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1. 发明申请

WO0236108A3 USE OF 20-HETE SYNTHESIZING ENZYME INHIBITORS AS THERAPY FOR CEREBRAL VASCULAR DISEASES 审中-公开
标题翻译：使用20-HETE合成酶抑制剂作为治疗脑血管疾病的治疗方法
公开(公告)号：WO0236108A3
公开(公告)日：2002-10-17
申请号：PCT/US0127605
申请日：2001-09-06
申请人： MCW RES FOUND INC , TAISHO PHARMA CO LTD , ROMAN RICHARD J , HARDER DAVID R , MIYATA NORIYUKI , SATO MASAKAZU , KAMEO KAZUYA , OKUYAMA SHIGERU
发明人： ROMAN RICHARD J , HARDER DAVID R , MIYATA NORIYUKI , SATO MASAKAZU , KAMEO KAZUYA , OKUYAMA SHIGERU
IPC分类号： A61K45/00 , A61K31/15 , A61K31/155 , A61K31/18 , A61K31/20 , A61K31/4164 , A61K31/4174 , A61K31/4192 , A61K31/7105 , A61K31/711 , A61K38/54 , A61K39/395 , A61K48/00 , A61P9/00 , A61P9/10 , A61P25/00 , A61P25/06 , A61P25/14 , A61P25/16 , A61P25/28 , A61P31/00 , A61P31/04 , A61P43/00 , A61K31/145
CPC分类号： A61K31/15 , A61K31/20 , A61K31/4164 , A61K31/4192 , A61K48/00
摘要： A method for treating cerebral vascular diseases in a human or non-human animal is disclosed. The method involves inhibiting 20-HETE synthesizing enzyme activity sufficiently to increase or prevent a decrease in cerebral blood flow in the human or non-human animal. This can be obtained by treating the animal with inhibitors of CYP4A or CYP4F family of enzymes, such as HET0016, 17-ODYA (17-octadecynoic acid), DDMS (dibromododecenyl methylsulfimide), 1-ABT (1-aminobenzotriazole) and miconazole, or with an antibody to 20-HETE synthetizing enzyme or with an antisense oligo-nucleotide directed against 5' end of CYP4A1, CYP4A2, CYP4A11, CYP4F2 or CYP4F3.
摘要翻译：公开了一种用于治疗人或非人动物的脑血管疾病的方法。所述方法包括充分抑制20-HETE合成酶活性以增加或防止人或非人动物中脑血流量的降低。这可以通过用CYP4A或CYP4F家族的抑制剂如HET0016,17-ODYA（17-十八炔酸），DDMS（二溴十二碳烯基甲基亚硫酰亚胺），1-ABT（1-氨基苯并三唑）和咪康唑处理动物来获得，或具有针对20-HETE合成酶的抗体或针对针对CYP4A1，CYP4A2，CYP4A11，CYP4F2或CYP4F3的5'末端的反义寡核苷酸。

2. 发明申请

WO2008034011A3 METHODS OF MODULATING CELL PROLIFERATION AND CYST FORMATION IN POLYCYSTIC KIDNEY AND LIVER DISEASES 审中-公开
标题翻译：调节多囊肾和肝病的细胞增殖和囊肿形成的方法
公开(公告)号：WO2008034011A3
公开(公告)日：2008-05-29
申请号：PCT/US2007078414
申请日：2007-09-13
申请人： MCW RES FOUND INC , SWEENEY WILLIAM E , AVNER ELLIS D , ROMAN RICHARD J
发明人： SWEENEY WILLIAM E , AVNER ELLIS D , ROMAN RICHARD J
IPC分类号： A61K31/155 , A61K31/18 , A61K31/20 , A61K31/201 , A61K31/202 , A61K31/5375 , A61P13/12
CPC分类号： A61K31/5375 , A61K31/155 , A61K31/18 , A61K31/20 , A61K31/201 , A61K31/202
摘要： The present invention provides a method for preferentially reducing the proliferation of cystic epithelial cells in the kidney or bile duct in a mammal in need thereof by administering a 20- HETE synthesizing enzyme inhibitor or a 20-HETE antagonist to the mammal in an amount sufficient to preferentially reduce the proliferation of cystic epithelial cells over normal epithelial cells such as tubule epithelial cells in the kidney or bile duct. The present invention also provides a method for preventing or treating autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), ARPKD associated congenital hepatic fibrosis, ARPKD associated Caroli's disease, or cholangiocarcinoma in a mammal in need thereof by administering a 20-HETE synthesizing enzyme inhibitor or a 20-HETE antagonist to the mammal in an amount sufficient to prevent or treat the disease.
摘要翻译：本发明提供了一种优先降低有需要的哺乳动物的肾脏或胆管中囊状上皮细胞增殖的方法，通过给予哺乳动物20-HETE合成酶抑制剂或20-HETE拮抗剂，优先减少囊性上皮细胞比正常上皮细胞例如肾或胆管中的肾小管上皮细胞的增殖。本发明还提供了通过给药有需要的哺乳动物中预防或治疗常染色体显性多囊肾病（ADPKD），常染色体隐性多囊肾病（ARPKD），ARPKD相关的先天性肝纤维化，ARPKD相关的卡利氏病或胆管癌的方法， 20-HETE合成酶抑制剂或20-HETE拮抗剂，其量足以预防或治疗该疾病。

