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1. 发明授权

US08604205B2 Cytoskeletal active rho kinase inhibitor compounds, composition and use 有权
标题翻译：细胞骨架活性激酶抑制剂化合物，组成和用途
公开(公告)号：US08604205B2
公开(公告)日：2013-12-10
申请号：US13614641
申请日：2012-09-13
申请人： John W. Lampe , Paul S. Watson , David J. Slade , Ward M. Peterson , Christopher S. Crean , Jason L. Vittitow , Jonathan Bryan DeCamp , Nicholas F. Pelz
发明人： John W. Lampe , Paul S. Watson , David J. Slade , Ward M. Peterson , Christopher S. Crean , Jason L. Vittitow , Jonathan Bryan DeCamp , Nicholas F. Pelz
IPC分类号： C07D211/32 , A01N43/40
CPC分类号： C07D401/12 , A61F9/00781 , A61K9/0048 , C07D401/14 , C07D403/12 , C07D405/14 , C07D409/14 , C07D413/12 , C07D413/14
摘要： The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.
摘要翻译：本发明涉及作为rho相关蛋白激酶抑制剂的合成细胞骨架活性化合物。本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。本发明另外涉及预防或治疗与细胞骨架重组相关的疾病或病症的方法。在本发明的一个实施方案中，该方法治疗增加的眼内压，例如原发性开角型青光眼。该方法包括向受试者施用治疗有效量的式I或式II的细胞骨架活性化合物，其中所述量可有效影响肌动球蛋白相互作用，例如通过导致细胞松弛和细胞粘附的变化。

2. 发明授权

US08207195B2 Method for treating neurological and neuropathic diseases using rho kinase inhibitor compounds 失效
标题翻译：使用rho激酶抑制剂化合物治疗神经和神经病变的方法
公开(公告)号：US08207195B2
公开(公告)日：2012-06-26
申请号：US12492848
申请日：2009-06-26
申请人： Tomas Navratil , John W. Lampe , Emilee H. Fulcher , Ward M. Peterson
发明人： Tomas Navratil , John W. Lampe , Emilee H. Fulcher , Ward M. Peterson
IPC分类号： A61K31/47 , A61K31/415 , A61K31/40
CPC分类号： A61K31/4245 , A61K9/0019 , A61K9/007 , A61K31/437 , A61K31/454 , A61K31/4709 , A61K31/497 , A61K31/506 , A61K31/5377 , A61K31/55
摘要： This invention is directed to methods of preventing or treating neurological or neuropathic diseases or conditions associated with excessive inflammation, neurodegeneration, neuro-remodeling, and axonal/neurite retraction. Particularly, this invention relates to methods treating neurological or neuropathic diseases such as cerebral ischemia, stroke, neuropathic pain, spinal cord injury, Alzheimer's disease, and multiple sclerosis, using novel rho kinase inhibitor compounds. The method comprises identifying a subject in need of the treatment, and administering to the subject an effective amount of a novel rho kinase inhibitor compound to treat the disease.
摘要翻译：本发明涉及预防或治疗与过度炎症，神经变性，神经重塑和轴突/神经突回缩有关的神经病学或神经病学疾病或病症的方法。特别地，本发明涉及使用新的rho激酶抑制剂化合物治疗神经病学或神经病学疾病如脑缺血，中风，神经性疼痛，脊髓损伤，阿尔茨海默病和多发性硬化的方法。该方法包括鉴定需要治疗的受试者，并向受试者施用有效量的新型rho激酶抑制剂化合物以治疗该疾病。

