物质可以例如通过其中从溶液中除去沉淀物（例如通过离心）并且残留在沉淀物中的水性溶剂升华的方法分离（例如，通过冷冻沉淀物并使其沉淀到真空）。分离的S-亚硝基化产物优选保护免受热，光，水分和氧气的影响。

6. 发明授权

US08961560B2 Bidirectional self-retaining sutures with laser-marked and/or non-laser marked indicia and methods 有权
标题翻译：具有激光标记和/或非激光标记标记的双向自保持缝合线和方法
公开(公告)号：US08961560B2
公开(公告)日：2015-02-24
申请号：US12970872
申请日：2010-12-16
申请人： Rui Avelar , Alexei Goraltchouk , Robert A. Herrmann , Brian H. Luscombe , William L. D'Agostino
发明人： Rui Avelar , Alexei Goraltchouk , Robert A. Herrmann , Brian H. Luscombe , William L. D'Agostino
IPC分类号： A61B17/04 , A61B17/06 , A61B19/00 , A61B17/00
CPC分类号： A61B17/06166 , A61B17/0469 , A61B34/30 , A61B90/90 , A61B90/92 , A61B90/94 , A61B90/98 , A61B2017/00115 , A61B2017/00526 , A61B2017/06009 , A61B2017/06014 , A61B2017/06057 , A61B2017/06176 , A61B2090/064 , A61B2090/0809 , A61B2090/365
摘要： A marked heterofunctional suture thread has two or more sections having different features. One or more sections of the suture thread are provided with laser-marked and non-laser marked indicia in order that they may be identified and differentiated from other sections. The suture thread may have retainers on the surface of one or more sections such that the suture thread can engage and retain tissue without knots. The markers may be used to indicate fixed features of a section of suture thread such as the presence and/orientation of retainers. In particular embodiments, laser-marked and non-laser marked indicia are used to identify the transition section of a bidirectional self-retaining suture.
摘要翻译：标记的异型功能缝合线具有两个或多个具有不同特征的部分。缝合线的一个或多个部分设置有激光标记和非激光标记的标记，以便它们可以被识别并且与其它部分区分开。缝合线可以在一个或多个部分的表面上具有保持器，使得缝合线可以接合并保持组织而没有结。标记可以用于指示缝合线的一部分的固定特征，例如保持器的存在和/取向。在特定实施例中，使用激光标记和非激光标记标记来识别双向自固位缝合线的过渡部分。

7. 发明授权

US08641732B1 Self-retaining suture with variable dimension filament and method 有权
标题翻译：具有可变尺寸长丝和方法的自固定缝合线
公开(公告)号：US08641732B1
公开(公告)日：2014-02-04
申请号：US12392955
申请日：2009-02-25
申请人： Alexei Goraltchouk , Alexander Naimagon , Gerald F. Cummings , Lev Drubetsky , Robert A. Herrmann
发明人： Alexei Goraltchouk , Alexander Naimagon , Gerald F. Cummings , Lev Drubetsky , Robert A. Herrmann
IPC分类号： A61B17/04
CPC分类号： A61B17/06166 , A61B2017/00526 , A61B2017/00849 , A61B2017/00893 , A61B2017/06176 , D01D5/20 , D01D5/22
摘要： A self-retaining suture comprises a variable-dimension filament which varies in size and/or shape along the length of the filament. The variation in size and/or shape results in a variation in the distribution of filament material from one region of the filament to the next. The filament has retainers formed in the surface such that the filament can engage and retain tissue. The retainers are formed in a manner that makes use of regions of the filament where additional material is distributed. The resulting self-retaining suture has a greater minimum cross-section than would be created using an equivalent uniform filament. The resulting self-retaining suture consequently has a greater tensile strength. Methods for manufacturing the filament and retainers are also described.
摘要翻译：自固位缝合线包括沿着长丝长度变化大小和/或形状的可变尺寸长丝。尺寸和/或形状的变化导致细丝材料从细丝的一个区域到下一个区域的分布的变化。灯丝具有形成在表面中的保持器，使得灯丝可以接合并保持组织。保持器以这样的方式形成，即使用分布有附加材料的细丝的区域。所产生的自固位缝合线具有比使用等效的均匀细丝产生的更大的最小横截面。因此，所得到的自固位缝合线具有更大的拉伸强度。还描述了制造丝和保持器的方法。

