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公开(公告)号：US06443942B1
公开(公告)日：2002-09-03
申请号：US09876569
申请日：2001-06-06
IPC分类号： A61L3300
摘要： The present invention provides medical devices such as medication infusion pumps having internal surfaces that are treated to inhibit protein denaturation. In accordance with the invention, hydrophilic internal surfaces and related coating methods are provided to reduce or eliminate accumulation of medication deposits which can otherwise occur when handling complex protein-based medications. Preferred hydrophilic pump surfaces include hydrophilic surfactants (PEO) or (PEG) coatings which exhibit very low protein adsorption characteristics. Several methods are disclosed for producing such treated surfaces including the covalent attachment of hydrophilic surfactants.
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公开(公告)号：US06734162B2
公开(公告)日：2004-05-11
申请号：US09733738
申请日：2000-12-08
IPC分类号： A61K3816
CPC分类号： A61K47/18 , A61K9/0019 , A61K38/28 , A61K47/02 , A61K47/12
摘要： The present invention is a pharmaceutical composition for polypeptide which are not stably soluble. A preferred polypeptide is monomeric insulin and a preferred formulation consists of a TRIS-phosphate combination buffer, zinc; a phenolic preservative and an isotonicity agent such as glycerol.
摘要翻译： 本发明是一种不稳定溶解的多肽药物组合物。 优选的多肽是单体胰岛素，优选的制剂由TRIS-磷酸盐组合缓冲液，锌; 酚类防腐剂和等渗剂如甘油。
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公开(公告)号：US06852694B2
公开(公告)日：2005-02-08
申请号：US10080034
申请日：2002-02-21
CPC分类号： A61K38/28 , A61K2300/00
摘要： The present invention is directed to stabilized insulin composition comprising a mixture of insulin species such as insulin and an insulin analog. As disclosed herein, insulin compositions comprising a mixture of insulin and insulin analog species form heterodimeric complexes having a greater stability than the homodimeric complexes formed in compositions comprising single insulin species. Consequently, the present invention provides methods for stabilizing insulin molecules, methods for identifying stable heterodimeric insulin complexes and stabilized insulin compositions.
摘要翻译： 本发明涉及包含胰岛素物质如胰岛素和胰岛素类似物的混合物的稳定的胰岛素组合物。 如本文所公开的，包含胰岛素和胰岛素类似物的混合物的胰岛素组合物形成具有比在包含单一胰岛素物质的组合物中形成的同型二聚体复合物更大稳定性的异二聚体复合物。 因此，本发明提供了稳定胰岛素分子的方法，用于鉴定稳定的异二聚体胰岛素复合物和稳定的胰岛素组合物的方法。
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4.发明授权Detection of biological molecules using boronate-based chemical amplification and optical sensors 有权使用基于硼酸盐的化学放大和光学传感器检测生物分子公开(公告)号：US06750311B1
公开(公告)日：2004-06-15
申请号：US09461627
申请日：1999-12-14
申请人： William Peter Van Antwerp , John Joseph Mastrototaro , Stephen M. Lane , Joe H. Satcher, Jr. , Christopher B. Darrow , Thomas A. Peyser , Jennifer Harder
发明人： William Peter Van Antwerp , John Joseph Mastrototaro , Stephen M. Lane , Joe H. Satcher, Jr. , Christopher B. Darrow , Thomas A. Peyser , Jennifer Harder
IPC分类号： C08G1810
CPC分类号： G01N33/66 , Y10T428/31551
摘要： Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.
摘要翻译： 提供了用于确定多羟基化合物，特别是葡萄糖的生物水平浓度的方法。 该方法利用扩增系统，其是固定在聚合物基质中的分析物传感器，其中系统是可植入的和生物相容的。 在通过光学系统询问时，放大系统产生能够在患者皮肤外部检测的信号。 感兴趣的分析物的定量通过测量发射的信号来实现。
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公开(公告)号：US6011984A
公开(公告)日：2000-01-04
申请号：US752945
申请日：1996-11-21
IPC分类号： G01N33/66 , A61B5/00 , A61B5/145 , A61B5/1455 , C12Q1/00
CPC分类号： A61B5/1459 , A61B5/14532 , C12Q1/005
摘要： Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.
