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1. 发明申请

WO1994004176A1 NOVEL PEPTIDES FOR HEPARIN ANTICOAGULATION REVERSAL 审中-公开
标题翻译： HEPARIN抗体逆转的新肽
公开(公告)号：WO1994004176A1
公开(公告)日：1994-03-03
申请号：PCT/US1992006829
申请日：1992-08-14
申请人： UNIVERSITY OF MICHIGAN , WAKEFIELD, Thomas, W. , STANLEY, James, C. , ANDREWS, Philip, C.
发明人： UNIVERSITY OF MICHIGAN
IPC分类号： A61K37/02
CPC分类号： C07K14/46 , A61K38/00 , C07K14/001
摘要： Less toxic agents for reversal of heparin anticoagulation which are synthetic protamine-like polycationic peptides having a total cationic charge which is less than that of n-protamine. In preferred embodiments, arginine residues of n-protamine are replaced with lysine residues for ease of manufacture. Selective positively charged arginine residues have been replaced with an uncharged amino acid residue or its analog, such as glycine or glutamine, in order to reduce the total cationic charge on the polycationic peptide to the range of about +14 to +18, preferably +16. In specific embodiments, there are sequences of 29 amino acid residues wherein 4 to 5 clusters of 2 to 4 positively charged amino acids are separated by 2 to 6 neutral amino acids.
摘要翻译：具有逆转肝素抗凝剂的毒性较小的药物，其是具有小于正精蛋白的总阳离子电荷的合成鱼精蛋白样聚阳离子肽。在优选的实施方案中，为了易于制造，将n-鱼精蛋白的精氨酸残基替换为赖氨酸残基。选择性带正电的精氨酸残基已被不带电荷的氨基酸残基或其类似物如甘氨酸或谷氨酰胺替代，以便将聚阳离子肽上的总阳离子电荷降低至约+14至+18，优选+16 。在具体实施方案中，存在29个氨基酸残基的序列，其中2至4个带正电荷的氨基酸的4至5个簇被2至6个中性氨基酸分离。

2. 发明申请

WO1992015312A1 PHARMACEUTICAL COMPOSITIONS AND USES OF WATER-SOLUBLE, HIGH-VISCOSITY GRADE CELLULOSE ETHERS 审中-公开
标题翻译：药物组合物和水溶性高粘度级纤维素醚的用途
公开(公告)号：WO1992015312A1
公开(公告)日：1992-09-17
申请号：PCT/US1992001515
申请日：1992-02-28
申请人： UNIVERSITY OF MICHIGAN , THE DOW CHEMICAL COMPANY
发明人： UNIVERSITY OF MICHIGAN , THE DOW CHEMICAL COMPANY , DRESSMAN, Jennifer, B. , REPPAS, Christos , TOBEY, Stephen, W. , SOWLE, Cynthia, W.
IPC分类号： A61K31/715
CPC分类号： A61K9/0056 , A21D2/188 , A21D13/80 , A61K31/715 , A61K31/717
摘要： Water-soluble, high-viscosity grade cellulose ether compositions are useful for the reduction of serum lipid levels, particularly total serum cholesterol, serum triglycerides, and low-density lipoprotein (LDL) levels or attenuate the postprandial rise of blood glucose levels in animals. The pharmaceutical uses of compositions for reducing cholesterol levels additionally include the treatment of diabetes and/or hypercholesterolemia, with avoidance of many of the undesirable side effects associated with other forms of treatment. The composition may be in the form of a prehydrated ingestible composition, such as a gelatin, or a comestible, such as a cookie. In addition, the compositions of the present invention are palatable to the patient, thereby enhancing patient compliance with the regimen.
摘要翻译：水溶性高粘度级纤维素醚组合物可用于降低血清脂质水平，特别是总血清胆固醇，血清甘油三酯和低密度脂蛋白（LDL）水平，或减弱动物血糖水平的餐后升高。用于降低胆固醇水平的组合物的药物用途另外包括治疗糖尿病和/或高胆固醇血症，避免与其它形式的治疗相关的许多不期望的副作用。组合物可以是预先水合的可摄入组合物的形式，例如明胶，或可食用的，例如饼干。此外，本发明的组合物对患者是可口的，从而增强患者对该方案的依从性。