3. 发明申请

WO0177674A3 FLUORESCENT HPLC ASSAY FOR 20-HETE AND OTHER P-450 METABOLITES OF ARACHIDONIC ACID 审中-公开
标题翻译：用于20-HETE和其他P-450代谢物的荧光HPLC分析
公开(公告)号：WO0177674A3
公开(公告)日：2002-06-13
申请号：PCT/US0111321
申请日：2001-04-06
申请人： MCW RES FOUND INC , ROMAN RICHARD J , MAIER KRISTOPHER G
发明人： ROMAN RICHARD J , MAIER KRISTOPHER G
IPC分类号： G01N21/64 , B01J20/281 , G01N30/02 , G01N30/04 , G01N30/06 , G01N30/26 , G01N30/34 , G01N30/62 , G01N30/74 , G01N30/86 , G01N30/88 , G01N33/92 , G01N33/88
CPC分类号： G01N33/92 , G01N30/34 , G01N30/74 , G01N2030/027 , G01N2030/625 , G01N21/64
摘要： The present invention provides a fluorescent HPLC assay for detecting the presence and/or measuring the level of 20-hydroxyeicosatetraenoic acid (20-HETE) and other P-450 metabolites of arachidonic acid in a sample. P-450 metabolites of arachidonic acid are first extracted from the sample and then labeled with 2-(2,3-naphthalimino)ethyl trifluoromethanesulfonate. The labeling reaction is catalyzed by N,N-diisopropylethylamine. Next, the labeled P-450 metabolites are separated on a 4.5 X 250-mm, 5 mu M particle size C18 reverse-phase HPLC column using a mobile phase of methanol:water:acetic acid (82:18:0.1, v/v/v) and an isocratic elution at a rate of about 1.3 ml per minute. Fluorescence intensities of the column eluent are monitored by a fluorescence detector. Quantitation of P-450 metabolites in a sample can be made by using an internal standard.
摘要翻译：本发明提供用于检测样品中存在和/或测量20-羟基二十碳四烯酸（20-HETE）和花生四烯酸的其它P-450代谢物的水平的荧光HPLC测定。首先从样品中提取花生四烯酸的P-450代谢物，然后用三氟甲磺酸2-（2,3-萘二甲酰基）乙酯标记。标记反应由N，N-二异丙基乙胺催化。接下来，使用甲醇：水：乙酸（82:18:0.1，v / v）的流动相，在4.5×250mm，5μm的粒度C18反相HPLC柱上分离标记的P-450代谢物 / v）和以每分钟约1.3ml的速度进行等度洗脱。通过荧光检测器监测柱洗脱液的荧光强度。样品中P-450代谢物的定量可以通过使用内标进行。

