公开(公告)号：WO2004064808A1

公开(公告)日：2004-08-05

申请号：PCT/US2003/025338

申请日：2003-08-12

Applicant: DOW GLOBAL TECHNOLOGIES INC. ,  SCHERZER, Brian, D. ,  EVANS, Jonathan, C. ,  HITT, James, E.

Inventor： SCHERZER, Brian, D. ,  EVANS, Jonathan, C. ,  HITT, James, E.

IPC: A61K9/19

CPC classification number: A61K9/1688 ,  A61K6/0008 ,  A61K9/14 ,  A61K9/145 ,  A61K9/1694 ,  A61K9/19 ,  A61K9/5089 ,  A61K31/192 ,  A61K31/38 ,  A61K31/4412 ,  A61K31/496 ,  A61K31/55 ,  A61K31/573 ,  A61K31/58 ,  A61K38/13 ,  F26B5/065 ,  F26B17/284

Abstract: The present invention is a method for preparing micron-sized or submicron-sized drug particles comprising contacting a solution comprising a poorly water soluble drug substance and at least one freezable organic solvent with a cold surface so as to freeze the solution; and removing the organic solvent. The resulting particles are also disclosed, as are several embodiments of an apparatus that can be used in performing the method of the present invention.

Abstract translation: 本发明是一种制备微米级或亚微米尺寸药物颗粒的方法，其包括将包含难溶于水的药物物质和至少一种可冷冻有机溶剂的溶液与冷表面接触以冷冻该溶液; 并除去有机溶剂。 还可以公开所得到的颗粒，以及可以用于执行本发明的方法的装置的几个实施方案。

公开(公告)号：WO2004012711A1

公开(公告)日：2004-02-12

申请号：PCT/US2003/021884

申请日：2003-07-14

Applicant: DOW GLOBAL TECHNOLOGIES INC. ,  TUCKER, Christopher, J. ,  SVENSON, Sonke ,  HITT, James, E. ,  CURTIS, Cathy, A.

Inventor： TUCKER, Christopher, J. ,  SVENSON, Sonke ,  HITT, James, E. ,  CURTIS, Cathy, A.

IPC: A61K9/14

CPC classification number: A61K9/146

Abstract: Drug particles which are essentially crystalline and have a mean particle size below 2 microns, when dispersed in water, are described. When added to an aqueous medium at 25-95% of the equilibrium solubility of the drug substance, the drug particles show complete dissolution, as characterized by a 95% reduction in turbidity, in less than 5 minutes. Using a controlled precipitation process to prepare such drug particles is also described. Such drug particles exhibit an enhanced dissolution rate and better stability as compared to particles prepared according to processes described in the prior art.

Abstract translation: 描述了当分散在水中时基本上是结晶的并且具有低于2微米的平均粒度的药物颗粒。 当以25-95％的药物物质的平衡溶解度加入到水性介质中时，药物颗粒显示完全溶解，其特征在于在不到5分钟内95％的浊度降低。 还描述了使用受控沉淀法制备这种药物颗粒。 与根据现有技术中描述的方法制备的颗粒相比，这样的药物颗粒显示出增强的溶解速率和更好的稳定性。

公开(公告)号：WO2006026502A1

公开(公告)日：2006-03-09

申请号：PCT/US2005/030543

申请日：2005-08-26

Applicant: THE DOW CHEMICAL COMPANY ,  BOARD OF REGENTS, UNIVERSITY OF TEXAS SYSTEM ,  HITT, James, E. ,  ROGERS, True, L. ,  GILLESPIE, Ian, B. ,  SCHERZER, Brian, D. ,  GARCIA, Paula, C. ,  BECK, Nicholas, S. ,  TUCKER, Christopher, J. ,  YOUNG, Timothy, J. ,  HAYES, David, A. ,  WILLIAMS, Robert, O., III ,  JOHNSTON, Keith, P. ,  MCCONVILLE, Jason, T. ,  PETERS, Jay, I. ,  TALBERT, Robert ,  BURGESS, David

Inventor： HITT, James, E. ,  ROGERS, True, L. ,  GILLESPIE, Ian, B. ,  SCHERZER, Brian, D. ,  GARCIA, Paula, C. ,  BECK, Nicholas, S. ,  TUCKER, Christopher, J. ,  YOUNG, Timothy, J. ,  HAYES, David, A. ,  WILLIAMS, Robert, O., III ,  JOHNSTON, Keith, P. ,  MCCONVILLE, Jason, T. ,  PETERS, Jay, I. ,  TALBERT, Robert ,  BURGESS, David

IPC: A61K9/12 ,  A61K31/496

CPC classification number: A61K31/496 ,  A61K9/0073 ,  A61K9/008 ,  A61K9/19

Abstract: Inhalable compositions are described. The inhalable compositions comprise one or more respirable aggregates, the respirable aggregates comprising one or more poorly water soluble active agents, wherein at least one of the active agents reaches a maximum lung concentration (C max ) of at least about 0.25 μg/gram of lung tissue and remains at such concentration for a period of at least one hour after being delivered to the lung. Methods for making such compositions and methods for using such compositions are also disclosed.

