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1. 发明申请

US20080033033A1 8-AZAPROSTAGLANDIN DERIVATIVES AND MEDICAL USE THEREOF 审中-公开
标题翻译： 8-AZAPROSTAGLANDIN衍生物及其医疗用途
公开(公告)号：US20080033033A1
公开(公告)日：2008-02-07
申请号：US11749531
申请日：2007-05-16
申请人： Tohru Kambe , Toru Maruyama , Kaoru Kobayashi , Kousuke Tani , Yoshihiko Nakai , Toshihiko Nagase , Takayuki Maruyama , Kiyoto Sakata , Hideyuki Yoshida , Shinsei Fujimura , Akio Nishiura , Nobutaka Abe
发明人： Tohru Kambe , Toru Maruyama , Kaoru Kobayashi , Kousuke Tani , Yoshihiko Nakai , Toshihiko Nagase , Takayuki Maruyama , Kiyoto Sakata , Hideyuki Yoshida , Shinsei Fujimura , Akio Nishiura , Nobutaka Abe
IPC分类号： A61K31/41 , A61K31/4015 , C07D207/18 , C07D257/04
CPC分类号： C07D417/12 , C07D417/14
摘要： The pharmaceutical composition comprising the compound of the invention having 8-azaprostaglandin skeleton represented by formula (I) (wherein, all the symbols have the same meanings as that of the specification.) a salt thereof, a solvate thereof or a cyclodextrin clathrate thereof, or a prodrug thereof and them as active ingredient have EP4 agonistic action and thus are considered useful for the prevention and/or treatment of immunological diseases, asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, shock and glaucoma, etc. Furthermore, the compounds also have an action of accelerating bone formation, so it is expected to be useful for the prevention and/or treatment of diseases associated with loss in bone mass, for example, primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss, osteonecrosis, bone formation after bone operation, alternative treatment for bone grafting.
摘要翻译：包含本发明化合物的盐，其盐，其溶剂合物或环糊精包合物，其具有由式（I）表示的8-氮杂前列腺素骨架（其中所有符号具有与说明书相同的含义）或其前药，并且它们作为活性成分具有EP 4激动作用，因此被认为可用于预防和/或治疗免疫疾病，哮喘，神经元细胞死亡，关节炎，肺衰竭，肺纤维化，肺气肿，支气管炎，慢性阻塞性肺疾病，肝损伤，急性肝炎，肾炎，肾功能不全，高血压，心肌缺血，全身炎症反应综合征，败血症，血液综合征，巨噬细胞活化综合征，静脉炎，川崎病，烧伤，系统性肉芽肿病，溃疡性结肠炎，克罗恩病，透析中的高细胞因子血症，多器官功能衰竭，休克和青光眼等。此外，化合物还具有促进骨形成的作用，因此预期可用于预防和/或治疗与骨量丧失相关的疾病，例如原发性骨质疏松症，继发性骨质疏松症，癌症的骨转移，高钙血症，佩吉特氏病，骨丢失，骨坏死，骨手术后的骨形成，骨移植的替代治疗。

2. 发明申请

US20050020686A1 Remedies for diseases with bone mass loss having ep4 agonist as the active ingredient 失效
标题翻译：用ep4激动剂作为活性成分治疗骨质量下降的疾病
公开(公告)号：US20050020686A1
公开(公告)日：2005-01-27
申请号：US10484500
申请日：2002-07-22
申请人： Toru Maruyama , Kaoru Kobayashi , Tohru Kambe , Takayuki Maruyama , Hideyuki Yoshida , Akio Nishiura , Nobutaka Abe
发明人： Toru Maruyama , Kaoru Kobayashi , Tohru Kambe , Takayuki Maruyama , Hideyuki Yoshida , Akio Nishiura , Nobutaka Abe
IPC分类号： A61K45/00 , A61K31/559 , A61P19/08 , A61P19/10 , C07C405/00 , A61K31/557
CPC分类号： C07C405/0033 , A61K9/0019 , A61K9/1647 , A61K9/19 , A61K9/2054 , A61K31/4015 , A61K31/41 , A61K31/5575 , A61K31/559
摘要： A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP4 agonist as an active ingredient. An EP4 agonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting).
摘要翻译：用于预防和/或治疗与包含EP4激动剂作为活性成分的骨量减少相关的疾病的局部施用的药物组合物。包含具有前列腺素骨架的化合物作为代表的EP4激动剂具有促进骨形成的作用，因此可用于预防和/或治疗与骨质量减少有关的疾病（骨疾病如原发性骨质疏松症，继发性骨质疏松症骨质疏松症，癌症的骨转移，高钙血症，佩吉特氏病，骨丢失和骨坏死，术后成骨，骨移植的替代疗法）。