3. 发明申请

WO1996035444A1 NOVEL PEPTIDES FOR HEPARIN AND LOW MOLECULAR WEIGHT HEPARIN ANTICOAGULATION REVERSAL 审中-公开
标题翻译： HEPARIN和低分子量HEPARIN抗体逆转的新肽
公开(公告)号：WO1996035444A1
公开(公告)日：1996-11-14
申请号：PCT/US1996006567
申请日：1996-05-08
申请人： UNIVERSITY OF MICHIGAN
发明人： UNIVERSITY OF MICHIGAN , WAKEFIELD, Thomas, W. , STANLEY, James, C. , ANDREWS, Philip, C.
IPC分类号： A61K38/10
CPC分类号： C07K14/001 , A61K38/00 , C07K14/46
摘要： Less toxic agents for reversal of heparin or low molecular weight heparin anticoagulation which are synthetic protamine-like polycationic peptides having a total cationic charge which is less than that of n-protamine. In preferred embodiments, arginine residues of n-protamine are replaced with lysine residues for ease of manufacture. Selective positively charged arginine residues have been replaced with an uncharged amino acid residue or its analog, such as glycine or glutamine, in order to reduce the total cationic charge on the polycationic peptide to the range of about [+14] to [+18], preferably [+16] to [+18]. In specific embodiments, there are sequences of 29 and 32 amino acid residues wherein 4 to 5 clusters of 2 to 4 positively charged amino acids are separated by 2 to 6 neutral amino acids. The C-terminus and the N-terminus can be modified to mitigate against in vivo degradation by carboxypeptidases and aminopeptidases. Another modification, specifically use of alpha -helix forming amino acids, such as glutamic acid, further promotes anticoagulation reversal. A still further modification includes the incorporation of a cell adhesion ligand, such as the RGD sequence, into the synthetic protamine-like polycationic peptide.
摘要翻译：具有逆转肝素或低分子量肝素抗凝剂的毒性较小的药物，其具有小于正精蛋白的总阳离子电荷的合成鱼精蛋白样聚阳离子肽。在优选的实施方案中，为了易于制造，将n-鱼精蛋白的精氨酸残基替换为赖氨酸残基。选择性带正电的精氨酸残基已被不带电荷的氨基酸残基或其类似物（如甘氨酸或谷氨酰胺）替代，以便将聚阳离子肽上的总阳离子电荷降低至约[+ 14]至[+ 18] ，优选[+ 16]至[+ 18]。在具体实施方案中，存在29和32个氨基酸残基的序列，其中2至4个带正电荷的氨基酸的4至5个簇被2至6个中性氨基酸分开。可以修饰C-末端和N-末端以减轻羧肽酶和氨基肽酶的体内降解。另一个修改，特别是使用α-螺旋形成氨基酸，如谷氨酸，进一步促进抗凝反转。另外的修饰包括将细胞粘附配体如RGD序列并入合成的鱼精蛋白样聚阳离子肽中。

