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1. 发明申请

WO1994021237A1 SYSTEM FOR CONTROLLED RELEASE OF ANTIARRHYTHMIC AGENTS 审中-公开
标题翻译：用于控制释放抗菌剂的系统
公开(公告)号：WO1994021237A1
公开(公告)日：1994-09-29
申请号：PCT/US1994002838
申请日：1994-03-15
申请人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN , LEVY, Robert, J. , SINTOV, Amnon
发明人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： A61K09/22
CPC分类号： A61K9/0024 , A61L31/16 , A61L2300/40 , A61L2300/602 , A61N1/362 , A61N1/3956
摘要： A system for controlled release, site-specific delivery of therapeutic agents, particularly myocardial agents such as antiarrhythmic agents, comprises a biocompatible polymeric patch (30) with an incorporated therapeutic agent for direct placement at the epicardium of heart (31). The dosage form is fabricated so as to tailor the release characteristics as required by the nature of the physical condition desired to be treated. In a specific illustrative embodiment, ibutilide, a potent, but toxic, Class III antiarrhythmic agent, is incorporated in polyurethane and solvent-cast to form a monolithic drug delivery device which can be co-implanted with an implantable cardiac defibrillator. Advantageously, very low doses of ibutilide administered directly to the epicardium in this manner produces a reduction in defibrillation threshold.
摘要翻译：治疗剂，特别是心肌药物如抗心律不齐剂的控释，位点特异性递送系统包括具有用于直接置于心脏心外膜（31）的并入治疗剂的生物相容性聚合物贴片（30）。制造剂型以根据期望治疗的物理条件的性质来定制释放特征。在具体的说明性实施方案中，将ibutilide（一种有效但有毒的III类抗心律失常药物）掺入聚氨酯和溶剂浇铸以形成可与植入式心脏除颤器共同植入的整体药物递送装置。有利地，以这种方式直接施用于心外膜的非常低剂量的伊布利特产生除颤阈值的降低。

2. 发明申请

WO2020037109A1 PROCESSES FOR FLUORINATION 审中-公开
公开(公告)号：WO2020037109A1
公开(公告)日：2020-02-20
申请号：PCT/US2019/046627
申请日：2019-08-15
申请人： DOW AGROSCIENCES LLC , THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： SANFORD, Melanie S. , SCHIMLER, Sydonie D. , RINGER, James W. , BLAND, Douglas , MELVIN, Patrick R. , FERGUSON, Devin
IPC分类号： A61K31/4196 , A61K31/435
摘要： The present technology relates to fluorination reactions. Specifically, processes useful for making the fungicide compound, DFT are disclosed. More broadly, also disclosed herein are processes useful for deoxyfluorination at the α-aromatic position of a given compound.

3. 发明申请

WO1995020008A1 CALCIFICATION-RESISTANT BIOMATERIALS 审中-公开
标题翻译：耐辐射生物材料
公开(公告)号：WO1995020008A1
公开(公告)日：1995-07-27
申请号：PCT/US1995000876
申请日：1995-01-20
申请人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN , LEVY, Robert, J. , JOSHI, Ravindra, R.
发明人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： C08K03/32
CPC分类号： C08K5/5353 , A61L27/14 , A61L27/18 , A61L27/50 , A61L27/54 , A61L33/0011 , A61L2400/02 , C08G59/1488 , C08L101/02 , C08L75/04 , C08L83/04 , C08L83/10
摘要： Synthetic biomaterials are provided with irreversibly bound amino diphosphonate, polyphosphonate, or other anticalcification agent to prevent in vivo calcification. Such biomaterials include biocompatible elastomers such as polyurethane and/or polydimethylsiloxane, and the like which are intended for invasive, or indwelling use in a human or animal body. Illustratively, reaction conditions utilizing bi- or polyfunctional epoxides result in epoxide bridge incorporation of an anticalcification agent and/or an anticoagulant, such as heparin, to the biomaterial elastomer.
摘要翻译：提供合成生物材料具有不可逆结合的氨基二膦酸盐，聚膦酸盐或其它抗细胞剂以防止体内钙化。这样的生物材料包括生物相容性弹性体，例如聚氨酯和/或聚二甲基硅氧烷等，其旨在用于人或动物体内的侵入性或留置性使用。说明性地，使用双官能或多官能环氧化物的反应条件导致抗氧化剂和/或抗凝血剂如肝素的环氧化物桥结合到生物材料弹性体。