3. 发明申请

US20120202773A1 PHARMACEUTICAL COMPOSITION FOR TREATMENT OF DISEASES ASSOCIATED WITH DECREASE IN BONE MASS COMPRISING EP4 AGONIST AS ACTIVE INGREDIENT 审中-公开
标题翻译：用于治疗与包含EP4激动剂作为主动成分的骨质疏松相关的疾病的药物组合物
公开(公告)号：US20120202773A1
公开(公告)日：2012-08-09
申请号：US13453434
申请日：2012-04-23
申请人： Toru Maruyama , Kaoru Kobayashi , Tohru Kambe , Takayuki Maruyama , Hideyuki Yoshida , Akio Nishiura , Nobutaka Abe
发明人： Toru Maruyama , Kaoru Kobayashi , Tohru Kambe , Takayuki Maruyama , Hideyuki Yoshida , Akio Nishiura , Nobutaka Abe
IPC分类号： A61K31/4015 , C08B37/16 , A61K31/724 , C07D409/06 , C07D405/10 , C07D405/06 , C07D417/12 , C07D413/12 , C07D417/14 , C07D263/24 , C07D403/12 , C07D409/12 , C07D409/14 , C07D401/12 , A61P19/08 , C07D413/14 , C07D207/26 , B82Y99/00 , B82Y5/00
CPC分类号： C07C405/0033 , A61K9/0019 , A61K9/1647 , A61K9/19 , A61K9/2054 , A61K31/4015 , A61K31/41 , A61K31/5575 , A61K31/559
摘要： A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP4 agonist as an active ingredient. An EP4 agonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting).
摘要翻译：用于预防和/或治疗与包含EP4激动剂作为活性成分的骨量减少相关的疾病的局部施用的药物组合物。包含具有前列腺素骨架的化合物作为代表的EP4激动剂具有促进骨形成的作用，因此可用于预防和/或治疗与骨质量减少有关的疾病（骨疾病如原发性骨质疏松症，继发性骨质疏松症骨质疏松症，癌症的骨转移，高钙血症，佩吉特氏病，骨丢失和骨坏死，术后成骨，骨移植的替代疗法）。

4. 发明申请

US20100010222A1 PHARMACEUTICAL COMPOSITION FOR TREATMENT OF DISEASES ASSOCIATED WITH DECREASE IN BONE MASS COMPRISING EP4 AGONIST AS ACTIVE INGREDIENT 有权
标题翻译：用于治疗与包含EP4激动剂作为主动成分的骨质疏松相关的疾病的药物组合物
公开(公告)号：US20100010222A1
公开(公告)日：2010-01-14
申请号：US12549136
申请日：2009-08-27
申请人： Toru MARUYAMA , Kaoru Kobayashi , Tohru Kambe , Takayuki Maruyama , Hideyuki Yoshida , Akio Nishiura , Nobutaka Abe
发明人： Toru MARUYAMA , Kaoru Kobayashi , Tohru Kambe , Takayuki Maruyama , Hideyuki Yoshida , Akio Nishiura , Nobutaka Abe
IPC分类号： C07D241/04 , C07C405/00 , C07D207/12 , C07D401/12
CPC分类号： C07C405/0033 , A61K9/0019 , A61K9/1647 , A61K9/19 , A61K9/2054 , A61K31/4015 , A61K31/41 , A61K31/5575 , A61K31/559
摘要： A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP4 agonist as an active ingredient. An EP4 agonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting).
摘要翻译：用于预防和/或治疗与包含EP4激动剂作为活性成分的骨量减少相关的疾病的局部施用的药物组合物。包含具有前列腺素骨架的化合物作为代表的EP4激动剂具有促进骨形成的作用，因此可用于预防和/或治疗与骨质量减少有关的疾病（骨疾病如原发性骨质疏松症，继发性骨质疏松症骨质疏松症，癌症的骨转移，高钙血症，佩吉特氏病，骨丢失和骨坏死，术后成骨，骨移植的替代疗法）。

