公开(公告)号：WO1993000063A1

公开(公告)日：1993-01-07

申请号：PCT/US1992005256

申请日：1992-06-25

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION ,  AEBISCHER, Patrick ,  MILLS, John, F. ,  WAHLBERG, Lars ,  DOHERTY, Edward, J.

IPC: A61J03/00

CPC classification number: A61K9/0024 ,  A61J3/07 ,  A61K9/5089 ,  B01J13/02 ,  B01J13/04 ,  C12N5/0012 ,  C12N5/0614 ,  C12N11/04 ,  C12N2533/30

Abstract: Methods for producing cell capsules are disclosed in which a coagulant (22), which can include a cell suspension or other biologically active factor, and a polymeric casting solution (26) are extruded through a common extrusion port (14) having at least two concentric bores, such that the coagulant is extruded through the inner bore (16) and the polymeric casting solution is extruded through the outer bore (18). The method involves initiating extrusion of the coagulant within a temporal range of about 10 msecs to about one second from initiating delivery of the casting solution through the respective bores. Delivery of the coagulant is then shut off, and extrusion of the casting solution is terminated either immediately or after some predetermined time.

Abstract translation: 公开了生产细胞胶囊的方法，其中可以包括细胞悬浮液或其它生物活性因子的凝结剂（22）和聚合物浇铸溶液（26）通过具有至少两个同心的共同挤出口（14）挤出 孔，使得凝结剂通过内孔（16）挤出，并且聚合物浇铸溶液通过外孔（18）挤出。 该方法包括在约10毫秒至约1秒的时间范围内启动凝结剂的挤出，从而引发浇铸溶液通过相应的孔的输送。 然后关闭凝结剂的输送，并且立即或在一些预定时间之后终止浇注溶液的挤出。

公开(公告)号：WO1992019195A1

公开(公告)日：1992-11-12

申请号：PCT/US1992003327

申请日：1992-04-22

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION ,  DIONNE, Keith, E. ,  EMERICH, Dwaine, F. ,  HOFFMAN, Diane ,  SCHARP, David, W. ,  LACY, Paul, E. ,  AEBISCHER, Patrick ,  SANBERG, Paul, R. ,  CHRISTENSON, Lisa ,  HEGRE, Orion, D. ,  VASCONCELLOS, Alfred, V. ,  LYSAGHT, Michael, J. ,  GENTILE, Frank, T.

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION

IPC: A61F13/00

CPC classification number: A61K9/0092 ,  A61K9/0024 ,  A61K9/4816 ,  A61K35/12 ,  A61K35/30 ,  A61K35/39 ,  A61K38/185 ,  A61K48/00 ,  A61K2035/126 ,  A61K2035/128 ,  C12N5/0012 ,  C12N5/0062 ,  C12N5/0614 ,  C12N5/0656 ,  C12N5/0677 ,  C12N2510/02 ,  Y10S514/814 ,  Y10S514/866

Abstract: An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual. The vehicle is particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and can also be used advantageously for delivery of high molecular weight products, such as products larger than IgG. A method of making a biocompatible, immunoisolatory implantable vehicle, consisting in a first embodiment of a coextrusion process, and in a second embodiment of a stepwise process. A method for isolating cells within a biocompatible, immunoisolatory implantable vehicle, which protects the isolated cells from attack by the immune system of an individual in whom the vehicle is implanted. A method of providing a needed biological product or metabolic function to an individual, comprising implanting into the individual an immunoisolatory vehicle containing isolated cells which produce the product or provide the metabolic function.

