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1. 发明授权

US10017536B2 Synthetic peptide amides and dimers thereof 有权
公开(公告)号：US10017536B2
公开(公告)日：2018-07-10
申请号：US15145901
申请日：2016-05-04
申请人： CARA THERAPEUTICS, INC.
发明人： Claudio D. Schteingart , Frédérique Menzaghi , Guangcheng Jiang , Roberta Vezza Alexander , Javier Sueiras-Diaz , Robert H. Spencer , Derek T. Chalmers , Zhiyong Luo
IPC分类号： C07K5/10 , A61K38/00 , C07K5/107 , C07K5/103 , C07K5/117 , C07K7/06
CPC分类号： C07K5/1016 , A61K38/00 , C07K5/1005 , C07K5/1008 , C07K5/1024 , C07K7/06
摘要： The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: The compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.

2. 发明申请

US20160376308A1 SYNTHETIC PEPTIDE AMIDES AND DIMERS THEREOF 审中-公开
标题翻译：合成肽类及其类似物
公开(公告)号：US20160376308A1
公开(公告)日：2016-12-29
申请号：US15145901
申请日：2016-05-04
申请人： CARA THERAPEUTICS, INC.
发明人： Claudio D. Schteingart , Frédérique Menzaghi , Guangcheng Jiang , Roberta Vezza Alexander , Javier Sueiras-Diaz , Robert H. Spencer , Derek T. Chalmers , Zhiyong Luo
IPC分类号： C07K5/107 , C07K7/06
CPC分类号： C07K5/1016 , A61K38/00 , C07K5/1005 , C07K5/1008 , C07K5/1024 , C07K7/06
摘要： The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: The compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.
摘要翻译：该化合物可用于预防和治疗与各种疾病和病症相关的疼痛和炎症。

3. 发明申请

US20150150935A1 PERIPHERAL KAPPA RECEPTOR AGONISTS FOR REDUCING PAIN AND INFLAMMATION 审中-公开
标题翻译：外周KAPPA受体激素减少疼痛和炎症
公开(公告)号：US20150150935A1
公开(公告)日：2015-06-04
申请号：US14403535
申请日：2013-06-05
申请人： CARA THERAPEUTICS, INC.
发明人： Derek T. Chalmers , James B. Jones , Robert H. Spencer
IPC分类号： A61K38/07 , A61K31/485 , A61K9/00 , A61K31/40
CPC分类号： A61K38/07 , A61K9/0019 , A61K9/0048 , A61K31/40 , A61K31/485
摘要： A method of treating of a mammalian subject suffering from an inflammatory disease or condition by administering a peripherally-restricted kappa opioid receptor agonist for reducing the inflammation is provided. The peripherally-restricted kappa opioid receptor agonist can include a peptide and the peptide can include D-amino acids. Administration of peripherally-restricted kappa opioid receptor agonists results in lowering of serum levels of pro-inflammatory cytokines and elevation of levels of anti-inflammatory cytokines.
摘要翻译：提供了通过施用用于减少炎症的外周限制性κ阿片受体激动剂来治疗患有炎性疾病或病症的哺乳动物受试者的方法。外周受限制的κ阿片受体激动剂可以包括肽，肽可以包括D-氨基酸。外周限制性κ阿片受体激动剂的施用导致促炎细胞因子的血清水平降低和抗炎细胞因子水平的升高。

4. 发明授权

US10793596B2 Synthetic peptide amides 有权
公开(公告)号：US10793596B2
公开(公告)日：2020-10-06
申请号：US16199308
申请日：2018-11-26
申请人： CARA THERAPEUTICS, INC.
发明人： Claudio D. Schteingart , Frédérique Menzaghi , Guangcheng Jiang , Roberta Vezza Alexander , Javier Sueiras-Diaz , Robert H. Spencer , Derek T. Chalmers , Robert Zhiyong Luo
IPC分类号： C07K5/107 , A61K38/07 , C07K5/103 , C07K7/02 , C07K5/10 , A61K38/00
摘要： The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: These compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.

5. 发明授权

US10138270B2 Synthetic peptide amides 有权
公开(公告)号：US10138270B2
公开(公告)日：2018-11-27
申请号：US15170201
申请日：2016-06-01
申请人： Cara Therapeutics, Inc.
发明人： Claudio D. Schteingart , Frédérique Menzaghi , Guangcheng Jiang , Roberta Vezza Alexander , Javier Sueiras-Diaz , Robert H. Spencer , Derek T. Chalmers , Robert Zhiyong Luo
IPC分类号： C07K5/107 , A61K38/07 , C07K5/103 , C07K7/02 , C07K5/10 , A61K38/00
摘要： The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.

