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41.发明申请PROCESSES FOR MAKING PARTICLE-BASED PHARMACEUTICAL FORMULATIONS FOR PARENTERAL ADMINISTRATION 审中-公开制备基于颗粒的药物制剂用于住院管理的方法公开(公告)号：US20070178165A1
公开(公告)日：2007-08-02
申请号：US11610791
申请日：2006-12-14
申请人： David Altreuter , Howard Bernstein , Luis Brito , Shaina Brito , Olinda Carneiro , Donald Chickering , Eric Huang , Rajeev Jain , Sridhar Narasimhan , Namrata Pandit , Julie Straub
发明人： David Altreuter , Howard Bernstein , Luis Brito , Shaina Brito , Olinda Carneiro , Donald Chickering , Eric Huang , Rajeev Jain , Sridhar Narasimhan , Namrata Pandit , Julie Straub
IPC分类号： A61K9/14
CPC分类号： A61K9/0019 , A61K9/145 , A61K9/146 , A61K9/19
摘要： A method is provided for making a parenteral dosage form of a pharmaceutical agent which includes (a) providing particles of a pharmaceutical agent; (b) blending the particles with particles of at least one bulking agent to form a first powder blend, which does not include a surfactant; (c) milling the first powder blend to form a milled blend which comprises microparticles or nanoparticles of the pharmaceutical agent; and (d) reconstituting the milled blend with a liquid vehicle, which includes at least one surfactant, for parenteral administration. A method also is provided which includes (a) providing particles of a pharmaceutical agent; (b) blending these particles with particles of an excipient to form a first blend; and (c) milling the first blend to form a milled blend that includes microparticles or nanoparticles, which exhibits a greater dispersibility, wettability, and suspendability as compared to the particles of step (a) or the first blend.
摘要翻译： 提供了制备药物的胃肠外剂型的方法，其包括（a）提供药剂的颗粒; （b）将颗粒与至少一种填充剂的颗粒混合以形成不包括表面活性剂的第一粉末混合物; （c）研磨第一粉末混合物以形成包含药剂的微粒或纳米颗粒的研磨混合物; 和（d）将研磨的共混物与包含至少一种表面活性剂的液体载体重组，用于肠胃外给药。 还提供了一种方法，其包括（a）提供药剂的颗粒; （b）将这些颗粒与赋形剂的颗粒混合以形成第一共混物; 和（c）研磨第一共混物以形成包含微粒或纳米颗粒的研磨的共混物，其与步骤（a）或第一共混物的颗粒相比表现出更大的分散性，润湿性和悬浮性。
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42.发明授权Matrices formed of polymer and hydrophobic compounds for use in drug delivery 有权由聚合物和疏水化合物形成的矩阵用于药物递送公开(公告)号：US07160557B2
公开(公告)日：2007-01-09
申请号：US09730694
申请日：2000-12-06
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“疏水性化合物”）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。
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公开(公告)号：US06932983B1
公开(公告)日：2005-08-23
申请号：US09706045
申请日：2000-11-03
IPC分类号： A61K9/16
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.
摘要翻译： 药物，特别是低含水溶性药物以多孔基质形式提供，优选微粒，其增强药物在水性介质中的溶解。 药物基质优选使用以下方法制备，所述方法包括（i）将挥发性溶剂中的药物（优选为低溶解度的药物）溶解以形成药物溶液，（ii）将至少一种成孔剂与药物溶液 以形成乳液，悬浮液或第二溶液，和（iii）从乳液，悬浮液或第二溶液中除去挥发性溶剂和成孔剂以产生药物的多孔基质。 成孔剂可以是与药物溶剂或挥发性固体化合物，优选挥发性盐不混溶的挥发性液体。 在优选的实施方案中，使用喷雾干燥来除去溶剂和成孔剂。 与药物的无孔基质形式相比，得到的多孔基质在给予患者后具有更快的溶解速率。 在优选的实施方案中，多孔药物基质的微粒用水性介质重新配制，并肠胃外给药，或使用标准技术加工成用于口服给药的片剂或胶囊。
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44.发明授权Matrices formed of polymer and hydrophobic compounds for use in drug delivery 失效由聚合物和疏水化合物形成的矩阵用于药物递送公开(公告)号：US06730322B1
公开(公告)日：2004-05-04
申请号：US10384902
申请日：2003-03-06
IPC分类号： A61K910
CPC分类号： A61K9/1647 , A61K9/1617
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。
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公开(公告)号：US06423345B1
公开(公告)日：2002-07-23
申请号：US09255179
申请日：1999-02-22
IPC分类号： A61K910
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.
