公开(公告)号：US20130317208A1

公开(公告)日：2013-11-28

申请号：US13864429

申请日：2013-04-17

Applicant: J. Michael Ramstack ,  Thomas C. Crawford

Inventor： J. Michael Ramstack ,  Thomas C. Crawford

IPC: C08B37/16

CPC classification number: C08B37/0012

Abstract: Processes for precipitating a polymer from a polymer-containing fluid are disclosed, which include providing a vessel housing a medium that provides one or more precipitation surfaces. A polymer-containing fluid, e.g., a polymer solution, dispersion or mixed solution/dispersion, and an anti-solvent can be introduced into the vessel so as to cause precipitation of at least a portion of the polymer on at least one of the precipitation surfaces. In some embodiments, the polymer contains one or more cyclic oligosaccharide moieties, such as one or more cyclodextrin moieties (e.g., α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin). The polymer can be any of a linear or branched polymer. The polymer can be any of polycation, a polyanion, or a non-ionic polymer. Also disclosed herein are precipitation surfaces with polymer precipitated thereon.

Abstract translation: 公开了从含聚合物的流体中沉淀聚合物的方法，其包括提供容纳提供一个或多个沉淀表面的介质的容器。 可以将含聚合物的流体，例如聚合物溶液，分散体或混合溶液/分散体和反溶剂引入容器中，以使至少一部分聚合物沉淀在至少一个沉淀 表面。 在一些实施方案中，聚合物含有一个或多个环状寡糖部分，例如一个或多个环糊精部分（例如α-环糊精，β-环糊精和γ-环糊精）。 聚合物可以是直链或支链聚合物中的任何一种。 聚合物可以是聚阳离子，聚阴离子或非离子聚合物中的任何一种。 本文还公开了其上沉淀有聚合物的沉淀表面。

公开(公告)号：US08404799B2

公开(公告)日：2013-03-26

申请号：US13479646

申请日：2012-05-24

Applicant: John Podobinski ,  J. Michael Ramstack ,  David S. Dickey

Inventor： John Podobinski ,  J. Michael Ramstack ,  David S. Dickey

IPC: C08G64/00 ,  C08G63/02

CPC classification number: C08L67/02 ,  A61J1/00 ,  A61K9/14 ,  A61K9/146 ,  A61K9/51 ,  A61K31/337 ,  A61K47/58 ,  A61K47/593 ,  A61K47/60 ,  B29B2009/125 ,  B82Y40/00 ,  C08F6/12 ,  C08J3/14 ,  C08L29/04 ,  Y10S977/895

Abstract: In one aspect, the present invention provides a process for forming polymeric nanoparticles, which comprises using a static mixer to create a mixed flowing stream of an anti-solvent, e.g., by introducing a liquid anti-solvent into a static mixer, and introducing a polymer solution into the mixed flowing anti-solvent stream such that controlled precipitation of polymeric nanoparticles occurs. The nanoparticles can then be separated from the anti-solvent steam.

Abstract translation: 一方面，本发明提供了一种形成聚合物纳米颗粒的方法，其包括使用静态混合器产生反溶剂的混合流动流，例如通过将液体抗溶剂引入静态混合器中，并引入 聚合物溶液进入混合流动的反溶剂流，从而发生聚合物纳米粒子的受控沉淀。 然后可以将纳米颗粒与反溶剂蒸汽分离。

公开(公告)号：US20110237748A1

公开(公告)日：2011-09-29

申请号：US13023163

申请日：2011-02-08

Applicant: John Podobinski ,  J. Michael Ramstack ,  David S. Dickey

Inventor： John Podobinski ,  J. Michael Ramstack ,  David S. Dickey

IPC: C08L29/04 ,  C08F116/06 ,  B29B9/12 ,  B82Y40/00

CPC classification number: C08L67/02 ,  A61J1/00 ,  A61K9/14 ,  A61K9/146 ,  A61K9/51 ,  A61K31/337 ,  A61K47/58 ,  A61K47/593 ,  A61K47/60 ,  B29B2009/125 ,  B82Y40/00 ,  C08F6/12 ,  C08J3/14 ,  C08L29/04 ,  Y10S977/895

