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1.发明授权Milling a compound useful in imaging elements using polymeric milling media 失效使用聚合物研磨介质研磨可用于成像元件的化合物
公开(公告)号：US5478705A
公开(公告)日：1995-12-26
申请号：US248925
申请日：1994-05-25
CPC分类号： B41M5/38207 , C09B67/0002 , G03C1/005 , G03G5/09
摘要： Particles of compound useful in imaging elements are milled using a milling media comprising a polymeric resin. The use of polymeric milling media permits the production of particles having an average particle size less than 1 micron. Further, the resulting particles are free from the contamination resulting from conventional milling media of, for example, glass, ceramic or steel.
摘要翻译： 用于成像元件的化合物颗粒使用包含聚合物树脂的研磨介质进行研磨。 使用聚合物研磨介质允许生产平均粒度小于1微米的颗粒。 此外，所得到的颗粒没有由例如玻璃，陶瓷或钢的常规研磨介质产生的污染物。
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2.发明授权Apparatus for preparing aqueous amorphous particle dispersions of high-melting microcrystalline solids 失效用于制备高熔点微晶固体含水无定形颗粒分散体的装置
公开(公告)号：US5411715A
公开(公告)日：1995-05-02
申请号：US140703
申请日：1993-10-21
申请人： David A. Czekai , John F. Bishop
发明人： David A. Czekai , John F. Bishop
CPC分类号： B01F3/1271 , G03C7/388 , G03C1/005
摘要： An apparatus for producing amorphous particle dispersions of high-melting microcrystalline solids in a continuous process. The apparatus comprises a pump, two heat exchangers, a back-pressure valve and conduits connecting them, whereby it is possible to make aqueous dispersions of particles whose melting points are above 100.degree. C.
摘要翻译： 一种在连续工艺中生产高熔点微晶固体的无定形颗粒分散体的装置。 该装置包括泵，两个热交换器，背压阀和连接它们的导管，由此可以使熔点高于100℃的颗粒的水分散体。
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公开(公告)号：US5145684A
公开(公告)日：1992-09-08
申请号：US647105
申请日：1991-01-25
IPC分类号： A61K9/107 , A61K9/14 , A61K9/51 , A61K47/00 , A61K47/32 , A61K47/34 , A61K47/42 , A61K47/48 , A61K49/04
CPC分类号： A61K49/049 , A61K49/0423 , A61K49/0428 , A61K9/145 , A61K9/146 , B82Y5/00
摘要： Dispersible particles consisting essentially of a crystalline drug substance having a surface modifier adsorbed on the surface thereof in an amount sufficient to maintain an effective average particle size of less than about 400 nm, methods for the preparation of such particles and dispersions containing the particles. Pharmaceutical compositions containing the particles exhibit unexpected bioavailability and are useful in methods of treating mammals.
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公开(公告)号：US5110717A
公开(公告)日：1992-05-05
申请号：US628969
申请日：1990-12-17
申请人： David A. Czekai , John F. Bishop
发明人： David A. Czekai , John F. Bishop
CPC分类号： B01F3/1207 , G03C1/815 , G03C7/388 , Y10S430/132 , Y10T428/2982
摘要： An object of the invention is to overcome disadvantages of prior practices. A further object of the invention is to provide a process for providing particles that result in improved UV absorption in photographic products.An additional object is to provide lower cost polymer particle dispersions.The invention is generally accomplished by mechanically grinding a crystalline material to a desired particle size in a liquid that is not a solvent for the material, heating said crystalline particles dispersed in said liquid to above their melting temperature, and cooling the melted particles in said liquid to form amorphous particles. In preferred forms of the invention, the material is a photographically useful material, such as ultraviolet light absorber or coupler.
