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1. 发明授权

US07595348B2 Butyl lactate emulsions for the precipitation of water-insoluble drug nanoparticles 有权
标题翻译：用于沉淀水不溶性药物纳米粒子的乳酸丁酯乳液
公开(公告)号：US07595348B2
公开(公告)日：2009-09-29
申请号：US11420035
申请日：2006-05-24
申请人： Pratibhash Chattopadhyay , Boris Y. Shekunov , Adam K. Gibson
发明人： Pratibhash Chattopadhyay , Boris Y. Shekunov , Adam K. Gibson
IPC分类号： C09K3/00
CPC分类号： A61K9/14 , A61K9/10 , A61K9/145
摘要： Emulsions for use in precipitating water-insoluble drug nanoparticles. The continuous phase of the emulsions include water and an external surfactant. The discontinuous phase of the emulsions include butyl lactate, a co-solvent, an internal surfactant and a water-insoluble drug that is solubilized in the discontinuous phase. The emulsions allow for the precipitation of nanoparticles of water-insoluble drugs that are otherwise difficult or impossible to precipitate using conventional emulsion techniques.
摘要翻译：用于沉淀水不溶性药物纳米粒子的乳液。乳液的连续相包括水和外部表面活性剂。乳液的不连续相包括乳酸丁酯，共溶剂，内表面活性剂和溶解在不连续相中的水不溶性药物。乳液允许使用常规乳液技术难于或不可能沉淀的水不溶性药物的纳米颗粒的沉淀。

2. 发明申请

US20070275076A1 Method For The Production Of Porous Particles 有权
标题翻译：多孔颗粒生产方法
公开(公告)号：US20070275076A1
公开(公告)日：2007-11-29
申请号：US11748095
申请日：2007-05-14
申请人： Pratibhash Chattopadhyay , Boris Y. Shekunov , Adam K. Gibson
发明人： Pratibhash Chattopadhyay , Boris Y. Shekunov , Adam K. Gibson
IPC分类号： A61K9/14
CPC分类号： A61K9/0075 , A61K9/146
摘要： The present invention provides a method for the production of porous particles that involves extracting an organic solvent from a water-in-oil-in-water emulsion. In accordance with the method of the invention, a first aqueous solution including a porosity-promoting agent is emulsified into an organic solution including a therapeutic constituent and, optionally, a matrix material to form a water-in-oil emulsion. The water-in-oil emulsion is then emulsified into a second aqueous solution including a surfactant to form the water-in-oil-in-water emulsion. Extraction of the organic solvent from the water-in-oil-in-water emulsion, such as by supercritical fluid extraction, causes the therapeutic constituent and optional matrix material to precipitate and thus form an aqueous suspension of porous particles. The aqueous suspension can be centrifuged, filtered and lyophilized to obtain dry porous particles suitable for use in the deep lung delivery of drugs and other therapeutic agents.
摘要翻译：本发明提供了一种生产多孔颗粒的方法，其涉及从水包油包水乳液萃取有机溶剂。根据本发明的方法，将包含孔隙促进剂的第一水溶液乳化成包括治疗成分和任选的基质材料的有机溶液，以形成油包水乳液。然后将油包水乳液乳化成包含表面活性剂的第二水溶液以形成水包油包水乳液。例如通过超临界流体萃取从水包油包水乳液中萃取有机溶剂使得治疗成分和任选的基质材料沉淀，从而形成多孔颗粒的水性悬浮液。可以将水性悬浮液离心，过滤并冻干，得到适合用于深部肺部递送药物和其它治疗剂的干燥多孔颗粒。