3. 发明申请

US20120000941A1 MEDICINE DISPENSER 审中-公开
标题翻译：医药分配器
公开(公告)号：US20120000941A1
公开(公告)日：2012-01-05
申请号：US12826951
申请日：2010-06-30
申请人： Ramesh Krishnamoorthy , Timothy S. Hansen
发明人： Ramesh Krishnamoorthy , Timothy S. Hansen
IPC分类号： B65D37/00
CPC分类号： B65D23/04 , A61F9/0008 , B65D1/0223 , B65D1/0261 , B65D1/32
摘要： A medicine dispenser is provided. The dispenser includes a container having a spout on a first end thereof for dispensing a medicine and defining a generally elongate base on a second end thereof. The base has a width greater than a width of the spout and further defines a sidewall having a pair of opposing sidewall portions that have generally continuous biconvex cross-sections and extend from respective wide ends of the spout and the base. The dispenser is configured for dispensing medicines of a high viscosity.
摘要翻译：提供药物分配器。分配器包括在其第一端具有喷口的容器，用于分配药物并在其第二端上限定大致细长的基部。底座具有大于喷口宽度的宽度，并且进一步限定具有一对相对的侧壁部分的侧壁，该侧壁部分具有大体上连续的双凸面并且从喷嘴和基部的相应宽的端部延伸。分配器被配置用于分配高粘度的药物。

4. 发明授权

US08071779B2 Cytoskeletal active rho kinase inhibitor compounds, composition and use 有权
标题翻译：细胞骨架活性激酶抑制剂化合物，组成和用途
公开(公告)号：US08071779B2
公开(公告)日：2011-12-06
申请号：US11958214
申请日：2007-12-17
申请人： John W. Lampe , Paul S. Watson , David J. Slade , Ward M. Peterson , Christopher S. Crean , Jason L. Vittitow , Jonathan Bryan DeCamp , Nicholas F. Pelz
发明人： John W. Lampe , Paul S. Watson , David J. Slade , Ward M. Peterson , Christopher S. Crean , Jason L. Vittitow , Jonathan Bryan DeCamp , Nicholas F. Pelz
IPC分类号： C07D211/32 , C07D231/56
CPC分类号： C07D401/12 , A61F9/00781 , A61K9/0048 , C07D401/14 , C07D403/12 , C07D405/14 , C07D409/14 , C07D413/12 , C07D413/14
摘要： The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.
摘要翻译：本发明涉及作为rho相关蛋白激酶抑制剂的合成细胞骨架活性化合物。本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。本发明另外涉及预防或治疗与细胞骨架重组相关的疾病或病症的方法。在本发明的一个实施方案中，该方法治疗增加的眼内压，例如原发性开角型青光眼。该方法包括向受试者施用治疗有效量的式I或式II的细胞骨架活性化合物，其中所述量可有效影响肌动球蛋白相互作用，例如通过导致细胞松弛和细胞粘附的变化。

5. 发明授权

US07749981B2 Drug-eluting stents coated with non-nucleotide P2Y12 receptor antagonist compound 失效
标题翻译：涂有非核苷酸P2Y12受体拮抗剂化合物的药物洗脱支架
公开(公告)号：US07749981B2
公开(公告)日：2010-07-06
申请号：US11267941
申请日：2005-11-04
申请人： José L. Boyer , James G. Douglass, III , Sammy R. Shaver
发明人： José L. Boyer , James G. Douglass, III , Sammy R. Shaver
IPC分类号： A01N43/04 , A61K31/70
CPC分类号： A61K31/519 , A61F2/82 , A61F2250/0067 , A61K31/52 , A61K31/522 , A61K31/7076 , A61K31/727 , A61K45/06 , A61K2300/00
摘要： The present invention provides a drug-eluting stent, wherein the stent is coated with one or more non-nucleotide P2Y12 receptor antagonist compounds or a pharmaceutically acceptable salt, solvate, or hydrate thereof. When the stent is placed in a narrowed or damaged arterial vessel, a therapeutically effective amount of the P2Y12 receptor antagonist compound is eluted continuously from the stent to the local environment of the stent. The P2Y12 receptor antagonist compound-eluting stents are useful in preventing thrombosis and restenosis, and are effective in inhibiting the contraction of vascular smooth muscle cells, inhibiting cell proliferation, and reducing inflammation.
摘要翻译：本发明提供一种药物洗脱支架，其中支架涂覆有一种或多种非核苷酸P2Y12受体拮抗剂化合物或其药学上可接受的盐，溶剂合物或水合物。当支架置于狭窄或损伤的动脉血管中时，将治疗有效量的P2Y12受体拮抗剂化合物从支架连续洗脱至支架的局部环境。 P2Y12受体拮抗剂化合物洗脱支架可用于预防血栓形成和再狭窄，并且有效抑制血管平滑肌细胞的收缩，抑制细胞增殖和减少炎症。

