公开(公告)号：US07045589B2

公开(公告)日：2006-05-16

申请号：US10298151

申请日：2002-11-15

Applicant: Jorge Heller ,  Steven Y. Ng

Inventor： Jorge Heller ,  Steven Y. Ng

IPC: C08G59/00 ,  C08G65/00 ,  C08G67/02

CPC classification number: A61K47/34 ,  A61K9/0024 ,  A61K9/1075 ,  C08G65/002 ,  C08G65/34 ,  C08G2650/42 ,  Y10S514/805

Abstract: Bioerodible poly(ortho esters) useful as orthopedic implants or vehicles for the sustained delivery of pharmaceutical, cosmetic and agricultural agents from dioxane-based di(ketene acetals). Block copolymers contain these bioerodible poly(ortho esters). These block copolymers have both hydrophilic and hydrophobic blocks. They form micelles in aqueous solution, making them suitable for encapsulation or solubilization of hydrophobic or water-insoluble materials; and they also form bioerodible matrices for the sustained release of active agents.

Abstract translation: 可用作骨科植入物或用于从二恶烷基二（乙烯酮缩醛））持续递送药物，化妆品和农药的生物可蚀解聚（原酸酯）。 嵌段共聚物含有这些可生物腐蚀的聚（原酸酯）。 这些嵌段共聚物具有亲水性和疏水性嵌段。 它们在水溶液中形成胶束，使其适合于疏水或水不溶性材料的包封或溶解; 并且它们还形成用于持续释放活性剂的生物可蚀解基质。

公开(公告)号：US5663292A

公开(公告)日：1997-09-02

申请号：US353928

申请日：1994-12-12

Applicant: Jean E. F. Rivier

Inventor： Jean E. F. Rivier

IPC: G01N33/15 ,  A61K38/00 ,  A61K38/04 ,  A61K45/00 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  C07K14/575 ,  G01N33/50 ,  G01N33/566 ,  G01N33/68 ,  G01N33/74 ,  C07K14/695 ,  C07K7/64

CPC classification number: G01N33/5008 ,  C07K14/57509 ,  G01N33/502 ,  G01N33/566 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/74 ,  A61K38/00 ,  G01N2333/5751 ,  Y10S514/805 ,  Y10S930/26

Abstract: Improved CRF antagonist peptides have the formula: ##STR1## wherein R.sub.30 is Cys or Glu; R.sub.33 is Cys, Lys or Orn; provided that when R.sub.30 is Cys, R.sub.33 is Cys and when R.sub.30 is Glu, R.sub.33 is Lys or Orn. The N-terminus may be extended by Asp-Leu-Thr. Lys may be substituted for Arg.sup.23 and its side chain connected by a lactam bridge to Glu.sup.20 to form a dicyclic peptide. Specific CRF antagonists disclosed include (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Lys.sup.33 ]rCRF(12-41); (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Orn.sup.33 ]rCRF(12-41), (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Cys.sup.30,33 ]rCRF (12-41) and (bicyclo 20-23,30-33) [D-Phe.sup.12, Nle.sup.21,38, Lys.sup.23,33, Glu.sup.30 ]-rCRF(12-41).

Abstract translation: 改进的CRF拮抗剂肽具有下式：（环30-33）DPheHisLeuLe​​uArgGluVal LeuGluNleAlaArgAlaGluGlnLeu LeuNleGluIleIleNH2其中R30是Cys或Glu; R33是Cys，Lys或Orn; 条件是当R30为Cys时，R33为Cys，当R30为Glu时，R33为Lys或Orn。 N末端可以被Asp-Leu-Thr延伸。 Lys可被Arg23取代，其侧链通过内酰胺桥连接至Glu20以形成双环肽。 公开的具体CRF拮抗剂包括（环30-33）[D-Phe12，Nle21,38，Glu30，Lys33] rCRF（12-41）; （环30-33）[D-Phe12，Nle21,38，Glu30，Orn33] rCRF（12-41），（环30-33）[D-Phe12，Nle21,38，Cys30,33] rCRF（12-41 ）和（双环20-23,30-33）[D-Phe12，Nle21,38，Lys23,33，Glu30] -rCRF（12-41）。

