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公开(公告)号：US08535720B2
公开(公告)日：2013-09-17
申请号：US10541909
申请日：2004-02-24
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。
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公开(公告)号：US20080286365A1
公开(公告)日：2008-11-20
申请号：US12124518
申请日：2008-05-21
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。
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公开(公告)号：US06998051B2
公开(公告)日：2006-02-14
申请号：US10423492
申请日：2003-04-25
CPC分类号： B01D11/0411 , B01J13/02
摘要： A method of producing microparticles and nanoparticles of a solute via the extraction of solvent, having the solute dissolved therein, from an emulsion using a supercritical fluid. The solute to be precipitated is dissolved in the solvent to form a solution, and the solution is dispersed in an immiscible or partially miscible liquid to form an emulsion. The particles are produced via the extraction of the solvent from the emulsion using the supercritical fluid. The process can produce an aqueous suspension of particles that are substantially insoluble in water, and the solvents used in the process to form the emulsion initially can be recovered and recycled.
摘要翻译： 通过使用超临界流体从乳液中提取溶质溶解溶剂的方法来生产溶质的微粒和纳米颗粒。 待沉淀的溶质溶解在溶剂中以形成溶液，并将溶液分散在不混溶或部分混溶的液体中以形成乳液。 通过使用超临界流体从乳液中提取溶剂来生产颗粒。 该方法可以产生基本上不溶于水的颗粒的水性悬浮液，并且可以回收和再循环用于形成乳液的方法中使用的溶剂。
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公开(公告)号：US06966990B2
公开(公告)日：2005-11-22
申请号：US10441137
申请日：2003-05-19
CPC分类号： B01D11/0411 , B01J13/02
摘要： A method for producing composite particles using a supercritical fluid extraction technique on an emulsion. First and second materials (for example; a polymer and a biologically active material) are dissolved or suspended in a preferably solvent to form a solution or dispersion. The solution or dispersion is emulsified in a polar solvent to form an oil-in-water or water-in-oil-in-water emulsion. The emulsion is contacted with a supercritical fluid to extract the solvent. Removal of the solvent by the supercritical fluid from the emulsion supersaturates at least the first material in the solution causing the first material to precipitate out of the solution as composite particles that include both the first and second materials.
摘要翻译： 一种使用超临界流体萃取技术在乳液上制备复合颗粒的方法。 将第一和第二材料（例如，聚合物和生物活性材料）溶解或悬浮在优选溶剂中以形成溶液或分散体。 将溶液或分散体在极性溶剂中乳化以形成水包油或水包油包水乳液。 将乳液与超临界流体接触以萃取溶剂。 由超临界流体从乳液中除去溶剂至少使溶液中的第一种材料过饱和，导致第一种材料沉淀出溶液，作为包括第一和第二种材料的复合颗粒。
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公开(公告)号：US08642091B2
公开(公告)日：2014-02-04
申请号：US12124518
申请日：2008-05-21
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。
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6.发明授权Butyl lactate emulsions for the precipitation of water-insoluble drug nanoparticles 有权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
IPC分类号： C09K3/00
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。
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7.发明授权Method and apparatus for producing composite particles using supercritical fluid as plasticizing and extracting agent 有权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
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。
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公开(公告)号：US07073349B2
公开(公告)日：2006-07-11
申请号：US11078554
申请日：2005-03-11
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。
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公开(公告)号：US20080269449A1
公开(公告)日：2008-10-30
申请号：US12017399
申请日：2008-01-22
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。
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公开(公告)号：US07208106B2
公开(公告)日：2007-04-24
申请号：US10536330
申请日：2004-10-15
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。
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