Abstract: In one aspect, the present invention provides a process for forming polymeric nanoparticles, which comprises using a static mixer to create a mixed flowing stream of an anti-solvent, e.g., by introducing a liquid anti-solvent into a static mixer, and introducing a polymer solution into the mixed flowing anti-solvent stream such that controlled precipitation of polymeric nanoparticles occurs. The nanoparticles can then be separated from the anti-solvent stream.

Abstract translation: 一方面，本发明提供了一种形成聚合物纳米颗粒的方法，其包括使用静态混合器产生反溶剂的混合流动流，例如通过将液体抗溶剂引入静态混合器中，并引入 聚合物溶液进入混合流动的反溶剂流，从而发生聚合物纳米粒子的受控沉淀。 然后可以将纳米颗粒与反溶剂流分离。

公开(公告)号：US20100303900A1

公开(公告)日：2010-12-02

申请号：US12856198

申请日：2010-08-13

Applicant: J. Michael Ramstack ,  M. Gary I. Riley ,  Stephen E. Zale ,  Joyce M. Hotz ,  Olufunmi L. Johnson

Inventor： J. Michael Ramstack ,  M. Gary I. Riley ,  Stephen E. Zale ,  Joyce M. Hotz ,  Olufunmi L. Johnson

IPC: A61K9/50 ,  A61K31/519 ,  A61P25/18

CPC classification number: A61K47/34 ,  A61K9/0019 ,  A61K9/1641 ,  A61K9/1647 ,  A61K9/1658 ,  A61K31/505 ,  A61K47/26 ,  A61K47/38

Abstract: Injectable compositions having improved injectability. The injectable compositions include microparticles suspended in an aqueous injection vehicle having a viscosity of at least 20 cp at 20° C. The increased viscosity of the injection vehicle that constitutes the fluid phase of the suspension significantly reduces in vivo injectability failures. The injectable compositions can be made by mixing dry microparticles with an aqueous injection vehicle to form a suspension, and then mixing the suspension with a viscosity enhancing agent to increase the viscosity of the fluid phase of the suspension to the desired level for improved injectability.

Abstract translation: 具有改进的注射性的可注射组合物。 可注射组合物包括悬浮在20摄氏度粘度至少为20cp的含水注射用载体中的微粒。构成悬浮液相的注射载体的增加的粘度显着降低体内注射性失败。 可注射组合物可以通过将干燥微粒与水性注射载体混合以形成悬浮液，然后将悬浮液与粘度增强剂混合以将悬浮液的流体相的粘度增加至所需水平以改善注射性，从而制备。

公开(公告)号：US07799345B2

公开(公告)日：2010-09-21

申请号：US11826994

申请日：2007-07-19

Applicant: Stephen E. Zale ,  J. Michael Ramstack ,  Joyce M. Hotz ,  M. Gary I. Riley ,  Olufunmi L. Johnson

Inventor： Stephen E. Zale ,  J. Michael Ramstack ,  Joyce M. Hotz ,  M. Gary I. Riley ,  Olufunmi L. Johnson

IPC: A61K9/14 ,  A61K9/16

CPC classification number: A61K47/34 ,  A61K9/0019 ,  A61K9/1641 ,  A61K9/1647 ,  A61K9/1658 ,  A61K31/505 ,  A61K47/26 ,  A61K47/38

Abstract: Injectable compositions having improved injectability. The injectable compositions include microparticles suspended in an aqueous injection vehicle having a viscosity of at least 20 cp at 20° C. The increased viscosity of the injection vehicle that constitutes the fluid phase of the suspension significantly reduces in vivo injectability failures. The injectable compositions can be made by mixing dry microparticles with an aqueous injection vehicle to form a suspension, and then mixing the suspension with a viscosity enhancing agent to increase the viscosity of the fluid phase of the suspension to the desired level for improved injectability.

