公开(公告)号：US08877229B2

公开(公告)日：2014-11-04

申请号：US11607382

申请日：2006-12-01

申请人： Kathleen M. Campbell ,  Pericles Calias ,  Gary P. Cook ,  Mary A. Ganley

发明人： Kathleen M. Campbell ,  Pericles Calias ,  Gary P. Cook ,  Mary A. Ganley

IPC分类号： A61K9/52 ,  A61P27/02 ,  A61K9/16 ,  A61K31/00 ,  A61K9/00

CPC分类号： A61K38/1866 ,  A61K9/0019 ,  A61K9/0048 ,  A61K9/1647 ,  A61K31/00

摘要： Formulations for controlled, sustained release of biologically active agents for the treatment of ocular disorders have been developed. These formulations are based on solid microparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof. The microparticles are characterized by low burst levels and efficient drug loading and sustained release.

摘要翻译： 已经开发了用于治疗眼部疾病的生物活性剂的受控持续释放的制剂。 这些制剂基于由可生物降解的合成聚合物如聚（乳酸）（PLA），聚（乙醇酸）（PGA）及其共聚物的组合形成的固体微粒。 微粒的特征在于低爆发水平和有效的药物负载和持续释放。

公开(公告)号：US08871269B2

公开(公告)日：2014-10-28

申请号：US10564494

申请日：2004-07-15

申请人： Gary P. Cook

发明人： Gary P. Cook

IPC分类号： A61K9/16 ,  A61K9/51 ,  A61K31/70

CPC分类号： A61K9/1647 ,  A61K9/1694 ,  A61K9/5153 ,  A61K9/5192 ,  A61K31/70 ,  Y10S977/906

摘要： The methods disclosed herein are of use for the production of controlled release compositions. In particular, the methods provide the contacting of an organic phase containing a bioactive agent and a polymer with an aqueous phase containing an organic ion to create controlled release compositions containing bioactive agents. The present invention also includes controlled release compositions including a polymer, an organic ion and a bioactive agent. The present invention also includes methods of using such controlled release compositions. The usefulness of the present invention is that the methods result in the production of controlled release compositions containing bioactive agent capable of administration in a concentrated low-dose form, having low burst and reduced production of degraded bioactive agent.

摘要翻译： 本文公开的方法可用于生产控释组合物。 特别地，所述方法提供了包含生物活性剂和聚合物的有机相与含有有机离子的水相的接触，以产生含有生物活性剂的控释组合物。 本发明还包括包含聚合物，有机离子和生物活性剂的控释组合物。 本发明还包括使用这种控释组合物的方法。 本发明的有用性是该方法导致含有能够以浓缩的低剂量形式施用的生物活性剂的控释组合物的生产，其具有低的破裂和降低的生物活性剂的产生。

公开(公告)号：US20100143485A1

公开(公告)日：2010-06-10

申请号：US10547958

申请日：2004-03-05

申请人： Paul S. Hudnut ,  Gary P. Cook

发明人： Paul S. Hudnut ,  Gary P. Cook

IPC分类号： A61K9/50 ,  A61K38/22 ,  A61P15/00 ,  A61P25/00

CPC分类号： A61K9/5031 ,  A61K9/5146 ,  A61K9/5153 ,  A61K38/095

摘要： The compositions disclosed herein are of use for the treatment of a wide variety of diseases. In particular, the compositions provide oxytocin and oxytocin analogs in sustained release formulations. In particular embodiments, the disclosed compositions concern oxytocin and oxytocin analogs, each of which may be associated with a biodegradable polymer and/or attached to a hydrophilic polymer. The methods include treatment of a wide variety of diseases and conditions. In particular, the methods include treatment of sexual dysfunction and disorders associated with repetitive behaviors, such as autism. The usefulness of the present invention is that the oxytocin, oxytocin analogs and mixtures thereof can be administered in a pharmaceutical formulation that increases their half-life and also provides for sustained release.