8. 发明授权

US08388678B2 Medical devices having porous component for controlled diffusion 有权
标题翻译：具有用于受控扩散的多孔成分的医疗装置
公开(公告)号：US08388678B2
公开(公告)日：2013-03-05
申请号：US12333909
申请日：2008-12-12
申请人： Anurag Singhal , Robert A. Herrmann , Yixin Xu , Young-Ho Song
发明人： Anurag Singhal , Robert A. Herrmann , Yixin Xu , Young-Ho Song
IPC分类号： A61F2/06
CPC分类号： A61L31/14 , A61L27/50 , A61L27/54 , A61L27/56 , A61L29/14 , A61L29/146 , A61L29/16 , A61L31/146 , A61L31/16 , A61L2300/602
摘要： According to an aspect of the present invention, implantable or insertable medical devices are provided which contain the following: (a) substrate having one or more depressions that contain at least one therapeutic agent and (b) a porous membrane disposed over the substrate and the one or more depressions, which regulate transport of chemical species between the therapeutic-agent-containing depressions and the exterior of the device. The substrate and the porous membrane are formed of different materials each with a different thermal expansion coefficient. Moreover, one of the substrate and the porous membrane at least partially surrounds the other. Other aspects of the present invention are directed to methods of making such medical devices, and methods of treatment using such medical devices.
摘要翻译：根据本发明的一个方面，提供了可植入或可插入的医疗装置，其包含以下内容：（a）具有一个或多个凹陷的基底，其含有至少一种治疗剂，和（b）设置在基底上的多孔膜，一个或多个凹陷，其调节化学物质在含治疗剂的凹陷和装置的外部之间的运输。基板和多孔膜由各自具有不同热膨胀系数的不同材料形成。此外，衬底和多孔膜中的一个至少部分地围绕另一个。本发明的其它方面涉及制造这种医疗装置的方法，以及使用这种医疗装置的治疗方法。

9. 发明申请

US20120248648A1 SELF-RETAINERS WITH SUPPORTING STRUCTURES ON A SUTURE 有权
标题翻译：具有支撑结构的自我保持者
公开(公告)号：US20120248648A1
公开(公告)日：2012-10-04
申请号：US13495550
申请日：2012-06-13
申请人： Alexei Goraltchouk , Lev Drubetsky , Gerald F. Cummings , Robert A. Herrmann , Alexander Naimagon
发明人： Alexei Goraltchouk , Lev Drubetsky , Gerald F. Cummings , Robert A. Herrmann , Alexander Naimagon
IPC分类号： D01D5/22
CPC分类号： A61B17/06166 , A61B2017/00526 , A61B2017/06176
摘要： In embodiments of the invention, a manufacturing process produces and an. Article produced has a self-retaining suture wherein a force is used to squeeze the suture causing retainers to form out of material from the suture body. In an embodiment of the invention, fins are formed between the retainers and the suture body, wherein said fins support the retainers. In another embodiment, retainer stops are provided in order to prevent the retainer from settling back in the body of the suture.
摘要翻译：在本发明的实施例中，制造过程产生和。制造的制品具有自固位缝合线，其中使用力来挤压缝合线，引起保持器从缝合线本体形成材料。在本发明的一个实施例中，翅片形成在保持器和缝合线本体之间，其中所述翅片支撑保持器。在另一个实施例中，提供保持器止动件以防止保持器沉降到缝合线的主体中。

10. 发明授权

US07696247B2 Lipid-based nitric oxide donors 有权
标题翻译：基于脂质的一氧化氮供体
公开(公告)号：US07696247B2
公开(公告)日：2010-04-13
申请号：US10885055
申请日：2004-07-06
申请人： Robert A. Herrmann , Wendy Naimark
发明人： Robert A. Herrmann , Wendy Naimark
IPC分类号： A61K31/20 , A01N33/26 , C07C205/00 , C07C207/00 , C07C241/00 , C07C243/00
CPC分类号： A61L29/16 , A61K45/06 , A61L15/44 , A61L31/16 , A61L2300/114 , A61L2300/416 , C07C243/42 , C07J41/0055 , Y10T436/104165
摘要： Novel nitric-oxide releasing lipid molecules are provided which comprise a lipid molecule selected from (a) phosphoglycerides, (b) lipids having a sphingosine base as a backbone, (c) monoacylglyerols, (d) diacylglycerols, (e) glycosylacylglycerols, and (f) sterol compounds of the formula: where R is a branched aliphatic chain of eight or more carbon atoms, wherein the lipid molecule is provided with a nitric-oxide containing group which comprises (a) a —S—N═O moiety, (b) a —O—N═O moiety, or (c) a a moiety. Also provided are methods of forming such nitric oxide releasing lipid molecules. Various pharmaceutical compositions, topical liquids and drug delivery systems comprising the nitric-oxide releasing lipid molecules are also described. Further provided are methods for therapeutically administering nitric oxide to patients, methods of treating or preventing various conditions, methods for promoting wound healing and methods of reducing the cells present in an atherosclerotic lesion, which methods utilize the nitric-oxide releasing lipid molecules.
摘要翻译：提供新的一氧化氮释放脂质分子，其包含选自（a）磷酸甘油酯，（b）具有鞘氨醇碱作为主链的脂质的脂质分子，（c）单酰基甘醇，（d）二酰基甘油，（e）糖基酰基甘油和（ f）下式的甾醇化合物：其中R是具有8个或更多个碳原子的支链脂族链，其中所述脂质分子具有含一氧化氮的基团，其包含（a）-S-N = O部分，（ b）-O-N = O部分，或（c）aa部分。还提供了形成这种一氧化氮释放脂质分子的方法。还描述了包含释放一氧化氮的脂质分子的各种药物组合物，局部液体和药物递送系统。还提供了向患者治疗性给予一氧化氮的方法，治疗或预防各种病症的方法，促进伤口愈合的方法以及减少存在于动脉粥样硬化病变中的细胞的方法，该方法利用释放一氧化氮的脂质分子。

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