公开(公告)号：US5830539A

公开(公告)日：1998-11-03

申请号：US565199

申请日：1995-11-17

申请人： Mingdi Yan ,  John F. W. Keana ,  Goran Karapetrov ,  Christopher J-P Sevrain ,  Martin N. Wybourne

发明人： Mingdi Yan ,  John F. W. Keana ,  Goran Karapetrov ,  Christopher J-P Sevrain ,  Martin N. Wybourne

IPC分类号： A61L27/28 ,  A61L33/00 ,  B05D1/18 ,  B05D7/14 ,  B05D3/06 ,  B05D3/10

CPC分类号： B82Y30/00 ,  A61L27/28 ,  A61L33/0076 ,  B05D1/185 ,  B82Y40/00 ,  B01J2219/00497 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/00617 ,  B01J2219/00626 ,  B01J2219/00637 ,  B01J2219/00659

摘要： Methods for coating substrates are described. The methods comprise coating at least a portion of a substrate with particular coating materials. The coating materials can be crosslinked and coated onto a substrate. Alternatively, the coating materials may be covalently bonded to the substrates. The coating materials might themselves functionalize the substrate, or provide a biocompatible coating on the substrate. The coating materials might also include electrophilic or nucleophilic groups that allow for the subsequent reaction of the coating materials with additional reagents. The present invention also provides coated workpieces, particularly medical workpieces having a surface for contacting tissue or blood. These workpieces comprise a first layer and a second layer. The first layer comprises a molecular tether covalently bonded to the surface. The second layer is bonded to the article by the first layer and comprises a bioactive agent selected from the group consisting of biocompatible polymers, antibiotics, antimicrobials and anticoagulants.

摘要翻译： 描述了涂覆基材的方法。 所述方法包括用特定涂层材料涂覆至少一部分基底。 涂层材料可以交联并涂覆在基材上。 或者，涂层材料可以共价键合到基底上。 涂层材料本身可以使基底功能化，或在基材上提供生物相容的涂层。 涂层材料还可以包括允许涂层材料随后与另外的试剂反应的亲电或亲核基团。 本发明还提供涂覆的工件，特别是具有用于接触组织或血液的表面的医疗工件。 这些工件包括第一层和第二层。 第一层包括共价结合到表面上的分子系链。 第二层通过第一层结合到制品上，并且包含选自生物相容性聚合物，抗生素，抗微生物剂和抗凝剂的生物活性剂。

公开(公告)号：US5582955A

公开(公告)日：1996-12-10

申请号：US495005

申请日：1995-06-26

申请人： John F. W. Keana ,  Martin N. Wybourne ,  Sui X. Cai ,  Mingdi Yan

发明人： John F. W. Keana ,  Martin N. Wybourne ,  Sui X. Cai ,  Mingdi Yan

IPC分类号： C08F8/30 ,  C08F8/34 ,  G03C5/00

CPC分类号： C08F8/30 ,  C08F8/34 ,  Y10S430/143

摘要： Methods for covalently modifying surfaces of various substrates are disclosed, along with various substrates having surfaces modified by such methods. Candidate surfaces include various polymeric, siliceous, metallic, allotrophic forms of carbon, and semiconductor surfaces. The surfaces are exposed to a reagent, having molecules each comprising a nitrenogenic group and a functionalizing group, in the presence of energized charged particles such as electrons and ions, photons, or heat, which transform the nitrenogenic reagent to a nitrene intermediate. The nitrene covalently reacts with any of various chemical groups present on the substrate surface, thereby effecting nitrene addition of the functionalizing groups to the substrate surface. The functionalizing groups can then participate in downstream chemistry whereby any of a large variety of functional groups, including biological molecules, can be covalently bonded to the surface, thereby dramatically altering the chemical behavior of the surface. Such functionalizations of the surface can be done in a single reactive step or in multiple reactive steps.

