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1. 发明授权

US5912015A Modulated release from biocompatible polymers 失效
公开(公告)号：US5912015A
公开(公告)日：1999-06-15
申请号：US56566
申请日：1998-04-07
申请人： Howard Bernstein , Yan Zhang , M. Amin Khan , Mark A. Tracy
发明人： Howard Bernstein , Yan Zhang , M. Amin Khan , Mark A. Tracy
IPC分类号： A61K9/16 , A61K9/22 , A61K9/70 , A61K38/21 , A61K38/27 , A61K38/35 , A61K38/46 , A61K9/14
CPC分类号： A61K9/7007 , A61K38/212 , A61K38/27 , A61K38/35 , A61K38/465 , A61K9/1611 , A61K9/1647 , A61K9/1694 , C12Y301/27005 , Y10S514/805 , Y10S514/965
摘要： The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution. The polymer solution is then solidified to form a polymeric matrix, wherein at least a significant portion of the metal cation component is dispersed in the polymeric matrix separately from the biologically active protein, and whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix.

2. 发明授权

US5656297A Modulated release from biocompatible polymers 失效
标题翻译：生物相容聚合物的调制释放
公开(公告)号：US5656297A
公开(公告)日：1997-08-12
申请号：US237057
申请日：1994-05-03
申请人： Howard Bernstein , Yan Zhang , M. Amin Khan , Mark A. Tracy
发明人： Howard Bernstein , Yan Zhang , M. Amin Khan , Mark A. Tracy
IPC分类号： A61K9/00 , A61K9/16 , A61K9/52 , A61K9/70 , A61K38/21 , A61K38/22 , A61K38/35 , A61K38/46 , A61K47/30 , A61K47/34 , A61K9/14
CPC分类号： A61K9/1694 , A61K33/10 , A61K33/30 , A61K38/212 , A61K38/27 , A61K38/35 , A61K38/465 , A61K9/1611 , A61K9/1647 , A61K9/7007 , C12Y301/27005 , Y10S514/805 , Y10S514/935
摘要： The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution. The polymer solution is then solidified to form a polymeric matrix, wherein at least a significant portion of the metal cation component is dispersed in the polymeric matrix separately from the biologically active protein, and whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix.
摘要翻译：本发明涉及用于调节释放生物活性剂的组合物。组合物包含生物相容性聚合物基质，分散在聚合物基质内的生物活性剂和分散分散在聚合物基质内的金属阳离子组分，由此金属阳离子组分调节生物活性剂从聚合物中的释放矩阵。本发明还涉及一种用于调节生物相容性聚合物基质释放生物活性剂的方法，包括以下步骤：将生物相容性聚合物溶解在溶剂中以形成聚合物溶液，并且还分别分散金属阳离子组分和生物相容性聚合物聚合物溶液中的活性剂。然后将聚合物溶液固化以形成聚合物基质，其中至少大部分金属阳离子组分与生物活性蛋白质分开分散在聚合物基质中，由此金属阳离子组分调节生物活性剂的释放从聚合物基质。

3. 发明授权

US06749866B2 Modulated release from biocompatible polymers 失效
公开(公告)号：US06749866B2
公开(公告)日：2004-06-15
申请号：US10039285
申请日：2002-01-03
申请人： Howard Bernstein , Yan Zhang , M. Amin Khan , Mark A. Tracy
发明人： Howard Bernstein , Yan Zhang , M. Amin Khan , Mark A. Tracy
IPC分类号： A61K914
CPC分类号： A61K9/7007 , A61K9/1611 , A61K9/1647 , A61K9/1694 , A61K38/212 , A61K38/27 , A61K38/35 , A61K38/465 , C12Y301/27005 , Y10S514/805 , Y10S514/965
摘要： The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution. The polymer solution is then solidified to form a polymeric matrix, wherein at least a significant portion of the metal cation component is dispersed in the polymeric matrix separately from the biologically active protein, and whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix.

