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。

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。

公开(公告)号：US06703376B2

公开(公告)日：2004-03-09

申请号：US09202825

申请日：1998-12-22

申请人： Karla M. Jacobus ,  H. Jeff Leighton

发明人： Karla M. Jacobus ,  H. Jeff Leighton

IPC分类号： A61K3152

CPC分类号： A61K31/7076 ,  A61K31/7072 ,  Y10S514/849 ,  Y10S514/851 ,  Y10S514/853 ,  Y10S514/855

摘要： A method of promoting drainage of mucous secretions in the congested airways of a bedridden/immobilized patient or an intubated/mechanically-ventilated patient is disclosed. The method comprises administering to the airways of the patient a uridine phosphate such as uridine 5′-triphsophate(UTP) or P1,P4-di(uridine-5′) tetraphosphate, an analog of UTP, or any other analog, in an amount effective to promote drainage of fluid in the congested airways, including sinuses, to create the ciliary beat frequency of cilia on the surface lumina epithelia cells, to increase the secretions of mucous by goblet cells and to promote the clearance of retained secretions by hydrating mucous secretions, by stimulating ciliary beat frequency in the airways and by stimulating surfactant production. 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 eye drops or spray), oral form (liquid or pill), aerosol inhalation, powder form, topical, injected, intra-operative installation or suppository form.

摘要翻译： 公开了一种促进卧床/固定化患者或插管/机械通气患者的拥挤气道中的粘液分泌物排泄的方法。 该方法包括向患者的气道施用尿苷磷酸盐，例如尿苷5'-三磷酸（UTP）或P1，P4-二（尿苷-5'）四磷酸，UTP类似物或任何其它类似物，其量为 有效地促进包括鼻窦在内的拥挤气道中的流体排出，以在表面腔上皮细胞上产生纤毛的睫毛拍频，增加杯状细胞粘液的分泌，并通过保湿粘液分泌物促进保留的分泌物的清除 通过刺激气道中的睫状肌搏动频率和刺激表面活性剂生成。 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（包括滴鼻剂或滴眼剂或喷雾剂），口服剂型（液体或药丸），气雾剂吸入剂，粉末形式，局部用药，注射用药，术中安装或栓剂形式。

公开(公告)号：US08097600B2

公开(公告)日：2012-01-17

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： 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。

公开(公告)号：US06887858B1

公开(公告)日：2005-05-03

申请号：US09171169

申请日：1998-02-06

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： A61K9/06 ,  A61K9/00 ,  A61K9/08 ,  A61K9/10 ,  A61K9/12 ,  A61K9/127 ,  A61K9/14 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/7084 ,  A61K45/06 ,  A61K47/02 ,  A61K47/14 ,  A61K47/26 ,  A61K47/32 ,  A61K47/34 ,  A61K47/36 ,  A61P27/02 ,  A61P27/04 ,  C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  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。

公开(公告)号：US6159952A

公开(公告)日：2000-12-12

申请号：US744367

申请日：1996-11-07

申请人： Christy L. Shaffer ,  Richard C. Boucher ,  Janet L. Rideout ,  Karla M. Jacobus

发明人： Christy L. Shaffer ,  Richard C. Boucher ,  Janet L. Rideout ,  Karla M. Jacobus

IPC分类号： C07H19/10 ,  A61K20060101 ,  A61K9/08 ,  A61K9/10 ,  A61K9/12 ,  A61K31/70 ,  A61K31/7024 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/7084 ,  A61P11/00 ,  A61P11/10 ,  A61P11/12 ,  C07D473/00 ,  C07H19/20 ,  C07H19/207

CPC分类号： A61K31/7076 ,  A61K31/7072

摘要： A method of promoting clearance of retained mucous secretions in the bronchi, bronchioles and small terminal airways of a subject in need of such treatment is disclosed. The method comprises administering to the bronchi 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 mucociliary clearance and/or cough clearance of retained fluid in the bronchi, bronchioles and small terminal airways. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: aerosol inhalation, any liquid suspension (including nasal drops or spray), oral form (liquid or pill), injected, intra-operative instillation or suppository form.