5. 发明授权

US08207223B2 Pharmaceutical composition for treatment of diseases associated with decrease in bone mass comprising EP4 agonist as active ingredient 有权
标题翻译：用于治疗与包含EP4激动剂作为活性成分的骨质量减少相关的疾病的药物组合物
公开(公告)号：US08207223B2
公开(公告)日：2012-06-26
申请号：US12549136
申请日：2009-08-27
申请人： Toru Maruyama , Kaoru Kobayashi , Tohru Kambe , Takayuki Maruyama , Hideyuki Yoshida , Akio Nishiura , Nobutaka Abe
发明人： Toru Maruyama , Kaoru Kobayashi , Tohru Kambe , Takayuki Maruyama , Hideyuki Yoshida , Akio Nishiura , Nobutaka Abe
IPC分类号： A01N37/08 , A01N53/00 , A61K31/215 , A61K31/19 , A61K31/557
CPC分类号： C07C405/0033 , A61K9/0019 , A61K9/1647 , A61K9/19 , A61K9/2054 , A61K31/4015 , A61K31/41 , A61K31/5575 , A61K31/559
摘要： A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP4 agonist as an active ingredient. An EP4 agonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting).
摘要翻译：用于预防和/或治疗与包含EP4激动剂作为活性成分的骨量减少相关的疾病的局部施用的药物组合物。包含具有前列腺素骨架的化合物作为代表的EP4激动剂具有促进骨形成的作用，因此可用于预防和/或治疗与骨质量减少有关的疾病（骨疾病如原发性骨质疏松症，继发性骨质疏松症骨质疏松症，癌症的骨转移，高钙血症，佩吉特氏病，骨丢失和骨坏死，术后成骨，骨移植的替代疗法）。

6. 发明授权

US07256211B1 8-azaprostaglandin derivatives and medical use thereof 失效
标题翻译： 8-氮杂普罗兰前列腺素衍生物及其医疗用途
公开(公告)号：US07256211B1
公开(公告)日：2007-08-14
申请号：US10542724
申请日：2004-01-20
申请人： Tohru Kambe , Toru Maruyama , Kaoru Kobayashi , Kousuke Tani , Yoshihiko Nakai , Toshihiko Nagase , Takayuki Maruyama , Kiyoto Sakata , Hideyuki Yoshida , Shinsei Fujimura , Akio Nishiura , Nobutaka Abe
发明人： Tohru Kambe , Toru Maruyama , Kaoru Kobayashi , Kousuke Tani , Yoshihiko Nakai , Toshihiko Nagase , Takayuki Maruyama , Kiyoto Sakata , Hideyuki Yoshida , Shinsei Fujimura , Akio Nishiura , Nobutaka Abe
IPC分类号： A61K31/40 , A61K31/426 , C07D207/12 , C07D207/36
CPC分类号： C07D417/12 , C07D417/14
摘要： The pharmaceutical composition comprising the compound of the invention having 8-azaprostaglandin skeleton represented by formula (I) (wherein, all the symbols have the same meanings as that of the specification) a salt thereof, a solvate thereof or a cyclodextrin clathrate thereof, or a prodrug thereof and them as active ingredient have EP4 agonistic action and thus are considered useful for the prevention and/or treatment of immunological diseases, asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, shock and glaucoma, etc. Furthermore, the compounds also have an action of accelerating bone formation, so it is expected to be useful for the prevention and/or treatment of diseases associated with loss in bone mass, for example, primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss, osteonecrosis, bone formation after bone operation, alternative treatment for bone grafting.
摘要翻译：该药物组合物包含本发明化合物，其具有式（I）表示的8-氮杂前列腺素骨架（其中所有符号具有与说明书相同的含义）其盐，其溶剂合物或环糊精包合物，或其前药和它们作为活性成分具有EP 4激动作用，因此被认为可用于预防和/或治疗免疫疾病，哮喘，神经元细胞死亡，关节炎，肺衰竭，肺纤维化，肺气肿，支气管炎，慢性阻塞性肺疾病，肝损伤，急性肝炎，肾炎，肾功能不全，高血压，心肌缺血，全身炎症反应综合征，败血症，血液综合征，巨噬细胞活化综合征，Still氏病，川崎病，烧伤，全身性肉芽肿病，溃疡性结肠炎，克罗恩病，透析中的高细胞因子血症，多器官功能衰竭，休克和青光眼等。该化合物还具有加速骨形成的作用，因此预期可用于预防和/或治疗与骨质量损失相关的疾病，例如原发性骨质疏松症，继发性骨质疏松症，癌症的骨转移，高钙血症，佩吉特氏病，骨丢失，骨坏死，骨手术后的骨形成，骨移植的替代治疗。