摘要翻译： 本发明的一个目的是克服现有实践的缺点。 本发明的另一个目的是提供一种提供在照相产品中导致改善的UV吸收的颗粒的方法。 另外的目的是提供较低成本的聚合物颗粒分散体。 本发明通常通过在不是该材料的溶剂的液体中将结晶材料机械研磨成所需的粒度来实现，将分散在所述液体中的所述结晶颗粒加热到其熔融温度以上，并将所述液体中的熔融颗粒冷却 以形成无定形颗粒。 在本发明的优选形式中，该材料是诸如紫外光吸收剂或耦合剂的照相用材料。
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公开(公告)号：US06745962B2
公开(公告)日：2004-06-08
申请号：US10037566
申请日：2001-10-19
IPC分类号： B02C1716
CPC分类号： B02C17/166 , B02C17/20 , Y10S977/775 , Y10S977/84
摘要： A small-scale or micro media-mill and a method of milling materials or products, especially pharmaceutical products, use a dispersion containing attrition milling media and the product to be milled. The milling media can be polymeric, formed of polystyrene or cross-linked polystyrene, having a nominal diameter of no greater than 500 microns. Other sizes include 200 microns and 50 microns and a mixture of these sizes. The mill has a relatively small vessel having an opening, an agitator, a coupling and a motor. The agitator can have a rotor and a shaft extending therefrom. The rotor can be cylindrical or have other configurations, and can have tapered end surfaces. The coupling can close the vessel opening, or attaching the coupling to the motor can close the opening. The coupling has an opening through which the rotor shaft extends into the motor. A sealing mechanism, such as a mechanical or lip seals the shaft while permitting the rotor shaft to rotate. The vessel can contain one or more ports for circulating the dispersion, where milling can be made in batches or recirculated through the milling chamber. The media can be retained in the vessel or recirculated along with the process fluid. The rotor is dimensioned so that its outer periphery is spaced with a small gap from an inner surface of the vessel. The vessel also can have a way of cooling the dispersion.
摘要翻译： 小型或微型培养基研磨机和研磨材料或产品，特别是药物产品的方法使用含有磨碎研磨介质和待研磨产品的分散体。 研磨介质可以是由聚苯乙烯或交联聚苯乙烯形成的聚合物，其标称直径不大于500微米。 其他尺寸包括200微米和50微米以及这些尺寸的混合物。 研磨机具有相对较小的具有开口的容器，搅拌器，联接器和马达。 搅拌器可以具有转子和从其延伸的轴。 转子可以是圆柱形的或具有其它构造，并且可以具有锥形端面。 联接器可以关闭容器开口，或者将联接器附接到马达可以关闭开口。 联轴器具有开口，转子轴通过该开口延伸到电动机中。 密封机构，例如机械或唇部，密封轴，同时允许转子轴旋转。 容器可以包含用于循环分散体的一个或多个端口，其中可以批量制造或再循环通过研磨室。 介质可以保留在容器中或与过程流体一起再循环。 转子的尺寸被设计成使得其外围与容器的内表面间隔开小间隙。 容器还可以具有冷却分散体的方法。
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公开(公告)号：US06582285B2
公开(公告)日：2003-06-24
申请号：US09842619
申请日：2001-04-26
申请人： David A. Czekai , Robert G. Reed
发明人： David A. Czekai , Robert G. Reed
IPC分类号： B24C326
CPC分类号： B02C17/16 , B02C17/163 , B02C17/18 , B02C17/20
摘要： Improved cleanability and contamination prevention are provided in a wet milling apparatus for the production of pharmaceutical grade milled products. The advantages are provided by a milling agitator that is characterized by a smooth, seamless agitating surface, without crevices or seams which might accumulate contamination and which might prevent removal of contamination during cleaning. The use of polymeric milling media reduces wear on the agitator and permits the agitator to be constructed with permanent, smooth welded joints. Seamless joints are also provided on the interior of the milling chamber and sanitary, threadless fasteners are provided for the media separation screen and other milling chamber fittings.
