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1. 发明申请

WO2013036775A1 SILICONE COATED IMPLANTS 审中-公开
标题翻译：硅胶涂层
公开(公告)号：WO2013036775A1
公开(公告)日：2013-03-14
申请号：PCT/US2012/054176
申请日：2012-09-07
申请人： AXXIA PHARMACEUTICALS, LLC , HOLL, Richard, J. , HARTMAN, Katherine , GROSSMAN, Stuart, A. , POLLOCK, Wayne, C.
发明人： HOLL, Richard, J. , HARTMAN, Katherine , GROSSMAN, Stuart, A. , POLLOCK, Wayne, C.
IPC分类号： A61K9/00 , A61K31/485 , A61K47/34
CPC分类号： A61K9/0002 , A61K9/0024 , A61K31/485 , A61K47/34
摘要： Implants for delivery of therapeutic agents such as opioids, and the manufacture and uses of such implants are provided. In particular, subcutaneous drug delivery systems having a biocompatible thermoplastic elastomeric polymer matrix, a therapeutic agent embedded homogeneously in said matrix, and a biocompatible drug impermeable cross-linked silicone polymer coating said matrix and methods of making the same are provided.
摘要翻译：提供用于递送治疗剂如阿片样物质的植入物，以及这种植入物的制造和用途。特别地，提供了具有生物相容性热塑性弹性体聚合物基质，均匀地嵌入所述基质中的治疗剂和涂覆所述基质的生物相容性药物不可渗透交联的硅氧烷聚合物的皮下药物递送系统及其制备方法。

2. 发明申请

WO2008127679A1 LYOPHILIZED PHARMACEUTICAL COMPOSITIONS AND METHODS OF MAKING AND USING SAME 审中-公开
公开(公告)号：WO2008127679A1
公开(公告)日：2008-10-23
申请号：PCT/US2008/004755
申请日：2008-04-11
申请人： CEPHALON, INC. , CEPHALON FRANCE , DULIEU, Claire , DURFEE, Steve, L. , HOLL, Richard, J. , NGUYEN, Tam
发明人： DULIEU, Claire , DURFEE, Steve, L. , HOLL, Richard, J. , NGUYEN, Tam
IPC分类号： A61K9/00 , A61K9/19 , A61K9/14 , A61K31/4178 , A61K31/135 , A61K31/4045 , A61K38/11
CPC分类号： A61K38/11 , A61K9/006 , A61K9/19 , A61K31/135 , A61K31/4045 , A61K31/4178 , A61K31/435 , A61K38/23 , A61K38/26 , A61K38/28 , A61K47/36 , A61K47/38
摘要： The present invention relates to a new lyophilized pharmaceutical composition capable of adhering to oral mucosal tissue for an extended period of time for delivering active pharmaceutical ingredient through the oral mucosal tissue using transmucosal absorption.
摘要翻译：本发明涉及一种新的冻干药物组合物，其能够通过使用经粘膜吸收通过口腔粘膜组织递送活性药物成分延长的时间段粘附于口腔粘膜组织。

3. 发明申请

WO2008127669A1 BILAYER LYOPHILIZED PHARMACEUTICAL COMPOSITIONS AND METHODS OF MAKING AND USING SAME 审中-公开
公开(公告)号：WO2008127669A1
公开(公告)日：2008-10-23
申请号：PCT/US2008/004737
申请日：2008-04-11
申请人： CEPHALON, INC. , CEPHALON FRANCE , DULIEU, Claire , DURFEE, Steve, L. , HOLL, Richard, J. , NGUYEN, Tam , PHADUNGPOJNA, Sasima
发明人： DULIEU, Claire , DURFEE, Steve, L. , HOLL, Richard, J. , NGUYEN, Tam , PHADUNGPOJNA, Sasima
IPC分类号： A61K9/24 , A61K31/165 , A61K31/135
CPC分类号： A61K9/0056 , A61K9/006 , A61K9/2086 , A61K9/209 , A61K9/2095
摘要： The present invention relates to a bilayer dosage form comprising: - an upper layer (a) comprising a lyophilized dosage form of active pharmaceutical ingredient(s) (API(s)). - a base line layer (b) formulated to adhere to the oral mucosa and intended for delayed, sustained or extended release of API(s) and/or excipient(s).
摘要翻译：本发明涉及双层剂型，其包含： - 包含活性药物成分（API）的冻干剂型的上层（a）。 - 配制成粘附到口腔粘膜并用于延迟，持续或延长释放API和/或赋形剂的基线层（b）。