4. 发明申请

WO2005046658A2 METHODS OF MODULATING ANGIOGENESIS AND CANCER CELL PROLIFERATION 审中-公开
标题翻译：调节血管生成和癌细胞增殖的方法
公开(公告)号：WO2005046658A2
公开(公告)日：2005-05-26
申请号：PCT/US2004037754
申请日：2004-11-12
申请人： MCW RES FOUND INC , ROMAN RICHARD J , GREENE ANDREW , AMARAL SANDRA , SCICLI GUILLERMO , BROWN STEPHEN L , CHEN PING , GUO MENG
发明人： ROMAN RICHARD J , GREENE ANDREW , AMARAL SANDRA , SCICLI GUILLERMO , BROWN STEPHEN L , CHEN PING , GUO MENG
IPC分类号： A61K31/00 , A61K31/155 , A61K31/18 , A61K31/20 , A61K31/255 , A61K31/335 , A61K31/4174 , A61K31/4192 , A61K31/4196 , A61K31/496 , A61K31/537 , A61K31/5375
CPC分类号： A61K31/335 , A61K31/00 , A61K31/155 , A61K31/18 , A61K31/20 , A61K31/255 , A61K31/4174 , A61K31/4192 , A61K31/4196 , A61K31/496 , A61K31/537 , A61K31/5375
摘要： Methods for regulating angiogenesis by modulating the activity of 20-HETE are disclosed. Further disclosed are methods of inhibiting cancer and tumor cell growth by exposing the cancer and tumor cells to 20-HETE inhibitors.
摘要翻译：公开了通过调节20-HETE的活性来调节血管生成的方法。进一步公开的是通过将癌症和肿瘤细胞暴露于20-HETE抑制剂来抑制癌症和肿瘤细胞生长的方法。

5. 发明申请

WO2007146262A3 METHOD FOR TREATING RENAL DISEASE 审中-公开
标题翻译：治疗肾病的方法
公开(公告)号：WO2007146262A3
公开(公告)日：2008-09-25
申请号：PCT/US2007013740
申请日：2007-06-12
申请人： MCW RES FOUND INC , ROMAN RICHARD J , DAHLY-VERNON ANNETTE J , SHARMA MUKUT
发明人： ROMAN RICHARD J , DAHLY-VERNON ANNETTE J , SHARMA MUKUT
IPC分类号： A61K31/18 , A01N1/02 , A61K31/20 , A61K31/201 , A61P13/12
CPC分类号： A61K31/18 , A61K31/20 , A61K31/201 , A61K31/202
摘要： A method for preventing and treating a renal1 disorder in a human or non-human animal is disclosed. The method involves administering 20-HETE or a 20-HETE agonist to the human or non- human animal in an amount sufficient to prevent or treat the renal disorder. Further disclosed is a method for preventing or treating ischemic acute renal failure in particular wherein the method involves administering 20-HETE or a 20-HETE agonist to the human or non-human animal in an amount sufficient to prevent or treat ischemic acute renal failure. A method for preventing or reducing the severity of damage to an ex vivo preserved kidney upon reperfusion is also disclosed. The method involves preserving the kidney ex vivo in a storage solution that contains 20-HETE or a 20-HETE agonist in an amount sufficient to prevent or reduce the severity of damage to the kidney upon reperfusion.
摘要翻译：公开了一种用于预防和治疗人或非人动物中的肾脏疾病的方法。该方法包括以足以预防或治疗肾脏疾病的量向人或非人动物施用20-HETE或20-HETE激动剂。进一步公开的是用于预防或治疗缺血性急性肾衰竭的方法，特别是其中所述方法涉及以足以预防或治疗缺血性急性肾衰竭的量向人或非人动物施用20-HETE或20-HETE激动剂。还公开了一种用于在再灌注时预防或降低对离体保存的肾的损伤的严重性的方法。该方法包括在含有20-HETE或20-HETE激动剂的储存溶液中离体保存足量的量以防止或降低再灌注对肾的损伤的严重性。

6. 发明申请

WO9943310A3 20-HETE ANTAGONISTS AND AGONISTS 审中-公开
标题翻译： 20-HETE ANTAGONISTS和AGONISTS
公开(公告)号：WO9943310A3
公开(公告)日：1999-10-07
申请号：PCT/US9904020
申请日：1999-02-24
申请人： MCW RES FOUND INC
发明人： ROMAN RICHARD J , FALCK JOHN R , ALONSO-GALICIA MAGDALENA , JACOBS ELIZABETH R , HARDER DAVID R
IPC分类号： A61K45/00 , A61K31/00 , A61K31/18 , A61K31/20 , A61K31/201 , A61K31/202 , A61P1/16 , A61P3/10 , A61P7/10 , A61P9/00 , A61P9/02 , A61P9/08 , A61P9/10 , A61P9/12 , A61P9/14 , A61P13/12 , A61P35/00
CPC分类号： A61K31/202 , A61K31/00 , A61K31/18 , A61K31/20 , A61K31/201 , Y10S514/826 , Y10S514/866
摘要： 20-HETE agonists and antagonists are disclosed along with therapeutic applications. In a preferable form of the invention, the 20-HETE agonists are selected from the group consisting of 21-hydroxyheneicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid, 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid and 20-,21-dimethyl 20-HETE. Preferable 20-HETE antagonists include 5(S)-HETE, 15(S)-HETE, 19(S)-HETE, 19-hydroxynonadeca-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid and 20-hydroxyeicosa 6(Z),15(Z)-dienoic acid.
摘要翻译： 20-HETE激动剂和拮抗剂以及治疗应用被公开。在本发明的优选形式中，20-HETE激动剂选自21-羟基乙烯基-5（Z），8（Z），11（Z），14（Z） - 四烯酸，20-羟基二十碳烯 -5（Z），14（Z） - 二烯酸和20-，21-二甲基20-HETE。优选的20-HETE拮抗剂包括5（S）-HETE，15（S）-HETE，19（S）-HETE，19-羟基十五碳五烯（Z），8（Z），11（Z）（Z），15（Z） - 二烯酸。

