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1.发明授权Methods for particle micronization and nanonization by recrystallization from organic solutions sprayed into a compressed antisolvent 失效通过从喷射到压缩抗溶剂中的有机溶液重结晶进行颗粒微粉化和纳米化的方法
公开(公告)号：US5874029A
公开(公告)日：1999-02-23
申请号：US723463
申请日：1996-10-09
CPC分类号： B05D1/025 , A61K9/1676 , A61K9/1688 , B01J2/04 , A61K9/1694 , A61K9/5089 , B05D2401/90 , Y10S977/773
摘要： A method and an apparatus useful for the production of microparticles and nanoparticles are disclosed in which a compressed fluid and a solution including a solvent and a solute are introduced into a nozzle to produce a mixture. The mixture is then passed out of the nozzle to produce a spray of atomized droplets. The atomized droplets are contacted with a supercritical antisolvent to cause depletion of the solvent in the droplets so that particles are produced from the solute. Preferably, these particles have an average diameter of 0.6 .mu.m or less. The invention can be used in the pharmaceutical, food, chemical, electronics, catalyst, polymer, pesticide, explosives, and coating industries, all of which have a need for small-diameter particles.
摘要翻译： 公开了一种用于生产微粒和纳米颗粒的方法和装置，其中将压缩流体和包含溶剂和溶质的溶液引入喷嘴中以产生混合物。 然后将混合物从喷嘴中排出以产生雾化液滴的喷雾。 雾化的液滴与超临界反溶剂接触以引起液滴中溶剂的消耗，使得从溶质中产生颗粒。 优选地，这些颗粒的平均直径为0.6μm以下。 本发明可用于制药，食品，化工，电子，催化剂，聚合物，农药，爆炸物和涂料工业，所有这些都需要小直径颗粒。
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2.发明授权Methods for a particle precipitation and coating using near-critical and supercritical antisolvents 失效使用近临界和超临界反溶剂进行颗粒沉淀和涂层的方法
公开(公告)号：US5833891A
公开(公告)日：1998-11-10
申请号：US805215
申请日：1997-02-27
CPC分类号： A61K9/1676 , A61K9/1688 , B01J2/04 , B05D1/025 , A61K9/1694 , A61K9/5089 , B05D2401/90
摘要： Improved methods and apparatus for particle precipitation and coating using near- or supercritical fluid conditions are described. A fluid dispersion having a continuous phase dispersant and at least one precipitatable substance therein is contacted with a supercritical fluid (SCF) antisolvent so as to generate focused high frequency antisolvent sonic waves, breaking up the dispersion into extremely small droplets; the enhanced mass transfer rates between the droplets and the antisolvent causes precipitation of very small particles on the order of 0.1-10 .mu.m. In coating processes, a turbulent fluidized flow of core particles is created using an SCF antisolvent in an enclosed zone. The core particles are contacted therein at near- or supercritical conditions by a fluid dispersion containing a dispersant together with a precipitatable substance. The antisolvent depletes the dispersant and the substance is precipitated onto the fluidized core particles. In another aspect of the invention, a process for preparing and administering a medicament using only a single container is provided. In such method, a fluid dispersion having a dispersant with the medicament therein is contacted with an antisolvent at near- or supercritical conditions within a use container, so as to directly precipitate small particles of the medicament in the container. The antisolvent is then removed and the use container is sealed with the medicament particles therein. Thereafter, dose(s) of the medicament can be withdrawn from the use container and administered to a patient.