4. 发明申请

WO0066087A8 EMULSION-BASED PROCESSES FOR MAKING MICROPARTICLES 审中-公开
公开(公告)号：WO0066087A8
公开(公告)日：2001-04-05
申请号：PCT/US0011781
申请日：2000-05-02
申请人： SOUTHERN BIOSYSTEMS INC , GIBSON JOHN W , HOLL RICHARD J , TIPTON ARTHUR J
发明人： GIBSON JOHN W , HOLL RICHARD J , TIPTON ARTHUR J
IPC分类号： A61K9/16 , B01J13/12
CPC分类号： B01J13/125 , A61K9/1647 , A61K9/1694 , Y10T428/2984 , Y10T428/2985
摘要： Processes for making microparticles, preferably containing an active agent, are provided. In a preferred embodiment, the process involves preparing (1) a dispersed phase containing an agent in a solution of polymer and a first solvent; (2) a continuous phase containing a surfactant, a second solvent that is totally or partially immiscible with the first solvent, and sufficient first solvent to saturate the continuous phase; and (3) an extraction phase that is a nonsolvent for the polymer, a solvent for the continuous phase components, and a solvent for the first solvent, wherein the first solvent has solubility in the extraction phase of between about 0,1 % and 25 % by weight. Then, the dispersed phase and the continuous phase are mixed to form an emulsion, and the emulsion is then briefly mixed with a suitable quantity of extraction phase to induce skin formation at the interface of the dispersed and continuous phases. Remaining solvent is removed by an evaporation process step. The emulsification and solvent removal steps are preferably conducted in a continuous process. The brief extraction step prior to evaporation minimizes the loss of active agent from the microparticles, and reduces the required volume of extraction phase as compared to other extraction-based processes. Alternate emulsification methods and solvent removal methods, such as incremental extraction, cryogenic extraction, or membrane separation, also are provided, and can be used in various combinations to make microparticles.

5. 发明申请

WO0066087A9 EMULSION-BASED PROCESSES FOR MAKING MICROPARTICLES 审中-公开
标题翻译：基于乳液的微粒制备工艺
公开(公告)号：WO0066087A9
公开(公告)日：2001-07-12
申请号：PCT/US0011781
申请日：2000-05-02
申请人： SOUTHERN BIOSYSTEMS INC , GIBSON JOHN W , HOLL RICHARD J , TIPTON ARTHUR J
发明人： GIBSON JOHN W , HOLL RICHARD J , TIPTON ARTHUR J
IPC分类号： A61K9/16 , B01J13/12
CPC分类号： B01J13/125 , A61K9/1647 , A61K9/1694 , Y10T428/2984 , Y10T428/2985
摘要： Processes for making microparticles, preferably containing an active agent, are provided. In a preferred embodiment, the process involves preparing (1) a dispersed phase containing an agent in a solution of polymer and a first solvent; (2) a continuous phase containing a surfactant, a second solvent that is totally or partially immiscible with the first solvent, and sufficient first solvent to saturate the continuous phase; and (3) an extraction phase that is a nonsolvent for the polymer, a solvent for the continuous phase components, and a solvent for the first solvent, wherein the first solvent has solubility in the extraction phase of between about 0,1 % and 25 % by weight. Then, the dispersed phase and the continuous phase are mixed to form an emulsion, and the emulsion is then briefly mixed with a suitable quantity of extraction phase to induce skin formation at the interface of the dispersed and continuous phases. Remaining solvent is removed by an evaporation process step. The emulsification and solvent removal steps are preferably conducted in a continuous process. The brief extraction step prior to evaporation minimizes the loss of active agent from the microparticles, and reduces the required volume of extraction phase as compared to other extraction-based processes. Alternate emulsification methods and solvent removal methods, such as incremental extraction, cryogenic extraction, or membrane separation, also are provided, and can be used in various combinations to make microparticles.
摘要翻译：提供了制造优选含有活性剂的微粒的方法。在一个优选的实施方案中，该方法涉及制备（1）在聚合物和第一溶剂的溶液中含有试剂的分散相; （2）含有表面活性剂，与第一溶剂完全或部分不混溶的第二溶剂和足以使连续相饱和的第一溶剂的连续相; 和（3）作为聚合物的非溶剂的萃取相，连续相组分的溶剂和第一溶剂的溶剂，其中第一溶剂在萃取相中的溶解度为约0.1％至25％重量％。然后，将分散相和连续相混合形成乳液，然后将乳液与适量的萃取相短暂混合，以在分散相和连续相的界面处诱导皮肤形成。剩余溶剂通过蒸发工艺步骤除去。乳化和溶剂去除步骤优选以连续方法进行。与其他基于提取的方法相比，在蒸发之前的简单提取步骤使来自微粒的活性剂的损失最小化，并且减少了所需的提取相体积。还提供了替代乳化方法和溶剂去除方法，如增量提取，深冷提取或膜分离，并且可以以各种组合使用以制造微粒。