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公开(公告)号：US6165508A
公开(公告)日：2000-12-26
申请号：US765558
申请日：1997-03-07
申请人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
发明人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
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。 本发明的制备用于控制干扰素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。
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公开(公告)号：US5611344A
公开(公告)日：1997-03-18
申请号：US611248
申请日：1996-03-05
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。
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公开(公告)号：US5413797A
公开(公告)日：1995-05-09
申请号：US268715
申请日：1994-06-30
申请人： M. Amin Khan , Howard Bernstein
发明人： M. Amin Khan , Howard Bernstein
IPC分类号： A61K9/16 , A61K9/52 , A61K9/70 , A61K38/21 , A61K38/22 , A61K38/35 , A61K38/46 , A61K47/34 , A61K9/50
CPC分类号： A61K38/35 , A61K9/1611 , A61K9/1647 , A61K9/1694 , A61K9/7007 , Y10S514/805 , Y10S514/963
摘要： ACTH polymeric controlled release systems are described wherein the ACTH retains good biological activity and is released over an extended period of time following administration by injection. In the preferred embodiment, the ACTH polymeric microspheres are made using very cold temperatures to freeze the polymer-ACTH mixtures into polymeric microspheres with very high retention of biological activity and material. Sustained release of biologically active ACTH is achieved when the microspheres are tested in vitro, extending over a period of greater than one day to several months. Altered release can be achieved by inclusion of degradation modifiers, pore forming agents, and stabilizers of the ACTH.
摘要翻译： 描述了ACTH聚合物控制释放系统，其中ACTH保持良好的生物活性并且通过注射施用后在延长的时间段内释放。 在优选的实施方案中，使用非常低的温度制备ACTH聚合物微球体，以将聚合物-ACTH混合物冷冻成具有非常高的生物活性和材料保留度的聚合物微球体。 当体外测试微球体时，持续释放生物活性ACTH，延长超过一天至几个月的时间。 改变释放可以通过包含降解改性剂，成孔剂和ACTH的稳定剂来实现。
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公开(公告)号：US4938359A
公开(公告)日：1990-07-03
申请号：US401498
申请日：1989-08-29
申请人： Howard Bernstein
发明人： Howard Bernstein
CPC分类号： B65D1/243 , B65D21/02 , B65D2501/24019 , B65D2501/24076 , B65D2501/24095 , B65D2501/24133 , B65D2501/24152 , B65D2501/2428 , B65D2501/24305 , B65D2501/24356 , B65D2501/24458 , B65D2501/24598 , B65D2501/24675 , B65D2501/24942
摘要： A receptacle for beverage containers is disclosed. The receptacle has a rigid bottom portion consisting of a plurality of framework members. A plurality of spring fingers extend generally vertically up from the bottom portion to secure at least the bases of the beverage containers. With this construction, the beverage containers are retained in a vertical position. The receptacle has side walls extending generally vertically upward from the bottom portion to define a generally open top for the receptacle. The side walls includes slots for the attachment of a handle so that the receptacle can be lifted. Each receptacle is designed so that it can be mechanically interlocked with the top or bottom of an adjacent identical receptacle.
摘要翻译： 公开了用于饮料容器的容器。 容器具有由多个框架构件组成的刚性底部部分。 多个弹簧指从底部大致垂直向上延伸以至少固定饮料容器的基部。 利用这种结构，饮料容器保持在垂直位置。 容器具有从底部大致垂直向上延伸的侧壁，以限定用于容器的大体上敞开的顶部。 侧壁包括用于附接手柄的槽，使得容器可以被提升。 每个容器设计成可以与相邻的相同容器的顶部或底部机械地互锁。
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公开(公告)号：US4863611A
公开(公告)日：1989-09-05
申请号：US44245
申请日：1987-04-30
CPC分类号： B01D15/02 , A61M1/3675 , B01J20/321 , B01J20/3212 , B01J20/3274
摘要： An apparatus for removing material from a biological solution consisting of a reactor chamber having an inlet and an outlet, a bioactive compound immobilized on particular supports within the reactor, means for retaining the particular supports within the reactor, means for recirculating the solution and the supports at a high flow rate within the reactor, and means for agitating or dispersing the recirculating solution-support mixture throughout the reactor chamber so as to prevent packing of the supports while not subjecting the solution to excessive or damaging forces.In the given example, an apparatus for the extracorporeal removal of heparin from blood is provided. Heparinase is immobilized on cross-linked agarose beads recirculated at a high flow rate through the reactor. Agitation of the blood-bead mixture sufficient to prevent packing of the beads within the reactor chamber is provided by means of a series of openings in the recirculation tube dispersing the mixture throughout the chamber.
摘要翻译： 用于从由具有入口和出口的反应器室组成的生物溶液中去除材料的装置，固定在反应器内的特定载体上的生物活性化合物，用于将特定载体保持在反应器内的装置，用于将溶液和载体 反应器内的高流速，以及用于搅拌或分散循环溶液 - 载体混合物到整个反应器室的装置，以防止支撑物的包装，同时不使溶液经受过度或破坏的力。 在给出的实施例中，提供了用于从血液中体外去除肝素的装置。 肝素酶固定在通过反应器以高流速再循环的交联琼脂糖珠上。 借助于将混合物分散在整个室中的循环管中的一系列开口提供足以防止珠在反应器室内堆积的血珠混合物的搅动。
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