公开(公告)号：US5580697A

公开(公告)日：1996-12-03

申请号：US267851

申请日：1994-06-23

申请人： John F. W. Keana ,  Martin N. Wybourne ,  Sui X. Cai ,  Mingdi Yan

发明人： John F. W. Keana ,  Martin N. Wybourne ,  Sui X. Cai ,  Mingdi Yan

IPC分类号： C08J7/12 ,  B01J19/08 ,  C01B31/04 ,  C08F8/34 ,  C23C16/02 ,  G01N21/45 ,  G01N21/77 ,  G01N33/543 ,  G03F7/20 ,  H01L21/368 ,  G03C5/00

CPC分类号： G01N33/54373 ,  C08F8/32 ,  G01N21/7703 ,  G03F7/2041 ,  G01N2201/0873 ,  Y10S430/143

摘要： Methods for covalently modifying surfaces of various substrates are disclosed, along with various substrates having surfaces modified by such methods. Candidate surfaces include various polymeric, siliceous, metallic, allotrophic forms of carbon, and semiconductor surfaces. The surfaces are exposed to a reagent, having molecules each comprising a nitrenogenic group and a functionalizing group, in the presence of energized charged particles such as electrons and ions, photons, or heat, which transform the nitrenogenic reagent to a nitrene intermediate. The nitrene covalently reacts with any of various chemical groups present on the substrate surface, thereby effecting nitrene addition of the functionalizing groups to the substrate surface. The functionalizing groups can then participate in downstream chemistry whereby any of a large variety of functional groups, including biological molecules, can be covalently bonded to the surface, thereby dramatically altering the chemical behavior of the surface. Such functionalizations of the surface can be done in a single reactive step or in multiple reactive steps.

公开(公告)号：US5567411A

公开(公告)日：1996-10-22

申请号：US316787

申请日：1994-09-29

申请人： John F. W. Keana ,  Vladimir Martin ,  William H. Ralston

发明人： John F. W. Keana ,  Vladimir Martin ,  William H. Ralston

IPC分类号： A61K49/18 ,  A61K49/20 ,  C07C291/04 ,  C07F11/00 ,  A61K49/00 ,  A61K51/00 ,  C07C69/80 ,  C07D207/38 ,  C07D209/48 ,  C12N9/96

CPC分类号： A61K49/20 ,  A61K49/1812 ,  C07C291/04 ,  Y10S436/803 ,  Y10S436/806 ,  Y10T436/24

摘要： Dendritic derivatives of 3,5-bis(aminomethyl)benzene and aminomethyl benzene core groups are disclosed. In each derivative, termed an "amplifier" because the dendritic structure on each molecule terminates with multiple termini to each of which an "active group" can be attached, the desired effect of the active group per mole is amplified compared to conventional compounds having only one active group per molecule. Amplifier molecules can include a targeting group permitting the molecules to preferentially attach to a particular anatomical or physiological situs. Active groups are any of various pharmacologically or therapeutically active moieties, including moieties useful for magnetic-resonance contrast enhancement. The dendritic structures comprise linkers and branch groups covalently bonded to each other in any of various structural combinations. The amplifiers can be prepared as a solution or mixture with a physiologically compatible carrier for administration to a warm-blooded animal subject. Also disclosed are methods for using the compounds in diagnosis and therapy, such as obtaining a magnetic resonance image of a subject.

摘要翻译： 公开了3,5-双（氨基甲基）苯和氨基甲基苯核心的树枝状衍生物。 在每个衍生物中，称为“放大器”，因为每个分子上的树突状结构终止于可以连接“活性基团”的每个末端的多个末端，与仅具有仅活性基团的常规化合物相比，活性基团每摩尔的期望效应被扩增 每个分子一个活性基团。 放大器分子可以包括允许分子优先附着到特定解剖或生理部位的靶向基团。 活性基团是各种药理学或治疗活性部分中的任何一种，包括可用于磁共振对比度增强的部分。 树枝状结构包括以各种结构组合中的任何一种彼此共价键合的接头和分支基团。 放大器可以制备成与生理相容的载体的溶液或混合物，用于给温血动物受试者施用。 还公开了在诊断和治疗中使用化合物的方法，例如获得受试者的磁共振图像。

