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21. 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。

22. 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。

23. 发明申请

US20060104916A1 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：US20060104916A1
公开(公告)日：2006-05-18
申请号：US10541909
申请日：2004-02-24
申请人： Boris Shekunov , Pratibhash Chattopadhyay , Jeffrey Seitzinger , Robert Huff
发明人： Boris Shekunov , Pratibhash Chattopadhyay , Jeffrey Seitzinger , Robert Huff
IPC分类号： A61K9/14 , A61L9/04 , 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 composte 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，将包含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堆肥颗粒。

24. 发明申请

US20060076293A1 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：US20060076293A1
公开(公告)日：2006-04-13
申请号：US10531008
申请日：2004-02-18
申请人： Boris Shekunov , Pratibhash Chattopadhyay , Jeffrey Seitzinger
发明人： Boris Shekunov , Pratibhash Chattopadhyay , Jeffrey Seitzinger
IPC分类号： B01D11/02
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。

25. 发明申请

US20060008531A1 METHOD FOR PRODUCING SOLID-LIPID COMPOSITE DRUG PARTICLES 审中-公开
标题翻译：生产固体脂肪复合药物颗粒的方法
公开(公告)号：US20060008531A1
公开(公告)日：2006-01-12
申请号：US11160367
申请日：2005-06-21
申请人： Boris Shekunov , Pratibhash Chattopadhyay , Robert Huff
发明人： Boris Shekunov , Pratibhash Chattopadhyay , Robert Huff
IPC分类号： A61K9/14
CPC分类号： A61K9/167 , A61K9/5123 , B01D11/0403 , B01D11/0407 , B01D11/0411 , B01D11/0484 , B01J13/02
摘要： A method of producing solid composite lipid/drug nanoparticles that includes the steps of: (1) dissolving a lipid and a drug in a suitable organic solvent to form a solution; (2) emulsifying the solution in a liquid to form an emulsion having a discontinuous phase of micelles comprising the organic solvent, the drug and the lipid, and a continuous phase comprising the liquid; and (3) contacting the emulsion with a supercritical fluid under conditions suitable to keep the supercritical fluid in a supercritical state, whereby the supercritical fluid extracts the organic solvent from the micelles, causing them to precipitate as organic-solvent free solid composite lipid/drug nanoparticles suspended or dispersed in the liquid.
摘要翻译：一种生产固体复合脂质/药物纳米颗粒的方法，其包括以下步骤：（1）将脂质和药物溶解在合适的有机溶剂中以形成溶液; （2）将溶液乳化在液体中以形成具有包含有机溶剂，药物和脂质的胶束不连续相的乳液和包含液体的连续相; 和（3）在适合于使超临界流体处于超临界状态的条件下使乳液与超临界流体接触，由此超临界流体从胶束中提取有机溶剂，导致它们作为无机溶剂固体复合脂质/药物沉淀悬浮或分散在液体中的纳米颗粒。

26. 发明申请

US20050178020A1 Lyophilization method and apparatus for producing particles 有权
公开(公告)号：US20050178020A1
公开(公告)日：2005-08-18
申请号：US11078554
申请日：2005-03-11
申请人： Boris Shekunov , Pratibhash Chattopadhyay , Jeffrey Seitzinger
发明人： Boris Shekunov , Pratibhash Chattopadhyay , Jeffrey Seitzinger
IPC分类号： A61K9/16 , A61K9/19 , F25B9/02 , F25D3/10 , F26B5/06 , A23F5/00
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.

27. 发明授权

US06620351B2 Method of forming nanoparticles and microparticles of controllable size using supercritical fluids with enhanced mass transfer 有权
标题翻译：使用具有增强的质量传递的超临界流体形成可控尺寸的纳米颗粒和微粒的方法
公开(公告)号：US06620351B2
公开(公告)日：2003-09-16
申请号：US09858301
申请日：2001-05-16
申请人： Ram B. Gupta , Pratibhash Chattopadhyay
发明人： Ram B. Gupta , Pratibhash Chattopadhyay
IPC分类号： B29B900
CPC分类号： B82Y30/00 , A61K9/14 , A61K9/1688 , B01J2/04 , B01J2/18 , B01J13/04 , Y10S977/773 , Y10S977/786 , Y10S977/84
摘要： The current invention, Supercritical Antisolvent Precipitation with Enhanced Mass Transfer (SAS-EM) provides a significantly improved method for the production of nano and micro-particles with a narrow size distribution. The processes of the invention utilize the properties of supercritical fluids and also the principles of virbrational atomization to provide an efficient technique for the effective nanonization or micronization of particles. Like the SAS technique, SAS-EM, also uses a supercritical fluid as the antisolvent, but in the present invention the dispersion jet is deflected by a vibrating surface that atomizes the jet into fine droplets. The vibrating surface also generates a vibrational flow field within the supercritical phase that enhances mass transfer through increased mixing. Sizes of the particles obtained by this technique are easily controlled by changing the vibration intensity of the deflecting surface, which in turn is controlled by adjusting the power input to the vibration source. A major advantage of the SAS-EM technique is that it can be successfully used to obtain nanoparticles of materials that usually yield fibers or large crystals in SAS method. Microencapsulation via coprecipitation of two or more materials can also be achieved using the SAS-EM technique.
摘要翻译：本发明，具有增强质量传递的超临界抗溶剂沉淀（SAS-EM）提供了用于生产具有窄尺寸分布的纳米和微粒的显着改进的方法。本发明的方法利用超临界流体的性质以及病毒雾化的原理，为颗粒的有效纳米化或微粉化提供了有效的技术。像SAS技术一样，SAS-EM也使用超临界流体作为反溶剂，但是在本发明中，分散射流被喷射成微小液滴的振动表面偏转。振动表面还在超临界相中产生振动流场，通过增加混合来增强传质。通过改变通过调节输入到振动源的功率来控制偏转表面的振动强度，可容易地控制通过该技术获得的颗粒的尺寸。 SAS-EM技术的主要优点是可以成功地用于获得通常在SAS方法中产生纤维或大晶体的材料的纳米颗粒。使用SAS-EM技术也可以实现通过两种或更多种材料的共沉淀的微胶囊化。

