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1. 发明授权

US06284283B1 Method of producing sub-micron particles of biologically active agents and uses thereof 有权
标题翻译：生产生物活性剂亚微米颗粒的方法及其应用
公开(公告)号：US06284283B1
公开(公告)日：2001-09-04
申请号：US09422751
申请日：1999-10-21
申请人： Henry R. Costantino , Warren E. Jaworowicz , Mark A. Tracy , Christopher P. Beganski
发明人： Henry R. Costantino , Warren E. Jaworowicz , Mark A. Tracy , Christopher P. Beganski
IPC分类号： A61K950
CPC分类号： A61K9/1688 , A61K9/1694 , Y10S977/906 , Y10T428/2985
摘要： Submicron particles of a biologically active agent are prepared by atomizing using multifluid atomization a dispersed system comprising at least one biologically active agent and at least one solvent to produce droplets, freezing the droplets to produce frozen droplets, lyophilizing the frozen droplets to obtain microstructures capable of being further fragmented into submicron particles by techniques such as probe sonication. The submicron particles can be incorporated into sustained release compositions having a reduced initial release of biologically active agent. The sustained release compositions can be administered to a human or animal.
摘要翻译：通过使用多流体雾化将包含至少一种生物活性剂和至少一种溶剂的分散系统进行雾化来制备生物活性剂的亚微米颗粒，以产生液滴，冷冻液滴以产生冷冻液滴，冻干冷冻液滴以获得能够通过诸如探针超声处理的技术进一步碎裂成亚微米颗粒。亚微米颗粒可以并入具有降低的生物活性剂的初始释放的缓释组合物中。持续释放组合物可以施用于人或动物。

2. 发明授权

US06428815B1 Method of producing sub-micron particles of biologically active agents and uses thereof 失效
标题翻译：生产生物活性剂亚微米颗粒的方法及其应用
公开(公告)号：US06428815B1
公开(公告)日：2002-08-06
申请号：US09898524
申请日：2001-07-03
申请人： Henry R. Costantino , Warren E. Jaworowicz , Mark A. Tracy , Christopher P. Beganski
发明人： Henry R. Costantino , Warren E. Jaworowicz , Mark A. Tracy , Christopher P. Beganski
IPC分类号： A61K950
CPC分类号： A61K9/1688 , A61K9/1694 , Y10S977/906 , Y10T428/2985
摘要： Submicron particles of a biologically active agent are prepared by atomizing using multifluid atomization a dispersed system comprising at least one biologically active agent and at least one solvent to produce droplets, freezing the droplets to produce frozen droplets, lyophilizing the frozen droplets to obtain microstructures capable of being further fragmented into submicron particles by techniques such as probe sonication. The submicron particles can be incorporated into sustained release compositions having a reduced initial release of biologically active agent. The sustained release compositions can be administered to a human or animal.
摘要翻译：通过使用多流体雾化将包含至少一种生物活性剂和至少一种溶剂的分散系统进行雾化来制备生物活性剂的亚微米颗粒，以产生液滴，冷冻液滴以产生冷冻液滴，冻干冷冻液滴以获得能够通过诸如探针超声处理的技术进一步碎裂成亚微米颗粒。亚微米颗粒可以并入具有降低的生物活性剂的初始释放的缓释组合物中。持续释放组合物可以施用于人或动物。

3. 发明授权

US06444223B1 Method of producing submicron particles of a labile agent and use thereof 失效
标题翻译：制备不稳定剂的亚微米颗粒的方法及其用途
公开(公告)号：US06444223B1
公开(公告)日：2002-09-03
申请号：US09321091
申请日：1999-05-28
申请人： Mark A. Tracy , Kevin L. Ward , Warren E. Jaworowicz
发明人： Mark A. Tracy , Kevin L. Ward , Warren E. Jaworowicz
IPC分类号： A61K910
CPC分类号： A61K9/146 , A61K9/1647 , A61K9/1694 , A61K9/5153 , A61K9/5192
摘要： The present invention relates to a sustained release composition comprising micron particles of labile agent and a method of preparing and using the sustained release composition. The invention further relates to micron particles of a labile agent and a method of preparing the micron particles. The method of the invention for preparing a composition for the sustained release of a labile agent, comprises forming a suspension comprising the labile agent dispersed in a polymer solution comprising at least one biocompatible polymer and at least one polymer solvent. The suspension is then wet milled to achieve micron particles of the labile agent. The polymer solvent is then removed resulting in a solid polymer/labile agent matrix. The method for preparing micron particles of a labile agent comprises forming a suspension comprising the labile agent, dispersed in a polymer solution comprising at least one biocompatible polymer and at least one polymer solvent, and wet milling of the suspension.
摘要翻译：本发明涉及包含不稳定剂的微米颗粒的缓释组合物和制备和使用持续释放组合物的方法。本发明还涉及不稳定剂的微米颗粒和制备微米颗粒的方法。制备用于缓释不稳定剂的组合物的本发明的方法包括形成包含分散在包含至少一种生物相容性聚合物和至少一种聚合物溶剂的聚合物溶液中的不稳定剂的悬浮液。然后将悬浮液湿磨，以获得不稳定剂的微米颗粒。然后除去聚合物溶剂，得到固体聚合物/不稳定剂基质。制备不稳定剂的微米颗粒的方法包括形成包含不稳定剂的悬浮液，其分散在包含至少一种生物相容性聚合物和至少一种聚合物溶剂的聚合物溶液中，并且对该悬浮液进行湿磨。