7. 发明授权

US07547715B2 Endogenous repair factor production accelerator 有权
标题翻译：内源性修复因子生产加速器
公开(公告)号：US07547715B2
公开(公告)日：2009-06-16
申请号：US10530685
申请日：2003-10-09
申请人： Yoshiki Sakai , Akio Nishiura , Teppei Ogata
发明人： Yoshiki Sakai , Akio Nishiura , Teppei Ogata
IPC分类号： A61K31/44
CPC分类号： A61K31/4406 , A61K9/1647 , A61K9/5031 , A61K31/19 , A61K31/343 , A61K31/403 , A61K45/06
摘要： It relates to an endogenous repair factor production accelerator which comprises one or at least two selected from prostaglandin (PG) I2 agonist, EP2 agonist and EP4 agonist. Since prostaglandin (PG) I2 agonist, EP2 agonist or EP4 agonist has various endogenous repair factor production accelerating action, angiogenesis acceleration action and stem cell differentiation induction action, it is useful as preventive and/or therapeutic agents for ischemic organ diseases (e.g., arteriosclerosis obliterans, Buerger disease, Raynaud disease, myocardial infarction, angina pectoris, diabetic neuropathy, spinal canal stenosis, cerebrovascular accidents, cerebral infarction, pulmonary hypertension, bone fracture, Alzheimer disease, etc.) and various cell and organ diseases.
摘要翻译：它涉及内源性修复因子产生促进剂，其包含选自前列腺素（PG）I2激动剂，EP2激动剂和EP4激动剂中的一种或至少两种。由于前列腺素（PG）I2激动剂，EP2激动剂或EP4激动剂具有各种内源性修复因子产生促进作用，血管生成加速作用和干细胞分化诱导作用，其可用作缺血性器官疾病（例如动脉硬化症）的预防和/或治疗剂闭塞性心脏病，勃起病，雷诺病，心肌梗死，心绞痛，糖尿病性神经病变，椎管狭窄，脑血管意外，脑梗塞，肺动脉高压，骨折，阿尔茨海默病等）和各种细胞和器官疾病。

8. 发明授权

US08436026B2 Endogeneous repair factor production promoters 有权
标题翻译：内生修复因子生产启动子
公开(公告)号：US08436026B2
公开(公告)日：2013-05-07
申请号：US12034614
申请日：2008-02-20
申请人： Yoshiki Sakai , Akio Nishiura , Teppei Ogata
发明人： Yoshiki Sakai , Akio Nishiura , Teppei Ogata
IPC分类号： A61K31/04
CPC分类号： A61K31/4406 , A61K9/1647 , A61K9/5031 , A61K31/19 , A61K31/343 , A61K31/403 , A61K45/06
摘要： It relates to an endogenous repair factor production accelerator which comprises one or at least two selected from prostaglandin (PG) 12 agonist, EP2 agonist and EP4 agonist. Since prostaglandin (PG) 12 agonist, EP2 agonist or EP4 agonist has various endogenous repair factor production accelerating action, angiogenesis acceleration action and stem cell differentiation induction action, it is useful as preventive and/or therapeutic agents for ischemic organ diseases (e.g., arteriosclerosis obliterans, Buerger disease, Raynaud disease, myocardial infarction, angina pectoris, diabetic neuropathy, spinal canal stenosis, cerebrovascular accidents, cerebral infarction, pulmonary hypertension, bone fracture, Alzheimer disease, etc.) and various cell and organ diseases.
摘要翻译：其涉及内源性修复因子产生促进剂，其包含选自前列腺素（PG）12激动剂，EP2激动剂和EP4激动剂中的一种或至少两种。由于前列腺素（PG）12激动剂，EP2激动剂或EP4激动剂具有各种内源性修复因子产生促进作用，血管生成加速作用和干细胞分化诱导作用，其可用作缺血性器官疾病（例如动脉硬化症）的预防和/或治疗剂闭塞性心脏病，勃起病，雷诺病，心肌梗死，心绞痛，糖尿病性神经病变，椎管狭窄，脑血管意外，脑梗塞，肺动脉高压，骨折，阿尔茨海默病等）和各种细胞和器官疾病。

