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1. 发明申请

US20130236524A1 SILICONE COATED IMPLANT 审中-公开
标题翻译：硅胶涂层
公开(公告)号：US20130236524A1
公开(公告)日：2013-09-12
申请号：US13606795
申请日：2012-09-07
申请人： Richard J. HOLL , Katherine HARTMAN , Stuart A. Grossman , Wayne C. Pollock
发明人： Richard J. HOLL , Katherine HARTMAN , Stuart A. Grossman , Wayne C. Pollock
IPC分类号： A61K9/00 , A61K31/485
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. 发明授权

US5554650A Antiphlogistic, analgesic, antipyretic injection preparation 失效
标题翻译：消炎止痛，解热注射制剂
公开(公告)号：US5554650A
公开(公告)日：1996-09-10
申请号：US281579
申请日：1994-07-28
申请人： Richard J. Holl , Thomas R. Tice , Laura L. Williams
发明人： Richard J. Holl , Thomas R. Tice , Laura L. Williams
IPC分类号： A61K9/107 , A61K31/196 , A61K31/135
CPC分类号： A61K31/196 , A61K9/1075
摘要： An antiphlogistic, analgesic, antipyretic parenteral preparation is disclosed comprising diclofenac, its salt, or both, a surfactant, cosurfactant, water, having a pH of 3-10, and optionally comprising an oily component, that can exhibit sustained therapeutic levels of diclofenac in plasma.
摘要翻译：公开了消炎止痛，解热肠胃外制剂，其包含双氯芬酸，其盐或两者，pH为3-10的表面活性剂，辅助表面活性剂，水，以及任选地包含油性组分，其可显示持续的治疗水平的双氯芬酸等离子体。

3. 发明申请

US20150157632A1 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） YL）苯基）-2,2,2-三氟乙基）嘧啶-4-基）苯基）丙酸酯
公开(公告)号：US20150157632A1
公开(公告)日：2015-06-11
申请号：US14619150
申请日：2015-02-11
申请人： Jinling CHEN , Matthew S. DEAVER , Richard J. HOLL , Kalyan NUGURU
发明人： Jinling CHEN , Matthew S. DEAVER , Richard J. HOLL , Kalyan NUGURU
IPC分类号： A61K31/506 , A61K9/28 , 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。

4. 发明申请

US20130172376A1 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） YL）苯基）-2,2,2-三氟乙基）嘧啶-4-基）苯基）丙酸酯
公开(公告)号：US20130172376A1
公开(公告)日：2013-07-04
申请号：US13652527
申请日：2012-10-16
申请人： Jinling CHEN , Matthew S. DEAVER , Richard J. HOLL , Kalyan NUGURU
发明人： Jinling CHEN , Matthew S. DEAVER , Richard J. HOLL , Kalyan NUGURU
IPC分类号： A61K31/506
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。

5. 发明授权

US08263108B2 Zero-order prolonged release coaxial implants 失效
标题翻译：零级延长释放同轴植入物
公开(公告)号：US08263108B2
公开(公告)日：2012-09-11
申请号：US10177997
申请日：2002-06-21
申请人： John W. Gibson , Arthur J. Tipton , Richard J. Holl , Stacey Meador
发明人： John W. Gibson , Arthur J. Tipton , Richard J. Holl , Stacey Meador
IPC分类号： A61F13/00 , A61F2/00
CPC分类号： A61K9/0002 , A61F2/02 , A61F2250/0067 , A61K9/0024
摘要： A coaxial implant has been developed using entirely biodegradable polymeric materials. As referred to herein, a coaxial implant is a device having a core containing drug, surrounded by a semi-permeable membrane that controls the rate of release of material from the core. The device is formed by extrusion, using a pre-milling and extruding step to maximize uniformity of drug dispersion within the polymeric material. In one embodiment, the polymer is processed to yield a semi-crystalline polymer, rather than an amorphous polymer. The core containing the drug and the polymer membrane(s) can be the same or different polymer. The polymer can be the same or different composition (i.e., both polycaprolactone, or both poly(lactide-co-glycolide) of different monomer ratios, or polycaprolactone outside of a core of poly(lactide)), of the same or different molecular weights, and of the same or different chemical structure (i.e., crystalline, semi-crystalline or amorphous). The core acts as a reservoir of drug, which partitions from the core polymer to form a saturated solution of at least 10% drug at the polymer membrane.
摘要翻译：已经开发了使用完全可生物降解的聚合材料的同轴植入物。如本文所提及的，同轴植入物是具有含核心的药物的装置，被半透膜隔断，半透膜控制材料从核心释放的速率。该装置通过挤出形成，使用预研磨和挤出步骤以最大化聚合物材料内药物分散的均匀性。在一个实施方案中，加工聚合物以产生半结晶聚合物，而不是无定形聚合物。含有药物和聚合物膜的核心可以是相同或不同的聚合物。聚合物可以具有相同或不同的组成（即，不同单体比的聚己内酯或聚（丙交酯 - 共 - 乙交酯）或聚（丙交酯）核心外的聚己内酯）具有相同或不同分子量，以及相同或不同的化学结构（即结晶，半结晶或无定形）。核心作为药物储存器，其与芯聚合物分隔开，以在聚合物膜上形成至少10％药物的饱和溶液。

6. 发明申请

US20110021583A1 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：US20110021583A1
公开(公告)日：2011-01-27
申请号：US12860978
申请日：2010-08-23
申请人： Richard J. Holl , Matthew Lentz
发明人： Richard J. Holl , Matthew Lentz
IPC分类号： A61K31/422 , A61K31/4045 , A61P25/06
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压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。

