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    Porous drug matrices and methods of manufacture thereof
    71.
    发明授权
    Porous drug matrices and methods of manufacture thereof 有权

    公开(公告)号：US06645528B1

    公开(公告)日：2003-11-11

    申请号：US09694407

    申请日：2000-10-23

    申请人： Julie Straub ,  Howard Bernstein ,  Donald E. Chickering, III ,  Sarwat Khattak ,  Greg Randall

    发明人： Julie Straub ,  Howard Bernstein ,  Donald E. Chickering, III ,  Sarwat Khattak ,  Greg Randall

    IPC分类号： A61K914

    CPC分类号： A61K9/1688 ,  A61K9/1611 ,  A61K9/1623 ,  A61K9/1635 ,  A61K9/1694 ,  Y10S514/951 ,  Y10S977/906 ,  Y10S977/923

    摘要： Drugs, especially low aqueous solubility drugs, are provided in a porous matrix form, preferably microparticles, which enhances dissolution of the drug in aqueous media. The drug matrices preferably are made using a process that includes (i) dissolving a drug, preferably a drug having low aqueous solubility, in a volatile solvent to form a drug solution, (ii) combining at least one pore forming agent with the drug solution to form an emulsion, suspension, or second solution, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of drug. The pore forming agent can be either a volatile liquid that is immiscible with the drug solvent or a volatile solid compound, preferably a volatile salt. In a preferred embodiment, spray drying is used to remove the solvents and the pore forming agent. The resulting porous matrix has a faster rate of dissolution following administration to a patient, as compared to non-porous matrix forms of the drug. In a preferred embodiment, microparticles of the porous drug matrix are reconstituted with an aqueous medium and administered parenterally, or processed using standard techniques into tablets or capsules for oral administration.

    Composition for sustained release of non-aggregated erythropoietin
    72.
    发明授权
    Composition for sustained release of non-aggregated erythropoietin 失效
    用于持续释放非聚集促红细胞生成素的组合物

    公开(公告)号：US5674534A

    公开(公告)日：1997-10-07

    申请号：US483318

    申请日：1995-06-07

    申请人： Stephen E. Zale ,  Paul A. Burke ,  Howard Bernstein ,  Avram Brickner

    发明人： Stephen E. Zale ,  Paul A. Burke ,  Howard Bernstein ,  Avram Brickner

    IPC分类号： A61K9/00 ,  A61K9/16 ,  A61K9/50 ,  A61K9/51 ,  A61K9/52 ,  A61K38/17 ,  A61K38/18 ,  A61K38/22 ,  A61K47/02 ,  A61K47/12 ,  A61K47/18 ,  A61K47/26 ,  A61K47/32 ,  A61K47/34 ,  A61K47/42 ,  B01J13/02 ,  B32B5/16

    CPC分类号： A61K9/1611 ,  A61K38/1816 ,  A61K9/0019 ,  A61K9/1647 ,  A61K9/1658 ,  A61K9/5031 ,  A61K9/5052 ,  A61K9/5153 ,  A61K9/5169 ,  A61K47/02 ,  A61K47/26 ,  A61K9/1694 ,  Y10T428/2984 ,  Y10T428/2985

    摘要： A composition, and methods of forming and using said composition, for the sustained release of non-aggregated, biologically active, erythropoietin (EPO). The sustained release composition of this invention comprises a polymeric matrix of a biocompatible polymer and particles of biologically active, aggregation-stabilized EPO, wherein said particles are dispersed within the biocompatible polymer. The method of the invention for producing a composition for the sustained release of biologically active EPO, includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, aggregation-stabilized EPO in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said EPO particles. The method for using a composition of the invention is a method for providing a therapeutically effective blood level of biologically active, non-aggregated erythropoietin in a subject for a sustained period. In this method, a subject is administered an effective dose of the sustained release composition of the present invention.

