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1. 再颁专利

USRE40493E1 Porous paclitaxel matrices and methods of manufacture thereof 有权
标题翻译：多孔紫杉醇基质及其制备方法
公开(公告)号：USRE40493E1
公开(公告)日：2008-09-09
申请号：US11213257
申请日：2005-08-26
申请人： Julie A. Straub , Howard Bernstein , Donald E. Chickering, III , Sarwat Khattak , Greg Randall
发明人： Julie A. Straub , Howard Bernstein , Donald E. Chickering, III , Sarwat Khattak , Greg Randall
IPC分类号： A61K9/14 , A61K9/70 , A61F2/00
CPC分类号： A61K9/1623 , A61K9/1611 , A61K9/1635 , A61K9/1694 , Y10S977/906
摘要： Paclitaxel is provided in a porous matrix form, which allows the drug to be formulated without Cremophor and administered as a bolus. The paclitaxel matrices preferably are made using a process that includes (i) dissolving paclitaxel in a volatile solvent to form a paclitaxel solution, (ii) combining at least one pore forming agent with the paclitaxel solution to form an emulsion, suspension, or second solution, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of paclitaxel. The pore forming agent can be either a volatile liquid that is immiscible with the paclitaxel solvent or a volatile solid compound, preferably a volatile salt. In a preferred embodiment, spray drying is used to remove the solvents and the pore forming agent. In a preferred embodiment, microparticles of the porous paclitaxel matrix are reconstituted with an aqueous medium and administered parenterally, or processed using standard techniques into tablets or capsules for oral administration.
摘要翻译：紫杉醇以多孔基质形式提供，其允许药物在没有Cremophor的情况下配制并作为大剂量给药。紫杉醇基质优选使用包括（i）将紫杉醇溶解在挥发性溶剂中以形成紫杉醇溶液的方法制备，（ii）将至少一种成孔剂与紫杉醇溶液组合以形成乳液，悬浮液或第二溶液，和（iii）从乳液，悬浮液或第二溶液中除去挥发性溶剂和成孔剂以产生紫杉醇的多孔基质。成孔剂可以是与紫杉醇溶剂或挥发性固体化合物，优选挥发性盐不混溶的挥发性液体。在优选的实施方案中，使用喷雾干燥来除去溶剂和成孔剂。在优选的实施方案中，多孔紫杉醇基质的微粒用水性介质重新配制，并肠胃外给药，或使用标准技术加工成用于口服给药的片剂或胶囊。

2. 发明授权

US06918991B2 Methods and apparatus for making particles using spray dryer and in-line jet mill 失效
公开(公告)号：US06918991B2
公开(公告)日：2005-07-19
申请号：US10752910
申请日：2004-01-07
申请人： Donald E. Chickering, III , Sridhar Narasimhan , David Altreuter , Paul Kopesky , Mark Keegan , Julie A. Straub , Howard Bernstein
发明人： Donald E. Chickering, III , Sridhar Narasimhan , David Altreuter , Paul Kopesky , Mark Keegan , Julie A. Straub , Howard Bernstein
IPC分类号： A61K9/16 , B01D1/18 , B01J2/04 , F26B3/12 , F26B17/10 , B01D1/16
CPC分类号： F26B17/102 , A61K9/1647 , A61K9/1688 , B01D1/18 , B01J2/04 , F26B3/12
摘要： Methods and apparatus are provided for making particles comprising: (a) spraying an emulsion, solution, or suspension, which comprises a solvent and a bulk material (e.g., a pharmaceutical agent), through an atomizer and into a primary drying chamber, having a drying gas flowing therethrough, to form droplets comprising the solvent and bulk material dispersed in the drying gas; (b) evaporating, in the primary drying chamber, at least a portion of the solvent into the drying gas to solidify the droplets and form particles dispersed in drying gas; and (c) flowing the particles and at least a portion of the drying gas through a jet mill to deagglomerate or grind the particles. By coupling spray drying with “in-line” jet milling, a single step process is created from two separate unit operations, and an additional collection step is advantageously eliminated. The one-step, in-line process has further advantages in time and cost of processing.

3. 发明授权

US06921458B2 Methods and apparatus for making particles using spray dryer and in-line jet mill 失效
公开(公告)号：US06921458B2
公开(公告)日：2005-07-26
申请号：US10752861
申请日：2004-01-07
申请人： Donald E. Chickering, III , Sridhar Narasimhan , David Altreuter , Paul Kopesky , Mark Keegan , Julie A. Straub , Howard Bernstein
发明人： Donald E. Chickering, III , Sridhar Narasimhan , David Altreuter , Paul Kopesky , Mark Keegan , Julie A. Straub , Howard Bernstein
IPC分类号： A61K9/16 , B01D1/18 , B01J2/04 , F26B3/12 , F26B17/10 , B01D1/16
CPC分类号： F26B17/102 , A61K9/1647 , A61K9/1688 , B01D1/18 , B01J2/04 , F26B3/12
摘要： Methods and apparatus are provided for making particles comprising: (a) spraying an emulsion, solution, or suspension, which comprises a solvent and a bulk material (e.g., a pharmaceutical agent), through an atomizer and into a primary drying chamber, having a drying gas flowing therethrough, to form droplets comprising the solvent and bulk material dispersed in the drying gas; (b) evaporating, in the primary drying chamber, at least a portion of the solvent into the drying gas to solidify the droplets and form particles dispersed in drying gas; and (c) flowing the particles and at least a portion of the drying gas through a jet mill to deagglomerate or grind the particles. By coupling spray drying with “in-line” jet milling, a single step process is created from two separate unit operations, and an additional collection step is advantageously eliminated. The one-step, in-line process has further advantages in time and cost of processing.

