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1. 发明授权

US07541339B2 Par-2-activating peptide derivative and pharmaceutical composition using the same 失效
标题翻译：对二激活肽衍生物和使用其的药物组合物
公开(公告)号：US07541339B2
公开(公告)日：2009-06-02
申请号：US10517803
申请日：2003-06-10
申请人： Robert Ramage , Robin Plevin , Kevin Thomas Shaw , Lu Jiang , Louise Claire Young , Alan Lang Harvey , Pu Wang , Toru Kanke , Junichi Kawagoe , Mototsugu Kabeya
发明人： Robert Ramage , Robin Plevin , Kevin Thomas Shaw , Lu Jiang , Louise Claire Young , Alan Lang Harvey , Pu Wang , Toru Kanke , Junichi Kawagoe , Mototsugu Kabeya
IPC分类号： A61K38/08 , C07K7/06
CPC分类号： C07K14/705 , A61K38/00 , C07K7/06
摘要： The present invention relates to a peptide derivative represented by the general formula (I) or a salt thereof: Z-(CH2)n—CO—NH-Leu-Ile-Gly-AA1-AA2-CO—R (I) wherein Z represents an aryl group which may or may not have a substituent or a heteroaryl group which may or may not have a substituent; n represents 0, 1 or 2: AA1-AA2 represents Lys-Val or Arg-Leu; and R represents —OH or —NH2, and relates to a pharmaceutical composition comprising a peptide derivative represented by the general formula (I) or a salt thereof, and a pharmaceutically acceptable carrier thereof. The peptide derivative is useful as a prophylactic and therapeutic agent of dysfunction of masticatory, dysphagia, dysgeusia, ozostomia, intra-oral cavity dysphoria, intra-oral cavity infections, intra-oral cavity inflammations, dry eye, ectocornea detachment, keratitis, corneal ulcer, conjunctivitis, stomach ulcer, duodenal ulcer, gastritis, diarrhea, enteritis or Sjogren's syndrome.
摘要翻译：本发明涉及由通式（I）表示的肽衍生物或其盐：Z-（CH2）n-CO-NH-Leu-Ile-Gly-AA1-AA2-CO-R（Ⅰ）其中Z 表示可以具有也可以不具有取代基的芳基或可以具有取代基的杂芳基; n表示0,1或2：AA1-AA2表示Lys-Val或Arg-Leu; 和R表示-OH或-NH 2，并且涉及包含由通式（I）表示的肽衍生物或其盐及其药学上可接受的载体的药物组合物。肽衍生物可用作咀嚼，吞咽困难，发重症，口臭，口腔内烦躁，口腔内感染，口腔内炎症，干眼症，异位角脱落，角膜炎，角膜溃疡功能障碍的预防和治疗剂，结膜炎，胃溃疡，十二指肠溃疡，胃炎，腹泻，肠炎或干燥综合征。

2. 发明授权

US07423009B2 Method for treatment of kidney diseases 失效
标题翻译：肾脏疾病治疗方法
公开(公告)号：US07423009B2
公开(公告)日：2008-09-09
申请号：US10673380
申请日：2003-09-30
申请人： Takashi Nakagawa , Hiroyuki Ishiwata , Toshiaki Takizawa , Toru Kanke , Yasushi Wada , Junichi Kawagoe
发明人： Takashi Nakagawa , Hiroyuki Ishiwata , Toshiaki Takizawa , Toru Kanke , Yasushi Wada , Junichi Kawagoe
IPC分类号： A61K38/00 , A61K38/43 , A61K38/48
CPC分类号： A61K38/4846 , A61K38/08 , A61K38/482 , A61K38/4826 , G01N33/6893 , G01N2500/00 , G01N2800/347
摘要： The present invention relates to a composition for prevention and treatment of kidney diseases comprising one or more effective component(s) of a PAR-2 activating agent which is able to activate PAR-2 and a pharmaceutically acceptable carrier. The present invention further relates to a method for prevention and treatment of kidney diseases comprising administration of a composition for prevention and treatment of kidney diseases containing a PAR-2 activating agent which is able to activate PAR-2 to patients suffering from kidney diseases, and also relates to the use of a PAR-2 activating agent which is able to activate PAR-2 for the manufacture of a composition for prevention and treatment of kidney diseases. The present invention furthermore relates to a method for screening an effective ingredient for prevention and treatment of kidney diseases comprising screening of the activating action of the test substance to PAR-2.
摘要翻译：本发明涉及一种用于预防和治疗肾脏疾病的组合物，其包含能够激活PAR-2的PAR-2活化剂的一种或多种有效成分和药学上可接受的载体。本发明还涉及一种用于预防和治疗肾脏疾病的方法，其包括给予含有能够使患有肾脏疾病的患者PAR-2的PAR-2激活剂的肾脏疾病的预防和治疗组合物，以及还涉及能够激活PAR-2用于制备用于预防和治疗肾脏疾病的组合物的PAR-2活化剂的用途。本发明还涉及筛选用于预防和治疗肾脏疾病的有效成分的方法，其包括将测试物质的活化作用筛选到PAR-2。

