公开(公告)号：US07550425B2

公开(公告)日：2009-06-23

申请号：US11102564

申请日：2005-04-08

申请人： Bjarne Due Larsen ,  Jørgen Søberg Petersen ,  Daniel R. Kapusta ,  Kenneth W. Harlow

发明人： Bjarne Due Larsen ,  Jørgen Søberg Petersen ,  Daniel R. Kapusta ,  Kenneth W. Harlow

IPC分类号： A61K38/00 ,  A61K38/04 ,  A61K38/08 ,  A61K38/10 ,  C07K7/00

CPC分类号： C07K14/665 ,  A61K38/00 ,  A61K45/06

摘要： Disclosed are a variety of peptide conjugates represented by the following general formula: R1-Z-X-Z′-R2 including methods of making and using such conjugates. Also provided are antibodies that specifically bind the peptide conjugates. The present invention has a wide spectrum of important applications including use in the treatment of disorders impacted by nociceptin and related opioid-like peptides.

摘要翻译： 公开了由以下通式表示的各种肽缀合物：<？in-line-formula description =“In-line Formulas”end =“lead”？> R1-ZX-Z'-R2 < 公式描述=“在线公式”end =“tail”？>包括制作和使用这种共轭物的方法。 还提供了特异性结合肽缀合物的抗体。 本发明具有广泛的重要应用，包括用于治疗受伤害感受肽和相关类阿片样肽类影响的障碍。

公开(公告)号：US06468971B1

公开(公告)日：2002-10-22

申请号：US09142153

申请日：1998-09-02

申请人： Daniel R. Kapusta

发明人： Daniel R. Kapusta

IPC分类号： A61K3800

CPC分类号： A61K31/40 ,  A61K31/00 ,  A61K31/4025 ,  A61K31/435 ,  A61K31/5513

摘要： Kappa-opioid agonists prevent the impairment of renal function otherwise caused by the combination of gaseous anesthesia and surgery or severe trauma. Not only do these agents preserve renal function and maintain urine output, they also maintain plasma electrolyte concentration and osmolality by reducing renal loss of sodium and potassium when compared to other diuretic agents. The preservation of urine flow as well as the ability to retain body sodium, potassium, calcium, and osmolality during surgery or severe trauma under gaseous anesthesia are novel and unique properties associated only with kappa opioid agonists. To date, no other clinically-used diuretic agent has been shown to provide constant urine flow, or to retain electrolytes during anesthesia and surgery. The kappa opioid agonists may be used in surgical patients with normal cardiovascular function, but are particularly useful in patients with compromised cardiovascular and/or renal function. Continuous intravenous infusion of the kappa agonist preferably begins about 30 to 90 minutes before induction of anesthesia, and continues throughout anesthesia and surgery. The result is a constant and adequate output of urine while maintaining homeostasis of blood volume, electrolyte concentration, and osmolality throughout surgery and anesthesia. The dose of the kappa opioid agonist needed to induce diuresis during anesthesia is significantly higher than the dose needed to induce diuresis in a conscious patient.

摘要翻译： 卡帕阿片激动剂预防肾功能的损害，否则由气体麻醉和手术或严重创伤的组合引起。 这些药物不仅能保持肾功能，维持尿量，而且与其他利尿剂相比，还可以通过减少钠和钾的肾损失来维持血浆电解质浓度和渗透压。 在气体麻醉期间，保持尿液流动以及在手术或重度创伤期间保持身体钠，钾，钙和重量摩尔渗透压浓度的能力是与κ阿片样物质激动剂相关的新颖独特的性质。 迄今为止，没有其他临床使用的利尿剂已显示出提供恒定的尿流量，或在麻醉和手术期间保留电解质。 卡帕阿片激动剂可用于具有正常心血管功能的手术患者，但在心血管和/或肾功能受损的患者中特别有用。 卡帕激动剂的连续静脉内输注优选在诱导麻醉前约30至90分钟开始，并且在整个麻醉和手术中继续进行。 结果是在整个手术和麻醉过程中保持尿液的恒定和足够的产量，同时维持血容量，电解质浓度和渗透压的体内平衡。 在麻醉期间需要诱导利尿所需的卡帕阿片类激动剂的剂量显着高于在有意识的患者中诱发利尿所需的剂量。

公开(公告)号：US07244701B2

公开(公告)日：2007-07-17

申请号：US09882291

申请日：2001-06-15

申请人： Bjarne Due Larsen ,  Daniel R. Kapusta

发明人： Bjarne Due Larsen ,  Daniel R. Kapusta

IPC分类号： A61K38/00 ,  A61K38/04 ,  A61K38/08 ,  A61K38/10 ,  C07K7/00

CPC分类号： C07K7/08 ,  A61K38/00 ,  C07K7/06

摘要： Disclosed are a variety of peptide conjugates represented by the following general formula: R1-Z-X-Z′-R2 including methods of making and using such conjugates. Also provided are antibodies that specifically bind the peptide conjugates. The present invention has a wide spectrum of important applications including use in the treatment of disorders impacted by nociceptin and related opioid-like peptides.

摘要翻译： 公开了由以下通式表示的各种肽缀合物：<？in-line-formula description =“In-line Formulas”end =“lead”？> R 1 -ZX-Z' 包括制作和使用这种共轭物的方法。“2”<？“in-line-formula description =”In-line Formulas“end =”tail“？ 还提供了特异性结合肽缀合物的抗体。 本发明具有广泛的重要应用，包括用于治疗受伤害感受肽和相关类阿片样肽类影响的障碍。

公开(公告)号：US5859043A

公开(公告)日：1999-01-12

申请号：US810832

申请日：1997-03-06

申请人： Daniel R. Kapusta

发明人： Daniel R. Kapusta

IPC分类号： A61K31/40

CPC分类号： A61K31/40

摘要： Kappa-opioid agonists prevent the impairment of renal function otherwise caused by the combination of gaseous anesthesia and surgery or severe trauma. Not only do these agents preserve renal function and maintain urine output, they also maintain plasma electrolyte concentration and osmolality by reducing renal loss of sodium and potassium when compared to other diuretic agents. The preservation of urine flow as well as the ability to retain body sodium, potassium, calcium, and osmolality during surgery or severe trauma under gaseous anesthesia are novel and unique properties associated only with kappa opioid agonists. To date, no other clinically-used diuretic agent has been shown to provide constant urine flow, or to retain electrolytes during anesthesia and surgery. The kappa opioid agonists may be used in surgical patients with normal cardiovascular function, but are particularly useful in patients with compromised cardiovascular and/or renal function.

摘要翻译： 卡帕阿片激动剂预防肾功能的损害，否则由气体麻醉和手术或严重创伤的组合引起。 这些药物不仅能保持肾功能，维持尿量，而且与其他利尿剂相比，还可以通过减少钠和钾的肾损失来维持血浆电解质浓度和渗透压。 在气体麻醉期间，保持尿液流动以及在手术或重度创伤期间保持身体钠，钾，钙和重量摩尔渗透压浓度的能力是与κ阿片样物质激动剂相关的新颖独特的性质。 迄今为止，没有其他临床使用的利尿剂已显示出提供恒定的尿流量，或在麻醉和手术期间保留电解质。 卡帕阿片激动剂可用于具有正常心血管功能的手术患者，但在心血管和/或肾功能受损的患者中特别有用。