6. 发明申请

US20180028594A1 PERIPHERAL KAPPA OPIOID RECEPTOR AGONISTS FOR HARD TISSUE PAIN 审中-公开
公开(公告)号：US20180028594A1
公开(公告)日：2018-02-01
申请号：US15523947
申请日：2015-11-03
申请人： Cara Therapeutics, Inc.
发明人： Derek T. Chalmers , James B Jones
IPC分类号： A61K38/08 , A61K31/485 , A61K31/40
CPC分类号： A61K38/08 , A61K31/40 , A61K31/485
摘要： A method for preventing, inhibiting or treating hard tissue pain in a mammalian subject, the method comprising administering an effective amount of a peripherally-restricted kappa opioid receptor agonist to the subject. The hard tissue pain can be associated with bone, tendons, or cartilage. The peripherally-restricted kappa opioid receptor agonist can be a L-amino acid-containing peptide, a D-amino acid-containing peptide, or a synthetic peptide amide, such as for instance, CR845.

7. 发明申请

US20160250277A1 PERIPHERAL KAPPA OPIOID RECEPTOR AGONISTS FOR PREVENTING, INHIBITING OR TREATING NAUSEA AND VOMITING 审中-公开
标题翻译：外用KAPPA OPIOID受体激素预防，抑制或治疗鼻炎和感冒
公开(公告)号：US20160250277A1
公开(公告)日：2016-09-01
申请号：US15032351
申请日：2014-10-27
申请人： CARA THERAPEUTICS, INC.
发明人： Derek T. CHALMERS , James B. JONES
IPC分类号： A61K38/07 , A61K31/40 , A61K31/485 , A61K9/00
CPC分类号： A61K38/07 , A61K9/0019 , A61K31/40 , A61K31/485 , A61K38/06 , C07K5/1016
摘要： A method for preventing, inhibiting or treating nausea and/or vomiting in a mammalian subject, the method comprising administering an effective amount of a peripherally-restricted kappa opioid receptor agonist to the subject. The nausea and/or vomiting can be associated with use of an opioid, such as morphine or fentanyl. The peripherally-restricted kappa opioid receptor agonist can be an L-amino acid-containing peptide, a D-amino acid-containing peptide, or a synthetic peptide amide, such as for instance, D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)]-OH (CR845).
摘要翻译：一种用于预防，抑制或治疗哺乳动物受试者的恶心和/或呕吐的方法，所述方法包括向所述受试者施用有效量的外周受限的κ阿片受体激动剂。恶心和/或呕吐可能与阿片类药物（如吗啡或芬太尼）的使用有关。外周受限制的κ阿片受体激动剂可以是含L-氨基酸的肽，含有D-氨基酸的肽或合成肽酰胺，例如D-Phe-D-Phe-D-Leu -D-Lys- [ω（4-氨基哌啶-4-羧酸）] -OH（CR845）。

8. 发明授权

US09334305B2 Synthetic peptide amides and dimers thereof 有权
公开(公告)号：US09334305B2
公开(公告)日：2016-05-10
申请号：US13959931
申请日：2013-08-06
申请人： Cara Therapeutics, Inc.
发明人： Claudio D. Schteingart , Frédérique Menzaghi , Guangcheng Jiang , Roberta Vezza Alexander , Javier Sueiras-Diaz , Robert H. Spencer , Derek T. Chalmers , Zhiyong Luo
IPC分类号： C07K5/107 , C07K5/117 , C07K5/103 , A61K38/00
CPC分类号： C07K5/1016 , A61K38/00 , C07K5/1005 , C07K5/1008 , C07K5/1024 , C07K7/06
摘要： The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: The compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.

