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1. 发明授权

US4374828A Biologically active thymones from the thymus 失效
标题翻译：来自胸腺的生物活性胸腺
公开(公告)号：US4374828A
公开(公告)日：1983-02-22
申请号：US199997
申请日：1980-11-17
申请人： Karl Folkers , Teresa M. Kubiak , Henryk M. Stepien , Naoki Sakura
发明人： Karl Folkers , Teresa M. Kubiak , Henryk M. Stepien , Naoki Sakura
IPC分类号： A61K35/26 , A61K37/00
CPC分类号： A61K35/26 , Y10S530/837 , Y10S930/18
摘要： A class of three substances has been isolated in highly purified form and in substantially pure form by utilizing thymus tissue as a source material. These three substances are designated thymone A, thymone B and thymone C. Thymones A and B are new peptides which yield approximately 13 and 14 individual amino acid moieties, respectively, on acid hydrolysis. Thymones A and B are chemically characterized by electrophoretic and chromatographic values which are appropriate for substances which are substantially pure. Thymone C was highly purified and its biological activity was reproducibly detected and measured. Thymones A, B and C stimulate the proliferation of lymphocytes. Thymone A stimulates the formation of cyclic adenosine monophosphate. Thymone B stimulates the formation of cyclic guanosine monophosphate.The biological activities of these thymones to stimulate the proliferation of lymphocytes and the formations of cyclic nucleotides are basic hormonal functions for the therapeutic enhancement of the immune system in patients who have immune deficiencies from diverse causes.
摘要翻译：通过利用胸腺组织作为源材料，已经以高度纯化的形式和基本上纯的形式分离了一类三种物质。这三种物质被称为胸腺嘧啶A，胸腺嘧啶B和胸腺素C.胸腺嘧啶A和B是分别在酸水解上产生大约13和14个单个氨基酸部分的新肽。百里香酮A和B的化学特征在于电泳和色谱值，其适用于基本上纯的物质。胸腺C高度纯化，其生物学活性被重复检测和测定。胸腺素A，B和C刺激淋巴细胞的增殖。 Thymone A刺激环磷酸腺苷的形成。胸腺B刺激环磷酸鸟苷的形成。刺激淋巴细胞增殖和循环核苷酸形成的这些胸腺嘧啶的生物活性是用于治疗增强免疫系统的基础激素功能，其具有不同原因的免疫缺陷。

2. 发明授权

US4504414A Synthetic pyridyl-alanyl decapeptides having antiovulatory activity 失效
标题翻译：具有抗疟药活性的合成吡啶基 - 丙氨酰基十肽
公开(公告)号：US4504414A
公开(公告)日：1985-03-12
申请号：US479645
申请日：1983-03-28
申请人： Karl Folkers , Cyril Y. Bowers , Teresa M. Kubiak , Janusz Stepinski
发明人： Karl Folkers , Cyril Y. Bowers , Teresa M. Kubiak , Janusz Stepinski
IPC分类号： A61K38/00 , C07K7/23 , C07C103/52
CPC分类号： C07K7/23 , A61K38/00 , Y10S930/13
摘要： Pyridyl-alanyl decapeptides have been effectively synthesized and found to have antiovulatory activity. The exemplary [N-Ac-D-2-Nal.sup.1,pCl-D-Phe.sup.2, D-3-Pal.sup.3,D-Arg.sup.6,D-Ala.sup.10 ]-LHRH has very high potency to inhibit ovulation, both parenterally and orally. Also, this exemplary pyridyl-alanyl-decapeptide showed an unexpected prolonged duration of antiovulatory activity. Such pyridyl-alanyl-decapeptides are useful to control reproduction.
摘要翻译：已经有效地合成了吡啶基丙氨酸十肽，发现具有抗疟药活性。示例性的[N-Ac-D-2-Nal1，pCl-D-Phe2，D-3-Pal3，D-Arg6，D-Ala10] -LHRH具有非常高的效力以抑制排卵，肠胃外和口服。此外，该示例性吡啶基 - 丙氨酰 - 十肽显示出预期的持久的抗疟药活性。这种吡啶基 - 丙氨酰 - 十肽可用于控制繁殖。