公开(公告)号：US5348729A

公开(公告)日：1994-09-20

申请号：US878608

申请日：1992-05-05

Applicant: Esther M. Sternberg ,  Philip W. Gold ,  Samuel W. Page

Inventor： Esther M. Sternberg ,  Philip W. Gold ,  Samuel W. Page

IPC: A61K31/135 ,  A61K31/35 ,  A61K31/365 ,  A61K31/40 ,  A61K31/485 ,  A61K31/495 ,  A61K31/565 ,  A61K31/57 ,  A61K31/585 ,  A61K38/22 ,  A61K45/06 ,  G01N33/50 ,  G01N33/564 ,  G01N33/74 ,  G01N1/00 ,  A61K37/60 ,  A61K45/05 ,  G01N33/48

CPC classification number: A61K31/40 ,  A61K31/135 ,  A61K31/35 ,  A61K31/365 ,  A61K31/485 ,  A61K31/495 ,  A61K31/565 ,  A61K31/57 ,  A61K31/585 ,  A61K45/06 ,  G01N33/5091 ,  G01N33/564 ,  G01N33/74 ,  G01N33/743 ,  G01N2800/102 ,  Y10S435/975 ,  Y10S514/805 ,  Y10S514/825 ,  Y10S514/885 ,  Y10S514/886

Abstract: The present invention is directed to a method for testing the susceptibility of a mammal to inflammatory diseases which comprises the steps of:administering to a mammal a compound selected from the group consisting of Type 1 mineralocorticoid receptor antagonists, opiate antagonists, estrogen antagonists or mixed estrogen agonists/antagonists, progesterone agonists; or a combination of an estrogen antagonist with one or a combination of a Type I glucocorticoid receptor antagonist, a Type II glucocorticoid agonist or a progesterone agonist which is effective in stimulating the hypothalamic-pituitary-adrenal (HPA) axis; andmeasuring the level of at least one hormone secreted by the hypothalamus, pituitary or adrenal glands of said mammal.The present invention is also directed to methods of treating inflammatory diseases.

Abstract translation: 本发明涉及一种用于测试哺乳动物对炎性疾病的敏感性的方法，其包括以下步骤：向哺乳动物施用选自1型盐皮质激素受体拮抗剂，阿片剂拮抗剂，雌激素拮抗剂或混合雌激素 激动剂/拮抗剂，孕酮激动剂; 或雌激素拮抗剂与有效刺激下丘脑 - 垂体 - 肾上腺（HPA）轴的I型糖皮质激素受体拮抗剂，II型糖皮质激素激动剂或孕酮激动剂的组合的组合。 并测量由所述哺乳动物的下丘脑，垂体或肾上腺分泌的至少一种激素的水平。 本发明还涉及治疗炎性疾病的方法。

公开(公告)号：US5109111A

公开(公告)日：1992-04-28

申请号：US498814

申请日：1990-03-23

Applicant: Jean E. F. Rivier ,  Wylie W. Vale, Jr. ,  Catherine L. Rivier ,  Jean-Francois Hernandez

Inventor： Jean E. F. Rivier ,  Wylie W. Vale, Jr. ,  Catherine L. Rivier ,  Jean-Francois Hernandez

IPC: A61K38/00 ,  C07K14/575

CPC classification number: C07K14/57509 ,  A61K38/00 ,  Y10S514/805 ,  Y10S530/857

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US5043321A

公开(公告)日：1991-08-27

申请号：US217237

申请日：1988-07-11

Applicant: Alex J. Baertschi

Inventor： Alex J. Baertschi

IPC: A61K38/22

CPC classification number: A61K38/2242 ,  Y10S514/805

Abstract: 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

Abstract translation: 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。

公开(公告)号：US4167562A

公开(公告)日：1979-09-11

申请号：US937533

申请日：1978-08-28

Applicant: H. Ray Evers

Inventor： H. Ray Evers

IPC: A61K35/55 ,  A61K33/14 ,  A61K37/40 ,  A61K31/725 ,  A61K31/68

CPC classification number: A61K35/55 ,  Y10S514/805

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US3873510A

公开(公告)日：1975-03-25

申请号：US38854673

申请日：1973-08-15

Applicant: RICHTER GEDEON VEGYESZET

Inventor： KISFALUDY LAJOS ,  LOW MIKLOS ,  DANCSI LAJOS ,  SCHON ISTVAN ,  SZIRTES TAMAS ,  NYEKI OLGA ,  SZIRMAI MARIA ,  SZPORNY LASZLO ,  HAJOS GYORGY

IPC: C07K14/575 ,  A61K38/00 ,  A61K38/22 ,  C07K1/06 ,  C07K14/695 ,  C07C103/52 ,  A61K17/06

CPC classification number: C07K14/6955 ,  A61K38/00 ,  C07K14/695 ,  Y10S514/805

Abstract: Novel peptides of ACTH activity, having a complete ACTH sequence from the N-terminal amino acid at least to the sixteenth amino acid, but containing optionally other amino acids in the place of the individual amino acids of the ACTH sequence, and always containing an Alpha -aminooxy acid in the place of the first amino acid have been prepared by deblocking the appropriate protected peptide derivatives. The new compounds, as well as their acid addition salts, derivatives or complexes possess potent ACTH activities and are resistant to enzymatic decomposition. They can be used in therapy with great advantages.