4. 发明申请

WO1995005268A1 MACHINE BALANCER WITH PERISTALTIC FLUID PUMP 审中-公开
标题翻译：机械平衡泵与普通液体泵
公开(公告)号：WO1995005268A1
公开(公告)日：1995-02-23
申请号：PCT/US1994009197
申请日：1994-08-12
申请人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN , MURTUZA, Syed , BOFFI, Luiz, V.
IPC分类号： B25B41/04
CPC分类号： F04B43/1292 , B24B41/042 , Y10T74/2123
摘要： A balancer arrangement (10) for a rotating machine element employs a peristaltic pump (18) which pumps a balancing fluid to respective balancing chambers (12/14) via flexible tubing (17). In an arrangement which employs four balancing chambers (12/14 and 13/15), two peristaltic pumps (18 and 23) may be employed to control the flow of balancing fluid between respective pairs of the chambers. The radial positioning of the peristaltic pumps is not fixed, but may be selected in response to specific characteristics of the application. In addition, the pump motors (25 and 26) may be configured to drive the peristaltic pump rollers by operation of the rotation of the motor shaft, or the motor housing. The tubing along which the balancing fluid is conducted need not have a circular cross-section, and may be installed in a groove or cavity (65) of the balancing arrangement so as to secure against centrifugal forces and prevent ballooning effects. Variations in air pressure which are developed amongst the balancing chambers by operating of the delivery and withdrawal of balancing fluid are equilized via capillary passages (28 and 29) which interconnect ones of the balancing chambers.
摘要翻译：用于旋转机器元件的平衡器装置（10）使用蠕动泵（18），其通过柔性管道（17）将平衡流体泵送到相应的平衡室（12/14）。在采用四个平衡室（12/14和13/15）的布置中，可以使用两个蠕动泵（18和23）来控制各对室之间的平衡流体的流动。蠕动泵的径向定位不是固定的，而是可以响应于应用的特定特性来选择。此外，泵马达（25,26）可以构造成通过马达轴或马达壳体的旋转运动来驱动蠕动泵辊。导向平衡流体的管道不必具有圆形横截面，并且可以安装在平衡装置的凹槽或空腔（65）中，以便抵抗离心力并防止气球效应。通过操作平衡流体的输送和取出在平衡室中产生的空气压力的变化通过将一个平衡室相互连接的毛细通道（28和29）来确定。

5. 发明申请

WO1995005596A1 HEPARIN-SELECTIVE POLYMERIC MEMBRANE 审中-公开
标题翻译： HEPARIN-选择性聚合物膜
公开(公告)号：WO1995005596A1
公开(公告)日：1995-02-23
申请号：PCT/US1994009220
申请日：1994-08-16
申请人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE BOARD OF REGENTS OF THE 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 and an anion exchange material suitable for heparin detection 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 (TDMAC), and 30-70 wt. % of a plasticizer, such as dioctyl sebacate. A solid state sensor (200) employs TDMAC dissolved in a polymeric compound, such as silicone rubber, to form a membrane (270) which is responsive to heparin concentration.
摘要翻译：用于离子大分子的阴离子交换膜（15），特别是由聚合物基体材料形成的肝素和适用于肝素检测的阴离子交换材料，可用于电化学传感器装置中，以直接测量血液中肝素离子的浓度，血液已经观察到对肝素的电位反应，包括30-70wt。％聚合物基质材料，例如聚氯乙烯，0.1-12wt。％季铵盐，如十三烷基甲基氯化铵（TDMAC）和30-70wt。％的增塑剂，如癸二酸二辛酯。固体传感器（200）使用溶解在诸如硅橡胶的聚合物中的TDMAC来形成对肝素浓度有响应的膜（270）。

