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1. 发明授权

US5656727A Antagonists of LHRH 失效
标题翻译： LHRH的拮抗剂
公开(公告)号：US5656727A
公开(公告)日：1997-08-12
申请号：US430602
申请日：1995-04-28
申请人： Cyril Y. Bowers , Karl A. Folkers , Anna Janecka
发明人： Cyril Y. Bowers , Karl A. Folkers , Anna Janecka
IPC分类号： A61K38/04 , A61K38/00 , C07K7/23 , C07K7/00 , C07K7/06
CPC分类号： C07K7/23 , A61K38/00
摘要： LHRH analogs and congeners with high water solubility have been synthesized. These new analogs had 0%-100% antiovulatory activity at a 0.5 .mu.g dosage and 0%-80% at 0.25 .mu.g. The ED.sub.50 for histamine release was 30.5 .mu.g/ml->300 .mu.g/ml.
摘要翻译：已经合成了具有高水溶性的LHRH类似物和同系物。这些新类似物在0.5μg剂量下具有0％-100％的抗肿瘤活性，在0.25μg下具有0％-80％。组胺释放的ED50为30.5μg/ ml->300μg/ ml。

2. 发明授权

US5480969A Antagonists of LHRH 失效
标题翻译： LHRH的拮抗剂
公开(公告)号：US5480969A
公开(公告)日：1996-01-02
申请号：US946056
申请日：1992-09-15
申请人： Cyril Y. Bowers , Karl A. Folkers , Anders Ljungqvist , Dong-Mei Feng , Anna Janceka
发明人： Cyril Y. Bowers , Karl A. Folkers , Anders Ljungqvist , Dong-Mei Feng , Anna Janceka
IPC分类号： A61K38/00 , C07K7/23 , C07K7/00 , C07K7/06
CPC分类号： C07K7/23 , A61K38/00
摘要： LHRH antagonists similar to antide and congeners with higher water solubility have been synthesized by substitutions in positions 1, 5 or 6 with hydrophilic residues. These peptides have antiovulatory activity with minimal histamine releasing effect.
摘要翻译： LHRH拮抗剂类似于具有较高水溶性的抗体和同源物已经通过在亲水性残基的位置1,5或6中的取代合成。这些肽具有抗肿瘤活性，具有最小的组胺释放作用。

3. 发明授权

US5316765A Use of coenzyme Q.sub.10 in combination with HMG-CoA reductase inhibitor therapies 失效
标题翻译：使用辅酶Q10与HMG-CoA还原酶抑制剂疗法组合使用
公开(公告)号：US5316765A
公开(公告)日：1994-05-31
申请号：US762312
申请日：1991-09-19
申请人： Karl A. Folkers , Per H. Langsjoen , Richard A. Willis
发明人： Karl A. Folkers , Per H. Langsjoen , Richard A. Willis
IPC分类号： A61K31/365 , A61K45/00 , A61K31/12 , A61K31/35 , A61K31/405
CPC分类号： A61K31/365 , Y10S514/922
摘要： Disclosed are methods for inhibiting the side effects attendant treatment with HMG-CoA reductase inhibitors. Treatment of a patient with and HMG-CoA reductase inhibitor in combination with coenzyme Q.sub.10 provides a reduction in patient cholesterol levels and guards against typical HMG-CoA reductase-inhibitor side effects, most notably liver dysfunction and cardiac dysfunction. The combination of lovastatin, an HMG-CoA reductase inhibitor, and coenzyme Q.sub.10 in ratios of between 1:2 to 1:29 provide significant enhancement of a patient's caridac condition. By way of example, other HMG-CoA reductase inhibitors which may be included in the claimed combinations include pravastatin, compactin, fluvastatin, dalvastatin, simvastatin, BMY 22089, GR-95030, HR-780, CI-981, SQ 33,600, and BMY 22566 and XU-62-320.
摘要翻译：公开了抑制伴随HMG-CoA还原酶抑制剂的副作用的方法。用HMG-CoA还原酶抑制剂与辅酶Q10联合治疗可降低患者胆固醇水平，防止典型的HMG-CoA还原酶抑制剂副作用，尤其是肝功能障碍和心脏功能障碍。洛伐他汀，HMG-CoA还原酶抑制剂和辅酶Q10的比例在1:2至1:29之间的组合提供了对患者的caridac病症的显着增强。作为实例，可以包括在所要求保护的组合中的其它HMG-CoA还原酶抑制剂包括普伐他汀，美伐他汀，氟伐他汀，达伐他汀，辛伐他汀，BMY 22089，GR-95030，HR-780，CI-981，SQ 33,600和BMY 22566和XU-62-320。