摘要翻译： 描述了使用近或超临界流体条件改进颗粒沉淀和涂层的方法和装置。 具有连续相分散剂和至少一种可沉淀物质的流体分散体与超临界流体（SCF）反溶剂接触，以产生聚焦的高频反溶剂声波，将分散体分解成极小的液滴; 液滴和抗溶剂之间的增强的传质速率导致非常小的颗粒的沉淀约0.1-10μm。 在涂覆过程中，使用封闭区域中的SCF反溶剂产生核心颗粒的湍流流化流。 核心颗粒在近或超临界条件下通过含有分散剂和可沉淀物质的流体分散体接触。 反溶剂消耗分散剂，物质沉淀在流化核心颗粒上。 在本发明的另一方面，提供了仅使用单一容器制备和施用药物的方法。 在这种方法中，将具有药物的分散剂的流体分散体与使用容器内的近临界或超临界条件下的反溶剂接触，从而将药物的小颗粒直接沉淀在容器中。 然后将抗溶剂除去，并将使用容器用其中的药物颗粒密封。 此后，药物的剂量可以从使用容器中取出并给予患者。
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3.发明授权Sulfoalkyl ether cyclodextrin based solid pharmaceutical formulations and their use 失效基于磺基烷基醚环糊精的固体药物制剂及其用途
公开(公告)号：US5874418A
公开(公告)日：1999-02-23
申请号：US851006
申请日：1997-05-05
CPC分类号： A61K47/40 , A61K9/205 , A61K9/2846 , A61K9/2866 , Y10S514/964 , Y10S514/965
摘要： Sulfoalkyl ether-cyclodextrin (SAE-CD) based pharmaceutical formulations are provided by the present invention. These formulations comprise SAE-CD derivatives and a therapeutic agent, a major portion of which is not complexed to the SAE-CD. The present formulations are advantageously easier to prepare than other SAE-CD based formulations in the art yet provide similar or improved effectiveness. The SAE-CD derivative can be used to modify the bioavailability and/or rate of bioabsorption of therapeutic agents.
摘要翻译： 基于磺基烷基醚 - 环糊精（SAE-CD）的药物制剂由本发明提供。 这些制剂包含SAE-CD衍生物和治疗剂，其主要部分不与SAE-CD复合。 本发明的制剂有利地比本领域中其他基于SAE-CD的制剂更容易制备，但提供相似或改进的效果。 SAE-CD衍生物可用于改变治疗剂的生物利用度和/或生物吸收速率。
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4.发明授权公开(公告)号：US07744923B2
公开(公告)日：2010-06-29
申请号：US11870554
申请日：2007-10-11
申请人： Roger A. Rajewski , Bala Subramaniam , Fenghui Niu
发明人： Roger A. Rajewski , Bala Subramaniam , Fenghui Niu
IPC分类号： A61K9/14
CPC分类号： A61K9/1688 , B01J2/02 , B01J2/04 , B01J2/18
摘要： Commercially feasible methods for lyophobic precipitation of liquid-dispersed or dissolved material (e.g., medicaments) are provided wherein a plurality of individual, open containers (22) each containing a quantity (84) of a solution or dispersion are treated within a common pressurizable chamber (12). In this process, desired near-supercritical or supercritical temperature and pressure conditions are established for a selected antisolvent gas such as carbon dioxide, and an ultrasonic device (14) is actuated to generate high energy ultrasonic waves in the chamber (12). This leads to intense mixing of the antisolvent with the liquid solution or dispersion within the containers (22), with consequent solvent removal and material precipitation.
摘要翻译： 提供了用于液体分散或溶解的材料（例如药物）的疏液沉淀的商业上可行的方法，其中每个含有（84）溶液或分散体的多个单独的开放容器（22）在共同的可加压室 （12）。 在这个过程中，为所选择的反溶剂气体例如二氧化碳建立了所需的近临界或超临界温度和压力条件，并且致动超声波装置（14）以在腔室（12）中产生高能超声波。 这导致反溶剂与容器（22）内的液体溶液或分散体的强烈混合，随后进行溶剂去除和材料沉淀。
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5.发明授权Compositions and methods for the delivery of poorly water soluble drugs and methods of treatment 有权用于递送水溶性差的药物的组合物和方法以及治疗方法公开(公告)号：US08221779B2
公开(公告)日：2012-07-17
申请号：US12394833
申请日：2009-02-27
IPC分类号： A61F2/02
CPC分类号： A61K9/10 , A61K9/0019 , A61K9/14 , A61K9/1688 , A61K47/44
摘要： The present embodiment of the invention is generally directed to compositions comprising suspensions of poorly water-soluble compounds recrystallized in nanoparticulate sizes ranging from 0.1 to 5 μm. In addition, the embodiment of the invention is directed to methods for preparation and administration of these compositions to a patient for prevention and treatment of disease states. In particular, the embodiment of the invention is directed to compositions comprising suspensions of poorly water-soluble compounds, such as antimitotics and antibiotics, in nanoparticulates and methods of prevention and treatment of chronic disease states, such as cancer, by intraperitoneal and intravenous administration of such compositions.