7. 发明申请

WO2004056317A8 COMPOSITIONS FOR THE TREATMENT AND PREVENTION OF NEPHROPATHY 审中-公开
标题翻译：用于治疗和预防非传染性疾病的组合物
公开(公告)号：WO2004056317A8
公开(公告)日：2005-12-15
申请号：PCT/US0340713
申请日：2003-12-19
申请人： AMYLIN PHARMACEUTICALS INC , BARON ALAIN D , HATHAWAY DAVID R , MISTRY MAHESH , ROMAN RICHARD J
发明人： BARON ALAIN D , HATHAWAY DAVID R , MISTRY MAHESH , ROMAN RICHARD J
IPC分类号： A61K20060101 , A61K31/70 , A61K38/00 , A61K38/22 , A61K38/26 , C07K1/00
CPC分类号： A61K38/26 , A61K31/7004 , A61K33/00 , A61K38/2278
摘要： Compositions and methods for the prevention and treatment of nephropathy, including hypertensive and diabetic nephropathy, and nephropathy associated with insulin resistance and metabolic syndrome are described. Compositions of the invention include a compound that binds to a receptor for the glucagon like peptide-1, an incretin, a glucagon-like peptide-1 (GLP-1), an exendin, or an analog (including an agonist analog), derivative, or variant of any of them.
摘要翻译：描述了预防和治疗肾病，包括高血压和糖尿病肾病以及与胰岛素抵抗和代谢综合征相关的肾病的组合物和方法。本发明的组合物包括与胰高血糖素样肽-1，肠降血糖素，胰高血糖素样肽-1（GLP-1），毒蜥外泌肽或类似物（包括激动剂类似物）衍生物的受体结合的化合物，或其任何变体。

8. 发明申请

WO2004056317A3 COMPOSITIONS FOR THE TREATMENT AND PREVENTION OF NEPHROPATHY 审中-公开
标题翻译：治疗和预防肾病的组合物
公开(公告)号：WO2004056317A3
公开(公告)日：2004-12-23
申请号：PCT/US0340713
申请日：2003-12-19
申请人： AMYLIN PHARMACEUTICALS INC , BARON ALAIN D , HATHAWAY DAVID R , MISTRY MAHESH , ROMAN RICHARD J
发明人： BARON ALAIN D , HATHAWAY DAVID R , MISTRY MAHESH , ROMAN RICHARD J
IPC分类号： A61K20060101 , A61K31/70 , A61K38/00 , A61K38/22 , A61K38/26 , C07K1/00
CPC分类号： A61K38/26 , A61K31/7004 , A61K33/00 , A61K38/2278
摘要： Compositions and methods for the prevention and treatment of nephropathy, including hypertensive and diabetic nephropathy, and nephropathy associated with insulin resistance and metabolic syndrome are described. Compositions of the invention include a compound that binds to a receptor for the glucagon like peptide-1, an incretin, a glucagon-like peptide-1 (GLP-1), an exendin, or an analog (including an agonist analog), derivative, or variant of any of them.
摘要翻译：描述了用于预防和治疗肾病（包括高血压和糖尿病性肾病）和与胰岛素抵抗和代谢综合征相关的肾病的组合物和方法。本发明的组合物包括结合胰高血糖素样肽-1，肠降血糖素，胰高血糖素样肽-1（GLP-1），毒蜥外泌肽或类似物（包括激动剂类似物）的受体，衍生物，或者它们中的任何一个的变体。

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