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6.发明授权Detection of biological molecules using chemical amplification and optical sensors 有权使用化学放大和光学传感器检测生物分子公开(公告)号：US06804544B2
公开(公告)日：2004-10-12
申请号：US09934390
申请日：2001-08-21
IPC分类号： A61B500
CPC分类号： A61B5/1459 , A61B5/14532 , C12Q1/005
摘要： Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.
摘要翻译： 提供了用于确定多羟基化合物，特别是葡萄糖的生物水平浓度的方法。 该方法利用扩增系统，其是固定在聚合物基质中的分析物传感器，其中系统是可植入的和生物相容的。 在通过光学系统询问时，放大系统产生能够在患者皮肤外部检测的信号。 感兴趣的分析物的定量通过测量发射的信号来实现。
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公开(公告)号：US06784274B2
公开(公告)日：2004-08-31
申请号：US10213265
申请日：2002-08-06
IPC分类号： C08G1852
CPC分类号： A61B5/14865 , A61B5/14532 , A61B5/411 , C08G18/4833 , C08G18/61 , C08G18/6674 , C08G77/458 , C08J5/2287 , C08J2323/06 , C12Q1/002 , C12Q1/006 , Y10T428/31551
摘要： Methods for reducing the electrode impedance of implantable biosensors by coating the surface of the biosensor with a uniform hydrogel which allows unimpeded water movement around the sensor are provided. The surface coatings are compositions which are biocompatible and are capable of water uptake of at least 120% of their weight, more preferably at least 200% of their weight. Upon the uptake of water, the hydrogels used in the present invention will also swell and provide a layer of water around the electrodes to which the hydrogels are attached. The hydrogels can be prepared from (a) a diisocyanate, (b) a hydrophilic polymer which is a hydrophilic diol, a hydrophilic diamine, or a combination thereof, and optionally, (c) a chain extender.
摘要翻译： 提供了通过用均匀的水凝胶涂覆生物传感器的表面来减少植入式生物传感器的电极阻抗的方法，其允许围绕传感器的不受阻碍的水移动。 表面涂层是生物相容性并且能够吸收其重量的至少120％，更优选至少其重量的200％的组合物。 在吸收水时，本发明中使用的水凝胶也将溶胀并在水凝胶附着的电极周围提供一层水。 水凝胶可以由（a）二异氰酸酯，（b）亲水性聚合物，亲水性二醇，亲水二胺或其组合，和任选的（c）扩链剂制备。
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公开(公告)号：US06462162B2
公开(公告)日：2002-10-08
申请号：US09123930
申请日：1998-07-28
IPC分类号： C08G1832
CPC分类号： A61B5/14865 , A61B5/14532 , A61B5/411 , C08G18/4833 , C08G18/61 , C08G18/6674 , C08G77/458 , C08J5/2287 , C08J2323/06 , C12Q1/002 , C12Q1/006 , Y10T428/31551
摘要： Methods for reducing the electrode impedance of implantable biosensors by coating the surface of the biosensor with a uniform hydrogel which allows unimpeded water movement around the sensor are provided. The surface coatings are compositions which are biocompatible and are capable of water uptake of at least 120% of their weight, more preferably at least 200% of their weight. Upon the uptake of water, the hydrogels used in the present invention will also swell and provide a layer of water around the electrodes to which the hydrogels are attached. The hydrogels can be prepared from (a) a diisocyanate, (b) a hydrophilic polymer which is a hydrophilic diol, a hydrophilic diamine, or a combination thereof, and optionally, (c) a chain extender.