    摘要翻译： 用于持续释放非聚集的，生物活性的促红细胞生成素（EPO）的组合物和形成和使用所述组合物的方法。 本发明的持续释放组合物包含生物相容性聚合物的聚合物基质和生物活性聚集稳定的EPO颗粒，其中所述颗粒分散在生物相容性聚合物内。 用于制备用于持续释放生物活性EPO的组合物的本发明的方法包括将生物相容性聚合物溶解在聚合物溶剂中以形成聚合物溶液，将生物活性聚集稳定的EPO的颗粒分散在聚合物溶液中，然后 固化聚合物以形成含有所述EPO颗粒的分散体的聚合物基质。 使用本发明组合物的方法是在持续时间内在受试者中提供治疗有效的血液中生物活性，非聚集的促红细胞生成素的方法。 在该方法中，给予受试者有效剂量的本发明的持续释放组合物。

    Ultrasound contrast agent dosage formulation
    74.
    发明授权
    Ultrasound contrast agent dosage formulation 有权
    超声造影剂剂量配方

    公开(公告)号：US08012457B2

    公开(公告)日：2011-09-06

    申请号：US11143170

    申请日：2005-06-02

    申请人： Richard Walovitch ,  Howard Bernstein ,  Donald Chickering ,  Julie Straub

    发明人： Richard Walovitch ,  Howard Bernstein ,  Donald Chickering ,  Julie Straub

    IPC分类号： A61B8/00 ,  A61K49/00

    CPC分类号： A61K49/223

    摘要： Clinical studies have been conducted and specific dosage formulations developed using polymeric microparticles having incorporated therein perfluorocarbon gases that provide significantly enhanced images of long duration. The dosage formulation includes microparticles formed of a biocompatible polymer, preferably including a lipid incorporated therein, and containing a perfluorocarbon that is a gas at body temperature. The microparticles are provided to a patient in an amount effective to enhance ultrasound imaging in the ventricular chambers for more than 5 minutes or in the mycocardium for more than a minute, in a dose ranging from 0.025 to 8.0 mg microparticles/kg body weight. Preferably the dose ranges from 0.05 to 4.0 mg microparticles/kg body weight. The dosage formulation typically is provided in a vial. A typical formulation is in the form of a dry powder that is reconstituted with sterile water prior to use by adding the water to the vial or syringe of the dry powder and shaking to yield an isosmotic or isotonic suspension of microparticles.

    摘要翻译： 已经进行了临床研究，并且使用其中结合有全氟化碳气体的聚合物微粒开发特定的剂型，其提供了长时间显着增强的图像。 剂量制剂包括由生物相容性聚合物形成的微粒，其优选包括掺入其中的脂质，并且含有在体温下作为气体的全氟化碳。 将微粒以有效量的方式提供给患者，剂量范围为0.025至8.0mg微粒/ kg体重的剂量，以在室室内超过5分钟或在心肌中增强超声成像超过一分钟。 剂量优选为0.05至4.0mg微粒/ kg体重。 剂型通常提供在小瓶中。 典型的制剂是干粉的形式，其在使用前通过将水添加到干粉末的小瓶或注射器中并且摇动以产生微粒的等渗或等渗悬浮液而在使用前用无菌水重构。

    SAMPLING DEVICE INTERFACES
    76.
    发明申请
    SAMPLING DEVICE INTERFACES 审中-公开
    采样设备接口

    公开(公告)号：US20110172508A1

    公开(公告)日：2011-07-14

    申请号：US13006165

    申请日：2011-01-13

    申请人： Donald E. Chickering, III ,  Shawn Davis ,  Ramin Haghgooie ,  Howard Bernstein ,  Douglas A. Levinson

    发明人： Donald E. Chickering, III ,  Shawn Davis ,  Ramin Haghgooie ,  Howard Bernstein ,  Douglas A. Levinson

    IPC分类号： A61B5/15 ,  A61B5/157

    CPC分类号： A61B5/14532 ,  A61B5/150022 ,  A61B5/150099 ,  A61B5/150221 ,  A61B5/150229 ,  A61B5/150236 ,  A61B5/150244 ,  A61B5/150297 ,  A61B5/150389 ,  A61B5/150412 ,  A61B5/150503 ,  A61B5/150755 ,  A61B5/150969 ,  A61B5/150977 ,  A61B5/150984 ,  A61B5/15105 ,  A61B5/15113 ,  A61B5/15117 ,  A61B5/15125 ,  A61B5/15144 ,  A61B5/15186 ,  A61B5/157 ,  A61B5/685