7. 发明申请

US20100080829A1 LYOPHILIZED PHARMACEUTICAL COMPOSITIONS AND METHODS OF MAKING AND USING SAME 审中-公开
公开(公告)号：US20100080829A1
公开(公告)日：2010-04-01
申请号：US12571809
申请日：2009-10-01
申请人： Claire Dulieu , Steve Durfee , Richard J. Holl , Tam Nguyen
发明人： Claire Dulieu , Steve Durfee , Richard J. Holl , Tam Nguyen
IPC分类号： A61K9/00 , A61K31/445 , A61K31/165 , A61K31/4164 , A61K31/439 , A61K31/404 , A61K31/135 , A61K38/08 , A61K38/16 , A61K38/28 , A61K38/02 , A61K31/337 , A61K47/36 , A61K47/26 , A61K47/30 , A61K47/34 , A61K47/38 , A61K47/12 , A61K47/14 , A61P43/00
CPC分类号： A61K31/135 , A61K9/006 , A61K9/19 , A61K9/2095 , A61K31/165 , A61K31/337 , A61K31/404 , A61K31/4164 , A61K31/439 , A61K31/445 , A61K38/00
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。

8. 发明授权

US06440493B1 Emulsion-based processes for making microparticles 有权
标题翻译：基于乳液的制备微粒的方法
公开(公告)号：US06440493B1
公开(公告)日：2002-08-27
申请号：US09726108
申请日：2000-11-29
申请人： John W. Gibson , Richard J. Holl , Arthur J. Tipton
发明人： John W. Gibson , Richard J. Holl , Arthur J. Tipton
IPC分类号： A61K916
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, and a second solvent that is totally or partially immiscible with the first solvent; 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：提供了制备微粒，优选含有活性剂的方法。在优选的实施方案中，该方法包括制备（1）在聚合物和第一溶剂的溶液中含有试剂的分散相; （2）含有表面活性剂的连续相和与第一溶剂完全或部分不混溶的第二溶剂; 和（3）作为聚合物的非溶剂的萃取相，连续相成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％〜25％之间，通过重量。然后，将分散相和连续相混合以形成乳液，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。通过蒸发处理步骤除去剩余的溶剂。乳化和溶剂去除步骤优选以连续方法进行。在蒸发之前的简单萃取步骤使得活性剂从微粒中的损失最小化，与其它基于萃取的方法相比，减少提取阶段所需的体积。还提供了交替乳化方法和溶剂去除方法，例如增量萃取，低温萃取或膜分离，并且可以以各种组合使用以制备微粒。

9. 发明授权

US06291013B1 Emulsion-based processes for making microparticles 有权
标题翻译：基于乳液的制备微粒的方法
公开(公告)号：US06291013B1
公开(公告)日：2001-09-18
申请号：US09303842
申请日：1999-05-03
申请人： John W. Gibson , Richard J. Holl , Arthur J. Tipton
发明人： John W. Gibson , Richard J. Holl , Arthur J. Tipton
IPC分类号： A61K916
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 continuous phase 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, such as nonstatic mixers or emulsion lag tube, 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：提供了制备微粒，优选含有活性剂的方法。在优选的实施方案中，该方法包括制备（1）在聚合物和第一溶剂的溶液中含有试剂的分散相; （2）含有表面活性剂的连续相，与第一溶剂完全或部分不混溶的第二溶剂和足够的第一溶剂使连续相饱和; 和（3）作为聚合物的非溶剂的萃取相，连续相成分的溶剂和第一溶剂的溶剂，其中连续相溶剂在萃取相中的溶解度为约0.1％〜25％重量。然后，将分散相和连续相混合以形成乳液，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。通过蒸发处理步骤除去剩余的溶剂。乳化和溶剂去除步骤优选以连续方法进行。在蒸发之前的简单萃取步骤使得活性剂从微粒中的损失最小化，与其它基于萃取的方法相比，减少提取阶段所需的体积。还提供了诸如非静态混合器或乳液滞后管的替代乳化方法和溶剂去除方法，例如增量提取，低温提取或膜分离，并且可以以各种组合使用以制备微粒。

10. 发明授权

US5747058A High viscosity liquid controlled delivery system 失效
标题翻译：高粘度液体控制输送系统
公开(公告)号：US5747058A
公开(公告)日：1998-05-05
申请号：US474337
申请日：1995-06-07
申请人： Arthur J. Tipton , Richard J. Holl
发明人： Arthur J. Tipton , Richard J. Holl
IPC分类号： A61K8/60 , A61K9/00 , A61K9/10 , A61K38/18 , A61K47/26 , A61L15/44 , A61L24/00 , A61L26/00 , A61L27/54 , A61L31/16 , A61Q11/00 , A61F2/02 , A61F6/06 , A61F9/02 , A61L9/04
CPC分类号： A61L31/16 , A61K47/26 , A61K8/60 , A61K9/0014 , A61K9/0019 , A61K9/0024 , A61L15/44 , A61L24/0015 , A61L26/0066 , A61L27/54 , A61Q11/00 , A61Q5/006 , A61L2300/602
摘要： A composition for the controlled release of substances is provided that includes: (i) a non-polymeric, non-water soluble liquid carrier material (HVLCM) of viscosity of at least 5,000 cP at 37.degree. C. that does not crystallize neat under ambient or physiological conditions; and (ii) a substance to be delivered.
摘要翻译：提供了用于控制释放物质的组合物，其包括：（i）在37℃下粘度为至少5,000cP的非聚合的非水溶性液体载体材料（HVLCM），其在环境下不结晶或生理条件; 和（ii）待送达的物质。

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