4. 发明申请

WO1994001388A1 CYCLOBUTABENZENE MONOMERS AND METHODS OF MAKING AND USING SAME 审中-公开
标题翻译：环己烷单体及其制备方法和使用方法
公开(公告)号：WO1994001388A1
公开(公告)日：1994-01-20
申请号：PCT/US1993006267
申请日：1993-07-01
申请人： UNIVERSITY OF MICHIGAN
发明人： UNIVERSITY OF MICHIGAN , MARTIN, David, C. , MOORE, Jeffrey, S. , MARKOSKI, Larry, J. , WALKER, Kenneth, A.
IPC分类号： C07C39/12
CPC分类号： C07C265/14 , C07C37/00 , C07C63/38 , C07C63/49 , C07C63/72 , C07C211/61 , C07C233/65 , C07C2602/06 , C07C2603/08 , C08G65/4012 , C08G69/26 , C08G69/32 , C07C39/17
摘要： Novel difunctionalized cyclobutabenzene monomers of general formula (I), wherein Z can be hydrogens or a cyclobutane ring; and X and Y are carboxyl, amino, alcohol, isocyanate, acid halide, or bis-acyl fluoride groups. Methods of making the novel cyclobutabenzene monomers regioselectively introduce a functionality onto the 3 and 6 positions. In a particularly preferred embodiment, the cyclobutabenzene derivative is 1,2-dihydrocyclobutabenzene-3,6-carboxylic acid. 1,2-Dihydrocyclobutabenzene-3-6-carboxylic acid, for example, can be used as a substitute for, or in conjuction with, terephthalic acid or its acid chloride analog to create high performance resins, such as poly(ether ether ketone ketone) or poly(paraphenylene diamine terephthalate) with the cyclobutabenzene moiety as part of the polymer backbone chain. The butane ring functionality on the cyclobutabenzene moiety can be easily opened to produce strong, covalent bond cross-linking between polymer chains.
摘要翻译：通式（I）的新型二官能化环丁苯类单体，其中Z可以是氢或环丁烷环; 并且X和Y是羧基，氨基，醇，异氰酸酯，酰卤或双酰基氟基团。制备新型环丁烯类单体的方法将功能区域选择性地引入到3和6位上。在一个特别优选的实施方案中，环丁苯衍生物是1,2-二氢环丁碱-3,6 - 羧酸。例如，1,2-二氢环丁烷-3-甲酸可用作对苯二甲酸或其酰基氯类似物的替代物，或与对苯二甲酸或其酰基氯类似物结合使用以产生高性能树脂，例如聚（醚醚酮酮）或聚（对苯二胺对苯二甲酸酯）与环丁基部分作为聚合物主链的一部分。环丁二烯部分上的丁烷环功能可以容易地打开以在聚合物链之间产生强的共价键交联。

5. 发明申请

WO1993009860A1 CONTINUOUS MULTICOMPONENT FOCUSING IN A MAGNETICALLY STABILIZED FLUIDIZED BED 审中-公开
标题翻译：连续多重聚焦于磁稳定流化床
公开(公告)号：WO1993009860A1
公开(公告)日：1993-05-27
申请号：PCT/US1992009866
申请日：1992-11-13
申请人： UNIVERSITY OF MICHIGAN
发明人： UNIVERSITY OF MICHIGAN , BURNS, Mark, A. , EVANS, Lisa, L.
IPC分类号： B01D15/04
CPC分类号： B01J47/10 , B01D15/02 , B01D15/1807 , B01D15/3885 , B01D2215/021
摘要： A device, and process, for continuously separating dissolved solutes and/or suspended particles from a multicomponent fluid phase in a magnetically stabilized fluidized bed (60). The process is of the type wherein a solid resin and a liquid buffer move countercurrent to each other in the bed. In steady state operation, a time invariant pH gradient will form in the bed and remain spatially fixed. Other condition variables, such as temperature, can be used to form a time invariant fixed gradient provided that equilibrium partition between the solid and liquid phases is a function of the condition variable.
摘要翻译：一种用于在磁稳定流化床（60）中从多组分流体相连续分离溶解的溶质和/或悬浮颗粒的装置和方法。该方法是其中固体树脂和液体缓冲液在床中相互逆流的类型。在稳态操作中，时间不变的pH梯度将形成在床上并保持空间固定。其他条件变量（如温度）可用于形成时间不变的固定梯度，条件是固相和液相之间的平衡分配是条件变量的函数。

6. 发明申请

WO1991005262A1 BIOANALYTICAL DETECTION SYSTEM 审中-公开
标题翻译：生物检测系统
公开(公告)号：WO1991005262A1
公开(公告)日：1991-04-18
申请号：PCT/US1990005511
申请日：1990-09-27
申请人： UNIVERSITY OF MICHIGAN
发明人： UNIVERSITY OF MICHIGAN , SCHRAMM, Willfried
IPC分类号： G01N33/543
CPC分类号： G01N33/54366 , G01N33/743 , Y10S435/817 , Y10S436/806 , Y10S436/807
摘要： A device and process for detecting the presence of organic molecular analytes in a fluid comprising a first binding (18) component having a predetermined first affinity for specifically reversibly binding an analyte, a molecular conjugate of the analyte with a signal generating molecule that generates a detectable signal, and a second binding (20) component having a predetermined second affinity for reversibly binding the signal generating molecule. In the presence of analyte, a fluid conducting system allows competitive binding of the analyte with the molecular conjugate and causes displacement of the conjugate and conducts the displaced conjugate to the second binding component. The signal generating molecule generates a detectable signal distinguishing binding thereof at the first or second binding components thereby indicating the presence of the analyte in the fluid.
摘要翻译：一种用于检测流体中有机分子分析物的存在的装置和方法，包括具有预定的第一亲和力的第一结合（18）组分，用于特异性可逆地结合分析物，分析物的分子结合物与产生可检测的信号产生分子信号，以及具有预定的第二亲和力的可逆结合信号产生分子的第二结合（20）组分。在分析物的存在下，流体传导系统允许分析物与分子共轭物的竞争性结合并引起缀合物的位移并将置换的缀合物导向第二结合成分。信号产生分子产生区分其在第一或第二结合组分上的结合的可检测信号，从而指示分析物在流体中的存在。

