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    Method of treating dry eye disease with non-drying antihistamines
    1.
    发明授权
    Method of treating dry eye disease with non-drying antihistamines 失效
    用非干性抗组胺药治疗干眼病的方法

    公开(公告)号：US07247623B2

    公开(公告)日：2007-07-24

    申请号：US11503029

    申请日：2006-08-10

    申请人： Benjamin R. Yerxa ,  Jason L. Vittitow ,  John C. Ice, Jr.

    发明人： Benjamin R. Yerxa ,  Jason L. Vittitow ,  John C. Ice, Jr.

    IPC分类号： A61K31/55

    CPC分类号： A61K31/55 ,  Y10S514/912

    摘要： A method and preparation for reducing dry eye symptoms and promoting tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the eyes of the subject a non-drying antihistamine compound, such as epinastine hydrochloride, in an amount effective to reduce dry eye symptoms and stimulate tear fluid secretion. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the compound include topical administration via a liquid, gel, cream, or as part of a contact lens or a continuous or selective release device; 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： 公开了减少需要这种治疗的受试者的干眼症状和促进泪液分泌的方法和制剂。 所述方法包括以有效减少干眼症状并刺激泪液分泌的量向患者的眼睛施用非干燥的抗组胺药化合物，例如盐酸依诺斯汀。 还公开了药物制剂及其制备方法。 施用化合物的方法包括通过液体，凝胶，霜剂或作为隐形眼镜或连续或选择性释放装置的一部分的局部给药; 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。

    METHOD OF REDUCING CONTACT LENS INTOLERANCE WITH NON-DRYING ANTIHISTAMINES
    2.
    发明申请
    METHOD OF REDUCING CONTACT LENS INTOLERANCE WITH NON-DRYING ANTIHISTAMINES 审中-公开
    使用非干性抗生素降低接触镜片不透明度的方法

    公开(公告)号：US20130344139A1

    公开(公告)日：2013-12-26

    申请号：US14013794

    申请日：2013-08-29

    申请人： Benjamin R. Yerxa ,  Jason L. Vittitow ,  John C. Ice ,  Ramesh Krisnamoorthy

    发明人： Benjamin R. Yerxa ,  Jason L. Vittitow ,  John C. Ice ,  Ramesh Krisnamoorthy

    IPC分类号： A61K31/55

    CPC分类号： A61K31/55 ,  Y10S514/912

    摘要： A method and preparation for reducing dry eye symptoms and promoting tear secretion in a subject in need of such treatment is disclosed. The method is useful in treating dry eye diseases. The method is also useful in reducing contact lens intolerance in the eyes. The method comprises administering to the eyes of a subject in need thereof a non-drying antihistamine compound, such as epinastine hydrochloride, in an amount effective to reduce dry eye symptoms and stimulate tear fluid secretion. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the compound include topical administration via a liquid, gel, cream, or as part of a contact lens or a continuous or selective release device; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form, injectable, intra-operative instillation or suppository form.

    摘要翻译： 公开了减少需要这种治疗的受试者的干眼症状和促进泪液分泌的方法和制剂。 该方法可用于治疗干眼病。 该方法也可用于减少眼睛中的隐形眼镜不耐受。 该方法包括以有效减少干眼症状并刺激泪液分泌的量向有需要的受试者的眼睛施用非干燥的抗组胺药化合物，例如盐酸依诺斯汀。 还公开了药物制剂及其制备方法。 施用化合物的方法包括通过液体，凝胶，霜剂或作为隐形眼镜或连续或选择性释放装置的一部分的局部给药; 或通过鼻滴或喷雾进行全身给药，通过喷雾器或其他装置吸入，口服形式，可注射的，术中滴注或栓剂形式。

    Method of treating dry eye disease with purinergic receptor agonists
    6.
    发明授权
    Method of treating dry eye disease with purinergic receptor agonists 有权
    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。

    Dinucleoside polyphosphate compositions and their therapuetic use as purinergic receptor agonists
    7.
    发明授权
    Dinucleoside polyphosphate compositions and their therapuetic use as purinergic receptor agonists 失效
    二核苷多磷酸盐组合物及其治疗用作嘌呤能受体激动剂

    公开(公告)号：US06555675B2

    公开(公告)日：2003-04-29

    申请号：US09817017

    申请日：2001-03-23

    申请人： Janet Rideout ,  Benjamin R. Yerxa ,  Sammy Ray Shaver ,  James G. Douglass, III

    发明人： Janet Rideout ,  Benjamin R. Yerxa ,  Sammy Ray Shaver ,  James G. Douglass, III

    IPC分类号： C07H2100

    CPC分类号： A61K31/7084 ,  C07H19/04 ,  C07H19/20 ,  C07H21/00

    摘要： The present invention relates to certain novel dinucleotide polyphosphates of general Formulae I, II and III, and formulations thereof which are selective agonists of the P2Y purinergic receptors. They are useful in the prevention, management or treatment of diseases and disorders associated with abnormalities of tissue fluid secretion, hydration and clearance, including chronic obstructive pulmonary diseases (chronic bronchitis, PCD, cystic fibrosis, immobility-associated pneumonia), sinusitis, otitis media, nasolacrimal duct obstruction, dry eye disease, glaucoma, retinal degeneration, and edematous retinal disorders, including retinal detachment, vaginal dryness, and gastrointestinal tract disease. Finally, these novel dinucleotides may be useful for diagnostic purposes, such as the facilitation of sputum induction and expectoration for the analysis of respiratory tract secretions.