9. 发明申请

US20090074844A1 TRENADERMAL ABSORPTION PREPARATION 审中-公开
标题翻译： TRENADERMAL吸收制剂
公开(公告)号：US20090074844A1
公开(公告)日：2009-03-19
申请号：US11912997
申请日：2006-04-27
申请人： Akio Nishiura , Hikaru Sugihara , Harumi Arai , Toshiya Kanaji
发明人： Akio Nishiura , Hikaru Sugihara , Harumi Arai , Toshiya Kanaji
IPC分类号： A61K31/216 , A61L15/44 , A61P7/00 , A61P19/00
CPC分类号： A61K9/0014 , A61K9/7053 , A61K31/5575
摘要： The present invention relates to a blood concentration regulation type percutaneous absorption preparation, which comprises an ester form of 4-{[2-((1R,2R,3R)-3-hydroxy-2-{(1E,3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-5-oxocyclopentyl)ethyl]sulfanyl}butanoic acid and a base for external preparations. The blood concentration regulation type percutaneous absorption preparation of the present invention can stably maintain blood concentration of the active form of the present invention and is safe since there are no side effects. Therefore, it can be used as a percutaneous absorption preparation which can be persistently administered.
摘要翻译：本发明涉及血液浓度调节型经皮吸收制剂，其包含4 - {[2 - （（1R，2R，3R）-3-羟基-2 - {（1E，3S）-3- 羟基-4- [3-（甲氧基甲基）苯基]丁-1-烯基} -5-氧代环戊基）乙基]硫烷基}丁酸和外用制剂的碱。本发明的血液浓度调节型经皮吸收制剂能够稳定地维持本发明的活性形式的血药浓度，因为没有副作用，因此是安全的。因此，可以作为能够持续施用的经皮吸收制剂使用。

10. 发明申请

US20060069018A1 Endogenous repair factor production promoters 有权
标题翻译：内源修复因子生产启动子
公开(公告)号：US20060069018A1
公开(公告)日：2006-03-30
申请号：US10530685
申请日：2003-10-09
申请人： Yoshiki Sakai , Akio Nishiura , Teppei Ogata
发明人： Yoshiki Sakai , Akio Nishiura , Teppei Ogata
IPC分类号： A61K38/18
CPC分类号： A61K31/4406 , A61K9/1647 , A61K9/5031 , A61K31/19 , A61K31/343 , A61K31/403 , A61K45/06
摘要： It relates to an endogenous repair factor production accelerator which comprises one or at least two selected from prostaglandin (PG) I2 agonist, EP2 agonist and EP4 agonist. Since prostaglandin (PG) I2 agonist, EP2 agonist or EP4 agonist has various endogenous repair factor production accelerating action, angiogenesis acceleration action and stem cell differentiation induction action, it is useful as preventive and/or therapeutic agents for ischemic organ diseases (e.g., arteriosclerosis obliterans, Buerger disease, Raynaud disease, myocardial infarction, angina pectoris, diabetic neuropathy, spinal canal stenosis, cerebrovascular accidents, cerebral infarction, pulmonary hypertension, bone fracture, Alzheimer disease, etc.) and various cell and organ diseases.
摘要翻译：它涉及内源性修复因子产生促进剂，其包含选自前列腺素（PG）I2激动剂，EP2激动剂和EP4激动剂中的一种或至少两种。由于前列腺素（PG）I2激动剂，EP2激动剂或EP4激动剂具有各种内源性修复因子产生促进作用，血管生成加速作用和干细胞分化诱导作用，其可用作缺血性器官疾病（例如动脉硬化症）的预防和/或治疗剂闭塞性心脏病，勃起病，雷诺病，心肌梗死，心绞痛，糖尿病性神经病变，椎管狭窄，脑血管意外，脑梗死，肺动脉高压，骨折，阿尔茨海默病等）和各种细胞和器官疾病。

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