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。