Abstract translation: 用于植入到产生所需产品或提供所需代谢功能的细胞个体中的免疫分析载体。 载体由含有分离的细胞和足以维持细胞的材料的核心区域组成，以及不含分离细胞的选择性选择性生物相容的外周区域，所述细胞免疫分离核心，但提供分泌产物或代谢功能的递送， 个人 该载体特别适合于从朗格汉斯的免疫隔离胰岛递送胰岛素，并且还可有利地用于递送高分子量产物，例如大于IgG的产物。 在共挤出方法的第一实施方案中和在逐步方法的第二实施方案中制备生物相容的免疫隔离可植入载体的方法。 一种用于分离生物相容的免疫隔离可植入载体中的细胞的方法，其保护分离的细胞免受被植入其中的个体的免疫系统的攻击。 向个体提供所需的生物制品或代谢功能的方法，包括向个体植入包含产生产物或提供代谢功能的分离细胞的免疫隔离载体。

公开(公告)号：WO1990005490A1

公开(公告)日：1990-05-31

申请号：PCT/US1989004894

申请日：1989-10-31

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION ,  AEBISCHER, Patrick ,  DARIO, Paolo ,  SABATINI, Angelo ,  VALENTINI, Robert, F.

IPC: A61B17/11

CPC classification number: A61B17/1128 ,  A61B17/00491 ,  A61F2002/30235 ,  A61F2230/0069 ,  A61L31/14 ,  A61L2430/32

Abstract: A medical device is disclosed for use in regenerating a severed nerve, including a tubular, biocompatible, electrically-charged membrane or guidance channel (10), having openings (12, 14) adapted to receive the ends of the severed nerve and defining a lumen (20) through which the nerve can regenerate. The electrically-charged membrane can further include a polymeric electret material that is electrically poled. A method for repairing a severed nerve is also disclosed and includes placing severed nerve ends (16, 18) in proximity to each other within the lumen of the guidance channel of the present invention and securing the nerve ends to the device.

Abstract translation: 公开了用于再生切断的神经的医疗装置，包括管状的，生物相容的，带电的膜或引导通道（10），其具有适于接收切断的神经的端部并限定内腔的开口（12,14） （20），神经可以通过它再生。 带电膜可以进一步包括电极化的聚合物驻极体材料。 还公开了修复切断的神经的方法，并且包括在本发明的引导通道的腔内彼此靠近地设置切断的神经末端（16,18），并将神经末端固定到装置上。

公开(公告)号：WO1997027466A1

公开(公告)日：1997-07-31

申请号：PCT/US1996020917

申请日：1996-12-31

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION ,  MARIS, Humphrey, J. ,  STONER, Robert, J.

IPC: G01N21/00

CPC classification number: G01N29/0681 ,  G01N21/1702 ,  G01N21/59 ,  G01N29/2418 ,  G01N2291/02827 ,  G01N2291/02881 ,  G01N2291/0426 ,  G01N2291/0427

Abstract: A system for the characterization of thin films and interfaces between thin films through measurements of their mechanical and thermal properties. In the system light, from laser (136) is absorbed in a thin film or in a structure made up of several thin films, and the change in optical transmission or reflection is measured and analyzed using analyser (134). The change in reflection or transmission is used to give information about the ultrasonic waves that are produced in the structure. The information that is obtained from the use of the measurement methods and apparatus of this invention can include: (a) a determination of the thickness of thin films with a speed and accuracy that is improved compared to earlier methods; (b) a determination of the thermal, elastic, and optical properties of thin films; (c) a determination of the stress in thin films; and (d) a characterization of the properties of interfaces, including the presence of roughness and defects.

Abstract translation: 通过测量薄膜的机械性能和热性能，可以对薄膜进行表征和界面界面的系统。 在系统光中，激光（136）被吸收在薄膜中或由几个薄膜构成的结构中，并且使用分析仪（134）测量和分析光透射或反射的变化。 反射或透射的变化用于提供关于在结构中产生的超声波的信息。 从使用本发明的测量方法和装置获得的信息可以包括：（a）与先前的方法相比，以与速度和准确性相比较的速度和准确度确定薄膜的厚度; （b）确定薄膜的热，弹性和光学性能; （c）确定薄膜中的应力; 和（d）表征界面的性质，包括粗糙度和缺陷的存在。

公开(公告)号：WO1996040277A2

公开(公告)日：1996-12-19

申请号：PCT/US1996008378

申请日：1996-06-03

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION ,  MATHIOWITZ, Edith ,  JACOB, Jules, S. ,  CHICKERING, Donald, E., III