    摘要： The present invention generally relates to systems and methods for delivering and/or withdrawing a substance or substances such as blood or interstitial fluid, from subjects, e.g., from the skin and/or from beneath the skin. In one aspect, the present invention is generally directed to devices and methods for withdrawing or extracting blood from a subject, e.g., from the skin and/or from beneath the skin, using devices containing a fluid transporter (for example, one or more microneedles), and a storage chamber having an internal pressure less than atmospheric pressure prior to receiving blood. In some cases, the device may be self-contained, and in certain instances, the device can be applied to the skin, and activated to withdraw blood from the subject. The device, in some cases, may be interfaced with external equipment to determine an analyte contained within a fluid contained within or collected by the device. For example, the device may be mounted or engaged on an external holder, the device may include a port for transporting fluid out of the device, the device may include a window for interrogating a fluid contained within the device, or the like. The device, or a portion thereof, may then be processed to determine the blood and/or an analyte within the blood, alone or with an external apparatus. For example, blood may be withdrawn from the device, and/or the device may contain sensors or agents able to determine the blood and/or an analyte suspected of being contained in the blood. Other aspects of the present invention are directed at other devices for withdrawing blood (or other bodily fluids, e.g., interstitial fluid), kits involving such devices, methods of making such devices, methods of using such devices, and the like.

    摘要翻译： 本发明一般涉及用于递送和/或从皮肤和/或皮肤下方的受试者递送和/或从物质或诸如血液或间质液体中取出物质的方法。 一方面，本发明一般涉及使用包含流体转运器（例如，一个或多个微针）的装置从例如皮肤和/或从皮肤下面抽取或提取血液的装置和方法 ）和在接收血液之前具有小于大气压的内部压力的储存室。 在一些情况下，该装置可以是独立的，并且在某些情况下，可以将该装置应用于皮肤并被激活以从受试者中抽出血液。 在一些情况下，该装置可以与外部设备接口以确定包含在装置内或由装置收集的流体中的分析物。 例如，该装置可以安装或接合在外部支架上，该装置可以包括用于将流体输送出装置的端口，该装置可包括询问包含在装置内的流体等的窗口。 然后可以处理装置或其一部分，以单独或与外部装置一起确定血液和/或血液内的分析物。 例如，血液可以从装置中取出，和/或该装置可以包含能够确定血液和/或怀疑含在血液中的分析物的传感器或试剂。 本发明的其它方面涉及用于抽出血液（或其他体液，例如间质液）的其他装置，涉及这种装置的试剂盒，制造这种装置的方法，使用这种装置的方法等。

    RELATIVELY SMALL DEVICES APPLIED TO THE SKIN, MODULAR SYSTEMS, AND METHODS OF USE THEREOF
    77.
    发明申请
    RELATIVELY SMALL DEVICES APPLIED TO THE SKIN, MODULAR SYSTEMS, AND METHODS OF USE THEREOF 审中-公开
    适用于皮肤的相对小的装置，模块化系统及其使用方法

    公开(公告)号：US20110105952A1

    公开(公告)日：2011-05-05

    申请号：US12915820

    申请日：2010-10-29

    申请人： Howard Bernstein ,  Donald E. Chickering, III ,  Douglas A. Levinson ,  David R. Walt ,  Shawn Davis ,  Ramin Haghgooie

    发明人： Howard Bernstein ,  Donald E. Chickering, III ,  Douglas A. Levinson ,  David R. Walt ,  Shawn Davis ,  Ramin Haghgooie

    IPC分类号： A61B5/00

    CPC分类号： A61B5/14514 ,  A61B5/150022 ,  A61B5/150099 ,  A61B5/150221 ,  A61B5/150229 ,  A61B5/150297 ,  A61B5/150305 ,  A61B5/150389 ,  A61B5/150412 ,  A61B5/150503 ,  A61B5/150755 ,  A61B5/150969 ,  A61B5/150977 ,  A61B5/150984 ,  A61B5/15105 ,  A61B5/15109 ,  A61B5/15113 ,  A61B5/15117 ,  A61B5/15125 ,  A61B5/15144 ,  A61B5/15186 ,  A61B5/157 ,  A61B5/685 ,  A61B2560/0412 ,  A61B2560/0443 ,  A61M5/425 ,  A61M35/00 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0046 ,  A61M2037/0061 ,  A61M2205/581 ,  A61M2205/582 ,  A61M2205/583 ,  A61M2205/588