4. 发明授权

US5082650A Amelioration of reductions of coenzyme Q.sub.10 in cardiomyopathy patients receiving lovastatin 失效
标题翻译：接受洛伐他汀治疗的心肌病患者辅酶Q10减少的改善
公开(公告)号：US5082650A
公开(公告)日：1992-01-21
申请号：US404228
申请日：1989-09-07
申请人： Karl A. Folkers , Per H. Langsjoen
发明人： Karl A. Folkers , Per H. Langsjoen
IPC分类号： A61K31/365
CPC分类号： A61K31/365 , Y10S514/922
摘要： The present invention comprises the serious side effect of mevinolin to depress body levels of coenzyme Q.sub.10 and to correspondingly depress cardiac function and the circumvention of this side effect by the clinical administration of a formulation of coenzyme Q.sub.10 concommitantly with the administration of the mevinolin.
摘要翻译：本发明包括维生素A对辅酶Q10的体内水平的严重副作用，并且相应地通过临床施用辅酶Q10与施用维维林蛋白的临床给药相应地抑制心脏功能和避免这种副作用。

5. 发明授权

US5011858A Therapy with coenzyme Q.sub.10 of patients having AIDS or other retroviral diseases 失效
标题翻译：用艾滋病或其他逆转录病毒病患者辅酶Q10治疗
公开(公告)号：US5011858A
公开(公告)日：1991-04-30
申请号：US99363
申请日：1987-09-21
申请人： Per H. Langsjoen , Karl A. Folkers , Peter H. Langsjoen
发明人： Per H. Langsjoen , Karl A. Folkers , Peter H. Langsjoen
IPC分类号： A61K31/12
CPC分类号： A61K31/12
摘要： Therapy with a pharmaceutical formulation of coenzyme Q.sub.10 (CoQ.sub.10) of patients with Acquired Immune Deficiency Syndrome, known by the acronym AIDS and of patients with other retroviral diseases including the AIDS-related complex known as ARC is useful to reduce or negate opportunistic infections, adenopathy and other undesirable clinical symptoms. CoQ.sub.10 therapy may be used in conjunction with antibiotic therapy to prevent or suppress secondary opportunistic infections.
摘要翻译：具有获得性免疫缺陷综合征的患者的辅酶Q10（CoQ10）药物制剂的疗法，其首字母缩写为艾滋病和其他包括AIDS相关复合物在内的其他逆转录病毒疾病的患者，可用于减少或否定机会性感染，腺病和其他不良临床症状。 CoQ10治疗可以与抗生素治疗结合使用，以预防或抑制次级机会性感染。

6. 发明授权

US5763404A Methods for using LHRH antagonists with low histamine release 失效
公开(公告)号：US5763404A
公开(公告)日：1998-06-09
申请号：US466333
申请日：1995-06-06
申请人： Karl A. Folkers , Cyril Y. Bowers , Anders Ljungqvist , Pui-Fun Louisa Tang , Minoru Kubota , Dong-Mei Feng
发明人： Karl A. Folkers , Cyril Y. Bowers , Anders Ljungqvist , Pui-Fun Louisa Tang , Minoru Kubota , Dong-Mei Feng
IPC分类号： A61K38/04 , A61K38/00 , A61P15/00 , C07K7/06 , C07K7/23 , A61K38/24
CPC分类号： C07K7/23 , A61K38/00 , Y10S930/13
摘要： Antide is the decapeptide, N-Ac-D-2-Nal,D-pClPhe, D-3-Pal, Ser,NicLys, D-NicLys, Leu, ILys, Pro, D-Ala,NH.sub.2 which is an antagonist of luteinizing hormone releasing hormone (LHRH). This decapeptide, like others of the present invention, has high antiovulatory activity (AOA) and releases negligible histamine. Antide is scheduled for scale-up, safety testing and evaluation in the experimental primate and in clinical medicine. Numerous other peptides having structures related to Antide were prepared and tested. These peptides had variations primarily in positions 5, 6, 7, and 8. Of these, N-Ac-D-2-Nal, D-pClPhe,D-3-Pal,Ser,PicLys,cis-DPzACAla,Leu,ILys,Pro,D-Ala-NH.sub.2 was one of the most potent and had higher antiovulatory activity than Antide, i.e. 73%/0.25 ug and 100%/0.5 ug vs. 36%/0.5 ug and 100%/1.0 ug. Antide showed significant, (p