3. 发明授权

US5602123A Therapeutic agent for myocardial ischemic damages or reperfusion 失效
标题翻译：心肌缺血损伤或再灌注治疗剂
公开(公告)号：US5602123A
公开(公告)日：1997-02-11
申请号：US548678
申请日：1995-10-26
申请人： Yasushi Abiko , Hiroko Hashizume , Akiyoshi Hara , Yoichi Yamauchi , Junichi Kawagoe
发明人： Yasushi Abiko , Hiroko Hashizume , Akiyoshi Hara , Yoichi Yamauchi , Junichi Kawagoe
IPC分类号： A61K31/551 , A61K31/55
CPC分类号： A61K31/551
摘要： A therapeutic agent for myocardial ischemic damages or reperfusion injuries which contains, as an active ingredient, a compound of the following formula (1), an acid addition salt thereof, or a hydrate thereof: ##STR1## wherein R.sup.1 to R.sup.6 are lower alkoxy groups and A and A' are lower alkylene groups; a method for treating those disorders which uses the above compound; and use of the compound in the manufacture of such a therapeutic agent. The therapeutic agent has an excellent action of recovering lowered heart functions caused by myocardial ischemia-reflow, and have low toxicity.
摘要翻译：含有下述式（1）的化合物或其酸加成盐或其水合物作为活性成分的心肌缺血性损伤或再灌注损伤的治疗剂：其中R1至R6为低级烷氧基，A和A'为低级亚烷基; 用于治疗使用上述化合物的那些疾病的方法; 以及在制造这种治疗剂中使用该化合物。治疗剂具有恢复由心肌缺血回流引起的心脏功能降低的优异作用，毒性低。

4. 发明申请

US20060183664A1 Pharmaceutical composition for delayed hypersensitivity 审中-公开
标题翻译：用于延迟超敏反应的药物组合物
公开(公告)号：US20060183664A1
公开(公告)日：2006-08-17
申请号：US10496851
申请日：2002-12-13
申请人： Toshiaki Takizawa , Masaki Tamiya , Naohiro Saito , Toru Kanke , Jiro Matsumoto , Yasushi Wada , Junichi Kawagoe , William Ferrell , John Lockhart
发明人： Toshiaki Takizawa , Masaki Tamiya , Naohiro Saito , Toru Kanke , Jiro Matsumoto , Yasushi Wada , Junichi Kawagoe , William Ferrell , John Lockhart
IPC分类号： A61K38/54
CPC分类号： A61K45/06 , A61K31/00 , Y02A50/423 , A61K2300/00
摘要： The present invention provides a pharmaceutical composition by a novel action mechanism without serious side effects for delayed hypersensitivity and a screening method of the same. The invention also provides a novel assay method of inhibitors/suppressive agents of PAR-2. The invention relates to a pharmaceutical composition for delayed hypersensitivity containing one or two or more active ingredients selected from the group consisting of inhibitors of PAR-2 and suppressive agents of PAR-2 gene expression and a pharmaceutically acceptable carrier, and to a method for screening active ingredients for pharmaceutical composition for delayed hypersensitivity by contacting a subject substance with cells expressing PAR-2 and by determining expression or activity of PAR-2. The invention also relates to a method for detecting or quantifying actions of the subject substance for PAR-2 using cells expressing PAR-2 in a culture containing inositol.
摘要翻译：本发明通过新颖的作用机理提供药物组合物，对迟发性超敏反应没有严重的副作用及其筛选方法。本发明还提供了PAR-2抑制剂/抑制剂的新型测定方法。本发明涉及一种用于延迟超敏反应的药物组合物，其含有选自PAR-2的抑制剂和PAR-2基因表达的抑制剂的一种或两种以上活性成分和药学上可接受的载体，以及筛选方法通过使受试物质与表达PAR-2的细胞接触并通过测定PAR-2的表达或活性来延迟超敏反应的药物组合物的活性成分。本发明还涉及使用含有肌醇的培养物中表达PAR-2的细胞检测或定量PAR-2的物质的作用的方法。