    摘要： The present invention generally relates, in certain aspects, to relatively small devices applied to the skin, modular systems, and methods of use thereof. In some aspects, the device is constructed and arranged to have more than one module. For instance, the device may have a module for delivering to and/or withdrawing fluid from the skin and/or beneath the skin of a subject and a module for transmitting a signal indicative of the fluid delivered to and/or withdrawn from the skin and/or beneath the skin of the subject, a module for analyzing a fluid withdrawn from the skin and/or beneath the skin of the subject, or the like. In some embodiments, the modules are connectable and/or detachable from each other, and in some cases, the connections and/or detachments may be performed while the device is in contact with the subject, e.g., while affixed to the subject. In some embodiments, the device may be repeatedly applicable to the skin of the subject to deliver to and/or withdraw fluid from the skin and/or beneath the skin of a subject, e.g., at the same location, or at different locations on the skin of the subject. In some aspects, the devices may be self-contained and/or have a relatively small size, and in some cases, the device may be sized such that it is wearable and/or able to be carried by a subject. For example, the device may have a mass and/or dimensions that allow the device to be carried or worn by a subject for various periods of time, e.g., at least about an hour, at least about a day, at least about a week, etc., or no more than about an hour, no more than about 10 min, etc.

    摘要翻译： 本发明在某些方面通常涉及应用于皮肤的相对小的装置，模块化系统及其使用方法。 在一些方面，设备被构造和布置成具有多个模块。 例如，该装置可以具有用于递送到和/或从对象皮肤和/或皮肤下方的流体递送的模块和用于传送指示输送到皮肤和/或从皮肤递送的流体的信号的模块，以及 /或受试者皮肤下方的用于分析从皮肤抽出的流体和/或在受试者的皮肤下方的流体的模块等。 在一些实施例中，模块可彼此连接和/或可拆卸，并且在一些情况下，可以在设备与对象接触时执行连接和/或拆卸，例如在固定到对象的同时。 在一些实施例中，该装置可以重复地应用于受试者的皮肤，以递送至/或从对象的皮肤和/或皮肤下方例如在相同位置或不同位置递送流体 受试者的皮肤。 在一些方面，装置可以是独立的和/或具有相对较小的尺寸，并且在一些情况下，该装置的尺寸可被设定为使得其可穿戴和/或能够被受试者携带。 例如，该装置可以具有质量和/或尺寸，其允许受试者携带或穿戴不同时间段，例如至少约一小时，至少约一天，至少约一周 等等，或不超过约一小时，不超过约10分钟等

    METHODS FOR MAKING AND USING PARTICULATE PHARMACEUTICAL FORMULATIONS FOR SUSTAINED RELEASE
    80.
    发明申请
    METHODS FOR MAKING AND USING PARTICULATE PHARMACEUTICAL FORMULATIONS FOR SUSTAINED RELEASE 审中-公开
    制备和使用颗粒状药物制剂用于持续释放的方法

    公开(公告)号：US20070264343A1

    公开(公告)日：2007-11-15

    申请号：US11829629

    申请日：2007-07-27

    申请人： Howard Bernstein ,  Donald Chickering ,  Eric Huang ,  Sridhar Narasimhan ,  Shaina Reese ,  Julie Straub

    发明人： Howard Bernstein ,  Donald Chickering ,  Eric Huang ,  Sridhar Narasimhan ,  Shaina Reese ,  Julie Straub

    IPC分类号： A61K9/14 ,  A61K31/56 ,  A61K31/7088 ,  A61K38/00 ,  A61K9/10

    CPC分类号： A61K9/1647 ,  A61K9/1617

    摘要： Pharmaceutical formulations and methods are provided for the sustained delivery of a pharmaceutical agent to a patient by injection. The injectable formulation includes porous microparticles which comprise a pharmaceutical agent and a matrix material, wherein upon injection of the formulation a therapeutically or prophylactically effective amount of the pharmaceutical agent is released from the microparticles for at least 24 hours. A method for making the injectable, sustained release pharmaceutical formulation may include dissolving a hydrophobic matrix material in a volatile solvent to form a first solution; adding a pharmaceutical agent to the first solution to form an emulsion, suspension, or second solution; and removing the volatile solvent from the emulsion, suspension, or second solution to yield porous microparticles which comprise the pharmaceutical agent dispersed, entrapped or encapsulated within the structure of the hydrophobic matrix material.

    摘要翻译： 提供药物制剂和方法用于通过注射将药剂持续递送至患者。 可注射制剂包括包含药剂和基质材料的多孔微粒，其中在注射制剂时，治疗或预防有效量的药剂从微粒释放至少24小时。 制备可注射的缓释药物制剂的方法可包括将疏水基质材料溶解在挥发性溶剂中以形成第一溶液; 向第一溶液中加入药剂以形成乳液，悬浮液或第二溶液; 并从乳液，悬浮液或第二溶液中除去挥发性溶剂以产生包含在疏水基质材料的结构内分散，包埋或包封的药剂的多孔微粒。