摘要翻译： 公开了一种促进需要这种治疗的受试者的支气管，细支气管和小型终端气道中保留的粘液分泌物的清除的方法。 该方法包括向受试者的支气管施用尿苷磷酸酯，例如尿苷5'-三磷酸（UTP）或P1，P4-二（尿苷-5'）四磷酸（U2P4），UTP的类似物或任何其它类似物 ，有效促进支气管，细支气管和小型终端气道中保留液体的粘膜纤毛清除和/或咳嗽清除。 还公开了药物制剂及其制备方法。 给药方法包括：气雾剂吸入，任何液体悬浮液（包括滴鼻剂或喷雾剂），口服形式（液体或药丸），注射液，术中滴注或栓剂形式。

公开(公告)号：US5968913A

公开(公告)日：1999-10-19

申请号：US996740

申请日：1997-12-23

申请人： Karol K. LaCroix ,  Christy L. Shaffer ,  Karla M. Jacobus ,  Janet L. Rideout ,  David J. Drutz ,  Richard C. Evans ,  William Pendergast

发明人： Karol K. LaCroix ,  Christy L. Shaffer ,  Karla M. Jacobus ,  Janet L. Rideout ,  David J. Drutz ,  Richard C. Evans ,  William Pendergast

IPC分类号： A61K9/00 ,  A61K9/08 ,  A61K9/72 ,  A61K31/70 ,  A61K31/7072 ,  A61K47/02 ,  A61P43/00

CPC分类号： A61K9/0078 ,  A61K31/7072 ,  A61K47/02 ,  A61K9/08

摘要： Novel pharmaceutical compositions of uridine 5'-triphosphate (UTP) for use in promoting increased mucociliary clearance of retained mucous secretions of the human airways, middle/inner ears or sinuses are disclosed. Novel Formulation I comprises UTP and aqueous solution having a therapeutic concentration between 5 and 45 mg/mL, a controlled tonicity within the range of 250 to 100 mOsM, a pH between 7.0 and 7.5, and is sterile. The pH-adjusted composition is capable of long-term storage in the refrigerated state with a shelf life of up to 30 months. Formulation I may be delivered therapeutically either in a nebulized form or in a liquid form. Novel Formulation II comprises UTP in an aqueous solution or suspension having a therapeutic concentration approaching the limit of UTP's solubility at ambient temperature. This high concentration allows delivery of a therapeutic amount of UTP in very small volumes (50 to 100 .mu.L) suitable for administration via portable hand-held devices such as metered dose inhalers. Formulation II has extended shelf life without the need for refrigeration after being dispensed to the patient.

摘要翻译： 公开了用于促进对人气道，中耳/内耳或窦的保留的粘液分泌物的增加的粘膜纤毛清除的尿苷5'-三磷酸（UTP）的新型药物组合物。 新型制剂I包括治疗浓度为5至45mg / mL的UTP和水溶液，在250至100mOsM范围内的控制张力度，7.0至7.5之间的pH，并且是无菌的。 经pH调节的组合物能够在冷藏状态下长期储存，保质期长达30个月。 制剂I可以以雾化形式或液体形式治疗性递送。 新型制剂II包含在具有接近UTP在环境温度下的溶解度的极限的治疗浓度的水溶液或悬浮液中的UTP。 这种高浓度允许以非常小的体积（50至100μL）递送治疗量的UTP，其适用于经由便携式手持式装置例如计量吸入器的给药。 制剂II具有延长的保存期限，而不需要在分配给患者后进行制冷。

公开(公告)号：US06916794B2

公开(公告)日：2005-07-12

申请号：US10041826

申请日：2002-01-03

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： A61K9/06 ,  A61K9/00 ,  A61K9/08 ,  A61K9/10 ,  A61K9/12 ,  A61K9/127 ,  A61K9/14 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/7084 ,  A61K45/06 ,  A61K47/02 ,  A61K47/14 ,  A61K47/26 ,  A61K47/32 ,  A61K47/34 ,  A61K47/36 ,  A61P27/02 ,  A61P27/04 ,  C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  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。

