公开(公告)号：US5916598A

公开(公告)日：1999-06-29

申请号：US71865

申请日：1998-05-04

Applicant: Michael E. Rickey ,  J. Michael Ramstack ,  Danny H. Lewis

Inventor： Michael E. Rickey ,  J. Michael Ramstack ,  Danny H. Lewis

IPC: A61K9/56 ,  A61K9/14 ,  A61K9/16 ,  A61K9/50 ,  A61K9/58 ,  A61K31/505 ,  A61K31/517 ,  A61K31/519 ,  A61K31/529 ,  A61K47/30 ,  A61K47/34 ,  B01J13/04 ,  B01J13/06 ,  B29B9/00 ,  B01J13/02 ,  B32B5/16

CPC classification number: B01J13/04 ,  A61K31/519 ,  A61K9/1647 ,  A61K9/1694 ,  A61K9/5089 ,  Y10T428/2985

Abstract: A method for preparing biodegradable, biocompatible microparticles. A first phase is prepared that includes a biodegradable, biocompatible polymer, an active agent, and a solvent. An immiscible second phase is prepared. The first and second phases are combined to form an emulsion in which the first phase is discontinuous and the second phase is continuous. The two phases are immersed in a quench liquid that includes a quench medium and a quantity of the solvent. The quantity of the solvent is selected to control a rate of extraction of the solvent from the first phase. The first phase is isolated in the form of microparticles. Also disclosed is a microencapsulated active agent prepared by the method for preparing biodegradable, biocompatible microparticles.

公开(公告)号：US20120263653A1

公开(公告)日：2012-10-18

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: C08G63/08 ,  A61K49/00 ,  A61K9/14 ,  A61K31/337 ,  A61K31/427 ,  A61P29/00 ,  A61P9/00 ,  A61P31/00 ,  C08G63/91 ,  C08L5/00 ,  A61K47/30 ,  A61P35/00 ,  B82Y30/00

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 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：US20110086104A1

公开(公告)日：2011-04-14

申请号：US12967757

申请日：2010-12-14

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

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

IPC: A61K9/50 ,  A61K38/09 ,  A61K38/38 ,  A61K31/519 ,  B29B9/12

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：US07875310B2

公开(公告)日：2011-01-25

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: B01J13/12 ,  A61K38/00

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：US20080227804A1

公开(公告)日：2008-09-18

申请号：US11860677

申请日：2007-09-25

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: A61K31/439 ,  C07D491/08

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：US07371406B2

公开(公告)日：2008-05-13

申请号：US10681142

申请日：2003-10-09

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: A61K9/14 ,  A61F13/00 ,  A61F2/00

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.

公开(公告)号：US06884372B2

公开(公告)日：2005-04-26

申请号：US10821941

申请日：2004-04-12

Applicant: J. Michael Ramstack

Inventor： J. Michael Ramstack

IPC: A61K9/16 ,  B01J13/12 ,  B01J13/02 ,  B32B5/16

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：US06379704B2

公开(公告)日：2002-04-30

申请号：US09870751

申请日：2001-06-01

Applicant: Steven G. Wright ,  Michael E. Rickey ,  J. Michael Ramstack ,  Shawn L. Lyons ,  Joyce M. Hotz

Inventor： Steven G. Wright ,  Michael E. Rickey ,  J. Michael Ramstack ,  Shawn L. Lyons ,  Joyce M. Hotz

IPC: A61K914

CPC classification number: A61K31/519 ,  A61K9/1647 ,  A61K9/1694 ,  B01J13/02

Abstract: A method for preparing microparticles having a selected polymer molecular weight. The hold time and temperature of a solution containing a nucleophilic compound and a polymer having a starting molecular weight are controlled in order to control the molecular weight of the polymer in the finished microparticle product. In this manner, a selected polymer molecular weight in the finished microparticle product can be achieved from a variety of starting material molecular weights.

Abstract translation: 一种制备具有选定的聚合物分子量的微粒的方法。 控制包含亲核化合物和具有起始分子量的聚合物的溶液的保持时间和温度以控制成品微粒产物中的聚合物的分子量。 以这种方式，可以从各种原料分子量获得成品微粒产物中所选择的聚合物分子量。

公开(公告)号：US06264987B1

公开(公告)日：2001-07-24

申请号：US09575075

申请日：2000-05-19

Applicant: Steven G. Wright ,  Michael E. Rickey ,  J. Michael Ramstack ,  Shawn L. Lyons ,  Joyce M. Hotz

Inventor： Steven G. Wright ,  Michael E. Rickey ,  J. Michael Ramstack ,  Shawn L. Lyons ,  Joyce M. Hotz

IPC: A61K914

CPC classification number: A61K31/519 ,  A61K9/1647 ,  A61K9/1694 ,  B01J13/02

Abstract: A method for preparing microparticles having a selected polymer molecular weight. The hold time and temperature of a solution containing a nucleophilic compound and a polymer having a starting molecular weight are controlled in order to control the molecular weight of the polymer in the finished microparticle product. In this manner, a selected polymer molecular weight in the finished microparticle product can be achieved from a variety of starting material molecular weights.

Abstract translation: 一种制备具有选定的聚合物分子量的微粒的方法。 控制包含亲核化合物和具有起始分子量的聚合物的溶液的保持时间和温度以控制成品微粒产物中的聚合物的分子量。 以这种方式，可以从各种原料分子量获得成品微粒产物中所选择的聚合物分子量。

公开(公告)号：US6110503A

公开(公告)日：2000-08-29

申请号：US263098

申请日：1999-03-05

Applicant: Michael E. Rickey ,  J. Michael Ramstack ,  Danny H. Lewis

Inventor： Michael E. Rickey ,  J. Michael Ramstack ,  Danny H. Lewis

IPC: A61K9/56 ,  A61K9/14 ,  A61K9/16 ,  A61K9/50 ,  A61K9/58 ,  A61K31/505 ,  A61K31/517 ,  A61K31/519 ,  A61K31/529 ,  A61K47/30 ,  A61K47/34 ,  B01J13/04 ,  B01J13/06 ,  B29B9/00 ,  B01J13/02 ,  B32B5/16 ,  B32B15/02

CPC classification number: B01J13/04 ,  A61K31/519 ,  A61K9/1647 ,  A61K9/1694 ,  A61K9/5089 ,  Y10T428/2985

Abstract: A method for preparing biodegradable, biocompatible microparticles. A first phase is prepared that includes a biodegradable, biocompatible polymer, an active agent, and a solvent. An immiscible second phase is prepared. The first and second phases are combined to form an emulsion in which the first phase is discontinuous and the second phase is continuous. The two phases are immersed in a quench liquid that includes a quench medium and a quantity of the solvent. The quantity of the solvent is selected to control a rate of extraction of the solvent from the first phase. The first phase is isolated in the form of microparticles. Also disclosed is a microencapsulated active agent prepared by the method for preparing biodegradable, biocompatible microparticles.

Abstract translation: 一种制备可生物降解的生物相容性微粒的方法。 制备包含可生物降解的生物相容性聚合物，活性剂和溶剂的第一相。 制备不混溶的第二相。 第一和第二相组合形成乳液，其中第一相是不连续的，第二相是连续的。 将两相浸入包括骤冷介质和一定量的溶剂的骤冷液体中。 选择溶剂的量以控制从第一相萃取溶剂的速率。 第一相以微粒的形式分离。 还公开了通过制备可生物降解的生物相容性微粒的方法制备的微囊化活性剂。