IPC: A61K49/00

CPC classification number: A61K49/223

Abstract: Methods are provided for the synthesis of synthetic polymeric delivery systems consisting of microparticles which contain a diagnostic imaging agent using spray drying of dilute synthetic polymer solutions, typically between 0.2 and 20 w/v% polymer. In a preferred embodiment, the imaging agent is a gas, the polymer is biodegradable, the polymer solution is saturated with gas and formed into an emulsion, then spray dried. Microparticles produced by this method typically have an average diameter of between about one to seven microns, and therefore freely pass through the pulmonary capillaries. Additional, or alternative, imaging agents can be incorporated within the microparticles. Larger microparticles can also be manufactured for administration to mucosal membranes or oral administration. Adhesion of these microparticles can be enhanced through the selection of bioadhesive polymers. Targeting can also be achieved by selection of the polymer or incorporation within or coupling to the polymer of ligands which specifically bind to particular tissue types or cell surface molecules. Additionally, ligands may be attached to the microspheres which affect the charge, lipophilicity or hydrophilicity of the particle. The polymeric microparticles are useful in a variety of diagnostic imaging procedures including ultrasound imaging, magnetic resonance imaging, fluoroscopy, X-ray, and computerized tomography. The microspheres may be used in a variety of imaging applications including cardiology applications, as well as for organ and peripheral vein imaging.

Abstract translation: 提供了用于合成包含微粒的合成聚合物递送系统的方法，所述微粒含有使用稀释的合成聚合物溶液（通常为0.2至20w / v％聚合物）的喷雾干燥的诊断显像剂。 在优选的实施方案中，成像剂是气体，聚合物是可生物降解的，聚合物溶液被气体饱和并形成乳液，然后喷雾干燥。 通过该方法生产的微粒通常具有约1至7微米的平均直径，因此自由地通过肺毛细血管。 另外或替代的成像剂可以并入微粒内。 也可以制造更大的微粒用于施用于粘膜或口服给药。 通过选择生物粘附性聚合物可以增强这些微粒的粘附性。 靶向也可以通过选择聚合物或并入特异性结合特定组织类型或细胞表面分子的配体的聚合物中或结合到其中来实现。 另外，可以将配体连接到影响颗粒的电荷，亲油性或亲水性的微球。 聚合物微粒可用于各种诊断成像程序，包括超声成像，磁共振成像，荧光透视，X线和计算机断层扫描。 微球可用于各种成像应用，包括心脏学应用，以及器官和外周静脉成像。

公开(公告)号：WO1996027807A1

公开(公告)日：1996-09-12

申请号：PCT/US1996003275

申请日：1996-03-07

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION ,  BRANDSTEIN, Michael, S. ,  ADCOCK, John, E. ,  SILVERMAN, Harvey, F.

IPC: G01V01/00

CPC classification number: H04N7/15 ,  G01V1/001

Abstract: Apparatus for determining the location of a signal-generating source (e.g., a conferee in a telephone conference) includes at least three sensors (e.g., microphones) arranged in a plurality of sets, each having two or more sensors. A surface-finding element responds to receipt at each sensor set of signals (e.g., speech) from the source for identifying a geometric surface (e.g., the surface of a hyperboloid or cone) representing potential locations of the source as a function of sensor locations and time difference of arrival of the signals. A location-approximating element coupled to two or more of the sets identifies a line that further defines potential source locations at the intersection of the surfaces. A location signal representing those potential locations is generated in accord with parameters of that line. Further functionality generates the location signal as a function of closest intersections the plural ones of the aforementioned lines.

Abstract translation: 用于确定信号发生源（例如，电话会议中的与会者）的位置的装置包括布置在多个集合中的至少三个传感器（例如，麦克风），每个传感器具有两个或更多个传感器。 表面测量元件响应来自源的每个传感器信号组（例如，语音）的接收，用于识别作为传感器位置的函数的源的潜在位置的几何表面（例如，双曲面或锥体的表面） 和信号的到达时间差。 耦合到两个或更多个集合的位置近似元素标识进一步限定表面交叉处的潜在源位置的线。 根据该行的参数生成表示那些潜在位置的位置信号。 另外的功能产生位置信号作为上述线中的多个之间的最接近的交点的函数。

