公开(公告)号：US20120271125A1

公开(公告)日：2012-10-25

申请号：US13443016

申请日：2012-04-10

申请人： Howard Bernstein ,  Timothy M. Blicharz

发明人： Howard Bernstein ,  Timothy M. Blicharz

IPC分类号： A61B5/157 ,  A61B5/145

CPC分类号： A61B5/1519 ,  A61B5/150022 ,  A61B5/150099 ,  A61B5/150175 ,  A61B5/150412 ,  A61B5/150503 ,  A61B5/150755 ,  A61B5/150946 ,  A61B5/150969 ,  A61B5/150984 ,  A61B5/15105 ,  A61B5/15107 ,  A61B5/15117 ,  A61B5/15119 ,  A61B5/15123 ,  A61B5/15125 ,  A61B50/30 ,  A61B2010/008 ,  A61M2037/0023

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, 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.

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。 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。

公开(公告)号：US20070269381A1

公开(公告)日：2007-11-22

申请号：US11834111

申请日：2007-08-06

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： A61K49/22

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。

公开(公告)号：US20070104656A1

公开(公告)日：2007-05-10

申请号：US11617935

申请日：2006-12-29

申请人： Howard Bernstein ,  Donald Chickering ,  Sarwat Khattak ,  Julie Straub

发明人： Howard Bernstein ,  Donald Chickering ,  Sarwat Khattak ,  Julie Straub

IPC分类号： A61K9/14

CPC分类号： A61K9/1617 ,  A61K9/1647 ,  Y10S514/951 ,  Y10S514/952

摘要： A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time as compared to release from the polymeric matrix not incorporating the hydrophobic compound into the polymeric material. In contrast to methods in which a surfactant or lipid is added as an excipient, the hydrophobic compound is actually integrated into the polymeric matrix, thereby modifying the diffusion of water into the microparticle and diffusion of solubilized drug out of the matrix. The integrated hydrophobic compound also prolongs degradation of hydrolytically unstable polymers forming the matrix, further delaying release of encapsulated drug.

摘要翻译： 将脂质或其它疏水性或两亲性化合物（本文统称为“疏水化合物”）整合到用于药物递送的聚合物基质中以改变药物释放动力学。 在药物是水溶性的实施方案中，与不将疏水化合物掺入聚合物材料的聚合物基质的释放相比，药物在更长的时间内释放。 与其中加入表面活性剂或脂质作为赋形剂的方法相反，疏水化合物实际上整合到聚合物基质中，从而改变水进入微粒的扩散并将溶解的药物扩散出基质。 整合的疏水化合物还延长了形成基质的水解不稳定聚合物的降解，进一步延缓了包封药物的释放。

公开(公告)号：US20060093678A1

公开(公告)日：2006-05-04

申请号：US11305620

申请日：2005-12-16

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

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

IPC分类号： A61K9/14

CPC分类号： B01D1/18 ,  A61K9/0075 ,  A61K9/145 ,  A61K9/1647 ,  A61K9/1694 ,  B01J2/04

摘要： Methods are provided for making a dry powder blend pharmaceutical formulation comprising (i) forming microparticles which comprise a pharmaceutical agent; (ii) providing at least one excipient in the form of particles having a volume average diameter that is greater than the volume average diameter of the microparticles; (iii) blending the microparticles with the excipient to form a powder blend; and (iv) jet milling the powder blend to deagglomerate at least a portion of any of the microparticles which have agglomerated, while substantially maintaining the size and morphology of the individual microparticles. Jet milling advantageously can eliminate the need for more complicated wet deagglomeration processes, can lower residual moisture and solvent levels in the microparticles (which leads to better stability and handling properties for dry powder formulations), and can improve wettability, suspendability, and content uniformity of dry powder blend formulations.