摘要翻译： 本文公开的组合物可用于治疗各种各样的疾病。 特别地，组合物在持续释放制剂中提供催产素和催产素类似物。 在具体实施方案中，所公开的组合物涉及催产素和催产素类似物，其各自可与生物可降解聚合物缔合和/或与亲水性聚合物连接。 这些方法包括治疗各种疾病和病症。 特别地，所述方法包括治疗性功能障碍和与重复行为相关的疾病，例如自闭症。 本发明的有用性是催产素，催产素类似物及其混合物可以在增加其半衰期并且还提供持续释放的药物制剂中施用。

公开(公告)号：US08088754B2

公开(公告)日：2012-01-03

申请号：US12388295

申请日：2009-02-18

申请人： Xiaoqin Cheng ,  Gary P. Cook ,  Gong-Xin He ,  Choung U. Kim ,  John C. Rohloff ,  Jianying Wang ,  Zheng-Yu Yang

发明人： Xiaoqin Cheng ,  Gary P. Cook ,  Gong-Xin He ,  Choung U. Kim ,  John C. Rohloff ,  Jianying Wang ,  Zheng-Yu Yang

IPC分类号： C07F9/6561 ,  A61K31/675 ,  A61P31/20

CPC分类号： C07F9/65616 ,  Y02P20/55

摘要： Compounds and compositions of Formula I are described, useful as anti-proliferative agents, and in particular anti-HPV, wherein: Y1A and Y1B are independently Y1; RX1 and RX2 are independently RX; Y1 is ═O, —O(RX), ═S, —N(RX), —N(O)(RX), —N(ORX), —N(O)(ORX), or —N(N(RX)(RX)); and pharmaceutically acceptable salts thereof.

摘要翻译： 描述了式I的化合物和组合物，其可用作抗增殖剂，特别是抗HPV，其中：Y1A和Y1B独立地为Y1; RX1和RX2独立为RX; Y1是ΟO，-O（RX），≡S，-N（RX），-N（O）（RX），-N（ORX），-N（O）（ORX） RX）（RX））; 及其药学上可接受的盐。

公开(公告)号：US08268802B2

公开(公告)日：2012-09-18

申请号：US12436004

申请日：2009-05-05

申请人： Xiaoqin Cheng ,  Gary P. Cook ,  Manoj C. Desai ,  Edward Doerffler ,  Gong-Xin He ,  Choung U. Kim ,  William A. Lee ,  John C. Rohloff ,  Jianying Wang ,  Zheng-Yu Yang

发明人： Xiaoqin Cheng ,  Gary P. Cook ,  Manoj C. Desai ,  Edward Doerffler ,  Gong-Xin He ,  Choung U. Kim ,  William A. Lee ,  John C. Rohloff ,  Jianying Wang ,  Zheng-Yu Yang

IPC分类号： C07F9/6561 ,  A61K31/675 ,  A61P31/20

CPC分类号： C07F9/65616 ,  Y02P20/55

摘要： Compounds and compositions of Formula I are described, useful as anti-proliferative agents, and in particular anti-HPV, wherein: Y1A and Y1B are independently Y1; RX1 and RX2 are independently RX; Y1 is ═O, —O(RX), ═S, —N(RX), —N(O)(RX), —N(ORX), —N(O)(ORX), or —N(N(RX)(RX)); RX is independently R1, R2, R4, W3, or a protecting group; R1 is independently —H or alkyl of 1 to 18 carbon atoms; R2 is independently R3 or R4 wherein each R4 is independently substituted with 0 to 3 R3 groups or taken together at a carbon atom, two R2 groups form a ring of 3 to 8 carbons and the ring may be substituted with 0 to 3 R3 groups; R3 is R3a, R3b, R3c or R3d, provided that when R3 is bound to a heteroatom, then R3 is R3c or R3d; R3a is —H, —F, —Cl, —Br, —I, —CF3, —CN, N3, —NO2, or —OR4; R3b is ═O, —O(R4), ═S, —N(R4), —N(O)(R4), —N(OR4), —N(O)(OR4), or —N(N(R4)(R4)); R3c is —R4, —N(R4)(R4), —SR4, —S(O)R4, —S(O)2R4, —S(O)(OR4), —S(O)2(OR4), —OC(R3b)R4, —OC(R3b)OR4, —OC(R3b)(N(R4)(R4)), —SC(R3b)R4, —SC(R3b)OR4, —SC(R3b)(N(R4)(R4)), —N(R4)C(R3b)R4, —N(R4)C(R3b)OR4, —N(R4)C(R3b) (N(R4)(R4)), W3 or —R5W3; R3d is —C(R3b)R4, —C(R3b)OR4, —C(R3b)W3, —C(R3b)OW3 or —C(R3b)(N(R4)(R4)); R4 is —H, or an alkyl of 1 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, or alkynyl of 2 to 18 carbon atoms; R5 is alkylene of 1 to 18 carbon atoms, alkenylene of 2 to 18 carbon atoms, or alkynylene of 2 to 18 carbon atoms; W3 is W4 or W5; W4 is R6, —C(R3b)R6, —C(R3b)W5, —SOM2R6, or —SOM2W5, wherein R6 is R4 wherein each R4 is substituted with 0 to 3 R3 groups; W5 is carbocycle or heterocycle wherein W5 is independently substituted with 0 to 3 R2 groups; and M2 is 0, 1 or 2; and pharmaceutically acceptable salts thereof.