    摘要翻译： 本发明涉及通式I，II和III的某些新型二核苷酸多磷酸酯及其制剂，它们是P2Y嘌呤能受体的选择性激动剂。 它们可用于预防，管理或治疗与组织液分泌异常，水合和清除相关的疾病和病症，包括慢性阻塞性肺疾病（慢性支气管炎，PCD，囊性纤维化，不动性相关性肺炎），鼻窦炎，中耳炎 ，鼻泪管阻塞，干性眼病，青光眼，视网膜变性和水肿性视网膜病变，包括视网膜脱离，阴道干燥和胃肠道疾病。 最后，这些新型二核苷酸可用于诊断目的，例如促进痰诱导和咳痰分析呼吸道分泌物。

    Method of treating ciliary dyskinesia with uridine triphosphates and related compounds
    8.
    发明授权
    Method of treating ciliary dyskinesia with uridine triphosphates and related compounds 失效
    用尿苷三磷酸和相关化合物治疗睫状肌运动障碍的方法

    公开(公告)号：US06420347B1

    公开(公告)日：2002-07-16

    申请号：US09101840

    申请日：1998-07-17

    申请人： Karla M. Jacobus ,  Benjamin R. Yerxa ,  William Pendergast ,  Richard C. Boucher, Jr. ,  Janet L. Rideout ,  David J. Drutz ,  Michael K. James ,  Monroe Jackson Stutts ,  Cary Geary ,  Edwardo R. Lazarowski

    发明人： Karla M. Jacobus ,  Benjamin R. Yerxa ,  William Pendergast ,  Richard C. Boucher, Jr. ,  Janet L. Rideout ,  David J. Drutz ,  Michael K. James ,  Monroe Jackson Stutts ,  Cary Geary ,  Edwardo R. Lazarowski

    IPC分类号： A61K3170

    CPC分类号： A61K31/70

    摘要： A method of stimulating ciliary beat frequency in a subject in need of such treatment is disclosed. The method comprises administering to the airways, ears, eyes, or genito-urinary tract of the subject a triphosphate nucleotide such as uridine 5′-triphosphate (UTP), an analog of UTP, or any other analog, in an amount effective to stimulate ciliary beat frequency. This method is useful for treating patients afflicted with ciliary dyskinesia, Kartagener's syndrome, or any other disease involving dysfunction of ciliary movement, such as male infertility caused by impairment of propulsion of the spermatozoa or immune deficiency caused by impairment of ciliary movement in neutrophils or macrophages. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include any liquid suspension (including nasal spray or nasal or eye drops), oral, inhaled by nebulization, topical, injected, suppository, intra-operative by instillation or application, or ex vivo direct application to spermatozoa.

    摘要翻译： 公开了一种在需要这种治疗的受试者中刺激睫状肌搏动频率的方法。 该方法包括向受试者的气道，耳朵，眼睛或生殖泌尿道施用有效刺激的量的三磷酸核苷酸，例如尿苷5'-三磷酸（UTP），UTP类似物或任何其它类似物 睫毛拍频。 该方法可用于治疗患有睫状肌运动障碍，Kartagener综合征或涉及睫状肌运动功能障碍的任何其他疾病，例如由嗜中性粒细胞或巨噬细胞的睫状肌运动损伤引起的精子推进或免疫缺陷引起的男性不育症 。 还公开了药物制剂及其制备方法。 给药方法包括任何液体悬浮液（包括鼻喷雾或鼻腔或滴眼液），口服，通过雾化吸入，局部注射，注射，栓剂，通过滴注或施用手术，或离体直接施用于精子。

    Di(uridine 5′-)tetraphosphate and salts thereof
    9.
    发明授权
    Di(uridine 5′-)tetraphosphate and salts thereof 有权
    二（尿苷5' - ）四磷酸及其盐

    公开(公告)号：US07939510B2

    公开(公告)日：2011-05-10

    申请号：US12430684

    申请日：2009-04-27

    申请人： Benjamin R. Yerxa ,  Edward G. Brown

    发明人： Benjamin R. Yerxa ,  Edward G. Brown

    IPC分类号： A61K31/70

    CPC分类号： A61K31/7048 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  Y10S514/851

    摘要： The present invention are directed to P1,P4-di(uridine 5′-)tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1,P4-di(uridine 5′-)tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1,P4-di(uridine 5′-)tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.

    摘要翻译： 本发明涉及P1，P4-二（尿苷5'-）四磷酸盐，四碱金属盐如四钠，四锂，四钾及其混合四碱金属阳离子。 P1，P4-二（尿苷5' - ）四磷酸的四碱金属盐是水溶性的，无毒的，在制造过程中易于处理。 这些四价一价碱金属盐比单 - ，二 - 或三 - 酸盐更耐水解，因此，它们提供了改进的稳定性和更长的储存期限。 本发明还提供了合成P1，P4-二（尿苷5' - ）四磷酸及其药学上可接受的盐的方法，并且证明了对大量生产的适用性。 所述方法基本上减少了合成二脯氨酸四磷酸酯所需的时间，例如为3天或更短。

    METHOD OF INCREASING TEAR PRODUCTION WITH PURINERGIC RECEPTOR AGONISTS
    10.
    发明申请
    METHOD OF INCREASING TEAR PRODUCTION WITH PURINERGIC RECEPTOR AGONISTS 有权
    增加与纯化受体激动剂进行生产的方法

    公开(公告)号：US20100330164A1

    公开(公告)日：2010-12-30

    申请号：US12825051

    申请日：2010-06-28

    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： A61K31/7076 ,  A61K31/7072 ,  A61K9/127 ,  A61P27/04

    CPC分类号： C07H19/10 ,  A61K9/0048 ,  A61K31/7084 ,  A61K45/06 ,  C07H19/20 ,  C07H21/00 ,  Y10S514/912 ,  Y10S514/915

    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。