6. 发明授权

US07504497B2 Orally bioavailable compounds and methods for inhibiting platelet aggregation 失效
标题翻译：口服生物可利用的化合物和抑制血小板聚集的方法
公开(公告)号：US07504497B2
公开(公告)日：2009-03-17
申请号：US11595837
申请日：2006-11-09
申请人： James G. Douglass, III , Paul S. Watson , Carl A. Samuelson , Christopher S. Crean
发明人： James G. Douglass, III , Paul S. Watson , Carl A. Samuelson , Christopher S. Crean
IPC分类号： C07H19/16 , A01N43/04 , A61K31/70
CPC分类号： A61K31/519 , A61F2250/0067 , A61K31/52 , A61K31/522 , A61K31/7076 , A61K31/727 , A61K45/06 , C07H19/16 , A61K2300/00
摘要： This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis or related disorders. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a non-nucleotide compound, preferably a P2Y12 receptor antagonist compound, wherein said amount is effective to inhibit platelet aggregation. The compounds useful for this invention include compounds of general Formulae III, IIIa, and IIIb, or salts, hydrates, and solvates thereof. The present invention also provides novel compounds of Formulae IIIa and IIIb, which are potent and have a good oral bioavailability.
摘要翻译：本发明涉及一种预防或治疗与血小板聚集有关的疾病或病症的方法。该方法还涉及治疗血栓形成或相关病症的方法。该方法包括向受试者施用包含有效量的非核苷酸化合物，优选P2Y12受体拮抗剂化合物的药物组合物，其中所述量有效抑制血小板聚集。可用于本发明的化合物包括通式III，IIIa和IIIb的化合物，或其盐，水合物和溶剂化物。本发明还提供新的式IIIa和IIIb化合物，它们是有效的并且具有良好的口服生物利用度。

7. 发明申请

US20080214490A1 METHOD OF PROMOTING CERVICAL AND VAGINAL SECRETIONS 审中-公开
标题翻译：促进宫颈和阴道分泌的方法
公开(公告)号：US20080214490A1
公开(公告)日：2008-09-04
申请号：US12043845
申请日：2008-03-06
申请人： William Pendergast , Sammy Ray Shaver , David J. Drutz , Janet L. Rideout , Benjamin R. Yerxa
发明人： William Pendergast , Sammy Ray Shaver , David J. Drutz , Janet L. Rideout , Benjamin R. Yerxa
IPC分类号： A61K31/7076 , A61P15/02
CPC分类号： C07H21/00 , A61K31/00
摘要： The present invention provides a method of stimulating cervical and vaginal secretions in a mammal by treatment with P2Y2 and/or P2Y4 purinergic receptor agonists. Treatment of vaginal dryness associated with menopause, chemotherapy, and various disease states as well as the treatment of vulvar pain is discussed. Suitable agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.
摘要翻译：本发明提供了通过用P2Y2和/或P2Y4N4嘌呤能受体激动剂治疗来刺激哺乳动物的宫颈和阴道分泌物的方法。讨论了与绝经，化疗和各种疾病状态相关的阴道干燥的治疗以及外阴疼痛的治疗。公开了合适的激动剂，例如UTP，CTP，ATP，二核苷酸及其类似物。

