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    • 4. 发明授权
    • CRF antagonists
    • CRF拮抗剂
    • US5109111A
    • 1992-04-28
    • US498814
    • 1990-03-23
    • Jean E. F. RivierWylie W. Vale, Jr.Catherine L. RivierJean-Francois Hernandez
    • Jean E. F. RivierWylie W. Vale, Jr.Catherine L. RivierJean-Francois Hernandez
    • A61K38/00C07K14/575
    • C07K14/57509A61K38/00Y10S514/805Y10S530/857
    • Several known members of the corticotropin releasing factor (CRF) family have been synthesized and tested, including human and rat CRF which have the formula: H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His- Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln- Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu- Ile-Ile-NH.sub.2. Peptides are herein disclosed that are potent competitive antagonists of CRF in mammals. One which has been found to be particularly potent is: H-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala- Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn- Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH.sub.2. One that has shown particularly prolonged duration of potency is: H-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala- Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn- Arg-Lys-CML-Nle-Glu-Ile-Ile-NH.sub.2. These antagonists or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, including humans, to achieve a prevent elevation of ACTH, .beta.-endorphin, .beta.-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels and/or a lowering of brain mediated responses to stress over an extended period of time. They may also be used to affect mood, memory and learning, as well as diagnostically.
    • 已经合成并测试了促肾上腺皮质激素释放因子(CRF)家族的几个已知成员,包括人和大鼠CRF,其具有下式:H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu- Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg- Lys-Leu-Met-Glu-Ile-Ile-NH2。 本文公开了肽,其是哺乳动物中CRF的有竞争力的拮抗剂。 已经发现特别有效的是:HD-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln -Ala-His-Ser-Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH2。 显示出特别延长的效力持续时间是:HD-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln -Ala-His-Ser-Asn-Arg-Lys-CML-Nle-Glu-Ile-Ile-NH2。 分散在药学或兽医学上可接受的液体或固体载体中的这些拮抗剂或其药学或兽医学上可接受的盐可以施用于包括人在内的哺乳动物,以达到预防ACTH,β-内啡肽,β-促渗素,其他产物 pro-opiomelanocortin基因和皮质酮水平和/或在长时间内脑介导的应激反应的降低。 它们也可能用于影响情绪,记忆和学习以及诊断。
    • 5. 发明授权
    • Adrenocorticotropin release inhibiting factor
    • 促肾上腺皮质激素释放抑制因子
    • US5043321A
    • 1991-08-27
    • US217237
    • 1988-07-11
    • Alex J. Baertschi
    • Alex J. Baertschi
    • A61K38/22
    • A61K38/2242Y10S514/805
    • A method for alleviating stress induced immunosuppression is accomplished by application of low doses of ANF[1-28] or other ANF analogs having intact N-terminal sequences. Atrial natriuretic factors (ANFs) with intact N-terminal sequences are shown to be effective inhibitors of CRF 41-stimulated ACTH secretion when the ANFs are present in low concentrations. ANF[1-28] significantly inhibited ACTH release stimulated by 1-5 nM CRF. At the most effective concentration of 100 pM, ACTH release was inhibited by 40.1% (p
    • 减轻应激诱导的免疫抑制的方法是通过应用低剂量ANF [1-28]或具有完整N末端序列的其他ANF类似物来实现的。 当ANF以低浓度存在时,具有完整N末端序列的心房利钠因子(ANFs)显示为CRF 41刺激的ACTH分泌的有效抑制剂。 ANF [1-28]显着抑制了1-5nM CRF刺激的ACTH释放。 在100 pM的最有效浓度下,ACTH释放被抑制了40.1%(p <0.001)。 这种效应在三个小时后表现,但不是在孵育只有一半或一个小时后。 相反,ANF [5-28],浓度为10至10,000 pM,对半衰期,1小时或3小时后的ACTH分泌无影响。 ANF [1-11]在100 pM和1000 pM的浓度下弱抑制ACTH分泌。 再次,需要三个小时的孵化来表现这些影响。
    • 6. 发明授权
    • Method and composition for treating arteriosclerosis
    • 用于治疗动脉硬化的方法和组合物
    • US4167562A
    • 1979-09-11
    • US937533
    • 1978-08-28
    • H. Ray Evers
    • H. Ray Evers
    • A61K35/55A61K33/14A61K37/40A61K31/725A61K31/68
    • A61K35/55Y10S514/805
    • New compositions and their method of use for treating cardiovascular diseases primarily due to arteriosclerosis and atherosclerosis. These new compositions are prepared from a base Ringers injection to which is added a B-complex, hydrochloric acid, sodium ascorbate, pyridoxine hydrochloride, magnesium sulfate, adrenal cortex, magnesium chloride, thiamine, heparin sodium, calcium gluconate and calcium d-saccharate. Additional embodiments of the solution composition are also disclosed containing niacin, vitamin B.sub.12, ether, algae and amino acids. The compositions are useful in removing plaques from the interior walls of the arteries and veins, thereby improving blood supply to body tissues.
    • 新的组合物及其用于治疗心血管疾病的方法主要由于动脉硬化和动脉粥样硬化。 这些新组合物由基础Ringers注射液制备,向其中加入B络合物,盐酸,抗坏血酸钠,盐酸吡哆醇,硫酸镁,肾上腺皮质,氯化镁,硫胺素,肝素钠,葡萄糖酸钙和d-糖酸钙。 还公开了溶液组合物的另外的实施方案,其包含烟酸,维生素B12,醚,藻类和氨基酸。 组合物可用于从动脉和静脉的内壁去除斑块,从而改善对身体组织的血液供应。