摘要翻译： 在用于生产药用级磨碎产品的湿式研磨设备中提供了可清洁性和防污染性的改善。 该优点由铣削搅拌器提供，其特征在于平滑无缝的搅拌表面，没有可能积聚污染的缝隙或接缝，并且可能防止在清洁期间去除污染物。 使用聚合物研磨介质可减少搅拌器的磨损，并允许搅拌器由永久，光滑的焊接接头构成。 铣床内部还提供无缝接头，卫生的无螺纹紧固件用于介质分离筛和其他铣床配件。
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公开(公告)号：US5718388A
公开(公告)日：1998-02-17
申请号：US249787
申请日：1994-05-25
申请人： David A. Czekai , Larry P. Seaman
发明人： David A. Czekai , Larry P. Seaman
CPC分类号： A61K9/146 , Y10S977/773 , Y10S977/775 , Y10S977/888 , Y10S977/896 , Y10S977/90 , Y10S977/915 , Y10S977/927
摘要： A continuous method of preparing submicron particles of a therapeutic or diagnostic agent comprises the steps of continuously introducing the agent and rigid grinding media into a milling chamber, contacting the agent with the grinding media while in the chamber to reduce the particle size of the agent, continuously removing the agent and the grinding media from the milling chamber, and thereafter separating the agent from the grinding media. In a preferred embodiment, the grinding media is a polymeric resin having a mean particle size of less than 300 .mu.m. In another preferred embodiment, the agent, grinding media and a liquid dispersion medium are continuously introduced into the milling chamber. In a further embodiment, the agent and grinding media are recirculated through the milling chamber. The method enables the use of fine grinding media, e.g., of a particle size of less than about 300 .mu.m, in a continuous grinding process which provides extremely fine particles of the agent, e.g., particles less than 100 nm in size, while avoiding problems, e.g., separator screen plugging, associated with prior art processes requiring the separation of agent from the grinding media in the milling chamber.
摘要翻译： 一种制备治疗剂或诊断剂的亚微米颗粒的连续方法包括以下步骤：将试剂和刚性研磨介质连续引入研磨室中，同时在该室中使试剂与研磨介质接触以减少试剂的粒度， 从研磨室中连续地除去试剂和研磨介质，然后将试剂从研磨介质中分离出来。 在优选的实施方案中，研磨介质是平均粒径小于300μm的聚合物树脂。 在另一优选实施方案中，将试剂，研磨介质和液体分散介质连续引入研磨室。 在另一个实施方案中，试剂和研磨介质通过研磨室再循环。 该方法能够在连续研磨过程中使用例如粒度小于约300μm的精细研磨介质，其提供极细颗粒的试剂，例如尺寸小于100nm的颗粒，同时避免 与现有技术方法相关的问题，例如分离器屏蔽堵塞，需要将研磨介质从研磨室中分离出来。
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公开(公告)号：US06431478B1
公开(公告)日：2002-08-13
申请号：US09583893
申请日：2000-05-31
IPC分类号： B02C1716
CPC分类号： B02C17/166 , B02C17/20 , Y10S977/775 , Y10S977/84
摘要： A small-scale or micro media-mill and a method of milling materials or products, especially pharmaceutical products, use a dispersion containing attrition milling media and the product to be milled. The milling media can be polymeric, formed of polystyrene or cross-linked polystyrene, having a nominal diameter of no greater than 500 microns. Other sizes include 200 microns and 50 microns and a mixture of these sizes. The mill has a relatively small vessel having an opening, an agitator, a coupling, and a motor. The agitator can have a rotor and a shaft extending therefrom. The rotor can be cylindrical or have other configurations, and can have tapered end surfaces. The coupling can close the vessel opening, or attaching the coupling to the motor can close the opening. The coupling has an opening through which the rotor shaft extends into the motor. A sealing mechanism, such as a mechanical or lip seals the shaft while permitting the rotor shaft to rotate. The vessel can contain one or more ports for circulating the dispersion, where milling can be made in batches or recirculated through the milling chamber. The media can be retained in the vessel or recirculated along with the process fluid. The rotor is dimensioned so that its outer periphery is spaced with a small gap from an inner surface of the vessel. The vessel also can have a way of cooling the dispersion.