摘要翻译： 本发明的本实施方案通常涉及包含以0.1至5μm的纳米颗粒尺寸重结晶的难溶于水的化合物的悬浮液的组合物。 此外，本发明的实施方案涉及用于制备和施用这些组合物给患者以预防和治疗疾病状态的方法。 特别地，本发明的实施方案涉及包含难溶性水溶性化合物如抗虚证和抗生素的悬浮液在纳米颗粒中的组合物，以及通过腹膜内和静脉内施用预防和治疗慢性疾病状态如癌症的方法 这样的组合物。
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公开(公告)号：US06562952B1
公开(公告)日：2003-05-13
申请号：US09703221
申请日：2000-10-31
IPC分类号： A23J100
CPC分类号： A61K9/1688
摘要： A process for forming small micron-sized (1-10 &mgr;m) protein particles is provided wherein a protein, a solvent system for the protein and an antisolvent for the protein solvent system are contacted under conditions to at least partially dissolve the protein solvent system in the antisolvent, thereby causing precipitation of the protein. The solvent system is made up of at least in part of a halogenated organic alcohol, most preferably 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). Preferably, a solution of the protein in the solvent system is sprayed through a nozzle into a precipitation zone containing the antisolvent (preferably CO2) under near- or supercritical conditions.
摘要翻译： 提供了形成小微米尺寸（1-10μm）蛋白质颗粒的方法，其中蛋白质，用于蛋白质的溶剂体系和蛋白质溶剂体系的抗溶剂在至少部分溶解蛋白质溶剂体系的条件下接触 抗溶剂，从而引起蛋白质的沉淀。 溶剂系统由至少部分卤代有机醇，最优选1,1,1,3,3,3-六氟-2-丙醇（HFIP）组成。 优选地，在近或超临界条件下，将蛋白质在溶剂系统中的溶液通过喷嘴喷射到含有抗溶剂（优选CO 2）的沉淀区中。
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7.发明申请COMPOSITIONS AND METHODS FOR THE DELIVERY OF POORLY WATER SOLUBLE DRUGS AND METHODS OF TREATMENT 有权用于输送不合适的水溶性药物的组合物和方法以及治疗方法公开(公告)号：US20090197821A1
公开(公告)日：2009-08-06
申请号：US12394833
申请日：2009-02-27
IPC分类号： A61K31/7048 , A61K31/337 , A61K31/4745 , A61K31/407 , A61K31/704 , A61P35/00
CPC分类号： A61K9/10 , A61K9/0019 , A61K9/14 , A61K9/1688 , A61K47/44
摘要： The present embodiment of the invention is generally directed to compositions comprising suspensions of poorly water-soluble compounds recrystallized in nanoparticulate sizes ranging from 0.1 to 5 μm. In addition, the embodiment of the invention is directed to methods for preparation and administration of these compositions to a patient for prevention and treatment of disease states. In particular, the embodiment of the invention is directed to compositions comprising suspensions of poorly water-soluble compounds, such as antimitotics and antibiotics, in nanoparticulates and methods of prevention and treatment of chronic disease states, such as cancer, by intraperitoneal and intravenous administration of such compositions
摘要翻译： 本发明的本实施方案通常涉及包含以0.1至5μm的纳米颗粒尺寸重结晶的难溶于水的化合物的悬浮液的组合物。 此外，本发明的实施方案涉及用于制备和施用这些组合物给患者以预防和治疗疾病状态的方法。 特别地，本发明的实施方案涉及包含难溶性水溶性化合物如抗虚证和抗生素的悬浮液在纳米颗粒中的组合物，以及通过腹膜内和静脉内施用预防和治疗慢性疾病状态如癌症的方法 这样的组合物
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8.发明申请公开(公告)号：US20080089944A1
公开(公告)日：2008-04-17
申请号：US11870554
申请日：2007-10-11
申请人： Roger A. Rajewski , Bala Subramaniam , Fenghui Niu
发明人： Roger A. Rajewski , Bala Subramaniam , Fenghui Niu