3. 发明授权

US08207236B2 Method for the production of porous particles 有权
标题翻译：生产多孔颗粒的方法
公开(公告)号：US08207236B2
公开(公告)日：2012-06-26
申请号：US11748095
申请日：2007-05-14
申请人： Pratibhash Chattopadhyay , Boris Y. Shekunov , Adam K. Gibson
发明人： Pratibhash Chattopadhyay , Boris Y. Shekunov , Adam K. Gibson
IPC分类号： C08J9/28 , C08J9/26 , A61K9/14
CPC分类号： A61K9/0075 , A61K9/146
摘要： The present invention provides a method for the production of porous particles that involves extracting an organic solvent from a water-in-oil-in-water emulsion. In accordance with the method of the invention, a first aqueous solution including a porosity-promoting agent is emulsified into an organic solution including a therapeutic constituent and, optionally, a matrix material to form a water-in-oil emulsion. The water-in-oil emulsion is then emulsified into a second aqueous solution including a surfactant to form the water-in-oil-in-water emulsion. Extraction of the organic solvent from the water-in-oil-in-water emulsion, such as by supercritical fluid extraction, causes the therapeutic constituent and optional matrix material to precipitate and thus form an aqueous suspension of porous particles. The aqueous suspension can be centrifuged, filtered and lyophilized to obtain dry porous particles suitable for use in the deep lung delivery of drugs and other therapeutic agents.
摘要翻译：本发明提供了一种生产多孔颗粒的方法，其涉及从水包油包水乳液萃取有机溶剂。根据本发明的方法，将包含孔隙促进剂的第一水溶液乳化成包括治疗成分和任选的基质材料的有机溶液，以形成油包水乳液。然后将油包水乳液乳化成包含表面活性剂的第二水溶液以形成水包油包水乳液。例如通过超临界流体萃取从水包油包水乳液中萃取有机溶剂使得治疗成分和任选的基质材料沉淀，从而形成多孔颗粒的水性悬浮液。可以将水性悬浮液离心，过滤并冻干，得到适合用于深部肺部递送药物和其它治疗剂的干燥多孔颗粒。

4. 发明授权

US07449136B2 Method and apparatus for producing composite particles using supercritical fluid as plasticizing and extracting agent 有权
标题翻译：使用超临界流体作为增塑剂和提取剂生产复合颗粒的方法和装置
公开(公告)号：US07449136B2
公开(公告)日：2008-11-11
申请号：US10531008
申请日：2004-02-18
申请人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger
发明人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger
IPC分类号： B29B9/00 , A61K9/14
CPC分类号： B01D11/0411 , B01D11/0203 , B01D11/0403
摘要： The present invention provides methods for producing composite particles using supercritical fluid as a plasticizing and extracting agent, composite particles formed in accordance with the methods and an apparatus for carrying out the methods. In accordance with the methods of the invention, a polymer, a wax and/or a lipid that is a solid at standard temperature and pressure is contacted with a supercritical fluid to form a melt, either before or after the polymer, wax and/or lipid has been contacted with a solution comprising a solute dissolved in a solvent. The supercritical fluid plasticizes the polymer, wax and/or lip and extracts the solvent from the solution, resulting in the formation of a two-fraction system including a first melt-rich fraction that includes the plasticized melt and fine particles of precipitated solute that are dispersed in the melt, and a second fraction that includes the supercritical fluid and the solvent. Expansion of the first fraction across a pressure drop results in the formation of composite particles that include the polymer, wax and/or lipid and the solute.
摘要翻译：本发明提供了使用超临界流体作为增塑萃取剂，根据所述方法形成的复合颗粒和用于实施所述方法的装置来生产复合颗粒的方法。根据本发明的方法，在标准温度和压力下作为固体的聚合物，蜡和/或脂质与超临界流体接触以形成熔体，在聚合物之前或之后，蜡和/或脂质已经与包含溶解在溶剂中的溶质的溶液接触。超临界流体使聚合物，蜡和/或脂肪增塑，并从溶液中提取溶剂，从而形成包括第一富熔体部分的双组分体系，其包括增塑的熔体和沉淀的溶质的细颗粒，分散在熔体中，第二部分包括超临界流体和溶剂。通过压降的第一级分的膨胀导致形成包括聚合物，蜡和/或脂质和溶质的复合颗粒。

5. 发明授权

US07073349B2 Lyophilization method and apparatus for producing particles 有权
标题翻译：冻干方法和生产颗粒的装置
公开(公告)号：US07073349B2
公开(公告)日：2006-07-11
申请号：US11078554
申请日：2005-03-11
申请人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger
发明人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger
IPC分类号： B01D9/04 , C02F1/22
CPC分类号： F25D3/102 , A61K9/1623 , A61K9/1694 , A61K9/19 , F25B9/02 , F26B5/065
摘要： A method and apparatus for producing particles, the apparatus includes a solution source that supplies a solution, and a fluid source that supplies a fluid. The solution includes a solvent and a solute. A mixer receives the solution and the fluid from the sources, and mixes the solution and the fluid together to form a mixture. The mixture is supplied from the mixer to an expansion assembly at first pressure. The expansion assembly sprays and expands the mixture substantially simultaneously to form frozen droplets, and preferably to form a low-density powder of frozen droplets. A freeze-dry apparatus sublimes the solvent from the particles. A high mass-transfer rate and a uniform open-structure of the powder bed enhances the freeze-drying process. Solid particles having a controlled size distribution are obtained. The particles preferably have a hollow or porous morphology suitable for differing drug delivery applications to include aerosol formulations.
摘要翻译：一种用于生产颗粒的方法和装置，该装置包括提供溶液的溶液源和供应流体的流体源。溶液包括溶剂和溶质。混合器接收来自源的溶液和流体，并将溶液和流体混合在一起形成混合物。混合物在第一压力下从混合器供应到膨胀组件。膨胀组件基本上同时喷雾和膨胀混合物以形成冷冻液滴，并且优选地形成冷冻液滴的低密度粉末。冷冻干燥装置使颗粒中的溶剂升华。粉末床的高质量转移率和均匀的开放结构提高了冷冻干燥过程。获得具有受控尺寸分布的固体颗粒。颗粒优选具有适于不同药物递送应用的中空或多孔形态以包括气溶胶制剂。