6. 发明申请

WO1996003121A1 ANTIPHLOGISTIC, ANALGESIC, ANTIPYRETIC INJECTION PREPARATION 审中-公开
标题翻译：抗生素，毒理学，抗生素注射制剂
公开(公告)号：WO1996003121A1
公开(公告)日：1996-02-08
申请号：PCT/US1995009331
申请日：1995-07-26
申请人： SOUTHERN RESEARCH INSTITUTE , HOLL, Richard, J. , TICE, Thomas, R. , WILLIAMS, Laura, L.
发明人： SOUTHERN RESEARCH INSTITUTE
IPC分类号： A61K31/135
CPC分类号： A61K31/196 , A61K9/1075
摘要： An antiphlogistic, analgesic, antipyretic parenteral preparation comprising diclofenac, its salt, or both, a surfactant, and cosurfactant, and water, and having a pH of 3-10 is provided. Another antiphlogistic, analgesic, antipyretic parenteral preparation comprising diclofenac, its salt, or both, a surfactant, and cosurfactant, an oily component, and water, and having a pH of 3-10 is provided. The parenteral preparation can be injected without pain, can avoid occurrence of side effects such as shock, due to the rapid diclofenac plasma concentration increase, that after administration of currently marketed diclofenac preparations, and can exhibit sustained therapeutic levels of diclofenac in plasma.
摘要翻译：提供包含双氯芬酸，其盐或两者的消炎止痛，解热肠胃外制剂，表面活性剂和辅助表面活性剂和水，pH为3-10。另外提供包含双氯芬酸，其盐或两者的表面活性剂，辅助表面活性剂，油性成分和水，并且pH为3-10的另外一种消炎止痛，解热肠胃外制剂。肠胃外制剂可以无疼痛地注射，可以避免由于快速的双氯芬酸血浆浓度增加而引起的副作用，如休克，在给药目前市售的双氯芬酸制剂后，可以显示血浆中持续的治疗水平的双氯芬酸。

7. 发明申请

WO2013059146A1 SOLID DOSAGE FORMS OF (S)-ETHYL 2-AMINO-3-(4-(2-AMINO-6-((R)-1-(4-CHLORO-2-(3-METHYL-1H-PYRAZOL-1-YL)PHENYL)-2,2,2-TRIFLUOROETHOXY)PYRIMIDIN-4-YL)PHENYL)PROPANOATE 审中-公开
标题翻译：（S） - 乙基2-氨基-3-（4-（2-氨基 - 6 - （（R）-1-（4-氯-2-（3-甲基-1H-吡唑-1-基）基）苯基）-2,2,2-三氟乙氧基）嘧啶-4-基）苯基）丙酸甲酯
公开(公告)号：WO2013059146A1
公开(公告)日：2013-04-25
申请号：PCT/US2012/060338
申请日：2012-10-16
申请人： LEXICON PHARMACEUTICALS, INC. , CHEN, Jinling , DEAVER, Matthew S. , HOLL, Richard J. , NUGURU, Kalyan
发明人： CHEN, Jinling , DEAVER, Matthew S. , HOLL, Richard J. , NUGURU, Kalyan
IPC分类号： A61K9/16 , A61K9/20
CPC分类号： A61K31/506 , A61K9/1623 , A61K9/1652 , A61K9/2018 , A61K9/2054 , A61K9/2095 , A61K9/2806 , A61K9/2893
摘要： Solid pharmaceutical dosage forms comprising (S)-ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate (telotristat) are disclosed, as well as methods of making them and compositions useful in their manufacture.
摘要翻译：包含（S）-2-氨基-3-（4-（2-氨基-6 - （（R）-1-（4-氯-2-（3-甲基-1H-吡唑-1-基） - 基）苯基）-2,2,2-三氟乙氧基）嘧啶-4-基）苯基）丙酸酯（telotristat），以及制备它们的方法和可用于其制备的组合物。