4. 发明授权

US06962006B2 Methods and apparatus for making particles using spray dryer and in-line jet mill 失效
公开(公告)号：US06962006B2
公开(公告)日：2005-11-08
申请号：US10324943
申请日：2002-12-19
申请人： Donald E. Chickering, III , Sridhar Narasimhan , David Altreuter , Paul Kopesky , Mark Keegan , Julie A. Straub , Howard Bernstein
发明人： Donald E. Chickering, III , Sridhar Narasimhan , David Altreuter , Paul Kopesky , Mark Keegan , Julie A. Straub , Howard Bernstein
IPC分类号： A61K9/16 , B01D1/18 , B01J2/04 , F26B3/12 , F26B17/10 , F26B3/08
CPC分类号： F26B17/102 , A61K9/1647 , A61K9/1688 , B01D1/18 , B01J2/04 , F26B3/12
摘要： Methods and apparatus are provided for making particles comprising: (a) spraying an emulsion, solution, or suspension, which comprises a solvent and a bulk material (e.g., a pharmaceutical agent), through an atomizer and into a primary drying chamber, having a drying gas flowing therethrough, to form droplets comprising the solvent and bulk material dispersed in the drying gas; (b) evaporating, in the primary drying chamber, at least a portion of the solvent into the drying gas to solidify the droplets and form particles dispersed in drying gas; and (c) flowing the particles and at least a portion of the drying gas through a jet mill to deagglomerate or grind the particles. By coupling spray drying with “in-line” jet milling, a single step process is created from two separate unit operations, and an additional collection step is advantageously eliminated. The one-step, in-line process has further advantages in time and cost of processing.

5. 发明授权

US5611344A Microencapsulated fluorinated gases for use as imaging agents 失效
标题翻译：微胶囊化氟化气体用作成像剂
公开(公告)号：US5611344A
公开(公告)日：1997-03-18
申请号：US611248
申请日：1996-03-05
申请人： Howard Bernstein , Julie A. Straub , Henry T. Brush , Richard E. Wing
发明人： Howard Bernstein , Julie A. Straub , Henry T. Brush , Richard E. Wing
IPC分类号： A61B8/00 , A61K49/22
CPC分类号： A61B8/481 , A61K49/223
摘要： It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.
摘要翻译：已经发现，与合并有空气的微粒相比，将氟化气体，特别是全氟化碳如八氟丙烷掺入到合成的聚合物微粒中显着增强回波反应性。制造微胶囊化全氟化碳，其直径适用于待成像的目标组织，例如用于静脉内或口服给药。在一个实施方案中，形成生物粘附微粒用于增强粘膜表面的成像。

6. 发明授权

US5541290A Optically pure calpain inhibitor compounds 失效
标题翻译：光学纯的钙蛋白酶抑制剂化合物
公开(公告)号：US5541290A
公开(公告)日：1996-07-30
申请号：US82274
申请日：1993-06-24
申请人： Scott L. Harbeson , Julie A. Straub
发明人： Scott L. Harbeson , Julie A. Straub
IPC分类号： A61K38/00 , C07C271/22 , C07C275/16 , C07C317/40 , C07D295/215 , C07K5/02 , A61K38/04 , C07K5/00
CPC分类号： C07D295/215 , C07C271/22 , C07C275/16 , C07C317/40 , C07K5/0202 , A61K38/00
摘要： Optically pure .alpha.-ketoamide compounds, and use therefor in treating neurodegenerative pathologies having enhanced Calpain activity, are disclosed. These compounds comprise optically pure .alpha.-ketoamides, and physiologically acceptable salts thereof, wherein the .alpha.-ketoamide contains an amino acid isomer which has an L-configuration about the chiral center which is structurally located in the .alpha. position to the ketone of the .alpha.-ketoamide, and wherein the amide functionality of the .alpha.-ketoamide portion of the compound's molecule is derived from an amine of an amino acid or an amine substituted with a sulfone functionality. The method of treating a human neurodegenerative pathology, having enhanced Calpain activity, with a Calpain inhibitor composition while reducing undesirable inhibition of other cysteine proteases and other side effects associated with the racemic calpain inhibitor composition includes administering an optically pure L-isomer of an .alpha.-ketoamide compound, wherein the L-isomer is substantially free of its D-isomer. The method of forming an optically pure L-.alpha.-ketoamide includes mixing an L-.beta.-amino-.alpha.-hydroxyamide in a solution containing a free radical catalyst and then mixing an oxidizing agent into said solution under conditions sufficient to form said optically pure L-.alpha.-ketoamide.
摘要翻译：公开了光学纯的α-酮酰胺化合物，并用于治疗具有增强的钙蛋白酶活性的神经退行性病变。这些化合物包括光学纯的α-酮酰胺及其生理上可接受的盐，其中α-酮酰胺含有氨基酸异构体，该氨基酸异构体在手性中心具有L-构型，其结构上位于α位酮的α位置，酮酰胺，并且其中化合物分子的α-酮酰胺部分的酰胺官能度衍生自氨基酸的胺或被砜官能团取代的胺。用钙蛋白酶抑制剂组合物治疗具有增强的钙蛋白酶活性的人类神经变性病理学方法同时减少对其它半胱氨酸蛋白酶的不期望的抑制以及与外消旋钙蛋白酶抑制剂组合物相关的其它副作用的方法包括给予光学纯的α- 酮酰胺化合物，其中L-异构体基本上不含其D-异构体。形成光学纯的L-α-酮酰胺的方法包括在含有自由基催化剂的溶液中混合L-β-氨基-α-羟基酰胺，然后在足以形成所述光学纯L的条件下将氧化剂混合到所述溶液中 α-酮酰胺。

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