公开(公告)号：US5476933A

公开(公告)日：1995-12-19

申请号：US341154

申请日：1994-11-16

申请人： John F. W. Keana ,  Anthony P. Guzikowski ,  Daniel F. Nogales ,  Sui X. Cai

发明人： John F. W. Keana ,  Anthony P. Guzikowski ,  Daniel F. Nogales ,  Sui X. Cai

IPC分类号： C07D223/16 ,  C07D223/32 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  C07D15/04 ,  A61K31/55

CPC分类号： C07D223/16 ,  C07D223/32 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04

摘要： Disclosed are methods of preparing azepines by a multistep synthesis including a Diels-Alder reaction. Also disclosed are methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, inducing anesthesia and treating or preventing opiate tolerance are disclosed by administering to an animal in need of such treatment an azepine which has high binding to the NMDA glycine site.

摘要翻译： 公开了通过包括Diels-Alder反应的多步合成来制备氮杂的方法。 还公开了治疗或预防与中风，缺血，CNS创伤，低血糖和手术相关的神经元损失以及治疗神经变性疾病包括阿尔茨海默病，肌萎缩性侧索硬化，亨廷顿病和唐氏综合征的治疗或预防方法，治疗或预防不良后果 兴奋性氨基酸的多动症以及治疗焦虑症，慢性疼痛，抽搐，诱导麻醉和治疗或预防阿片剂耐受性的公开通过向需要这种治疗的动物施用与NMDA甘氨酸位点具有高结合性的吖庚因 。

公开(公告)号：US5465151A

公开(公告)日：1995-11-07

申请号：US14425

申请日：1993-02-05

申请人： Martin N. Wybourne ,  John F. W. Keana ,  Sui X. Cai ,  Mingdi Yan ,  Jong Wu

发明人： Martin N. Wybourne ,  John F. W. Keana ,  Sui X. Cai ,  Mingdi Yan ,  Jong Wu

IPC分类号： C08J7/12 ,  B01J19/08 ,  C01B31/04 ,  C08F8/34 ,  C23C16/02 ,  G01N21/27 ,  G01N21/45 ,  G01N21/64 ,  G01N21/75 ,  G01N21/77 ,  G01N33/543 ,  G01N33/566 ,  G03F7/20 ,  H01L21/368 ,  G01B9/02

CPC分类号： G01N21/7703 ,  C08F8/32 ,  G01N33/54373 ,  G03F7/2041 ,  G01N2021/7779 ,  G01N2201/0873

摘要： Chemical and biosensors are disclosed. An optical waveguide is used to conduct electromagnetic radiation by total internal reflection in parallel through a reference waveguide portion and at least one analyte waveguide portion. The electromagnetic radiation is then converged into an exit beam. The external surface of at least the analyte portion is covalently modified, or functionalized, relative to the reference portion. Resulting interaction of the functionalized surface with molecules comprising an analyte causes a phase change in the electromagnetic radiation passing through the analyte portion relative to the reference portion sufficient to generate a corresponding and measurable interference pattern in the exit beam. A waveguide surface is functionalized by exposure to a reagent, having molecules each comprising a nitrenogenic group and a functionalizing group, in the presence of energized charged particles such as electrons and ions, photons, or heat, which transform the nitrenogenic reagent to a nitrene intermediate. The resulting reaction causes the functionalizing groups to covalently bond to the surface. The functionalizing groups can then participate in downstream chemistry whereby any of a large variety of functional groups, including biological molecules, can be covalently bonded to the surface. Thus, the waveguide surface can be made selectively responsive to a wide variety of analytes, including cells and other biological structures.

