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    METHOD OF INCREASING TEAR PRODUCTION WITH PURINERGIC RECEPTOR AGONISTS
    13.
    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。

    Method of treating dry eye disease with purinergic receptor agonists
    14.
    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：US07759322B2

    公开(公告)日：2010-07-20

    申请号：US11821091

    申请日：2007-06-20

    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： A01N43/04 ,  A61K31/70

    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。

    Method of treating lung diseases with uridine 5′-diphosphate and analogs thereof
    15.
    发明授权
    Method of treating lung diseases with uridine 5′-diphosphate and analogs thereof 有权
    用尿苷5'-二磷酸治疗肺部疾病的方法及其类似物

    公开(公告)号：US06451288B1

    公开(公告)日：2002-09-17

    申请号：US09645161

    申请日：2000-08-24

    申请人： Richard C. Boucher, Jr. ,  Sammy Ray Shaver ,  William Pendergast ,  Benjamin Yerxa ,  Janet L. Rideout ,  Robert Dougherty ,  Dallas Croom

    发明人： Richard C. Boucher, Jr. ,  Sammy Ray Shaver ,  William Pendergast ,  Benjamin Yerxa ,  Janet L. Rideout ,  Robert Dougherty ,  Dallas Croom

    IPC分类号： A61K912

    CPC分类号： A61K31/7068 ,  A61K9/0073 ,  A61K31/7072 ,  A61K45/06 ,  C07H19/10 ,  Y10S514/826 ,  Y10S514/851 ,  A61K2300/00

    摘要： Compounds of Formula I: wherein: X1, and X2 are each independently either O− or S−; X3 and X4 are each independently either —H or —OH, with the proviso that X3 and X4 are not simultaneously —H; R1 is selected from the group consisting of O, imido, methylene and dihalomethylene; R2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido; R3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; and R4 is selected from the group consisting of —OR′, —SR′, —NR′, and —NR′R″, wherein R′ and R″ are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R′ is absent when R4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.

    摘要翻译： 式I化合物：其中：X 1和X 2各自独立地为O-或S-; X 3和X 4各自独立地为-H或-OH，条件是X 3和X 4不同时为-H; R 1为选自 由O，亚氨基，亚甲基和二卤代亚甲基组成的组; R 2选自H，卤素，烷基，取代的烷基，烷氧基，硝基和叠氮基; R 3选自H，烷基，酰基， 芳基和芳基烷基; 和R 4选自-OR'，-SR'，-NR'和-NR'R“，其中R'和R”独立地选自H，烷基，取代的烷基， 芳基，取代的芳基，芳基烷基，烷氧基和芳氧基，条件是当R4与氧或硫原子双键连接到嘧啶环的4位上的碳时，R'不存在，用于水合 肺粘液分泌物和治疗肺部疾病如囊性纤维化，呼吸机相关肺炎，慢性支气管炎，慢性阻塞性肺病和原发性纤毛运动障碍。 还描述了含有式I化合物和式I的新化合物的药物组合物。

    Method of promoting mucosal hydration with certain uridine, adenine and cytidine diphosphates and analogs thereof
    16.
    发明授权
    Method of promoting mucosal hydration with certain uridine, adenine and cytidine diphosphates and analogs thereof 失效
    用某些尿苷，腺嘌呤和胞苷二磷酸及其类似物促进粘膜水合的方法

    公开(公告)号：US06331529B1

    公开(公告)日：2001-12-18

    申请号：US09512867

    申请日：2000-02-25

    申请人： Benjamin R. Yerxa ,  Janet L. Rideout ,  Arthur C. Jones

    发明人： Benjamin R. Yerxa ,  Janet L. Rideout ,  Arthur C. Jones

    IPC分类号： A61K3170

    CPC分类号： A61K31/7064 ,  A61K31/7048 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  Y10S514/912

    摘要： A method and preparation for the stimulation of mucosal hydration in a subject in need of such treatment is disclosed. The method comprises administering to the mucosal surfaces of the subject a purinergic receptor agonist such as uridine 5′-diphosphate (UDP), dinucleotides, cytidine 5′-diphosphate (CDP), adenosine 5′-diphosphate (ADP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate mucin secretion. 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. A method for facilitating the expectoration of sputum for the purpose of detecting cellular abnormalities indicative of lung disease is also disclosed.

    摘要翻译： 公开了在需要这种治疗的受试者中刺激粘膜水合的方法和制备方法。 该方法包括向受试者的粘膜表面施用嘌呤能受体激动剂如尿苷5'-二磷酸（UDP），二核苷酸，胞苷5'-二磷酸（CDP），腺苷5'-二磷酸（ADP）或其治疗上有用的 类似物和衍生物，有效刺激粘蛋白分泌的量。 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。 还公开了为了检测指示肺部疾病的细胞异常的目的而促进痰吐出的方法。

    Therapeutic dinucleotide and derivatives
    17.
    发明授权
    Therapeutic dinucleotide and derivatives 失效
    治疗二核苷酸和衍生物

    公开(公告)号：US06323187B1

    公开(公告)日：2001-11-27

    申请号：US09316571

    申请日：1999-05-21

    申请人： Benjamin R. Yerxa ,  William Pendergast ,  Janet L. Rideout ,  Maryse Picher ,  Richard C. Boucher, Jr. ,  M. Jackson Stutts

    发明人： Benjamin R. Yerxa ,  William Pendergast ,  Janet L. Rideout ,  Maryse Picher ,  Richard C. Boucher, Jr. ,  M. Jackson Stutts

    IPC分类号： A01N4304

    CPC分类号： A61K31/7048 ,  A61K31/70 ,  C07H19/207 ,  C07H21/00

    摘要： The present invention relates to P1-(cytidine 5′-)-P-(uridine 5′-)tetraphosphates and its salts, esters and amides, and formulations thereof which are highly stable and selective agonists of the P2Y2 and/or P2Y4 purinergic receptor. The compounds of the invention are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, primary ciliary dyskinesia, cystic fibrosis, as well as prevention of pneumonia due to immobility, and the induction of sputum and its expectoration. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis and otitis media.

    摘要翻译： 本发明涉及P2Y2和/或P2Y4嘌呤能受体的高度稳定和选择性激动剂的P1-（胞苷5' - ） - （ - 尿苷5' - ）四磷酸及其盐，酯和酰胺及其制剂 。 本发明的化合物可用于治疗慢性阻塞性肺疾病如慢性支气管炎，原发性纤毛运动障碍，囊性纤维化，以及预防由于不动的肺炎，以及诱导痰及其咳痰。 此外，由于它们具有清除保留的粘液分泌物和刺激睫状肌搏动频率的一般能力，本发明的化合物也可用于治疗鼻窦炎和中耳炎。

    Method of promoting cervical and vaginal secretions
    18.
    发明授权
    Method of promoting cervical and vaginal secretions 有权
    促进子宫颈和阴道分泌物的方法

    公开(公告)号：US07432252B1

    公开(公告)日：2008-10-07

    申请号：US09531851

    申请日：2000-03-20

    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： A61K31/70

    CPC分类号： C07H21/00

    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。