公开(公告)号：WO1993023390A1

公开(公告)日：1993-11-25

申请号：PCT/US1993004134

申请日：1993-05-03

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION ,  CHU, Shih, Hsi ,  CHENG, Yung, Chi ,  PAN, Bai, Chuan

IPC: C07D401/12

CPC classification number: C07D401/12

Abstract: Novel 6-pyridyl substituted pyrimidine derivatives are disclosed for use as antiviral agents, particularly for the treatment of retroviral infections such as HIV infections and related disorders, as well as for use in anti-cancer therapies to improve the efficacy of anti-cancer therapeutics. These compounds and their pharmacologically acceptable salts operate to disrupt viral replication and exhibit lower cell toxicity, thereby providing more efficient agents for use alone or in conjunction with other chemical or biological agents to provide prolonged antiviral therapy. In addition, the compounds can be used to increase the efficacy of anti-cancer therapeutics including 5-fluoropyrimidines such as 5-fluorouracil, thereby reducing the dosage requirement of the therapeutic in anti-cancer therapies so as to decrease toxic effects to the host.

公开(公告)号：WO1991016315A1

公开(公告)日：1991-10-31

申请号：PCT/US1991002522

申请日：1991-04-12

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION ,  NAGUIB, Fardos, N., M. ,  EL KOUNI, Mahmoud, H. ,  PANZICA, Raymond, P. ,  CHA, Sungman

IPC: C07D239/62

CPC classification number: C07D239/62

Abstract: 5-benzyl barbiturate compounds for use as water-soluble uridine phosphorylase inhibitors are disclosed. These compounds are useful for reducing the toxicity and anemia induced by antiviral drugs, such as AZT, as well as for potentiating anticancer drugs and combatting their host-toxicity.

公开(公告)号：WO1990002580A1

公开(公告)日：1990-03-22

申请号：PCT/US1989003705

申请日：1989-08-28

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION ,  AEBISCHER, Patrick ,  GALLETTI, Pierre, M. ,  MIRACOLI, Luigi ,  PANOL, George

IPC: A61M31/00

CPC classification number: A61M5/14276 ,  A61F2/022 ,  A61M2205/3523

Abstract: Devices and methods are disclosed to provide hybrid, modular systems for the constitutive delivery of appropriate dosages of active factors to a subject and, in some instances, to specific anatomical regions of the subject. The systems include a cell reservoir (30) containing living cells capable of secreting an active agent, which is preferably adapted for implantation within the body of the subject and further includes at least one semipermeable membrane (36, 38), whereby the transplanted cells can be nourished by nutrients transported across the membrane while at the same time protected from immunological, bacterial, and viral assault. The systems further include a pumping means (50), which can be implantable or extracorporeal, for drawing a body fluid from the subject into the cell reservoir and for actively transporting the secreted biological factors from the cell reservoir to a selected region of the subject.

公开(公告)号：WO1986007171A1

公开(公告)日：1986-12-04

申请号：PCT/US1986001153

申请日：1986-05-28

Applicant: BROWN UNIVERSITY RESEARCH FOUNDATION

Inventor： BROWN UNIVERSITY RESEARCH FOUNDATION ,  RISEN, William, M., Jr. ,  KAMITSOS, Efstratios, I.

IPC: G03C01/49

CPC classification number: G03C1/735 ,  G03C5/56 ,  H01L21/2254 ,  H01L21/265 ,  H01L21/312 ,  H01L31/0224 ,  H01L51/0051 ,  Y10S430/143 ,  Y10S430/165

Abstract: Metallic salts of organic charge-transfer agents, such as TCNQ, TNAP, TCNE and DDQ and their derivatives, can be processed by an electron beam for a variety of useful electronic and optical applications. The metallic charge transfer salts can be used to deposit high resolution conductive lines directly without developing solutions or subsequent metallization steps. The compounds can also be employed in the conventional manner as resists for doping (i.e., ion diffusion or implantation) and to diffuse metals into substrates. In particular, electronic devices, optical devices and image-storage devices are disclosed which can be formed by simple electron beam processed of metal charge-transfer salt films deposited on substrates.