公开(公告)号：US20120244192A1

公开(公告)日：2012-09-27

申请号：US13266718

申请日：2010-04-26

申请人： Gary P. Cook

发明人： Gary P. Cook

IPC分类号： A61K38/08 ,  A61P9/10 ,  A61P29/00 ,  A61K9/14 ,  A61P27/02

CPC分类号： A61K38/08 ,  A61K9/0051 ,  A61K9/5031 ,  A61K9/5138 ,  A61K9/5146 ,  A61K9/5153 ,  A61K9/5169 ,  A61K31/00 ,  A61K31/513

摘要： The invention provides sustained release formulations comprising a C5a receptor antagonist. In certain embodiments the sustained-release formulations include microparticles that comprise a complement C5aR antagonist and a biodegradable polymeric matrix. Methods of treatment comprising the sustained release formulations of the invention are also provided.

摘要翻译： 本发明提供包含C5a受体拮抗剂的持续释放制剂。 在某些实施方案中，缓释制剂包括包含补体C5aR拮抗剂和可生物降解的聚合物基质的微粒。 还提供了包含本发明的缓释制剂的治疗方法。

公开(公告)号：US20090291922A1

公开(公告)日：2009-11-26

申请号：US12436004

申请日：2009-05-05

申请人： Xiaoqin Cheng ,  Gary P. Cook ,  Manoj C. Desai ,  Edward Doerffler ,  Gong-Xin He ,  Choung U. Kim ,  William A. Lee ,  John C. Rohloff ,  Jianying Wang ,  Zheng-Yu Yang

发明人： Xiaoqin Cheng ,  Gary P. Cook ,  Manoj C. Desai ,  Edward Doerffler ,  Gong-Xin He ,  Choung U. Kim ,  William A. Lee ,  John C. Rohloff ,  Jianying Wang ,  Zheng-Yu Yang

IPC分类号： A61K31/675 ,  C07D473/16 ,  A61K31/52 ,  C07F9/02

CPC分类号： C07F9/65616 ,  Y02P20/55

摘要： Compounds and compositions of Formula I are described, useful as anti-proliferative agents, and in particular anti-HPV, wherein: Y1A and Y1B are independently Y1; RX1 and RX2 are independently RX; Y1 is ═O, —O(RX), ═S, —N(RX), —N(O)(RX), —N(ORX), —N(O)(ORX), or —N(N(RX)(RX)); RX is independently R1, R2, R4, W3, or a protecting group; R1 is independently —H or alkyl of 1 to 18 carbon atoms; R2 is independently R3 or R4 wherein each R4 is independently substituted with 0 to 3 R3 groups or taken together at a carbon atom, two R2 groups form a ring of 3 to 8 carbons and the ring may be substituted with 0 to 3 R3 groups; R3 is R3a, R3b, R3c or R3d, provided that when R3 is bound to a heteroatom, then R3 is R3c or R3d; R3a is —H, —F, —Cl, —Br, —I, —CF3, —CN, N3, —NO2, or —OR4; R3b is ═O, —O(R4), ═S, —N(R4), —N(O)(R4), —N(OR4), —N(O)(OR4), or —N(N(R4)(R4)); R3c is —R4, —N(R4)(R4), —SR4, —S(O)R4, —S(O)2R4, —S(O)(OR4), —S(O)2(OR4), —OC(R3b)R4, —OC(R3b)OR4, —OC(R3b)(N(R4)(R4)), —SC(R3b)R4, —SC(R3b)OR4, —SC(R3b)(N(R4)(R4)), —N(R4)C(R3b)R4, —N(R4)C(R3b)OR4, —N(R4)C(R3b) (N(R4)(R4)), W3 or —R5W3; R3d is —C(R3b)R4, —C(R3b)OR4, —C(R3b)W3, —C(R3b)OW3 or —C(R3b)(N(R4)(R4)); R4 is —H, or an alkyl of 1 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, or alkynyl of 2 to 18 carbon atoms; R5 is alkylene of 1 to 18 carbon atoms, alkenylene of 2 to 18 carbon atoms, or alkynylene of 2 to 18 carbon atoms; W3 is W4 or W5; W4 is R6, —C(R3b)R6, —C(R3b)W5, —SOM2R6, or —SOM2W5, wherein R6 is R4 wherein each R4 is substituted with 0 to 3 R3 groups; W5 is carbocycle or heterocycle wherein W5 is independently substituted with 0 to 3 R2 groups; and M2 is 0, 1 or 2; and pharmaceutically acceptable salts thereof.