摘要翻译： 公开了化学和生物传感器。 光波导用于通过参考波导部分和至少一个分析物波导部分并行地通过全内反射来传导电磁辐射。 电磁辐射然后会聚到出射光束中。 至少分析物部分的外表面相对于参考部分共价修饰或官能化。 功能化表面与包含分析物的分子的相互作用导致相对于参考部分通过分析物部分的电磁辐射的相变足以在出射光束中产生相应和可测量的干涉图案。 波导表面通过暴露于具有各自包含硝基衍生基团和官能化基团的分子的试剂而被功能化，所述分子在有电的带电粒子例如电子和离子，光子或热的情况下，其将硝化反应试剂转变为硝酸中间体 。 所得到的反应使官能团共价键合到表面。 官能团然后可以参与下游化学，因此包括生物分子在内的各种各样的官能团中的任何一个可以共价键合到表面上。 因此，波导表面可以选择性地响应于各种各样的分析物，包括细胞和其他生物结构。

公开(公告)号：US5135737A

公开(公告)日：1992-08-04

申请号：US403595

申请日：1989-09-05

申请人： John F. W. Keana

发明人： John F. W. Keana

IPC分类号： A61K49/18 ,  A61K49/20 ,  C07C291/04

CPC分类号： C07C291/04 ,  A61K49/1812 ,  A61K49/20 ,  Y10T436/24

摘要： Disclosed are amplifier molecules: various organic compounds having branched structures terminating with amine groups to which pharmacologically active groups can be chemically attached. A number of MRI contrast-enhancing agents were synthesized, each comprising plural active groups, such as stable nitroxides and complexes of trivalent metal cations. Such syntheses were successfully performed using a number of amplifiers having different branched structures, demonstrating the general utility of the pertinent chemistry in the synthesis of amplifiers having any of a wide variety of pharmacologically active groups. Amplifiers were also synthesized having linkers terminating with chemically reactive groups such as isothiocyanates, which render the amplifier bifunctional: attachable to polymers, biomacromolecules, or other biocompatible entity possessing multiple reactive sites such as terminal amines. Via such chemistry, the amplifiers are attachable to monoclonal antibodies for concentration of pharmacologically active groups at a desired site in the body.

摘要翻译： 公开了放大器分子：具有分支结构的各种有机化合物，其末端具有可以化学连接药理活性基团的胺基团。 合成了许多MRI对比增强剂，每种都包含多个活性基团，如稳定的氮氧化物和三价金属阳离子的络合物。 使用具有不同支化结构的许多放大器成功地进行了这种合成，表明了合成具有各种药理学活性基团的放大器的相关化学物质的一般用途。 还合成放大器，其具有以化学反应性基团如异硫氰酸酯终止的接头，其使放大器具有双功能性：可附着于聚合物，生物大分子或具有多个反应性位点的其它生物相容性实体，例如末端胺。 通过这样的化学，放大器可附着于单体抗体，用于在体内所需位点浓集药理活性基团。

公开(公告)号：US4863717A

公开(公告)日：1989-09-05

申请号：US928943

申请日：1986-11-10

申请人： John F. W. Keana

发明人： John F. W. Keana

IPC分类号： A61K49/18 ,  A61K49/20 ,  C07C291/04

CPC分类号： C07C291/04 ,  A61K49/1812 ,  A61K49/20 ,  Y10S436/803 ,  Y10S436/806 ,  Y10T436/24

摘要： Nitroxide contrast agents for MRI have a long useful life and can be administered in low concentration doses. Such agents include nitroxide-doped liposomes that encapsulate an oxidant and large molecules having surfaces covered with persistent nitroxide free radicals.

摘要翻译： 用于MRI的硝酸氧化物造影剂具有较长的使用寿命并且可以以低浓度剂量施用。 这些试剂包括氮氧化物掺杂的脂质体，其包裹氧化剂和具有被持续的氮氧自由基覆盖的表面的大分子。