4. 发明授权

US06368630B1 Modulated release from biocompatible polymers 失效
公开(公告)号：US06368630B1
公开(公告)日：2002-04-09
申请号：US09274613
申请日：1999-03-23
申请人： Howard Bernstein , Yan Zhang , M. Amin Khan , Mark A. Tracy
发明人： Howard Bernstein , Yan Zhang , M. Amin Khan , Mark A. Tracy
IPC分类号： A61K914
CPC分类号： A61K9/7007 , A61K9/1611 , A61K9/1647 , A61K9/1694 , A61K38/212 , A61K38/27 , A61K38/35 , A61K38/465 , C12Y301/27005 , Y10S514/805 , Y10S514/965
摘要： The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution. The polymer solution is then solidified to form a polymeric matrix, wherein at least a significant portion of the metal cation component is dispersed in the polymeric matrix separately from the biologically active protein, and whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix.

5. 发明授权

US06780434B2 Controlled release of metal cation-stabilized interferon 失效
标题翻译：金属阳离子稳定的干扰素的控制释放
公开(公告)号：US06780434B2
公开(公告)日：2004-08-24
申请号：US10092365
申请日：2002-03-06
申请人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
发明人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
IPC分类号： A61K910
CPC分类号： B82Y5/00 , A61K9/1611 , A61K9/1647 , A61K38/212 , C07K14/56
摘要： This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation stabilized-interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.
摘要翻译：本发明涉及用于控制释放干扰素的组合物和形成所述组合物的方法。本发明的控释组合物包含生物相容性聚合物和金属阳离子稳定化干扰素颗粒，其中颗粒分散在生物相容性聚合物内。本发明的制备用于干扰素控制释放的组合物的方法包括将聚合物溶解在聚合物溶剂中以形成聚合物溶液，将金属阳离子稳定的干扰素颗粒的颗粒分散在聚合物溶液中，然后固化聚合物以形成含有干扰素颗粒的分散体的聚合物基质。

6. 发明授权

US06379701B1 Controlled release of metal cation-stabilized interferon 失效
标题翻译：金属阳离子稳定的干扰素的控制释放
公开(公告)号：US06379701B1
公开(公告)日：2002-04-30
申请号：US09664299
申请日：2000-09-18
申请人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
发明人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
IPC分类号： A61K910
CPC分类号： B82Y5/00 , A61K9/1611 , A61K9/1647 , A61K38/212 , C07K14/56
摘要： This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation stabilized-interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.
摘要翻译：本发明涉及用于控制释放干扰素的组合物和形成所述组合物的方法。本发明的控释组合物包含生物相容性聚合物和金属阳离子稳定化干扰素颗粒，其中颗粒分散在生物相容性聚合物内。本发明的用于制备用于控制释放干扰素的组合物的方法包括将聚合物在聚合物溶剂中以形成聚合物溶液，将金属阳离子稳定的干扰素颗粒的颗粒分散在聚合物溶液中，然后固化聚合物以形成含有干扰素颗粒分散体的聚合物基质。

7. 发明授权

US6165508A Controlled release of metal cation-stabilized interferon 失效
标题翻译：金属阳离子稳定的干扰素的控制释放
公开(公告)号：US6165508A
公开(公告)日：2000-12-26
申请号：US765558
申请日：1997-03-07
申请人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
发明人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
IPC分类号： A61K9/16 , A61K38/21 , A61K47/30 , C07K14/56 , A61K9/10
CPC分类号： B82Y5/00 , A61K9/1611 , A61K9/1647 , A61K38/212 , C07K14/56
摘要： This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation-stabilized interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.
摘要翻译：本发明涉及用于控制释放干扰素的组合物和形成所述组合物的方法。本发明的控释组合物包含生物相容性聚合物和金属阳离子稳定化干扰素颗粒，其中颗粒分散在生物相容性聚合物内。本发明的制备用于控制干扰素释放的组合物的方法包括将聚合物溶解在聚合物溶剂中以形成聚合物溶液，将金属阳离子稳定的干扰素颗粒的颗粒分散在聚合物溶液中，然后固化聚合物以形成含有干扰素颗粒的分散体的聚合物基质。