7. 发明申请

WO1994003948A1 MODE-LOCKED UPCONVERSION LASER SOURCE 审中-公开
标题翻译：模式锁定的UPCONVERSION激光源
公开(公告)号：WO1994003948A1
公开(公告)日：1994-02-17
申请号：PCT/US1993007355
申请日：1993-08-05
申请人： UNIVERSITY OF MICHIGAN
发明人： UNIVERSITY OF MICHIGAN , RAND, Stephen, C.
IPC分类号： H01S03/090
CPC分类号： H01S3/094 , H01S3/081 , H01S3/094038 , H01S3/094092 , H01S3/1121 , H01S3/117 , H01S3/1608 , H01S3/165 , H01S3/1653
摘要： A laser source which operated under the principle of cooperative upconversion produces controllable optical pulses at wavelengths which are shorter than the wavelength of the laser energy which pumps the gain medium. The source is a solid-state laser which employs a five percent Er:LiYF crystal (Xtal) which is arranged in an astigmatically-compensated 3-mirror cavity (M1, M2, and M3). Pumping is achieved at 1.5 microns in the infrared, and the system operates in a continuous-wave, mode-lock fashion in the green spectral region at approximately 544 nm. The cooperative inversion mechanism involves energy pooling by trios of excited rare earth dopant ions in the laser medium. Q-switching is achieved with the use of intracavity amplitude modulation so as to achieve three-fold upconversion. A 3-mirror astigmatically-compensated cavity with the gain medium permits modulation of losses in a manner which cannot be achieved with known systems and achieves high stability.
摘要翻译：在协调上变频原理下运行的激光源产生的脉冲长度比泵浦增益介质的激光能量的波长短。该源是使用布置在散光补偿的3镜腔（M1，M2和M3）中的5％Er：LiYF晶体（Xtal）的固态激光器。在红外线中以1.5微米的速度实现泵送，并且系统以约544nm的绿色光谱区域中的连续波模式锁定方式工作。合作反演机制涉及在激光介质中通过激发的稀土掺杂剂离子三元组的能量汇集。通过使用腔内振幅调制实现Q开关，以实现三倍上变频。具有增益介质的3镜式散光补偿腔允许以已知系统无法实现的方式调制损耗并实现高稳定性。

8. 发明申请

WO1993023757A1 HIGH-SPEED, HIGH-IMPEDANCE EXTERNAL PHOTOCONDUCTIVE-TYPE SAMPLING PROBE/PULSER 审中-公开
标题翻译：高速，高阻抗外部光电导型采样探头/脉冲
公开(公告)号：WO1993023757A1
公开(公告)日：1993-11-25
申请号：PCT/US1993004535
申请日：1993-05-12
申请人： UNIVERSITY OF MICHIGAN
发明人： UNIVERSITY OF MICHIGAN , WILLIAMSON, Steven, Lee
IPC分类号： G01R01/073
CPC分类号： G01R1/06772
摘要： A photoresponsive pulser/sampler system for investigating electrical signals and responses in VLSI systems employs a microtip (36)which communicates electrically and mechanically with the device under test, and electrically with an electrode (33, 34) via a photoresponsive gate (37, 38). The photoresponsive gate (37, 38) is formed of interdigitated electrodes which have interdigital spacings therebetween on the order of 1 νm. The structure of the invention is operable in the dual modalities of probe and pulser which share a common probe tip (36). Simultaneous implementation of the pulser and sampler functions is achieved with the use of a lock-in amplifier and the technique of difference frequency mixing, where the pulser optical pulse frequency is f1 and the gate optical pulse frequency is f2. Multiple photoresponsive gates (37, 38) coupled to a common probe tip (36) and having respective electrodes (33, 34) are disclosed for achieving respective pulsing and sampling functions, and also for effecting S-parameter measurements. The lock-in amplifier is tuned to the difference between the two frequencies (f2-f1). Piezoelectric apparatus is employed for translating the probe tip (36) over the device under test.