7. 发明授权

US5470947A CHRH antagonists with low histamine release 失效
标题翻译：低组胺释放的CHRH拮抗剂
公开(公告)号：US5470947A
公开(公告)日：1995-11-28
申请号：US371552
申请日：1989-06-26
申请人： Karl A. Folkers , Anders Ljungqvist , Dong-Mei Feng , Minoru Kubota , Pui-Fun L. Tang , Cyril Y. Bowers
发明人： Karl A. Folkers , Anders Ljungqvist , Dong-Mei Feng , Minoru Kubota , Pui-Fun L. Tang , Cyril Y. Bowers
IPC分类号： A61K38/04 , A61K38/00 , A61P15/00 , C07K7/06 , C07K7/23
CPC分类号： C07K7/23 , A61K38/00 , Y10S930/13
摘要： Antide is the decapeptide, N--Ac--D--2--Nal,D--pClPhe, D--3--Pal, Ser,NicLys, D--NicLys, Leu, ILys, Pro, D--Ala,NH.sub.2 which is an antagonist of luteinizing hormone releasing hormone (LHRH). This decapeptide, like others of the present invention, has high antiovulatory activity (AOA) and releases negligible histamine. Antide is scheduled for scale-up, safety testing and evaluation in the experimental primate and in clinical medicine. Numerous other peptides having structures related to Antide were prepared and tested. These peptides had variations primarily in positions 5, 6, 7, and 8. Of these, N--Ac--D--2--Nal, D--pClPhe,D--3--Pal,Ser,PicLys,cis--DpzACAla, Leu,ILys,pro,D--Ala--NH.sub.2 was one of the most potent and had higher antiovulatory activity than Antide, i.e. 73%/0.25 ug and 100%/0.5 ug vs. 36%/0.5 ug and 100%/1.0 ug. Antide showed significant, (p
摘要翻译： Antide是黄素化拮抗剂的十肽，N-Ac-D-2-Nal，D-pClPhe，D-3-Pal，Ser，NicLys，D-NicLys，Leu，ILys，Pro，D-Ala，NH2 激素释放激素（LHRH）。这种十肽与本发明的其它物质一样，具有高的抗疟药活性（AOA），释放出可忽略的组胺。 Antide计划在实验灵长类动物和临床医学中进行放大，安全测试和评估。制备并测试了许多具有与Antide有关的结构的其它肽。这些肽主要在第5,6,7和8号位置有变化。其中，N-Ac-D-2-Nal，D-pClPhe，D-3-Pal，Ser，PicLys，cis-DpzACAla，Leu，ILys ，pro-D-Ala-NH2是最有效的并且具有比Antide更高的抗肿瘤活性，即73％/ 0.25ug和100％/ 0.5ug，而36％/ 0.5ug和100％/1.0μg。当在50ng激动剂[D-3-Qal6] -LHRH之前以10μg，44小时的剂量注射时，Antide显示显着的（p <0.001）作用持续时间。 Antide在600ug（73％）和1200μg（100％）下显示口服AOA，水和玉米油口服制剂之间的差异可以忽略不计。

8. 发明授权

US4110321A Synthetic tridecapeptide [Gln.sup.4 ]-neurotensin having hormonal activity 失效
标题翻译：合成十三肽{8 Gln {hu 4 {b {9-神经丝氨酸具有激素活性
公开(公告)号：US4110321A
公开(公告)日：1978-08-29
申请号：US785208
申请日：1977-04-06
申请人： Karl A. Folkers
发明人： Karl A. Folkers
IPC分类号： A61K38/00 , C07K7/08 , C07C103/52
CPC分类号： C07K7/083 , A61K38/00
摘要： A tridecapeptide, [Gln.sup.4 ]-neurotensin, has been effectively synthesized and which has the sequence (pyro)glutamyl-leucyl-tyrosyl-glutaminyl-asparaginyl-lysyl-prolyl-arginyl-arginyl-prolyl-tyrosinyl-isoleucyl-leucyl-acid. [Gln.sup.4 ]-neurotensin has the unique hormonal activities and chemical structure of the native hormone in bovine hypothalamic tissue.
摘要翻译：已经有效地合成了十三肽[Gln4] - 神经丝氨酸，其具有序列（pyro）谷氨酰 - 亮氨酰 - 酪氨酰 - 谷氨酰胺基 - 天冬酰胺酰赖氨酰 - 脯氨酰基 - 芳基 - 脯氨酰 - 脯氨酰基 - 酪氨酰 - 异亮氨酰 - 亮氨酸。 [Gln4] - 神经降压素在牛下丘脑组织中具有独特的荷尔蒙活性和天然激素的化学结构。

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