3. 发明授权

US4642332A Effective hormonal peptides: D-3-Pal.sup.6 -LHRH 失效
标题翻译：有效的激素肽：D-3-Pal6-LHRH
公开(公告)号：US4642332A
公开(公告)日：1987-02-10
申请号：US727711
申请日：1985-04-26
申请人： Karl Folkers , Xu Jie-Cheng , Cyril Y. Bowers
发明人： Karl Folkers , Xu Jie-Cheng , Cyril Y. Bowers
IPC分类号： A61K38/00 , C07K7/23 , C07K7/20
CPC分类号： C07K7/23 , A61K38/00 , Y10S930/13
摘要： Two sets of hormonal peptides are synthesized which are super agonists of the luteinizing hormone releasing hormone (LHRH). Chronic administration results in the inhibition of LHRH which is responsible for stimulating cell growth in the testes. One peptide has the D(dextro)-form of a monoheterocyclic amino acid in position six (D-3-pyridyl-alanine) while the other peptide has a bi-heterocyclic amino acid in that same position (.beta.-(3-quinolyl)-D-.alpha.-alanine. Both peptides are less metabolically reactive than those in the prior art and yet both peptides are significantly more potent than LHRH itself.
摘要翻译：合成两组激素肽，它们是促黄体激素释放激素（LHRH）的超激动剂。慢性给药导致LHRH的抑制，其负责刺激睾丸中的细胞生长。一个肽具有位置6（D-3-吡啶基 - 丙氨酸）的单杂环氨基酸的D（右旋）形式，而另一个肽在同一位置具有双杂环氨基酸（β-（3-喹啉基） -D-α-丙氨酸。两种肽的代谢反应性都低于现有技术，但两种肽都比LHRH本身显着更强。

4. 发明授权

US4824669A Formulations of coenzyme Q.sub.10 for intravenous use 失效
标题翻译：辅酶Q10用于静脉使用的制剂
公开(公告)号：US4824669A
公开(公告)日：1989-04-25
申请号：US31487
申请日：1987-03-27
申请人： Karl Folkers , Kazumasa Muratsu
发明人： Karl Folkers , Kazumasa Muratsu
IPC分类号： A61K9/00 , A61K31/12 , A61K47/44
CPC分类号： A61K9/0019 , A61K31/12 , A61K47/44
摘要： The present invention comprises a stable and non-toxic coenzyme Q.sub.10 formulation suitable for intravenous administration to an animal to produce clinically effective blood levels of coenzyme Q.sub.10. Clinically effective blood levels of coenzyme Q.sub.10 are generally agreed to be between about 2 ug/ml and about 4 ug/ml. The formulation consists essentially of a clinically accepted fatty emulsion having an oil phase and coenzyme Q.sub.10 dissolved in the oil phase. The formulation preferably contains coenzyme Q.sub.10 at a level between about 7.5 ug/ml and about 30 ug/ml. The clinically accepted fatty emulsion comprises at least one vegetable oil, preferably corn oil, peanut oil, safflower oil, olive oil or soybean oil.
摘要翻译：本发明包括稳定且无毒的辅酶Q10制剂，其适于静脉内施用于动物以产生临床有效的辅酶Q10血液水平。辅酶Q10的临床有效血液水平通常约为约2μg/ ml至约4μg/ ml。该制剂基本上由具有溶于油相中的油相和辅酶Q10的临床可接受的脂肪乳剂组成。制剂优选含有约7.5μg/ ml至约30μg/ ml水平的辅酶Q10。临床上接受的脂肪乳剂包含至少一种植物油，优选玉米油，花生油，红花油，橄榄油或大豆油。