28. 发明申请

US20060074010A1 METHOD AND APPARATUS FOR PURIFYING PHARMACEUTICAL COMPOSITIONS USING SUPERCRITICAL FLUIDS 审中-公开
标题翻译：使用超临界流体净化药物组合物的方法和装置
公开(公告)号：US20060074010A1
公开(公告)日：2006-04-06
申请号：US11162698
申请日：2005-09-20
申请人： Pratibhash Chattopadhyay , Boris Shekunov
发明人： Pratibhash Chattopadhyay , Boris Shekunov
IPC分类号： A61K38/00 , C07K14/00
CPC分类号： C07K1/14 , Y02P20/544
摘要： The present invention provides a method and an apparatus for removing impurities from biodegradable polymers and/or pharmaceutical compounds. In accordance with the method, a stream of supercritical fluid and, optionally, a modifying co-solvent, is used to dissolve the impurities. The pressure and temperature of the supercritical fluid or supercritical fluid/co-solvent mixture is controlled such that the supercritical fluid or mixture acts as a solvent for the impurities, but not for the biodegradable polymers and/or pharmaceutical compounds.
摘要翻译：本发明提供了用于从可生物降解的聚合物和/或药物化合物中除去杂质的方法和装置。根据该方法，使用超临界流体和任选的改性共溶剂流来溶解杂质。控制超临界流体或超临界流体/共溶剂混合物的压力和温度，使得超临界流体或混合物用作杂质的溶剂，但不用作可生物降解的聚合物和/或药物化合物。

29. 发明申请

US20060039983A1 Nanoparticles from supercritical fluid antisolvent process using particle growth and agglomeration retardants 有权
标题翻译：纳米颗粒超临界流体反溶剂法使用颗粒生长和聚集阻滞剂
公开(公告)号：US20060039983A1
公开(公告)日：2006-02-23
申请号：US10531160
申请日：2004-05-28
申请人： Boris Shekunov , Pratibhash Chattopadhyay , Jeffrey Seitzinger
发明人： Boris Shekunov , Pratibhash Chattopadhyay , Jeffrey Seitzinger
IPC分类号： A61K9/14
CPC分类号： A61K9/1694 , A61K9/1635 , A61K9/1641 , A61K9/1647
摘要： The present invention provides a method of forming particles using supercritical fluid (SCF). In accordance with the method, one or more growth retardant compounds having both SCF-philic and SCF-phobic groups are present when one or more solute materials reach a supersaturation point and begin to form particle nuclei. The growth retardant compounds can reduce the particle growth rate, increase the nucleation rate and also prevent particle agglomeration. Preferred growth retardant compounds include sugar acetates and fluorocarbons.
摘要翻译：本发明提供使用超临界流体（SCF）形成颗粒的方法。根据该方法，当一种或多种溶质材料达到过饱和点并开始形成粒子核时，存在一种或多种具有SCF亲和和SCF-疏水基团的生长阻滞化合物。生长阻滞化合物可以降低颗粒生长速率，增加成核速率，并且还可防止颗粒聚集。优选的生长阻滞化合物包括糖醋酸盐和碳氟化合物。

30. 发明申请

US20070267768A1 Production of Porous Materials by Supercritical Fluid Processing 有权
标题翻译：超临界流体加工生产多孔材料
公开(公告)号：US20070267768A1
公开(公告)日：2007-11-22
申请号：US10552008
申请日：2005-06-21
申请人： Pratibhash Chattopadhyay , Boris Shekunov , Jeffrey Seitzinger
发明人： Pratibhash Chattopadhyay , Boris Shekunov , Jeffrey Seitzinger
IPC分类号： B29B9/00
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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