公开(公告)号：US08900636B2

公开(公告)日：2014-12-02

申请号：US10565401

申请日：2004-07-15

申请人： Gary P. Cook

发明人： Gary P. Cook

IPC分类号： A61K9/14 ,  A61K9/16 ,  A61K47/48 ,  A61K38/28 ,  A61K9/50 ,  A61K38/31 ,  A61K38/11 ,  A61K31/715 ,  A61K9/51 ,  A61K38/09

CPC分类号： A61K9/1694 ,  A61K9/1647 ,  A61K9/5031 ,  A61K9/5153 ,  A61K31/715 ,  A61K38/09 ,  A61K38/11 ,  A61K38/28 ,  A61K38/31 ,  A61K47/4803 ,  A61K47/48215 ,  A61K47/541 ,  A61K47/60

摘要： The compositions disclosed herein are for use as controlled release therapeutics for the treatment of a wide variety of diseases. In particular, the compositions provide water soluble bioactive agents, organic ions and polymers where the bioactive agent is efficiently released over time with minimal degradation products. The resulting controlled release composition is capable of administration in a decreased dose volume due to the high drug content and predominance of non-degraded bioactive agent after release. Additionally, the compositions, of the present invention are capable of long term, sustained releases.

摘要翻译： 本文公开的组合物用作治疗各种疾病的控释药物。 特别地，组合物提供水溶性生物活性剂，有机离子和聚合物，其中生物活性剂随着时间的推移有效地释放出最少的降解产物。 所得的控释组合物由于药物含量高，释放后非降解生物活性剂的优势而能够以降低的剂量体积施用。 另外，本发明的组合物能够长期持续释放。

公开(公告)号：US07553825B2

公开(公告)日：2009-06-30

申请号：US11026303

申请日：2004-12-29

申请人： Xiaoqin Cheng ,  Gary P. Cook ,  Manoj C. Desai ,  Edward Doerffler ,  Gong-Xin He ,  Choung U. Kim ,  William A. Lee ,  John C. Rohloff ,  Jianying Wang ,  Zheng-Yu Yang

发明人： Xiaoqin Cheng ,  Gary P. Cook ,  Manoj C. Desai ,  Edward Doerffler ,  Gong-Xin He ,  Choung U. Kim ,  William A. Lee ,  John C. Rohloff ,  Jianying Wang ,  Zheng-Yu Yang

IPC分类号： C07F9/6561 ,  A61K31/675 ,  A61P31/20

CPC分类号： C07F9/65616 ,  Y02P20/55

摘要： Compounds and compositions of Formula I are described, useful as anti-proliferative agents, and in particular anti-HPV, wherein: Y1A and Y1B are independently Y1; RX1 and RX2 are independently RX; Y1 is ═O, —O(RX), ═S, —N(RX), —N(O)(RX), —N(ORX), —N(O)(ORX), or —N(N(RX) (RX)); RX is independently R1, R2, R4, W3, or a protecting group; R1 is independently —H or alkyl of 1 to 18 carbon atoms; R2 is independently R3 or R4 wherein each R4 is independently substituted with 0 to 3 R3 groups or taken together at a carbon atom, two R2 groups form a ring of 3 to 8 carbons and the ring may be substituted with 0 to 3 R3 groups; R3 is R3a, R3b, R3c or R3d, provided that when R3 is bound to a heteroatom, then R3 is R3c or R3d; R3a is —H, —F, —Cl, —Br, —I, —CF3, —CN, N3, —NO2, or —OR4; R3b is ═O, —O(R4), ═S, —N(R4), —N(O)(R4), —N(OR4), —N(O)(OR4), or —N(N(R4) (R4)); R3c is —R4, —N(R4)(R4), —SR4, —S(O)R4, —S(O)2R4, —S(O)(OR4), —S(O)2(OR4), —OC(R3b)R4, —OC(R3b)OR4, —OC(R3b)(N(R4)(R4)), —SC(R3b)R4, —SC(R3b)OR4, SC(R3b)(N(R4)(R4)), —N(R4)C(R3b)R4, —N(R4)C(R3b)OR4, N(R4)C(R3b)(N(R4)(R4)), W3 or —R5W3; R3d is —C(R3b)R4, —C(R3b)OR4, —C(R3b)W3, —C(R3b)OW3 or —C(R3b)(N(R4)(R4)); R4 is —H, or an alkyl of 1 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, or alkynyl of 2 to 18 carbon atoms; R5 is alkylene of 1 to 18 carbon atoms, alkenylene of 2 to 18 carbon atoms, or alkynylene of 2 to 18 carbon atoms; W3 is W4 or W5; W4 is R6, —C(R3b)R6, —C(R3b)W5, —SOM2R6, or —SOM2W5, wherein R6 is R4 wherein each R4 is substituted with 0 to 3 R3 groups; W5 is carbocycle or heterocycle wherein W5 is independently substituted with 0 to 3 R2 groups; and M2 is 0, 1 or 2; and pharmaceutically acceptable salts thereof.