Abstract translation: 具有ACTH活性的新肽，具有至少至第十六氨基酸的N-末端氨基酸的完整ACTH序列，但含有任选的其它氨基酸代替ACTH序列的各个氨基酸，并且总是含有α - 氨基氧酸代替第一个氨基酸已经通过解封合适当的保护肽衍生物来制备。

公开(公告)号：US3770715A

公开(公告)日：1973-11-06

申请号：US3770715D

申请日：1970-06-02

Applicant: CIBA GEIGY CORP

Inventor： TESSER G ,  RITTEL W

IPC: C07K14/575 ,  A61K38/00 ,  A61K38/22 ,  C07K1/113 ,  C07K14/695 ,  C07K19/00 ,  C07C103/52 ,  C07G7/00 ,  C08H1/00

CPC classification number: C07K14/695 ,  A61K38/00 ,  Y10S514/805

Abstract: ADRENOCORTICOTROPICALLY ACTIVE PEPTIDES WHICH DIFFER FROM (ALL-L)-ACTH-ACTIVE PEPTIDES HAVING A SEQUENCE OF 18-39 AMINOACIDS IN THAT THEY CONTAIN AS FIRST AMINOACID (FROM THE N-TERMINUS) D-SERINE AND AS AMINOACID IN THE POSITIONS 11 OR 11 AND 15-16 OR 11 AND 15-18, LORNITHINE, AND THEIR C-TERMINAL AMIDES AND ACID ADDITION SALTS AND COMPLEXES OF THESE COMPOUNDS.

公开(公告)号：US3679653A

公开(公告)日：1972-07-25

申请号：US3679653D

申请日：1968-09-27

Applicant: MONSANTO CO

Inventor： SCHUCK JAMES M ,  WILDI BERNARD S

IPC: A61K38/00 ,  A61K47/48 ,  A61K17/00 ,  C07C103/52 ,  C08F27/08

CPC classification number: A61K38/27 ,  A61K38/11 ,  A61K38/28 ,  A61K38/35 ,  A61K47/58 ,  Y10S514/805 ,  Y10S530/815

Abstract: A HORMONOALY-ACITVE REACTION PRODUCT OF A PEPTIDIC HORMONE SUCH AS BOVINE GROWTH HORMONE, INSULIN, VASOPRESSIN, ADRENOCORTICOTROPIC HORMONE, AND THE LIKE, WITH A COPOLYMER OF AN OLEFINICALLY UNSATURATED POLYCARBOXYLIC ACID AND AN OLEFIN. THE HORMONE IS COVALENTLY BOUND TO THE POLYMER THROUGH AN AMINO, HYDROXYL, OR SULFHYDRYL GROUP OF THE HORMONE WHICH IS NOT ESSENTIAL FOR HORMONAL ACITIVITY. THESE PRODUCTS HAVE IMPROVED STABILITY, ARE SUBSTANTIALLY ODORLESS AND COLORLESS, AND HAVE PROLONGED ACITIVITY WHEN CONTRASTED WITH THE NATIVE HORMONE.

公开(公告)号：US3639383A

公开(公告)日：1972-02-01

申请号：US3639383D

申请日：1968-01-23

Applicant: CIBA GEIGY CORP

Inventor： GELLER LEO

IPC: C07K14/575 ,  A61K9/107 ,  A61K38/00 ,  A61K38/22 ,  C07K1/113 ,  C07K14/695 ,  A61K17/16 ,  C07C103/52

CPC classification number: C07K14/695 ,  A61K38/00 ,  Y10S514/805

Abstract: COMPLEXES HAVING A PROLONGED ADRENOCORTICOTROPIC ACTIVITY, CONSISTING OF ADRENOCORTICOTROPICALLY ACTIVE PEPTIDES AND POLYPHOSPHORIC ACIDS CONTAINING ON AN AVERAGE AT LEAST 7 PHOSPHORUS ATOMS, OR THEIR SALTS.