摘要翻译： 提供了通过用均匀的水凝胶涂覆生物传感器的表面来减少植入式生物传感器的电极阻抗的方法，其允许围绕传感器的不受阻碍的水移动。 表面涂层是生物相容性并且能够吸收其重量的至少120％，更优选至少其重量的200％的组合物。 在吸收水时，本发明中使用的水凝胶也将溶胀并在水凝胶附着的电极周围提供一层水。 水凝胶可以由（a）二异氰酸酯，（b）亲水性聚合物，亲水性二醇，亲水二胺或其组合，和任选的（c）扩链剂制备。
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9.发明授权Long wave fluorophore sensor compounds and other fluorescent sensor compounds in polymers 有权长波荧光团传感器化合物等聚合物中的荧光传感器化合物公开(公告)号：US06766183B2
公开(公告)日：2004-07-20
申请号：US10033240
申请日：2001-12-28
申请人： Joseph C. Walsh , Aaron M. Heiss , Glenn Noronha , David J. Vachon , Stephen M. Lane , Joe H. Satcher, Jr. , Thomas A. Peyser , William Peter Van Antwerp , John Joseph Mastrototaro
发明人： Joseph C. Walsh , Aaron M. Heiss , Glenn Noronha , David J. Vachon , Stephen M. Lane , Joe H. Satcher, Jr. , Thomas A. Peyser , William Peter Van Antwerp , John Joseph Mastrototaro
IPC分类号： A61B500
CPC分类号： A61B5/1455 , A61B5/0071 , A61B5/14532 , C12Q1/005 , G01N33/66 , Y10T436/143333 , Y10T436/144444
摘要： Fluorescent biosensor molecules, fluorescent biosensors and systems, as well as methods of making and using these biosensor molecules and systems are described. Embodiments of these biosensor molecules exhibit fluorescence emission at wavelengths greater than about 650 nm. Typical biosensor molecules include a fluorophore that includes an iminium ion, a linker moiety that includes a group that is an anilinic type of relationship to the fluorophore and a boronate substrate recognition/binding moiety, which binds glucose. The fluorescence molecules modulated by the presence or absence of polyhydroxylated analytes such as glucose. This property of these molecules of the invention, as well as their ability to emit fluorescent light at greater than about 650 nm, renders these biosensor molecules particularly well-suited for detecting and measuring in-vivo glucose concentrations.
摘要翻译： 描述荧光生物传感器分子，荧光生物传感器和系统，以及制造和使用这些生物传感器分子和系统的方法。 这些生物传感器分子的实施例在大于约650nm的波长处表现出荧光发射。 典型的生物传感器分子包括包含亚胺离子的荧光团，连接部分，其包含与荧光团相关的苯胺型的基团和结合葡萄糖的硼酸酯底物识别/结合部分。 通过存在或不存在多羟基化分析物如葡萄糖来调节荧光分子。 本发明的这些分子的这种性质以及它们在大于约650nm发射荧光的能力使得这些生物传感器分子特别适用于检测和测量体内葡萄糖浓度。
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10.发明授权Detection of biological molecules using chemical amplification and optical sensors 有权使用化学放大和光学传感器检测生物分子公开(公告)号：US06319540B1
公开(公告)日：2001-11-20
申请号：US09401147
申请日：1999-09-22
IPC分类号： A61L5103
CPC分类号： A61B5/1459 , A61B5/14532 , C12Q1/005
摘要： Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal. Specifically, the analyte transducer immobilized in a polymeric matrix can be a boronic acid moiety.
摘要翻译： 提供了用于确定多羟基化合物，特别是葡萄糖的生物水平浓度的方法。 该方法利用扩增系统，其是固定在聚合物基质中的分析物传感器，其中系统是可植入的和生物相容的。 在通过光学系统询问时，放大系统产生能够在患者皮肤外部检测的信号。 感兴趣的分析物的定量通过测量发射的信号来实现。 具体地，固定在聚合物基质中的分析物传感器可以是硼酸部分。
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