5. 发明授权

US3953416A Synthetic decapeptide having the activity of the luteinizing hormone releasing hormone and method for manufacturing the same 失效
标题翻译：具有黄体激素释放激素活性的合成十肽及其制造方法
公开(公告)号：US3953416A
公开(公告)日：1976-04-27
申请号：US432903
申请日：1974-01-14
申请人： Karl Folkers , Bruce L. Currie , Jaw-Kang Chang , Hans Sievertsson , Conny Bogentoft
发明人： Karl Folkers , Bruce L. Currie , Jaw-Kang Chang , Hans Sievertsson , Conny Bogentoft
IPC分类号： A61K38/00 , C07K5/103 , C07K7/23 , C07C103/52 , C07G7/00
CPC分类号： C07K5/1005 , C07K7/23 , A61K38/00 , Y10S514/80 , Y10S930/13
摘要： A synthetic decapeptide, L-pglutamyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosyl-glycyl-L-leucyl-L-arginyl-L-prolyl-glycinamide which has the hormonal activities of the luteinizing hormone releasing hormone (LRH) of the hypothalamus gland of mammals is produced by utilizing as the key starting materials, the amino acids, glutamic acid or pyroglutamic acid, histidine, tryptophan, serine, tyrosine, glycine, leucine, arginine, and proline. Synthesis of the decapeptide is accomplished by coupling, in appropriate combinations of appropriate protected forms of the amino acids, and finally deprotecting to yield the amide, L-pglutamyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosyl-glycyl-L-leucyl-L-arginyl-L-prolyl-glycinamide.
摘要翻译：具有黄体生成激素释放激素的激素活性的合成十肽L- L-谷氨酰-L-组氨酰-LL-色氨酰-L-丝氨酰-L-酪氨酰 - 甘氨酰-L-赖氨酸-L-精氨酰-L-脯氨酰甘氨酰胺通过利用氨基酸，谷氨酸或焦谷氨酸，组氨酸，色氨酸，丝氨酸，酪氨酸，甘氨酸，亮氨酸，精氨酸和脯氨酸的关键起始物质产生哺乳动物下丘脑的LRH）。十肽的合成通过以合适的保护形式的氨基酸的适当组合偶联，最后脱保护得到酰胺，L-谷氨酰基-L-组氨酰基-L-色氨酸-L-丝氨酰-L-酪氨酰 - 甘氨酰基 -L-赖氨酸-L-精氨酰-L-脯氨酰基 - 甘氨酰胺。

6. 发明授权

US3944659A Folliculotropin releasing hormone 失效
标题翻译：促卵泡激素释放激素
公开(公告)号：US3944659A
公开(公告)日：1976-03-16
申请号：US314750
申请日：1972-12-13
申请人： Karl Folkers , Karl Nils Gunnar Johansson , Bruce L. Currie
发明人： Karl Folkers , Karl Nils Gunnar Johansson , Bruce L. Currie
IPC分类号： A61K38/00 , C07K14/575 , A61K27/04 , A61K17/08
CPC分类号： C07K14/575 , A61K38/00 , Y10S436/804 , Y10S436/814 , Y10S436/817
摘要： A method for producing the Folliculotropin Releasing Hormone (FRH) biosynthetically is provided by utilizing, as key starting materials, fresh hypothalamic tissue, a buffered incubation medium, an ATP synthesizing system, radioactively labeled amino acids and a mixture of 21 naturally occuring amino acids. Biosynthesis of the FRH is accomplished by incubation of the hypothalamic tissue for a short period of time in the presence of all the reagents necessary to promote the biosynthetic system to produce the Folliculotropin Releasing Hormone (FRH) of the hypothalamus gland of mammals. Examples of methods to isolate the FRH free of the luteotropin releasing hormone (LRH) are provided.
摘要翻译：通过利用新鲜的下丘脑组织，缓冲培养基，ATP合成系统，放射性标记的氨基酸和21种天然存在的氨基酸的混合物作为关键起始材料，提供了通过生物合成生产毛囊激素释放激素（FRH）的方法。 FRH的生物合成是通过在存在促进生物合成系统以产生哺乳动物下丘脑的Folliculotropin释放激素（FRH））所必需的所有试剂存在的情况下，短时间内孵育下丘脑组织而实现的。提供了分离不含促黄体激素释放激素（LRH）的FRH的方法的实例。