9. 发明申请

WO1993018396A1 HEPARIN-SELECTIVE POLYMERIC MEMBRANE ELECTRODE 审中-公开
标题翻译： HEPARIN-选择性聚合物膜电极
公开(公告)号：WO1993018396A1
公开(公告)日：1993-09-16
申请号：PCT/US1993002149
申请日：1993-03-10
申请人： UNIVERSITY OF MICHIGAN
发明人： UNIVERSITY OF MICHIGAN , MA, Shu-Ching , MEYERHOFF, Mark, E. , YANG, Victor, C.
IPC分类号： G01N27/26
CPC分类号： G01N27/3335 , Y10S435/817
摘要： An anion exchange membrane (15) for ionic macromolecules, specifically heparin, which is formed of a polymeric matrix material, an anion exchange material suitable for heparin detection, and a plasticizer can be employed in an electrochemical sensor arrangement to directly measure the concentration of heparin ions in blood or blood fluid. Potentiometric response to heparin has been observed with membranes comprising 30-70 wt.% polymeric matrix material, such as polyvinyl chloride, 0.1-12 wt.% quaternary ammonium salt, such as tridodecyl methyl ammonium chloride, and 30-70 wt.% of a plasticizer, such as dioctyl sebacate.

10. 发明申请

WO1991003745A1 MULTI-ELEMENT-AMORPHOUS-SILICON-DETECTOR-ARRAY FOR REAL-TIME IMAGING AND DOSIMETRY OF MEGAVOLTAGE PHOTONS AND DIAGNOSTIC X-RAYS 审中-公开
标题翻译：多元非晶硅检测器阵列用于实时成像和量子化学测量光子和诊断X射线
公开(公告)号：WO1991003745A1
公开(公告)日：1991-03-21
申请号：PCT/US1990005029
申请日：1990-09-06
申请人： UNIVERSITY OF MICHIGAN , XEROX CORPORATION
发明人： UNIVERSITY OF MICHIGAN , XEROX CORPORATION , ANTONUK, Larry, E. , STREET, Robert, A.
IPC分类号： G01T01/20
CPC分类号： A61B6/032 , A61N5/1048 , A61N5/1049 , A61N2005/1054 , A61N2005/1072 , G01T1/2018 , G01T1/2928 , H01L27/14609 , H01L27/14618 , H01L27/14663 , H01L2924/0002 , H01L2924/00
摘要： A multi-element-amorphous-silicon detector-array real-time imager and dosimeter for diagnostic or megavoltage X rays having megavoltage photons having a plurality of photodiodes (30) made of hydrogenated amorphous silicon arrayed in columns and rows upon a glass substrate (12). Each photodiode (30) is connected to a thin film field effect transistor (52) also located upon the glass substrate (12). Upper and lower metal contacts (22, 38) are located below and above the photodiodes (30) to provide the photodiodes (30) with a reverse bias. The capacitance of each photodiode (30) when multiplied by the resistance of the field effect transistor (52) to which it is connected yields an RC time constant sufficiently small to allow real time imaging.
摘要翻译：一种用于诊断或兆伏X射线的多元非晶硅检测器阵列实时成像器和剂量计，具有兆伏特光子，其具有由玻璃基板（12）上的列和列排列的氢化非晶硅制成的多个光电二极管（30））。每个光电二极管（30）连接到也位于玻璃基板（12）上的薄膜场效应晶体管（52）。上和下金属触点（22,38）位于光电二极管（30）的下方和上方，以向光电二极管（30）提供反向偏压。当与其连接的场效应晶体管（52）的电阻相乘时，每个光电二极管（30）的电容产生足够小的RC时间常数以允许实时成像。

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