9. 发明申请

US20160310558A1 USES OF KAPPA OPIOID SYNTHETIC PEPTIDE AMIDES 审中-公开
标题翻译： KAPPA OPIOID合成肽类药物的使用
公开(公告)号：US20160310558A1
公开(公告)日：2016-10-27
申请号：US15137033
申请日：2016-04-25
申请人： Cara Therapeutics, Inc.
发明人： Claudio D. SCHTEINGART , Frédérique MENZAGHI , Guangcheng JIANG , Roberta Vezza ALEXANDER , Javier SUEIRAS-DIAZ , Robert H. SPENCER , Derek T. CHALMERS , Robert Zhiyong LUO
IPC分类号： A61K38/07 , A61K38/08
CPC分类号： A61K38/07 , A61K38/08 , C07K5/101 , C07K5/1016 , C07K5/1019 , C07K7/02
摘要： The invention relates to methods of use of synthetic peptide amides that are ligands of the kappa opioid receptor in the treatment and prevention of kappa opioid receptor-associated diseases and conditions; and particularly to uses of these agonists in the prophylaxis, inhibition and treatment of pain, inflammation and pruritis associated with a variety of diseases, disorders and conditions. Inflammatory conditions preventable or treatable by the methods of the invention include diseases and conditions associated with elevated levels of a proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, MMP-1 and MMP-3. Such diseases and conditions include cardiovascular inflammation, neurological inflammation, skeletal inflammation, muscular inflammation, gastrointestinal inflammation, ocular inflammation, otic inflammation, inflammation due to insect bites and inflammation due to wound healing; atherosclerosis, ischemia, restenosis and vasculitis; of asthma, Sjogren's syndrome, pulmonary inflammation, chronic airway inflammation and chronic obstructive pulmonary disease (COPD), allergy, psoriasis, psoriatic arthritis, eczema, scleroderma, atopic dermatitis and systemic lupus erythematosus, arthritis, synovitis, osteomyelitis, rheumatoid arthritis, osteoarthritis and ankylosing spondylitis; septicemia and septic shock, diabetes, glucose intolerance, insulin resistance and obesity, colitis, ulcerative colitis, Crohn's disease, IBD and IBS, and the inflammatory diseases and conditions due to tumor proliferation, tumor metastasis or transplantation rejection.
摘要翻译：本发明涉及使用作为κ阿片样物质受体的配体的合成肽酰胺在治疗和预防κ阿片受体相关疾病和病症中的使用方法; 特别是这些激动剂在预防，抑制和治疗与各种疾病，病症和病症相关的疼痛，炎症和瘙痒症中的用途。通过本发明的方法可预防或治疗的炎症状态包括与升高的促炎细胞因子如TNF-α，IL-1β，IL-6，MMP-1和MMP-3水平相关的疾病和病症。这些疾病和病症包括心血管炎症，神经炎症，骨骼炎症，肌肉炎症，胃肠道炎症，眼部炎症，耳炎，由于昆虫叮咬引起的炎症和由于伤口愈合引起的炎症; 动脉粥样硬化，局部缺血，再狭窄和血管炎; 哮喘，干燥综合征，肺部炎症，慢性气道炎症和慢性阻塞性肺病（COPD），过敏，牛皮癣，银屑病关节炎，湿疹，硬皮病，特应性皮炎和系统性红斑狼疮，关节炎，滑膜炎，骨髓炎，类风湿性关节炎，骨关节炎和强直性脊柱炎; 败血病和败血性休克，糖尿病，葡萄糖不耐受，胰岛素抵抗和肥胖，结肠炎，溃疡性结肠炎，克罗恩病，IBD和IBS，以及由于肿瘤增殖，肿瘤转移或移植排斥引起的炎症疾病和病症。

10. 发明授权

US09359399B2 Synthetic peptide amides 有权
标题翻译：合成肽酰胺
公开(公告)号：US09359399B2
公开(公告)日：2016-06-07
申请号：US14585438
申请日：2014-12-30
申请人： Cara Therapeutics, Inc.
发明人： Claudio D. Schteingart , Frédérique Menzaghi , Guangcheng Jiang , Roberta Vezza Alexander , Javier Sueiras-Diaz , Robert H. Spencer , Derek T. Chalmers , Robert Zhiyong Luo
IPC分类号： C07K5/10 , A61K38/07 , C07K5/103 , C07K5/107 , C07K7/02
CPC分类号： C07K5/1016 , A61K38/00 , A61K38/07 , C07K5/10 , C07K5/1008 , C07K5/101 , C07K7/02
摘要： The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
摘要翻译：本发明涉及κ阿片样物质受体的合成肽酰胺配体，特别是涉及低P450 CYP抑制和低渗透入脑的κ阿片受体激动剂。本发明的合成肽酰胺符合式I的结构：含有这些化合物的药物组合物可用于预防和治疗与各种疾病和病症相关的疼痛和炎症。这种可治疗的疼痛包括内脏痛，神经性疼痛和痛觉过敏。与IBD和IBS等条件相关的炎症，眼部和耳部炎症，其他疾病和病症如瘙痒症，水肿，低钠血症，低钾血症，肠梗阻，肠炎和青光眼均可用本发明的药物组合物治疗或预防。

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