Abstract translation: 描述了可吸入组合物。 可吸入组合物包含一种或多种可呼吸聚集体，可呼吸聚集体包含一种或多种难溶于水的活性剂，其中至少一种活性剂达到最大肺浓度（C

公开(公告)号：WO2004012710A8

公开(公告)日：2005-06-30

申请号：PCT/US0321882

申请日：2003-07-14

Applicant: DOW GLOBAL TECHNOLOGIES INC ,  SVENSON SONKE ,  TUCKER CHRISTOPHER J ,  HITT JAMES E

Inventor： SVENSON SONKE ,  TUCKER CHRISTOPHER J ,  HITT JAMES E

IPC: A61K9/14 ,  A61K47/24 ,  A61K47/30 ,  B01D9/00

CPC classification number: A61K9/146 ,  A61K9/145

Abstract: Particles having a plurality of crystalline domains are described. Each crystalline domain is oriented differently than any of the adjacent domains and comprises a drug substance. A plurality of interfacial regions surround the crystalline domains, each interfacial region comprising at least one stabilizer. A process used to prepare the particles of the present invention is also described. The particles of the present invention exhibit relatively fast dissolution times as compared to particles prepared by processes described in the prior art.

Abstract translation: 描述具有多个结晶域的颗粒。 每个结晶结构域的取向与任何相邻的结构域不同，并且包含药物物质。 多个界面区域围绕结晶域，每个界面区域包括至少一个稳定剂。 还描述了用于制备本发明的颗粒的方法。 与通过现有技术中描述的方法制备的颗粒相比，本发明的颗粒表现出相对较快的溶解时间。

公开(公告)号：WO2003032951A1

公开(公告)日：2003-04-24

申请号：PCT/US2002/027444

申请日：2002-08-27

Applicant: DOW GLOBAL TECHNOLOGIES INC. ,  HITT, James, E. ,  TUCKER, Christopher, J. ,  EVANS, Jonathan, C. ,  CURTIS, Cathy, A. ,  SVENSON, Sonke

Inventor： HITT, James, E. ,  TUCKER, Christopher, J. ,  EVANS, Jonathan, C. ,  CURTIS, Cathy, A. ,  SVENSON, Sonke

IPC: A61K9/14

CPC classification number: A61K9/5146 ,  A61K9/1635 ,  A61K9/1688 ,  B01D9/005 ,  B82Y5/00

Abstract: A process for preparing crystalline particles of a drug substance is disclosed, said process comprising recirculating an anti-solvent through a mixing zone, dissolving the drug substance in a solvent to form a solution, adding the solution to the mixing zone to form a article slurry in the anti-solvent, and recirculating at least a portion of the particle slurry back through the mixing zone. Particles produced from the process are also disclosed. The present invention has the ability to be operated in a continuous fashion, resulting in a more efficient process and a more uniform product. The present invention has the additional advantage of having the ability to operate at a relatively low solvent ratio, thereby increasing the drug to excipient ratio.

Abstract translation: 公开了一种制备药物结晶颗粒的方法，所述方法包括通过混合区使反溶剂再循环，将药物溶解在溶剂中以形成溶液，将溶液加入混合区以形成制品浆料 在反溶剂中，并且将至少一部分颗粒浆料再循环通过混合区。 还公开了从该方法生产的颗粒。 本发明具有以连续方式操作的能力，从而产生更有效的工艺和更均匀的产品。 本发明具有能够以相对低的溶剂比操作的能力的另外的优点，从而将药物增加到赋形剂比例。

公开(公告)号：WO2004012710A1

公开(公告)日：2004-02-12

申请号：PCT/US2003/021882

申请日：2003-07-14

Applicant: DOW GLOBAL TECHNOLOGIES INC. ,  SVENSON, Sonke ,  TUCKER, Christopher, J. ,  HITT, James, E.

Inventor： SVENSON, Sonke ,  TUCKER, Christopher, J. ,  HITT, James, E.

IPC: A61K9/14

CPC classification number: A61K9/146 ,  A61K9/145

Abstract: Particles having a plurality of crystalline domains are described. Each crystalline domain is oriented differently than any of the adjacent domains and comprises a drug substance. A plurality of interfacial regions surround the crystalline domains, each interfacial region comprising at least one stabilizer. A process used to prepare the particles of the present invention is also described. The particles of the present invention exhibit relatively fast dissolution times as compared to particles prepared by processes described in the prior art.

Abstract translation: 描述具有多个结晶域的颗粒。 每个结晶结构域的取向与任何相邻的结构域不同，并且包含药物物质。 多个界面区域围绕结晶域，每个界面区域包括至少一个稳定剂。 还描述了用于制备本发明的颗粒的方法。 与通过现有技术中描述的方法制备的颗粒相比，本发明的颗粒表现出相对较快的溶解时间。