6. 发明申请

US20080269449A1 METHODS FOR THE PURIFICATION OF POLYMERS 有权
标题翻译：聚合物的纯化方法
公开(公告)号：US20080269449A1
公开(公告)日：2008-10-30
申请号：US12017399
申请日：2008-01-22
申请人： Pratibhash Chattopadhyay , Boris Y. Shekunov , K. Adam Gibson
发明人： Pratibhash Chattopadhyay , Boris Y. Shekunov , K. Adam Gibson
IPC分类号： C08F120/18 , C08G63/08 , C08G65/04
CPC分类号： C08G63/90 , C08G63/08 , C08G65/30 , Y02P20/544
摘要： The present invention provides methods for purifying polymers. In each embodiment of the invention disclosed herein, a supercritical fluid is contacted with an organic solution that includes a polymer to be purified dissolved in an organic solvent. The supercritical fluid extracts the organic solvent from the organic solution. Impurities such as residual monomers and process solvents are removed with the organic solvent and supercritical fluid, thereby purifying the polymer. The methods of the invention are particularly suitable for use in the purification of biodegradable polymers for use in pharmaceutical applications.
摘要翻译：本发明提供了纯化聚合物的方法。在本文公开的本发明的每个实施方案中，将超临界流体与包含要溶解在有机溶剂中的待纯化聚合物的有机溶液接触。超临界流体从有机溶液中萃取有机溶剂。用有机溶剂和超临界流体除去残留单体和工艺溶剂等杂质，从而纯化聚合物。本发明的方法特别适用于纯化用于制药应用的可生物降解的聚合物。

7. 发明授权

US07208106B2 Method of forming particles 有权
标题翻译：形成颗粒的方法
公开(公告)号：US07208106B2
公开(公告)日：2007-04-24
申请号：US10536330
申请日：2004-10-15
申请人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger
发明人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger
IPC分类号： B29B9/00
CPC分类号： A61K9/14 , A61K9/1688 , B01J2/04 , B01J2/06
摘要： The present invention provides a method of forming particles that involves contacting a solution, which includes a solute and/or other material to be precipitated dissolved or dispersed in a solvent, with a first compressed or liquefied gas at an initial temperature to form a mixture. The mixture is then expanded at a first temperature to form droplets. Depending upon the composition of the droplets and the first temperature, the droplets may be in a solid state or a liquid state. The droplets are then contacted with an extracting fluid at a second temperature to extract the solvent from the droplets. The method can be used to produce micro and nanoparticles suitable for various drug delivery systems.
摘要翻译：本发明提供一种形成颗粒的方法，该方法包括使初始温度下与第一压缩或液化气体接触的溶液（包括溶解或分散在溶剂中的溶质或其他物质）溶液形成混合物。然后将混合物在第一温度下膨胀以形成液滴。根据液滴的组成和第一温度，液滴可以是固体状态或液体状态。然后在第二温度下使液滴与萃取液接触以从液滴中提取溶剂。该方法可用于生产适用于各种药物递送系统的微型和纳米颗粒。