4. 发明授权

US06713087B2 Method of producing submicron particles of a labile agent and use thereof 失效
标题翻译：制备不稳定剂的亚微米颗粒的方法及其用途
公开(公告)号：US06713087B2
公开(公告)日：2004-03-30
申请号：US10200057
申请日：2002-07-18
申请人： Mark A. Tracy , Kevin L. Ward , Warren E. Jaworowicz
发明人： Mark A. Tracy , Kevin L. Ward , Warren E. Jaworowicz
IPC分类号： A61K910
CPC分类号： A61K9/146 , A61K9/1647 , A61K9/1694 , A61K9/5153 , A61K9/5192
摘要： The present invention relates to a sustained release composition comprising micron particles of labile agent and a method of preparing and using the sustained release composition. The invention further relates to micron particles of a labile agent and a method of preparing the micron particles. The method of the invention for preparing a composition for the sustained release of a labile agent, comprises forming a suspension comprising the labile agent dispersed in a polymer solution comprising at least one biocompatible polymer and at least one polymer solvent. The suspension is then wet milled to achieve micron particles of the labile agent. The polymer solvent is then removed resulting in a solid polymer/labile agent matrix. The composition for sustained release of a labile agent is likewise prepared according to the method of the invention. The sustained release composition of the present invention can be used in a method for providing a therapeutically effective blood level of a labile agent, in a subject in need of treatment with said agent, for a sustained period comprising administering to the subject the sustained release composition described herein. The method for preparing micron particles of a labile agent comprises forming a suspension comprising the labile agent, dispersed in a polymer solution comprising at least one biocompatible polymer and at least one polymer solvent, and wet milling of the suspension. The submicron particles of labile agent, as described herein, are prepared according to this method.
摘要翻译：本发明涉及包含不稳定剂的微米颗粒的缓释组合物和制备和使用持续释放组合物的方法。本发明还涉及不稳定剂的微米颗粒和制备微米颗粒的方法。本发明的制备用于缓释不稳定剂的组合物的方法包括形成悬浮液，其包含分散在聚合物中的不稳定剂溶液，其包含至少一种生物相容性聚合物和至少一种聚合物溶剂。然后将悬浮液湿磨，以获得不稳定剂的微米颗粒。然后除去聚合物溶剂，得到固体聚合物/不稳定剂基质。用于持续释放不稳定剂的组合物同样根据本发明的方法制备。本发明的持续释放组合物可用于在受试者中提供治疗有效的不稳定性血液水平的方法需要用所述药剂治疗持续时间，包括向受试者施用本文所述的持续释放组合物。制备不稳定剂的微米颗粒的方法包括形成包含不稳定剂的悬浮液，其分散在至少包含至少一种生物相容性聚合物和至少一种聚合物溶剂，以及该悬浮液的湿磨。如本文所述的不稳定剂的亚微米颗粒根据该方法制备。

5. 发明申请

US20090041851A1 Composition for the delivery of live cells and methods of use thereof 审中-公开
标题翻译：用于递送活细胞的组合物及其使用方法
公开(公告)号：US20090041851A1
公开(公告)日：2009-02-12
申请号：US12070503
申请日：2008-02-19
申请人： Henry R. Costantino , Lawrence J. Bonassar , Mark A. Tracy
发明人： Henry R. Costantino , Lawrence J. Bonassar , Mark A. Tracy
IPC分类号： A61K35/12 , A61K9/14 , A61K35/32 , A61K35/39 , A61P3/10 , A61P19/04
CPC分类号： A61K35/32 , A61K35/30 , A61K35/39 , C12N5/0655 , C12N2531/00 , C12N2533/40
摘要： The invention relates to an improved method for administering live cells to a patient and compositions useful in the method. The composition comprises live cells and biocompatible, biodegradable polymer microparticles. The cells and microparticles of the cell/microparticle composition can be contacted immediately prior to administration, or can be contacted in culture for a specified period of time prior to administration. In the method of the invention, an effective amount of the cell/microparticle composition is administered to a patient in need thereof by injection to a treatment site of the patient to provide a therapeutic effect in the patient. The therapeutic effect can be, for example, the formation of new tissue at the treatment site, or the production and secretion of a biologically active secretory molecule at the treatment site. The therapeutic effect resulting from injection of the cell/microparticle composition into a treatment site, is determined by the type of cell present in the composition. The composition comprising lives cells and biocompatible, biodegradable polymer microparticles can further comprise a biologically active agent. In a preferred embodiment, the biologically active agent is incorporated into the microparticle. The biologically active agent can be, for example, factors which modulate cell growth.
摘要翻译：本发明涉及向患者施用活细胞的改进方法和用于该方法的组合物。该组合物包含活细胞和生物相容的可生物降解的聚合物微粒。细胞/微粒组合物的细胞和微粒可以在给药前立即接触，或者可以在施用之前在培养中接触指定的时间段。在本发明的方法中，将有效量的细胞/微粒组合物通过注射给患者的治疗部位给予有需要的患者，以在患者体内提供治疗效果。治疗效果可以是例如在治疗部位形成新组织，或者在治疗部位生产和分泌生物活性分泌分子。将细胞/微粒组合物注入治疗部位所产生的治疗效果由组合物中存在的细胞类型决定。包含生命细胞和生物相容的可生物降解的聚合物微粒的组合物可进一步包含生物活性剂。在优选的实施方案中，将生物活性剂掺入微粒中。生物活性剂可以是例如调节细胞生长的因子。