7. 发明授权

US4885167A Restoration of impaired cardiac function of patients with diverse muscular dystrophies by therapy with coenzyme Q10 失效
标题翻译：通过辅酶Q10治疗恢复多发性肌营养不良患者的心脏功能受损
公开(公告)号：US4885167A
公开(公告)日：1989-12-05
申请号：US155891
申请日：1988-02-16
申请人： Karl Folkers , Janusz Wolaniuk
发明人： Karl Folkers , Janusz Wolaniuk
IPC分类号： A61K38/43
CPC分类号： A61K31/122 , Y10S514/907
摘要： The present invention relates to the use of Coenzyme Q in the treatment of slow muscle degeneration, commonly known to those of skill in the art so a dystrophy or atrophy, and the accompanying cardiac complications typically identified in such patients. Administration of Coenzyme Q, and particularly the analog Coenzyme Q.sub.10 (CoQ.sub.10) to humans increases the pumping of blood by the heart, and thereby increases tissue oxygeneration throughout the body. The net physiological effect halts the progression of muscle deterioration and improves cardiac function. An overall improvement in the quality of life for these human subjects is also observed, said patients reportedly experiencing less fatigue.A method for treating human patients with progressive muscular dystrophies or the neurogenic atrophies with Coenzyme Q.sub.10 (CoQ.sub.10) specifically disclosed. The method is similarly effective for the treatment of any form of muscle degeneration or cardiac muscular dysfunction independently.
摘要翻译：本发明涉及辅酶Q用于治疗慢性肌肉变性的用途，本领域技术人员通常已知营养不良或萎缩，以及通常在这些患者中鉴定的伴随的心脏并发症。辅酶Q，特别是对人类的辅酶Q10（CoQ10）的施用增加了心脏对血液的泵吸，从而增加整个身体的组织氧合。净生理效应阻止肌肉退化进展，改善心脏功能。还观察到这些人类受试者的生活质量的总体改善，据说患者身体疲劳较少。专门公开了用辅酶Q10（CoQ10）治疗进行性肌营养不良或神经源性萎缩的人类患者的方法。该方法类似地有效地用于独立地治疗任何形式的肌肉变性或心脏肌肉功能障碍。

8. 发明授权

US4656247A Effective hormonal peptides: D-3-QA1 6-LHRH 失效
标题翻译：有效激素肽：D-3-QA1 6-LHRH
公开(公告)号：US4656247A
公开(公告)日：1987-04-07
申请号：US727710
申请日：1985-04-26
申请人： Karl Folkers , Xu Jie-Cheng , Cyril Y. Bowers
发明人： Karl Folkers , Xu Jie-Cheng , Cyril Y. Bowers
IPC分类号： A61K38/00 , C07K7/23 , C07K7/20
CPC分类号： C07K7/23 , A61K38/00 , Y10S930/13
摘要： Two sets of hormonal peptides are synthesized which are super agonists of the lutenizing hormone releasing hormone (LHRH). Chronic administration results in the inhibition of LHRH which is responsible for stimulating cell growth in the testes. One peptide has the D(dextro)-form of a mono-heterocyclic amino acid in position six (D-3-pyridyl-alanine) while the other peptide has a bi-heterocyclic amino acid in that same position (.beta.-(3-quinolyl)-D-.alpha.-alanine. Both peptides are less metabolically reactive than those in the prior art and yet both peptides are significantly more potent than LHRH itself.
摘要翻译：合成了两组激素释放激素（LHRH）的超激动剂。慢性给药导致LHRH的抑制，其负责刺激睾丸中的细胞生长。一个肽具有位置6上的单杂环氨基酸（D-3-吡啶基 - 丙氨酸）的D（右旋）形式，而另一个肽在相同位置具有双杂环氨基酸（β-（3- 喹啉基）-D-α-丙氨酸。两种肽的代谢反应性都低于现有技术，但两种肽比LHRH本身显着更有效。