5. 发明授权

US5824675A Preventive and therapeutic agent for kidney diseases 失效
标题翻译：肾脏疾病的预防和治疗剂
公开(公告)号：US5824675A
公开(公告)日：1998-10-20
申请号：US817639
申请日：1997-04-28
申请人： Yoichi Yamauchi , Takashi Nakagawa , Junichi Kawagoe
发明人： Yoichi Yamauchi , Takashi Nakagawa , Junichi Kawagoe
IPC分类号： A61K31/00 , A61K31/55 , C07D295/096
CPC分类号： C07D295/096 , A61K31/00 , A61K31/55 , A61K31/551
摘要： The present invention is directed to a preventive and therapeutic agent for kidney diseases containing as its active component a compound of the following formula (1): ##STR1## (wherein each of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6, which may be identical to or different from one another, represents a lower alkoxyl group, and each of A and A', which may be identical to or different from each other, represents a lower alkylene group); an acid addition salt thereof; or a hydrate of the compound of formula (1) or of the acid addition salt thereof. This compound is useful for the prevention and treatment of kidney diseases, as it exhibits excellent preventive and therapeutic effect against acute renal failure, potent inhibitory effect against ischemia-reperfusion disorder in the kidney, and suppressed toxicity.
摘要翻译： PCT No.PCT / JP96 / 02341 Sec。 371日期1997年04月28日 102（e）日期1997年4月28日PCT 1996年8月22日PCT公布。第WO97 / 07806号公报日期：1997年3月6日本发明涉及含有作为活性成分的下述式（1）的化合物的肾脏疾病的预防和治疗剂：其中R1，R2，R3， R 4，R 5和R 6可以相同或不同，表示低级烷氧基，A和A'可以相同或不同，表示低级亚烷基）。其酸加成盐; 或式（1）化合物或其酸加成盐的水合物。该化合物可用于预防和治疗肾脏疾病，因为它对急性肾衰竭具有优异的预防和治疗作用，对肾脏缺血再灌注障碍的有效抑制作用和抑制毒性。

6. 发明申请

US20050222384A1 Par-2-activating peptide derivative and pharmaceutical composition using the same 失效
标题翻译：对二激活肽衍生物和使用其的药物组合物
公开(公告)号：US20050222384A1
公开(公告)日：2005-10-06
申请号：US10517803
申请日：2003-06-10
申请人： Robert Ramage , Robin Plevin , Kevin Shaw , Lu Jiang , Louise Young , Alan Harvey , Pu Wang , Toru Kanke , Junichi Kawagoe , Mototsugu Kabeya
发明人： Robert Ramage , Robin Plevin , Kevin Shaw , Lu Jiang , Louise Young , Alan Harvey , Pu Wang , Toru Kanke , Junichi Kawagoe , Mototsugu Kabeya
IPC分类号： A61K38/00 , A61P1/00 , A61P1/02 , A61P1/04 , A61P1/12 , A61P1/14 , A61P27/02 , A61P27/04 , A61P43/00 , C07K7/06 , C07K14/705 , A61K38/08 , C07K5/06
CPC分类号： C07K14/705 , A61K38/00 , C07K7/06
摘要： The present invention relates to a peptide derivative represented by the general formula (I) or a salt thereof: Z-(CH2)n—CO—NH-Leu-Ile-Gly-AA1-AA2-CO—R (I) wherein Z represents an aryl group which may or may not have a substituent or a heteroaryl group which may or may not have a substituent; n represents 0, 1 or 2: AA1-AA2 represents Lys-Val or Arg-Leu; and R represents —OH or —NH2, and relates to a pharmaceutical composition comprising a peptide derivative represented by the general formula (I) or a salt thereof, and a pharmaceutically acceptable carrier thereof.
摘要翻译：本发明涉及由通式（I）表示的肽衍生物或其盐：Z-（CH 2 CH 2）n -CO-NH-Leu-Ile 其中Z表示可以具有或可以不具有取代基的芳基或可以不具有取代基的芳基或可以具有取代基的杂芳基，可能没有取代基; n表示0,1或2：AA 1 -A 2 2表示Lys-Val或Arg-Leu; 并且R表示-OH或-NH 2，并且涉及包含由通式（I）表示的肽衍生物或其盐及其药学上可接受的载体的药物组合物。