6. 发明授权

US07282216B2 Biocompatible polymer blends and uses thereof 失效
标题翻译：生物相容性聚合物共混物及其用途
公开(公告)号：US07282216B2
公开(公告)日：2007-10-16
申请号：US10293974
申请日：2002-11-12
申请人： Henry R. Costantino , Mark A. Tracy , Kevin L. Ward , Wendy W. Nelson
发明人： Henry R. Costantino , Mark A. Tracy , Kevin L. Ward , Wendy W. Nelson
IPC分类号： A61K9/22
CPC分类号： A61K9/1647
摘要： The present invention relates to a novel series of polymers which have been prepared by blending hydrophobic biocompatible, biodegradable polymers or copolymers, such as poly(lactide-co-glycolide), and a biocompatible, amphipathic copolymer having a water absorption ratio of about 2 or less. A process for the preparation of the novel polymer blends and sustained release compositions comprising the novel polymer blends are also part of the invention described herein. Further the sustained release compositions can be used to deliver a biologically active with a desirable release profile and in a sustained fashion to a patient in need thereof.
摘要翻译：本发明涉及一种新型的聚合物系列，其通过将疏水性生物相容的可生物降解的聚合物或共聚物如聚（丙交酯 - 共 - 乙交酯）和生物相容性两亲性共聚物与吸水比为约2或减。包含新型聚合物共混物的新型聚合物共混物和持续释放组合物的制备方法也是本文所述的本发明的一部分。此外，持续释放组合物可以用于以期望的释放曲线递送具有生物学活性并且以持续的方式递送给有需要的患者。

7. 发明授权

US06719970B1 Method of generating cartilage 失效
标题翻译：产生软骨的方法
公开(公告)号：US06719970B1
公开(公告)日：2004-04-13
申请号：US09612744
申请日：2000-07-10
申请人： Henry R. Costantino , Lawrence J. Bonassar , Mark A. Tracy
发明人： Henry R. Costantino , Lawrence J. Bonassar , Mark A. Tracy
IPC分类号： C12N506
CPC分类号： A61K35/32 , A61K35/30 , A61K35/39 , C12N5/0655 , C12N2531/00 , C12N2533/40
摘要： The invention relates to an improved method for administering live cells to a patient and compositions useful in the method. The composition comprises live cells and biocompatible, biodegradable polymer microparticles. The cells and microparticles of the cell/microparticle composition can be contacted immediately prior to administration, or can be contacted in culture for a specified period of time prior to administration. In the method of the invention, an effective amount of the cell/microparticle composition is administered to a patient in need thereof by injection to a treatment site of the patient to provide a therapeutic effect in the patient. The therapeutic effect can be, for example, the formation of new tissue at the treatment site, or the production and secretion of a biologically active secretory molecule at the treatment site. The composition comprising lives cells and biocompatible, biodegradable polymer microparticles can further comprise a biologically active agent. In a preferred embodiment, the biologically active agent is incorporated into the microparticle. The biologically active agent can be, for example, factors which modulate cell growth.
摘要翻译：本发明涉及向患者施用活细胞的改进方法和用于该方法的组合物。该组合物包含活细胞和生物相容的可生物降解的聚合物微粒。细胞/微粒组合物的细胞和微粒可以在给药前立即接触，或者可以在施用之前在培养中接触指定的时间段。在本发明的方法中，将有效量的细胞/微粒组合物通过注射给患者的治疗部位给予有需要的患者，以在患者体内提供治疗效果。治疗效果可以是例如在治疗部位形成新组织，或者在治疗部位生产和分泌生物活性分泌分子。包含生命细胞和生物相容的可生物降解的聚合物微粒的组合物可进一步包含生物活性剂。在优选的实施方案中，将生物活性剂掺入微粒中。生物活性剂可以是例如调节细胞生长的因子。

8. 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。

9. 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。

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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