6. 发明申请

WO1995031181A1 HEPATOCYTE-SELECTIVE OIL-IN-WATER EMULSION 审中-公开
标题翻译：肝脏选择性水中乳化液
公开(公告)号：WO1995031181A1
公开(公告)日：1995-11-23
申请号：PCT/US1995005974
申请日：1995-05-16
申请人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN , COUNSELL, Raymond, E. , LONGINO, Marc, A. , WEICHERT, Jamey, P. , BAKAN, Douglas, A.
发明人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： A61K09/107
CPC分类号： A61K9/1075 , A61K9/1275 , A61K49/0433 , A61K49/1806 , A61K51/1217 , Y10S514/893 , Y10S514/894 , Y10S514/938 , Y10S514/941 , Y10S516/923 , Y10S516/93
摘要： A heat and shelf-stable oil-in-water emulsion useful as a tissue or cell-selective delivery vehicle. Radioactive or stable, synthetic or semi-synthetic polyhalogenated triglycerides, such as 2-oleoylglycerol-1,3-bis[7-(3-amino-2,4,6-triiodophenyl)heptanoate] or 2-oleoylglycerol-1,3-bis[ omega -(3,5-bis-trifluoromethyl)-heptanoate] or phenyl acetate, can be incorporated into the lipophilic core of a lipoprotein-like emulsion particle. The lipophilic core is surrounded by a phospholipid membrane comprising cholesterol and apolipoproteins. For hepatocyte-selective delivery, the emulsion is chylomicron remnant-like by being in a size range of 50 to 200 nm as measured by number weighting analysis with a narrow size distribution (
摘要翻译：可用作组织或细胞选择性递送载体的热和储存稳定的水包油乳液。放射性或稳定的合成或半合成多卤甘油三酸酯，如2-油酰甘油-1,3-双[7-（3-氨基-2,4,6-三碘苯基）庚酸酯]或2-油酰甘油-1,3-二双（ω-（3,5-双 - 三氟甲基） - 庚酸酯]或乙酸苯酯可加入脂蛋白样乳液颗粒的亲脂性核心中。亲脂性核被包含胆固醇和载脂蛋白的磷脂膜包围。对于肝细胞选择性递送，通过具有窄尺寸分布的数量加权分析（<3％大于300nm）测量并具有自然模拟的组成，通过在50至200nm的尺寸范围内，乳液是乳糜微粒残留的发生乳糜微粒残留物。在乳液配方中使用胆固醇促进载脂蛋白，特别是由肝细胞识别并且是结合和摄取所必需的Apo E的缔合。稳定性和尺寸限制可以通过超高能量混合设备（例如MicroFluidizer（Microfluidics Corp.，Newton，MA））来实现，以形成乳液。在优选的实施方案中，乳液的重量摩尔渗透压浓度由甘油而不是生理盐水控制。