IPC分类号： A61K9/14
CPC分类号： A61K9/1688 , B01J2/02 , B01J2/04 , B01J2/18
摘要： Commercially feasible methods for lyophobic precipitation of liquid-dispersed or dissolved material (e.g., medicaments) are provided wherein a plurality of individual, open containers (22) each containing a quantity (84) of a solution or dispersion are treated within a common pressurizable chamber (12). In this process, desired near-supercritical or supercritical temperature and pressure conditions are established for a selected antisolvent gas such as carbon dioxide, and an ultrasonic device (14) is actuated to generate high energy ultrasonic waves in the chamber (12). This leads to intense mixing of the antisolvent with the liquid solution or dispersion within the containers (22), with consequent solvent removal and material precipitation.
摘要翻译： 提供了用于液体分散或溶解的材料（例如药物）的疏液沉淀的商业上可行的方法，其中每个含有（84）溶液或分散体的多个单独的开放容器（22）在共同的可加压室 （12）。 在这个过程中，为所选择的反溶剂气体例如二氧化碳建立了所需的近临界或超临界温度和压力条件，并且致动超声波装置（14）以在腔室（12）中产生高能超声波。 这导致抗溶剂与容器（22）内的液体溶液或分散体的强烈混合，随后进行溶剂去除和材料沉淀。
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9.发明授权Process and apparatus for size selective separation of micro- and nano-particles 有权用于微粒和纳米颗粒尺寸选择性分离的方法和装置
公开(公告)号：US6113795A
公开(公告)日：2000-09-05
申请号：US193660
申请日：1998-11-17
CPC分类号： B01D11/0407 , B01D61/14 , C30B29/605 , C30B7/00
摘要： Processes and apparatuses are provided for continuously harvesting particles from organic solution-laden near-critical and supercritical fluids. Broadly, the processes and apparatuses utilize a filter or separator comprising a thin membrane supported on a sintered stainless steel tube. A feed stream comprising the desired particles, a supercritical antisolvent for the particles (preferably CO.sub.2), and a solvent for the particles, is contacted with the membrane layer of the filter under supercritical conditions for the mixture of antisolvent and solvent. The preferred antisolvents are substantially miscible with the solvent and have a critical temperature of less than 160.degree. C. The desired particles are retained by the filter while the solvent and most of the antisolvent pass through the filter, resulting in separation of the particles from the solvent.
摘要翻译： 提供了从有机溶液附近临界和超临界流体中连续收集颗粒的方法和装置。 广泛地，该方法和设备利用一种过滤器或分离器，其包括负载在烧结的不锈钢管上的薄膜。 包含所需颗粒的进料流，用于颗粒的超临界反溶剂（优选CO 2）和颗粒的溶剂在超临界条件下与反应溶剂和溶剂的混合物与过滤器的膜层接触。 优选的反溶剂与溶剂基本上是可混溶的并且具有小于160℃的临界温度。所需的颗粒被过滤器保留，而溶剂和大部分反溶剂通过过滤器，导致颗粒从 溶剂。
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公开(公告)号：US08900629B2
公开(公告)日：2014-12-02
申请号：US13335067
申请日：2011-12-22
CPC分类号： A61K9/0056 , A61K9/4816 , A61K47/36
摘要： The present disclosure provides rapidly dissolving oral capsules and films comprising pullulan, a plasticizer, and a dissolution enhancing agent.
摘要翻译： 本发明提供快速溶解的口服胶囊和包含支链淀粉，增塑剂和溶解增强剂的薄膜。
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