公开(公告)号：US20090149400A1

公开(公告)日：2009-06-11

申请号：US12388295

申请日：2009-02-18

申请人： Xiaoqin Cheng ,  Gary P. Cook ,  Manoj C. Desai ,  Edward Doerffler ,  Gong-Xin He ,  Choung U. Kim ,  William A. Lee ,  John C. Rohloff ,  Jianying Wang ,  Zheng-yu Yang

发明人： Xiaoqin Cheng ,  Gary P. Cook ,  Manoj C. Desai ,  Edward Doerffler ,  Gong-Xin He ,  Choung U. Kim ,  William A. Lee ,  John C. Rohloff ,  Jianying Wang ,  Zheng-yu Yang

IPC分类号： A61K31/675 ,  C07F9/6512 ,  A61K31/7056 ,  A61P31/12

CPC分类号： C07F9/65616 ,  Y02P20/55

摘要： Compounds and compositions of Formula I are described, useful as anti-proliferative agents, and in particular anti-HPV, wherein: Y1A and Y1B are independently Y1; RX1 and RX2 are independently RX; Y1 is ═O, —O(RX), ═S, —N(RX), —N(O)(RX), —N(ORX), —N(O)(ORX), or —N(N(RX)(RX)); RX is independently R1, R2, R4, W3, or a protecting group; R1 is independently —H or alkyl of 1 to 18 carbon atoms; R2 is independently R3 or R4 wherein each R4 is independently substituted with 0 to 3 R3 groups or taken together at a carbon atom, two R2 groups form a ring of 3 to 8 carbons and the ring may be substituted with 0 to 3 R3 groups; R3 is R3a, R3b, R3c or R3d, provided that when R3 is bound to a heteroatom, then R3 is R3c or R3d; R3a is —H, —F, —Cl, —Br, —I, —CF3, —CN, N3, —NO2, or —OR4; R3b is ═O, —O(R4), ═S, —N(R4), —N(O)(R4), —N(OR4), —N(O)(OR4), or —N(N(R4)(R4)); R3c is —R4, —N(R4)(R4), —SR4, —S(O)R4, —S(O)2R4, —S(O)(OR4), —S(O)2(OR4), —OC(R3b)R4, —OC(R3b)OR4, —OC(R3b)(N(R4)(R4)), —SC(R3b)R4, —SC(R3b)OR4, —SC(R3b)(N(R4)(R4)), —N(R4)C(R3b)R4, —N(R4)C(R3b)OR4, —N(R4)C(R3b)(N(R4)(R4)), W3 or —R5W3; R3d is —C(R3b)R4, —C(R3b)OR4, —C(R3b)W3, —C(R3b)OW3 or —C(R3b)(N(R4)(R4)); R4 is —H, or an alkyl of 1 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, or alkynyl of 2 to 18 carbon atoms; R5 is alkylene of 1 to 18 carbon atoms, alkenylene of 2 to 18 carbon atoms, or alkynylene of 2 to 18 carbon atoms; W3 is W4 or W5; W4 is R6, —C(R3b)R6, —C(R3b)W5, —SOM2R6, or —SOM2W5, wherein R6 is R4 wherein each R4 is substituted with 0 to 3 R3 groups; W5 is carbocycle or heterocycle wherein W5 is independently substituted with 0 to 3 R2 groups; and M2 is 0, 1 or 2; and pharmaceutically acceptable salts thereof.