9. 发明授权

US4481139A Peptide antagonists of substance P 失效
标题翻译：物质P的肽拮抗剂
公开(公告)号：US4481139A
公开(公告)日：1984-11-06
申请号：US484646
申请日：1983-04-13
申请人： Karl Folkers , Xu Jie-cheng
发明人： Karl Folkers , Xu Jie-cheng
IPC分类号： A61K38/00 , C07K7/22 , C07C103/52
CPC分类号： C07K7/22 , A61K38/00 , Y10S930/13
摘要： Undecapeptides retaining the amino acids in positions 2, 3, 4, 5, 6, 8 and 10 of substance P (Arg.sup.1 -Pro.sup.2 -Lys.sup.3 -Pro.sup.4 -Gln.sup.5 -Gln.sup.6 -Phe.sup.7 -Phe.sup.8 -Gly.sup.9 -Leu.sup.10 -Met.sup.11 -NH.sub.2), but having substitutions in positions 1, 7, 9 and 11 of substance P have been discovered to have high antagonistic activity to block substance P in biological systems. Exemplifying these potent antagonists is D-Arg.sup.1,D-Trp.sup.7,D-Trp.sup.9 -Leu.sup.11 -Substance P, which is an effective inhibitor and has high potency. These antagonists of substance P are useful to elucidate some biological mechanisms of substance P, and to treat inflammatory responses in the eye for medical practice in ophthalmology, and to be novel analgesic agents for medical applications.
摘要翻译：保留物质P（Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-Phe8-Gly9-Leu10-Met11-NH2）的2,3,4,5,6,8和10位的氨基酸的十一肽，但是已经发现在物质P的位置1,7,9和11中具有取代在生物系统中具有高的阻断物质P的拮抗活性。这些有效的拮抗剂的例子是D-Arg1，D-Trp7，D-Trp9-Leu11-物质P，其是有效的抑制剂并且具有高效力。物质P的这些拮抗剂可用于阐明物质P的一些生物学机制，并且用于治疗眼睛中用于眼科医学实践的炎症反应，并且是用于医学应用的新型止痛剂。

10. 发明授权

US06461593B1 Therapy with coenzyme Q10 to reduce subgingival microorganisms in patients with periodontal disease 失效
标题翻译：用辅酶Q10治疗减少牙周病患者的龈下微生物
公开(公告)号：US06461593B1
公开(公告)日：2002-10-08
申请号：US07838604
申请日：1992-02-19
申请人： Takashi Hanioka , Judson T. McRee , Karl Folkers
发明人： Takashi Hanioka , Judson T. McRee , Karl Folkers
IPC分类号： A61K716
CPC分类号： A61K31/122 , A61K8/355 , A61K9/0063 , A61Q11/00
摘要： The presence of diverse microorganisms in the gingiva of patients having periodontal disease is very well known to be deleterious to gingival health, and particularly to facilitate the appearance and development of dental cavities. Such microorganisms are always associated with periodontal disease, and if such microorganisms remain unchecked or uncontrolled, extraction of teeth are likely to occur. In the past, the presence of microorganisms in the gingiva of patients with periodontal disease has been periodically and erratically treated with anti-microbial agents, including antibiotics. For anti-microbial agents and antibiotics to be effective in the gingiva, such agents and antibiotics must come into direct contact with microorganisms, and such contact is known to be incomplete, partly because there may be barriers of fluid and tissue which prevent direct contact between the agents and antibiotics with the microorganisms. Also, such agents can be inactive for certain microorganisms and even when there is activity, such microorganisms can become metabolically resistant to the agents and antibiotics. A more effective way to reduce and to control microorganisms in the gingiva of patients with periodontal disease is to increase the efficacy of the immune system of the host. Coenzyme Q10 (CoQ10) has been known to increase the immune system, but previously it was unknown that CoQ10 could be a very effective mechanism to reduce and to eliminate microorganisms in the gingiva of patients with periodontal disease.
摘要翻译：具有牙周病的患者牙龈中多种微生物的存在是众所周知的，对牙龈健康有害，特别是促进牙腔的外观和发育。这样的微生物总是与牙周病有关，如果这种微生物保持不受控制或不受控制，则可能会出现牙齿的提取。在过去，牙周病患者的牙龈中的微生物的存在已经定期地和不定期地用抗 - 微生物剂，包括抗生素。为了使抗微生物剂和抗生素在牙龈中有效，这种药剂和抗生素必须与微生物直接接触，这种接触已知是不完全的，部分原因是可能存在妨碍液体和组织之间直接接触的障碍代理商和抗生素与微生物。此外，这些药剂对于某些微生物也是无活性的，甚至当有活性时，这样的微生物可以代谢对药物和抗生素的抗性。减少和控制牙周病患者牙龈中微生物的更有效的方法是增加宿主免疫系统的功效。已知辅酶Q10（CoQ10）可增加免疫系统，但以前不知道CoQ10可能是减少和消除牙周病患者牙龈中微生物的非常有效的机制。

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