8. 发明授权

US07084128B2 Method for reducing intraocular pressure 失效
公开(公告)号：US07084128B2
公开(公告)日：2006-08-01
申请号：US10347255
申请日：2003-01-15
申请人： Benjamin R. Yerxa , Robert Plourde, Jr. , Edward G. Brown , Ward M. Peterson
发明人： Benjamin R. Yerxa , Robert Plourde, Jr. , Edward G. Brown , Ward M. Peterson
IPC分类号： A61K31/70 , C07H21/00
CPC分类号： C07H19/20 , Y10S514/912 , Y10S514/913
摘要： The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a purinerginic receptor ligand, which is a mononucleoside polyphosphate or dinucleoside polyphosphate defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with other therapeutic agents or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure.

9. 发明授权

US06921755B2 Method of treating dry eye disease with purinergic receptor agonists 有权
标题翻译：用嘌呤能受体激动剂治疗干眼病的方法
公开(公告)号：US06921755B2
公开(公告)日：2005-07-26
申请号：US10010055
申请日：2001-11-09
申请人： Benjamin R. Yerxa , Karla M. Jacobus , William Pendergast , Janet L. Rideout
发明人： Benjamin R. Yerxa , Karla M. Jacobus , William Pendergast , Janet L. Rideout
IPC分类号： A61K45/06 , A61K31/70
CPC分类号： A61K45/06 , Y10S514/912
摘要： A method and preparation for the stimulation of tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5′-triphosphate (UTP), dinucleotides, cytidine 5′-triphosphate (CTP), adenosine 5′-triphosphate (ATP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.
摘要翻译：公开了用于刺激需要这种治疗的受试者的泪液分泌的方法和制剂。该方法包括向受试者的眼表面施用嘌呤能受体激动剂如尿苷5'-三磷酸（UTP），二核苷酸，胞苷5'-三磷酸（CTP），腺苷5'-三磷酸（ATP）或其治疗上有用的类似物和衍生物，其量有效地刺激泪液分泌并增强泪液系统的引流。还公开了药物制剂及其制备方法。施用该方法的方法将包括：通过液体，凝胶，霜剂或作为隐形眼镜或选择性释放膜的一部分局部给药; 或通过鼻滴或喷雾进行全身给药，通过喷雾器或其它装置吸入，口服形式（液体或丸剂），可注射的，术中滴注或栓剂形式。

10. 发明授权

US5972904A Method of treating sinusitis with uridine triphosphates and related compounds 失效
公开(公告)号：US5972904A
公开(公告)日：1999-10-26
申请号：US4786
申请日：1998-01-09
申请人： Karla Jacobus , Janet Rideout , Ben Yerxa , William Pendergast , Suhaib Siddiqi , David Drutz
发明人： Karla Jacobus , Janet Rideout , Ben Yerxa , William Pendergast , Suhaib Siddiqi , David Drutz
IPC分类号： C07H19/067 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61P11/02 , A61P43/00 , C07H19/10 , C07H19/167 , C07H19/20 , A61K31/70
CPC分类号： A61K31/7048 , A61K31/7068 , A61K31/7072 , A61K31/7076 , C07H19/10 , C07H19/20
摘要： A method of promoting drainage of congested mucous secretions in the sinuses of a subject in need of such treatment is disclosed. The method comprises administering to the sinuses of the subject a uridine phosphate such as uridine 5'-triphosphate (UTP) or P.sup.1,P.sup.4 -di(uridine-5') tetraphosphate (U.sub.2 P.sub.4), an analog of UTP, or any other analog, in an amount effective to promote drainage of congested fluid in the sinuses by hydrating mucous secretions or by stimulating ciliary beat frequency in the sinuses. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include any liquid suspension (including nasal drops or spray), oral form (liquid or pill), aerosol inhalation, powder form, topical, injected, intra-operative instillation or suppository form.

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