7. 发明授权

US07976837B2 Method of preventing and treating brain infarction 失效
标题翻译：预防和治疗脑梗死的方法
公开(公告)号：US07976837B2
公开(公告)日：2011-07-12
申请号：US11573429
申请日：2005-06-17
申请人： Koji Abe , Junichi Kawagoe
发明人： Koji Abe , Junichi Kawagoe
IPC分类号： A61K38/48
CPC分类号： C07K14/705 , A61K45/06
摘要： The present invention is intended to clarify the relationship between PAR-2 and cerebral infarction and thereby provide an efficient method of preventing and treating cerebral infarction, as well as a pharmaceutical composition therefore. Namely, the present invention relates to a method of preventing and treating cerebral infarction by activating PAR-2 and/or promoting expression of PAR-2 gene. The present invention further relates to a pharmaceutical composition for preventing and treating cerebral infarction, comprising one, or two or more of the active ingredients selected from the group consisting of a PAR-2 activator and/or a PAR-2 gene expression promoter; as well as a pharmaceutically acceptable carrier. It further relates to a method of screening an active ingredient for preventing and treating cerebral infarction using as an indicator the PAR-2 activation promoted by a test substance.
摘要翻译：本发明旨在阐明PAR-2与脑梗死之间的关系，从而提供预防和治疗脑梗塞的有效方法，以及由此产生的药物组合物。即，本发明涉及通过激活PAR-2和/或促进PAR-2基因的表达来预防和治疗脑梗死的方法。本发明还涉及一种预防和治疗脑梗塞的药物组合物，其包含一种或两种以上选自PAR-2激活剂和/或PAR-2基因表达启动子的活性成分; 以及药学上可接受的载体。本发明还涉及一种筛选用于预防和治疗脑梗死的活性成分的方法，所述方法使用由测试物质促进的PAR-2活化作为指标。

8. 发明申请

US20090263374A1 METHOD OF PREVENTING AND TREATING BRAIN INFARCTION 失效
标题翻译：预防和治疗脑梗塞的方法
公开(公告)号：US20090263374A1
公开(公告)日：2009-10-22
申请号：US11573429
申请日：2005-06-17
申请人： Koji Abe , Junichi Kawagoe
发明人： Koji Abe , Junichi Kawagoe
IPC分类号： A61K38/48 , A61K38/16 , A61K38/06 , A61K38/07 , A61K38/08 , C12Q1/68 , A61P25/00
CPC分类号： C07K14/705 , A61K45/06
摘要： The present invention is intended to clarify the relationship between PAR-2 and cerebral infarction and thereby provide an efficient method of preventing and treating cerebral infarction, as well as a pharmaceutical composition therefore. Namely, the present invention relates to a method of preventing and treating cerebral infarction by activating PAR-2 and/or promoting expression of PAR-2 gene. The present invention further relates to a pharmaceutical composition for preventing and treating cerebral infarction, comprising one, or two or more of the active ingredients selected from the group consisting of a PAR-2 activator and/or a PAR-2 gene expression promoter; as well as a pharmaceutically acceptable carrier. It further relates to a method of screening an active ingredient for preventing and treating cerebral infarction using as an indicator the PAR-2 activation promoted by a test substance.
摘要翻译：本发明旨在阐明PAR-2与脑梗死之间的关系，从而提供预防和治疗脑梗塞的有效方法，以及由此产生的药物组合物。即，本发明涉及通过激活PAR-2和/或促进PAR-2基因的表达来预防和治疗脑梗死的方法。本发明还涉及一种预防和治疗脑梗塞的药物组合物，其包含一种或两种以上选自PAR-2激活剂和/或PAR-2基因表达启动子的活性成分; 以及药学上可接受的载体。本发明还涉及一种筛选用于预防和治疗脑梗死的活性成分的方法，所述方法使用由测试物质促进的PAR-2活化作为指标。

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