摘要翻译： 提供用于制备干粉混合物药物制剂的方法，其包含（i）形成包含药剂的微粒; （ii）提供至少一种具有体积平均直径大于微粒的体积平均直径的颗粒形式的赋形剂; （iii）将微粒与赋形剂混合以形成粉末混合物; 和（iv）喷射研磨粉末共混物以使至少一部分具有附聚的任何微粒分解，同时基本保持各个微粒的尺寸和形态。 喷射铣削有利地可以消除对更复杂的湿解聚过程的需要，可以降低微粒中的残留水分和溶剂水平（这导致干粉配方的更好的稳定性和处理性能），并且可以改善润湿性，悬浮性和含量均匀性 干粉混合配方。

公开(公告)号：US20050209099A1

公开(公告)日：2005-09-22

申请号：US11142917

申请日：2005-06-02

申请人： Donald Chickering ,  Sridhar Narasimhan ,  David Altreuter ,  Paul Kopesky ,  Mark Keegan ,  Julie Straub ,  Howard Bernstein

发明人： Donald Chickering ,  Sridhar Narasimhan ,  David Altreuter ,  Paul Kopesky ,  Mark Keegan ,  Julie Straub ,  Howard Bernstein

IPC分类号： A61K9/16 ,  B01D1/18 ,  B01J2/04 ,  F26B3/12 ,  F26B17/10 ,  B01J23/00

CPC分类号： F26B17/102 ,  A61K9/1647 ,  A61K9/1688 ,  B01D1/18 ,  B01J2/04 ,  F26B3/12

摘要： Methods and apparatus are provided for making particles comprising: (a) spraying an emulsion, solution, or suspension, which comprises a solvent and a bulk material (e.g., a pharmaceutical agent), through an atomizer and into a primary drying chamber, having a drying gas flowing therethrough, to form droplets comprising the solvent and bulk material dispersed in the drying gas; (b) evaporating, in the primary drying chamber, at least a portion of the solvent into the drying gas to solidify the droplets and form particles dispersed in drying gas; and (c) flowing the particles and at least a portion of the drying gas through a jet mill to deagglomerate or grind the particles. By coupling spray drying with “in-line” jet milling, a single step process is created from two separate unit operations, and an additional collection step is advantageously eliminated. The one-step, in-line process has further advantages in time and cost of processing.

摘要翻译： 提供了用于制备颗粒的方法和装置，包括：（a）通过雾化器喷雾包含溶剂和散装材料（例如药剂）的乳液，溶液或悬浮液，并进入初级干燥室，其具有 干燥气体流过其中以形成包含分散在干燥气体中的溶剂和散装材料的液滴; （b）在初级干燥室中将至少一部分溶剂蒸发到干燥气体中以固化液滴并形成分散在干燥气体中的颗粒; 和（c）使颗粒和至少一部分干燥气体流过喷射磨机以使颗粒解聚或研磨。 通过将喷雾干燥与“直列式”喷射研磨相结合，由两个单独的单元操作产生单步骤，有利地消除了另外的收集步骤。 一步一步的在线过程在处理时间和成本方面具有进一步的优势。

公开(公告)号：US06780434B2

公开(公告)日：2004-08-24

申请号：US10092365

申请日：2002-03-06

申请人： Mark A. Tracy ,  Howard Bernstein ,  M. Amin Khan

发明人： Mark A. Tracy ,  Howard Bernstein ,  M. Amin Khan

IPC分类号： A61K910

CPC分类号： B82Y5/00 ,  A61K9/1611 ,  A61K9/1647 ,  A61K38/212 ,  C07K14/56

摘要： This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation stabilized-interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.

摘要翻译： 本发明涉及用于控制释放干扰素的组合物和形成所述组合物的方法。 本发明的控释组合物包含生物相容性聚合物和金属阳离子稳定化干扰素颗粒，其中颗粒分散在生物相容性聚合物内。 本发明的制备用于干扰素控制释放的组合物的方法包括将聚合物溶解在聚合物溶剂中以形成聚合物溶液，将金属阳离子稳定的干扰素颗粒的颗粒分散在聚合物溶液中，然后固化聚合物 以形成含有干扰素颗粒的分散体的聚合物基质。

公开(公告)号：US06500448B1

公开(公告)日：2002-12-31

申请号：US09505508

申请日：2000-02-17

申请人： OluFunmi Lily Johnson ,  Medha M. Ganmukhi ,  Howard Bernstein ,  Henry Auer ,  M. Amin Khan