公开(公告)号：US06673779B2

公开(公告)日：2004-01-06

申请号：US10163804

申请日：2002-06-05

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 ,  Cara Geary ,  Eduardo 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 ,  Cara Geary ,  Eduardo R. Lazarowski

IPC分类号： A61K3170

CPC分类号： A61K31/7076 ,  A61K9/0048 ,  A61K31/70 ,  A61K31/7072 ,  C07H19/10 ,  C07H19/20 ,  C07H21/00

摘要： The present invention is directed to a method of stimulating ciliary beat frequency to promote mucociliary or cough clearance of retained mucus secretions from the lungs, sinuses, upper airways, ears, eyes, genito-urinary tract, spermatozoa, ovaries, fallopian tubes, neutrophils, and macrophages of a patient. The method comprises administering uridine triphosphates, adenosine triphosphates, cytidine triphosphates, or dinucleoside tetraphosphates and the derivatives thereof to an affected body of a patient, to treat dysfunction of the mucociliary clearance system as a result of impaired ciliary movement in the patient.

摘要翻译： 本发明涉及一种刺激睫状脉搏频率以促进从肺，鼻窦，上呼吸道，耳朵，眼睛，生殖泌尿道，精子，卵巢，输卵管，嗜中性粒细胞，粘液分泌物中保留的粘液分泌物的粘液纤毛或咳嗽清除的方法， 和巨噬细胞。 该方法包括给患者的受影响的体内施用三磷酸尿苷，三磷酸腺苷，胞苷三磷酸或二核苷四磷酸及其衍生物，以治疗患者睫状肌移动受损的粘液纤毛清除系统的功能障碍。

公开(公告)号：US5763447A

公开(公告)日：1998-06-09

申请号：US685216

申请日：1996-07-23

申请人： Karla M. Jacobus ,  H. Jeff Leighton

发明人： Karla M. Jacobus ,  H. Jeff Leighton

IPC分类号： C07H19/10 ,  A61K31/7064 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/7084 ,  A61P11/00 ,  C07H19/12 ,  C07H19/20 ,  C07H19/207 ,  A61K31/52 ,  A61K31/505

CPC分类号： A61K31/7076 ,  A61K31/7072 ,  Y10S514/849 ,  Y10S514/851 ,  Y10S514/853 ,  Y10S514/855

摘要： A method of promoting drainage of mucous secretions in the congested airways of a bedridden/immobilized patient or an intubated/mechanically-ventilated patient is disclosed. The method comprises administering to the airways of the patient a uridine phosphate such as uridine 5'-triphosphate (UTP) or P.sup.1,P.sup.4 -di(uridine-5')tetraphosphate, an analog of UTP, or any other analog, in an amount effective to promote drainage of fluid in the congested airways, including sinuses, by hydrating mucous secretions or by stimulating ciliary beat frequency in the airways. 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 eye drops or spray), oral form (liquid or pill), aerosol inhalation, powder form, topical, injected, intra-operative instillation or suppository form.

摘要翻译： 公开了一种促进卧床/固定化患者或插管/机械通气患者的拥挤气道中的粘液分泌物排泄的方法。 该方法包括向患者的气道施用尿苷磷酸酯，例如尿苷5'-三磷酸（UTP）或P1，P4-二（尿苷-5'）四磷酸，UTP类似物或任何其它类似物，其量为 有效地促进包括鼻窦在内的拥挤气道中的液体的流出，通过保湿粘液分泌物或刺激气道中的睫状肌搏动频率。 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（包括滴鼻剂或滴眼剂或喷雾剂），口服剂型（液体或药丸），气雾剂吸入剂，粉末形式，局部用药，注射剂，术中滴注剂或栓剂形式。