8. 发明授权

US06931888B2 Lyophilization method and apparatus for producing particles 有权
标题翻译：冻干方法和生产颗粒的装置
公开(公告)号：US06931888B2
公开(公告)日：2005-08-23
申请号：US10434435
申请日：2003-05-08
申请人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger
发明人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger
IPC分类号： A61K9/16 , A61K9/19 , F25B9/02 , F25D3/10 , F26B5/06 , B01D9/04 , B01D37/00 , B01D43/00 , C02F1/22
CPC分类号： F25D3/102 , A61K9/1623 , A61K9/1694 , A61K9/19 , F25B9/02 , F26B5/065
摘要： A method and apparatus for producing particles, the apparatus includes a solution source that supplies a solution, and a fluid source that supplies a fluid. The solution includes a solvent and a solute. A mixer receives the solution and the fluid from the sources, and mixes the solution and the fluid together to form a mixture. The mixture is supplied from the mixer to an expansion assembly at first pressure. The expansion assembly sprays and expands the mixture substantially simultaneously to form frozen droplets, and preferably to form a low-density powder of frozen droplets. A freeze-dry apparatus sublimes the solvent from the particles. A high mass-transfer rate and a uniform open-structure of the powder bed enhances the freeze-drying process. Solid particles having a controlled size distribution are obtained. The particles preferably have a hollow or porous morphology suitable for differing drug delivery applications to include aerosol formulations.
摘要翻译：一种用于生产颗粒的方法和装置，该装置包括提供溶液的溶液源和供应流体的流体源。溶液包括溶剂和溶质。混合器接收来自源的溶液和流体，并将溶液和流体混合在一起形成混合物。混合物在第一压力下从混合器供应到膨胀组件。膨胀组件基本上同时喷雾和膨胀混合物以形成冷冻液滴，并且优选地形成冷冻液滴的低密度粉末。冷冻干燥装置使颗粒中的溶剂升华。粉末床的高质量转移率和均匀的开放结构提高了冷冻干燥过程。获得具有受控尺寸分布的固体颗粒。颗粒优选具有适于不同药物递送应用的中空或多孔形态以包括气溶胶制剂。

9. 发明授权

US08535720B2 Method and apparatus for enhanced size reduction of particles 有权
标题翻译：增加颗粒尺寸减小的方法和装置
公开(公告)号：US08535720B2
公开(公告)日：2013-09-17
申请号：US10541909
申请日：2004-02-24
申请人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger , Robert W. Huff
发明人： Boris Y. Shekunov , Pratibhash Chattopadhyay , Jeffrey S. Seitzinger , Robert W. Huff
IPC分类号： A61K9/14 , B29B9/00
CPC分类号： B01F3/0853 , A61K9/146 , A61K9/1652 , A61K9/1694 , B01D3/06 , B01D11/0411 , B01F2003/0064 , B01J2/02 , C08J3/12 , C08J2305/00 , C08J2333/00 , C08J2367/00 , C08J2371/00 , C08J2389/00
摘要： The present invention provides methods and apparatus for producing particles via supercritical fluid processing. In one embodiment, the method includes expanding a supercritical fluid plasticized melt across a pressure drop to form solid composite particles that are simultaneously dispersed, foamed and cooled, and milling the solid particles produced to achieve the desired size distribution. In another embodiment, a pressure vessel containing a supercritical fluid plasticized melt is depressurized to form a cooled solid porous mass, which is then milled to obtain solid composite particles.
摘要翻译：本发明提供了通过超临界流体处理生产颗粒的方法和装置。在一个实施方案中，该方法包括在压降下扩张超临界流体增塑的熔体，以形成同时分散，发泡和冷却的固体复合颗粒，并研磨生产的固体颗粒以达到所需的尺寸分布。在另一个实施方案中，将含有超临界流体增塑的熔体的压力容器减压以形成冷却的固体多孔质量块，然后将其研磨以获得固体复合颗粒。

10. 发明授权

US07901606B2 Production of porous materials by supercritical fluid processing 有权
标题翻译：通过超临界流体处理生产多孔材料
公开(公告)号：US07901606B2
公开(公告)日：2011-03-08
申请号：US10552008
申请日：2005-06-21
申请人： Pratibhash Chattopadhyay , Boris Y. Shekunov , Jeffrey S. Seitzinger
发明人： Pratibhash Chattopadhyay , Boris Y. Shekunov , Jeffrey S. Seitzinger
IPC分类号： C08J9/26
CPC分类号： A61K9/1688 , A61K9/0073 , A61K9/1647
摘要： The present invention provides a method of producing porous structures, particles or matrixes, which may be comprised of one or a plurality of components, an apparatus for carrying out the method and particles formed in accordance with the method. The method is particularly suitable for producing porous composite or pure particles for pharmaceutical applications. In accordance with the method, a composite comprising a material such as a pharmaceutical, a biodegradable polymers and/or a biological agent is formed. The composite must further comprise a material that is soluble in supercritical fluid. Extraction of the supercritical fluid soluble material produces porous structures, which may be in the form of particles or matrixes.
摘要翻译：本发明提供一种生产可由一种或多种组分组成的多孔结构，颗粒或基体的方法，用于实施根据该方法形成的方法和颗粒的装置。该方法特别适用于生产用于药物应用的多孔复合物或纯颗粒。根据该方法，形成包含诸如药物，可生物降解的聚合物和/或生物试剂的材料的复合材料。复合材料还必须包含可溶于超临界流体的材料。超临界流体可溶物质的提取产生多孔结构，其可以是颗粒或基体的形式。

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