Abstract translation: 具有改进的注射性的可注射组合物。 可注射组合物包括悬浮在20摄氏度粘度至少为20cp的含水注射用载体中的微粒。构成悬浮液相的注射载体的增加的粘度显着降低体内注射性失败。 可注射组合物可以通过将干燥微粒与水性注射载体混合以形成悬浮液，然后将悬浮液与粘度增强剂混合以将悬浮液的流体相的粘度增加至所需水平以改善注射性，从而制备。

公开(公告)号：US20090194894A1

公开(公告)日：2009-08-06

申请号：US12382637

申请日：2009-03-20

Applicant: Michael E. Rickey ,  J. Michael Ramstack ,  Rajesh Kumar

Inventor： Michael E. Rickey ,  J. Michael Ramstack ,  Rajesh Kumar

IPC: B01J13/02

CPC classification number: A61K38/09 ,  A61K9/1641 ,  A61K9/1647 ,  A61K9/1682 ,  A61K9/1694 ,  A61K9/5089 ,  A61K31/519 ,  B01J8/025 ,  B01J13/08 ,  B01J13/12 ,  B01J13/206 ,  B01J14/00 ,  B01J19/121 ,  B01J19/122 ,  B01J19/2415 ,  B01J2219/0877

Abstract: Methods for preparing microparticles having reduced residual solvent levels. Microparticles are contacted with a non-aqueous washing system to reduce the level of residual solvent in the microparticles. Preferred non-aqueous washing systems include 100% ethanol and a blend of ethanol and heptane. A solvent blend of a hardening solvent and a washing solvent can be used to harden and wash microparticles in a single step, thereby eliminating the need for a post-hardening wash step.

公开(公告)号：US07279579B2

公开(公告)日：2007-10-09

申请号：US10860608

申请日：2004-06-03

Applicant: Harry G. Brittain ,  David A. Dickason ,  Joyce Hotz ,  Shawn L. Lyons ,  J. Michael Ramstack ,  Steven G. Wright

Inventor： Harry G. Brittain ,  David A. Dickason ,  Joyce Hotz ,  Shawn L. Lyons ,  J. Michael Ramstack ,  Steven G. Wright

IPC: C07D489/02 ,  A61K31/485

CPC classification number: A61K31/485 ,  C07B2200/13 ,  C07C19/03 ,  C07D489/06 ,  C07D489/08

Abstract: This invention relates to the discovery of novel polymorphic forms of naltrexone, including solvates, hydrates, anhydrous and other crystalline forms and combinations thereof. These novel forms of naltrexone impart advantages in pharmaceutical formulations incorporating them, including sustained release, or long acting, formulations.

Abstract translation: 本发明涉及纳曲酮的新型多晶型物的发现，包括溶剂合物，水合物，无水和其它结晶形式及其组合。 纳曲酮的这些新型形式赋予其掺入它们的药物制剂中的优点，包括持续释放或长效制剂。

公开(公告)号：US07223440B2

公开(公告)日：2007-05-29

申请号：US11312371

申请日：2005-12-21

Applicant: Michael E. Rickey ,  J. Michael Ramstack ,  Rajesh Kumar

Inventor： Michael E. Rickey ,  J. Michael Ramstack ,  Rajesh Kumar

IPC: B01J13/12

CPC classification number: A61K38/09 ,  A61K9/1641 ,  A61K9/1647 ,  A61K9/1682 ,  A61K9/1694 ,  A61K9/5089 ,  A61K31/519 ,  B01J8/025 ,  B01J13/08 ,  B01J13/12 ,  B01J13/206 ,  B01J14/00 ,  B01J19/121 ,  B01J19/122 ,  B01J19/2415 ,  B01J2219/0877

Abstract: Methods for preparing microparticles having reduced residual solvent levels. Microparticles are contacted with a non-aqueous washing system to reduce the level of residual solvent in the microparticles. Preferred non-aqueous washing systems include 100% ethanol and a blend of ethanol and heptane. A solvent blend of a hardening solvent and a washing solvent can be used to harden and wash microparticles in a single step, thereby eliminating the need for a post-hardening wash step.