8. 发明授权

US06514533B1 Device for the sustained release of aggregation-stabilized, biologically active agent 失效
标题翻译：用于持续释放聚集稳定的生物活性剂的装置
公开(公告)号：US06514533B1
公开(公告)日：2003-02-04
申请号：US08934830
申请日：1997-09-22
申请人： Paul A. Burke , Stephen E. Zale , Mark A. Tracy , OluFunmi Lily Johnson , Howard Bernstein , M. Amin Khan , Henry E. Auer
发明人： Paul A. Burke , Stephen E. Zale , Mark A. Tracy , OluFunmi Lily Johnson , Howard Bernstein , M. Amin Khan , Henry E. Auer
IPC分类号： A61K910
CPC分类号： A61K9/5153 , A61K9/0019 , A61K9/1611 , A61K9/1647 , A61K9/1658 , A61K9/1694 , A61K9/5031 , A61K9/5052 , A61K38/1816 , A61K38/212 , A61K38/27 , A61K47/02 , A61K47/26 , C07K14/56 , Y10S514/97
摘要： A device for the sustained release in vivo of a water soluble, biologically active agent wherein the agent is susceptible to aggregation comprising a drug delivery device and aggregation-stabilized, biologically active agent wherein the aggregation-stabilized agent is disposed within the drug delivery device.
摘要翻译：用于在体内持续释放水溶性生物活性剂的装置，其中所述试剂易于凝集，其包含药物递送装置和聚集稳定的生物活性剂，其中所述聚集稳定的试剂置于所述药物递送装置内。

9. 发明授权

US5711968A Composition and method for the controlled release of metal cation-stabilized interferon 失效
标题翻译：金属阳离子稳定化干扰素的控制释放的组成和方法
公开(公告)号：US5711968A
公开(公告)日：1998-01-27
申请号：US279784
申请日：1994-07-25
申请人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
发明人： Mark A. Tracy , Howard Bernstein , M. Amin Khan
IPC分类号： A61K9/16 , A61K38/21 , A61K47/30 , C07K14/56 , A61K9/10
CPC分类号： B82Y5/00 , A61K38/212 , A61K9/1611 , A61K9/1647 , C07K14/56
摘要： This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation stabilized-interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.
摘要翻译：本发明涉及用于控制释放干扰素的组合物和形成所述组合物的方法。本发明的控释组合物包含生物相容性聚合物和金属阳离子稳定化干扰素颗粒，其中颗粒分散在生物相容性聚合物内。本发明的制备用于干扰素控制释放的组合物的方法包括将聚合物溶解在聚合物溶剂中以形成聚合物溶液，将金属阳离子稳定的干扰素颗粒的颗粒分散在聚合物溶液中，然后固化聚合物以形成含有干扰素颗粒的分散体的聚合物基质。

10. 发明授权

US07097857B2 Methods and compositions for the targeted delivery of biologically active agents 失效
标题翻译：用于靶向递送生物活性剂的方法和组合物
公开(公告)号：US07097857B2
公开(公告)日：2006-08-29
申请号：US10342448
申请日：2003-01-14
申请人： Mark A. Tracy , David S. Scher
发明人： Mark A. Tracy , David S. Scher
IPC分类号： A61K9/14 , A61K9/00
CPC分类号： A61K9/1647 , Y02A50/411 , Y02A50/423
摘要： The present invention relates to a sustained release composition for the targeted delivery of biologically active agents to specific tissues and cells. The composition comprises microparticles containing a biocompatible polymer, a water-soluble polymer and a biologically active agent. In one embodiment, the biologically active agent is an antigen or an immunomodulator. In another embodiment, the biologically is a labile agent. The microparticles have a number median diameter of greater than 20 microns upon administration. The water-soluble polymer is present in the sustained released composition in at least about 20% of the dry weight of the microparticle. The sustained release composition provides for the dissolution of the water-soluble polymer of the composition upon hydration, at a much greater rate than the degradation of the biocompatible polymer. This variance in solubility generates pseudo-microparticles which have a number median diameter which is substantially smaller than the size of the administered microparticles. The pseudo-microparticles can be engulfed by antigen presenting cells of the immune system, or absorbed by the Peyer's patches in the gut.
摘要翻译：本发明涉及用于将生物活性剂靶向递送至特定组织和细胞的持续释放组合物。该组合物包含含有生物相容性聚合物，水溶性聚合物和生物活性剂的微粒。在一个实施方案中，生物活性剂是抗原或免疫调节剂。在另一个实施方案中，生物学上是不稳定剂。微粒在给药时的中值直径大于20微米。水溶性聚合物以至少约20％的微粒干重存在于持续释放的组合物中。持续释放组合物以比生物相容性聚合物的降解更大的速率使组合物的水溶性聚合物溶解在水合中。溶解度的这种变化产生具有基本上小于施用的微粒尺寸的数字中值直径的假微粒。伪微粒可以被免疫系统的抗原呈递细胞吞噬，或被肠道中的派耶氏斑块吸收。

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