发明人： OluFunmi Lily Johnson ,  Medha M. Ganmukhi ,  Howard Bernstein ,  Henry Auer ,  M. Amin Khan

IPC分类号： A61F202

CPC分类号： B82Y5/00 ,  A61K9/1611 ,  A61K9/1647 ,  A61K9/1694 ,  A61K38/27 ,  Y10S514/839 ,  Y10S530/839 ,  Y10T428/2985

摘要： A pharmaceutical composition for the sustained release of human growth hormone from a polymer matrix is disclosed. The pharmaceutical composition comprises a biocompatible polymer, particles of metal cation-complexed human growth hormone wherein said particles are dispersed within the biocompatible polymer and an aqueous injection vehicle.

摘要翻译： 公开了用于从聚合物基质中持续释放人生长激素的药物组合物。 药物组合物包含生物相容性聚合物，金属阳离子络合的人生长激素的颗粒，其中所述颗粒分散在生物相容性聚合物和水性注射载体中。

公开(公告)号：US06379701B1

公开(公告)日：2002-04-30

申请号：US09664299

申请日：2000-09-18

申请人： Mark A. Tracy ,  Howard Bernstein ,  M. Amin Khan

发明人： Mark A. Tracy ,  Howard Bernstein ,  M. Amin Khan

IPC分类号： A61K910

CPC分类号： B82Y5/00 ,  A61K9/1611 ,  A61K9/1647 ,  A61K38/212 ,  C07K14/56

摘要： This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation stabilized-interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.

摘要翻译： 本发明涉及用于控制释放干扰素的组合物和形成所述组合物的方法。 本发明的控释组合物包含生物相容性聚合物和金属阳离子稳定化干扰素颗粒，其中颗粒分散在生物相容性聚合物内。本发明的用于制备用于控制释放干扰素的组合物的方法包括将 聚合物在聚合物溶剂中以形成聚合物溶液，将金属阳离子稳定的干扰素颗粒的颗粒分散在聚合物溶液中，然后固化聚合物以形成含有干扰素颗粒分散体的聚合物基质。

公开(公告)号：US6132699A

公开(公告)日：2000-10-17

申请号：US158295

申请日：1998-09-22

申请人： Howard Bernstein ,  Julie Ann Straub ,  Henry T. Brush ,  Richard E. Wing

发明人： Howard Bernstein ,  Julie Ann Straub ,  Henry T. Brush ,  Richard E. Wing

IPC分类号： A61K47/06 ,  A61B8/00 ,  A61K49/00 ,  A61K49/22 ,  A61B8/13

CPC分类号： A61B8/481 ,  A61K49/223

摘要： It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.

摘要翻译： 已经发现，与合并有空气的微粒相比，将氟化气体，特别是全氟化碳如八氟丙烷掺入到合成的聚合物微粒中显着增强回波反应性。 制造微胶囊化全氟化碳，其直径适用于待成像的目标组织，例如用于静脉内或口服给药。 在一个实施方案中，形成生物粘附微粒用于增强粘膜表面的成像。

公开(公告)号：US5853698A

公开(公告)日：1998-12-29

申请号：US745676

申请日：1996-11-08

申请人： Julie Ann Straub ,  Edith Mathiowitz ,  Howard Bernstein ,  Henry T. Brush ,  Richard E. Wing

发明人： Julie Ann Straub ,  Edith Mathiowitz ,  Howard Bernstein ,  Henry T. Brush ,  Richard E. Wing

IPC分类号： A61B8/00 ,  A61K49/22 ,  A61B8/13

CPC分类号： A61B8/481 ,  A61K49/223

摘要： It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.

摘要翻译： 已经发现，与合并有空气的微粒相比，将氟化气体，特别是全氟化碳如八氟丙烷掺入到合成的聚合物微粒中显着增强回波反应性。 制造微胶囊化全氟化碳，其直径适用于待成像的目标组织，例如用于静脉内或口服给药。 在一个实施方案中，形成生物粘附微粒用于增强粘膜表面的成像。