Abstract translation: 制备具有降低的残留溶剂水平的微粒的方法。 微粒与非水洗涤体系接触以降低微粒中残留溶剂的含量。 优选的非水洗涤系统包括100％乙醇和乙醇与庚烷的混合物。 可以使用硬化溶剂和洗涤溶剂的溶剂共混物在一个步骤中硬化和洗涤微粒，从而不需要后硬化洗涤步骤。

公开(公告)号：US06830737B2

公开(公告)日：2004-12-14

申请号：US10235534

申请日：2002-09-06

Applicant: J. Michael Ramstack

Inventor： J. Michael Ramstack

IPC: B01D1104

CPC classification number: A61K9/1647 ,  A61K9/1694 ,  B01J13/12 ,  Y10T428/2982

Abstract: Method and apparatus for preparing microparticles using liquid-liquid extraction. A first phase and a second phase are combined to form an emulsion. A portion of the second phase is separated from the emulsion (solvent rich), and the solvent is extracted from the separated second phase, which is then returned (solvent poor) to the emulsion. This process of separation of a solvent rich phase, extraction of solvent, and return of a solvent poor phase, is carried out until a selected level of solvent in the emulsion is achieved. Alternatively, the separated solvent rich phase is not returned to the emulsion, but replaced with another solution, such as an aqueous solution, that is free from solvent. The solvent is preferably extracted into an extraction liquid that functions as a “solvent sink” for the solvent.

Abstract translation: 使用液 - 液萃取制备微粒的方法和装置。 将第一相和第二相组合形成乳液。 将第二相的一部分与乳液分离（富溶剂），并从分离的第二相中提取溶剂，然后将其返回（溶剂不良）至乳液。 进行富溶相的分离，萃取溶剂和返回溶剂不良阶段的过程，直到达到乳液中所选择的溶剂含量。 或者，分离的富溶相不会返回到乳液中，而是用不含溶剂的另一溶液如水溶液代替。 优选将溶剂萃取到作为溶剂的“溶剂槽”的萃取液中。

公开(公告)号：US06495164B1

公开(公告)日：2002-12-17

申请号：US09577875

申请日：2000-05-25

Applicant: J. Michael Ramstack ,  M. Gary I. Riley ,  Stephen E. Zale ,  Joyce M. Hotz ,  Olufunmi L. Johnson

Inventor： J. Michael Ramstack ,  M. Gary I. Riley ,  Stephen E. Zale ,  Joyce M. Hotz ,  Olufunmi L. Johnson

IPC: A61K914

CPC classification number: A61K47/34 ,  A61K9/0019 ,  A61K9/1641 ,  A61K9/1647 ,  A61K9/1658 ,  A61K31/505 ,  A61K47/26 ,  A61K47/38

Abstract: Injectable compositions having improved injectability. The injectable compositions include microparticles suspended in an aqueous injection vehicle having a viscosity of at least 20 cp at 20° C. The increased viscosity of the injection vehicle that constitutes the fluid phase of the suspension significantly reduces in vivo injectability failures. The injectable compositions can be made by mixing dry microparticles with an aqueous injection vehicle to form a suspension, and then mixing the suspension with a viscosity enhancing agent to increase the viscosity of the fluid phase of the suspension to the desired level for improved injectability.

Abstract translation: 具有改进的注射性的可注射组合物。 可注射组合物包括悬浮在20摄氏度粘度至少为20cp的含水注射用载体中的微粒。构成悬浮液相的注射载体的增加的粘度显着降低体内注射性失败。 可注射组合物可以通过将干燥微粒与水性注射载体混合以形成悬浮液，然后将悬浮液与粘度增强剂混合以将悬浮液的流体相的粘度增加至所需水平以改善注射性，从而制备。