摘要翻译： 小型或微型培养基研磨机和研磨材料或产品，特别是药物产品的方法使用含有磨碎研磨介质和待研磨产品的分散体。 研磨介质可以是由聚苯乙烯或交联聚苯乙烯形成的聚合物，其标称直径不大于500微米。 其他尺寸包括200微米和50微米以及这些尺寸的混合物。 研磨机具有相对较小的具有开口的容器，搅拌器，联接器和马达。 搅拌器可以具有转子和从其延伸的轴。 转子可以是圆柱形的或具有其它构造，并且可以具有锥形端面。 联接器可以关闭容器开口，或者将联接器附接到马达可以关闭开口。 联轴器具有开口，转子轴通过该开口延伸到电动机中。 密封机构，例如机械或唇部，密封轴，同时允许转子轴旋转。 容器可以包含用于循环分散体的一个或多个端口，其中可以批量制造或再循环通过研磨室。 介质可以保留在容器中或与过程流体一起再循环。 转子的尺寸被设计成使得其外围与容器的内表面间隔开小间隙。 容器还可以具有冷却分散体的方法。
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公开(公告)号：US5609998A
公开(公告)日：1997-03-11
申请号：US417876
申请日：1995-04-06
申请人： John Texter , Ravi Sharma , David A. Czekai
发明人： John Texter , Ravi Sharma , David A. Czekai
摘要： A process for dispersing a particulate solid substance in a continuos aqueous phase comprising the steps of:providing a comminution reactor;providing a particulate solid substance comprising a weak acid functional group, having effective pK.sub.a1 >1 and less than 1% by weight aqueous solubility at pH=pK.sub.a1 ;providing an aqueous solution consisting essentially of water or a mixture of water with water-miscible solvent, at pH less than the greater of 7 and pK.sub.a1 +2;providing a buffering salt of a weak acid, where the weak acid associated with this buffering salt has pK.sub.a2 and wherepK.sub.a1 -2.ltoreq.pK.sub.a2 ;providing milling media;combining said particulate solid substance, said aqueous solution, said buffering salt, and said milling media in said comminution reactor to produce a multiphase mixture; andmilling said mixture to produce a reduced particle size slurry of said particulate solid substance is disclosed.
摘要翻译： 一种将颗粒状固体物质分散在连续水相中的方法，包括以下步骤：提供粉碎反应器; 提供包含弱酸官能团的颗粒固体物质，其在pH = pKa1时具有有效的pKa1> 1且小于1重量％的水溶解度; 提供基本上由水或水与水混溶性溶剂的混合物组成的水溶液，pH小于7和pKa1 + 2以上的pH; 提供弱酸的缓冲盐，其中与该缓冲盐相关的弱酸具有pKa2，并且其中pKa1-2是pKa2;提供研磨介质; 将所述颗粒状固体物质，所述水溶液，所述缓冲盐和所述研磨介质在所述粉碎反应器中混合以产生多相混合物; 并研磨所述混合物以产生所述颗粒状固体物质的还原粒度浆料。
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公开(公告)号：US07713551B2
公开(公告)日：2010-05-11
申请号：US10659706
申请日：2003-09-11
申请人： Simon L. McGurk , David A. Czekai
发明人： Simon L. McGurk , David A. Czekai
IPC分类号： A61K9/14
CPC分类号： A61K9/0095 , A61K9/0056 , A61K9/145 , A61K9/146
摘要： Disclosed is a solid or semi-solid gelatin nanoparticulate active agent dosage form comprising at least one nanoparticulate active agent and at least one gel forming substance which exhibits gelation sufficient to retain excess water in the solid or semi-solid gelatin form. The active agent particles have an effective average diameter prior to inclusion in the dosage form of less than about 2000 nm. The dosage form of the invention has the advantages of easy administration combined with rapid dissolution of the active agent following administration.
摘要翻译： 公开了一种固体或半固体明胶纳米颗粒活性剂剂型，其包含至少一种纳米颗粒活性剂和至少一种形成凝胶的物质，其表现出足以保持固体或半固体明胶形式的过量水的凝胶化。 活性剂颗粒在以小于约2000nm的剂型包含之前具有有效的平均直径。 本发明的剂型具有易于给药的优点，与施用后活性剂快速溶解。
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