8. 发明申请

WO2009114192A3 ENHANCED TRANSMUCOSAL COMPOSITION AND DOSAGE FORM 审中-公开
标题翻译：增强转运组合物和剂型
公开(公告)号：WO2009114192A3
公开(公告)日：2010-07-08
申请号：PCT/US2009001626
申请日：2009-03-13
申请人： CEPHALON INC , HOLL RICHARD J , LENTZ MATTHEW J
发明人： HOLL RICHARD J , LENTZ MATTHEW J
IPC分类号： A61K9/00
CPC分类号： A61K9/006 , A61K9/0007
摘要： The invention provides a transmucosal pharmaceutical composition comprising an active compound, a bile salt and an osmolality adjusting ingredient, wherein the osmolality adjusting ingredient generates a localized hyperosmotic environment and maintains an osmolality level for a period of time sufficient to produce hypertonicity- facilitated transmucosal transport of said active compound across the mucosal tissue. The invention also provides a solid transmucosal dosage form containing the composition, as well as a method of treatment comprising administering the same. In one embodiment, the active compound is a triptan compound, e.g., sumatriptan and zolmitriptan.
摘要翻译：本发明提供了包含活性化合物，胆汁盐和重量摩尔渗透压浓度调节成分的透粘膜药物组合物，其中所述重量克分子渗透浓度调节成分产生局部高渗环境并保持渗透压浓度足以产生高渗性促进的经粘膜转运所述活性化合物穿过粘膜组织。本发明还提供了含有该组合物的固体透粘膜剂型，以及一种治疗方法，其包括施用该组合物。在一个实施方案中，活性化合物是曲坦类化合物，例如舒马曲坦和佐米曲坦。

9. 发明申请

WO2009114192A2 ENHANCED TRANSMUCOSAL COMPOSITION AND DOSAGE FORM 审中-公开
标题翻译：增强转运组合物和剂型
公开(公告)号：WO2009114192A2
公开(公告)日：2009-09-17
申请号：PCT/US2009/001626
申请日：2009-03-13
申请人： CEPHALON, INC. , HOLL, Richard, J. , LENTZ, Matthew, J.
发明人： HOLL, Richard, J. , LENTZ, Matthew, J.
IPC分类号： A61K9/70
CPC分类号： A61K9/006 , A61K9/0007
摘要： The invention provides a transmucosal pharmaceutical composition comprising an active compound, a bile salt and an osmolality adjusting ingredient, wherein the osmolality adjusting ingredient generates a localized hyperosmotic environment and maintains an osmolality level for a period of time sufficient to produce hypertonicity- facilitated transmucosal transport of said active compound across the mucosal tissue. The invention also provides a solid transmucosal dosage form containing the composition, as well as a method of treatment comprising administering the same. In one embodiment, the active compound is a triptan compound, e.g., sumatriptan and zolmitriptan.
摘要翻译：本发明提供了包含活性化合物，胆汁盐和重量摩尔渗透压浓度调节成分的透粘膜药物组合物，其中所述重量克分子渗透浓度调节成分产生局部高渗环境并保持渗透压浓度足以产生高渗性促进的经粘膜转运所述活性化合物穿过粘膜组织。本发明还提供了含有该组合物的固体透粘膜剂型，以及一种治疗方法，其包括施用该组合物。在一个实施方案中，活性化合物是曲坦类化合物，例如舒马曲坦和佐米曲坦。

10. 发明授权

US3034977A Nuclear superheater for boiling water reactor 失效
标题翻译：沸水反应堆核过热器
公开(公告)号：US3034977A
公开(公告)日：1962-05-15
申请号：US72227458
申请日：1958-03-18
申请人： HOLL RICHARD J , KLECKER RAYMOND W , GRAHAM CLIFTON B
发明人： HOLL RICHARD J , KLECKER RAYMOND W , GRAHAM CLIFTON B
IPC分类号： G21C1/08 , G21C3/36 , G21C15/26
CPC分类号： G21C15/26 , G21C1/082 , G21C3/36 , Y02E30/31

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