7. 发明授权

EP0871431B1 HEPATOCYTE-SELECTIVE OIL-IN-WATER EMULSION 失效
标题翻译：肝细胞选择性油包水乳液
公开(公告)号：EP0871431B1
公开(公告)日：2005-07-20
申请号：EP95919814.4
申请日：1995-05-16
申请人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： COUNSELL, Raymond, E. , LONGINO, Marc, A. , WEICHERT, Jamey, P. , BAKAN, Douglas, A., Molecular Biosystems, Inc.
IPC分类号： A61K9/107 , A61K49/00 , A61K49/04 , A61K51/12
CPC分类号： A61K9/1075 , A61K9/1275 , A61K49/0433 , A61K49/1806 , A61K51/1217 , Y10S514/893 , Y10S514/894 , Y10S514/938 , Y10S514/941 , Y10S516/923 , Y10S516/93
摘要： A heat and shelf-stable oil-in-water emulsion useful as a tissue or cell-selective delivery vehicle. Radioactive or stable, synthetic or semi-synthetic polyhalogenated triglycerides, such as 2-oleoylglycerol-1,3-bis[7-(3-amino-2,4,6-triiodophenyl)heptanoate] or 2-oleoylglycerol-1,3-bis[ omega -(3,5-bis-trifluoromethyl)-heptanoate] or phenyl acetate, can be incorporated into the lipophilic core of a lipoprotein-like emulsion particle. The lipophilic core is surrounded by a phospholipid membrane comprising cholesterol and apolipoproteins. For hepatocyte-selective delivery, the emulsion is chylomicron remnant-like by being in a size range of 50 to 200 nm as measured by number weighting analysis with a narrow size distribution (

8. 发明公开

EP0917592A1 ATTENUATED RESPIRATORY SYNCYTIAL VIRUS 失效
标题翻译：减毒RSV
公开(公告)号：EP0917592A1
公开(公告)日：1999-05-26
申请号：EP97920111.0
申请日：1997-04-03
申请人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： MAASSAB, Hunein, F. , HERLOCHER, M., Louise
IPC分类号： A61K39 , C07K14 , C12N7
CPC分类号： C07K14/005 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/543 , A61K2039/545 , A61K2039/55566 , A61K2039/57 , C12N7/00 , C12N2760/18522 , C12N2760/18534 , C12N2760/18564
摘要： Attenuated respiratory syncytial viruses (RSV) and in particular temperature sensitive RSV are provided. The viruses of the present invention may be used in pharmaceutical compositions such as vaccines. Methods of making and using such pharmaceutical compositions are also provided.

9. 发明公开

EP0737073A1 NOVEL PEPTIDES FOR HEPARIN AND LOW MOLECULAR WEIGHT HEPARIN ANTICOAGULATION REVERSAL 失效
标题翻译：其中反向肝素或轻微分子量肝素的抗凝血作用的肽
公开(公告)号：EP0737073A1
公开(公告)日：1996-10-16
申请号：EP95901217.0
申请日：1994-11-10
申请人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： WAKEFIELD, Thomas, W. , STANLEY, James, C. , ANDREWS, Philip, C.
IPC分类号： C07K7 , C07K14 , A61K38
CPC分类号： C07K7/08 , A61K38/00 , C07K14/001 , 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 α-helix forming amino acids, such as glutamic acid, further promotes anticoagulation reversal.

10. 发明公开

EP0313351A3 Electric field dependent fluids 失效
标题翻译：电场依赖流体
公开(公告)号：EP0313351A3
公开(公告)日：1989-10-11
申请号：EP88309857.6
申请日：1988-10-20
申请人： THE BOARD OF REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： Filisko, Frank E. , Armstrong, William F.
IPC分类号： C10M171/00 , C10M125/26
CPC分类号： C10M171/001 , C10M125/26 , C10M2201/103 , C10N2240/20 , C10N2240/201 , C10N2240/202 , C10N2240/203 , C10N2240/204 , C10N2240/205
摘要： An improved method of inducing a change in the dynamic torque transmission of an electrorheological fluid in response to an electric field at low current comprising the steps of: (a) selecting a nonconductive liquid phase (e.g. high dielectric hydrocarbon oil); (b) dispersing in the nonconductive liquid phase a particulate phase substantially free of adsorbed water (e.g. zeolite): and (c) subjecting the resulting electrorheological fluid to an electric potential in excess of about one kilovolt at a current density of less than about one-third microamp per square inch. Such a method achieves a rate of increase of dynamic transmission of torque per unit voltage, dM/dV, in excess of about 0.034 ft-lbs x 10⁻³/kV and a ratio of dynamic transmission of torque at an electric field strength of at least 2.4 kV to the dynamic transmission of torque at zero field strength, M/Mo, of at leeast about 2.

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