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1. 发明授权

US5243027A Method of preparing angiotensin converting enzyme inhibitors 失效
标题翻译：制备血管紧张素转换酶抑制剂的方法
公开(公告)号：US5243027A
公开(公告)日：1993-09-07
申请号：US737852
申请日：1991-07-31
申请人： Tsutomu Mimura , Yasuhiro Kohama , Kazuhiko Nagata , Ryoichi Tsurutani
发明人： Tsutomu Mimura , Yasuhiro Kohama , Kazuhiko Nagata , Ryoichi Tsurutani
IPC分类号： A61K38/00 , C12N9/04
CPC分类号： C12N9/0006 , A61K38/00
摘要： A method of preparing an angiotensin converting enzyme inhibitor having the amino acid sequence selected from the group consisting of:Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg (SEQ ID No: 1),Gly-Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr (SEQ ID No: 2) andAla-Tyr-Ile-Ala-Ser-Lys-Gly-Leu (SEQ ID No: 3); which comprises the steps of:(a) disrupting bacteria to obtain a cell extract, wherein the disruption is at least one of mechanical and chemical disruption;(b) exposing said cell extract to an acid mixture comprising acetic acid and hydrochloric acid, wherein said acid mixture comprises acetic acid in a concentration of 0.01 to 10M and hydrochloric acid in a concentration of 1 to 100 mM, to produce an acid hydrolysate; and(c) purifying from said acid hydrolysate a peptide having the amino acid sequence selected from the group consisting of:Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg (SEQ ID No: 1),Gly-Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr (SEQ ID No: 2) andAla-Tyr-Ile-Ala-Ser-Lys-Gly-Leu (SEQ ID No: 3).
摘要翻译：一种制备具有选自Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg（SEQ ID No：1），Gly- Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr（SEQ ID No：2）和Ala-Tyr-Ile-Ala-Ser-Lys-Gly-Leu（SEQ ID No：3）; 其包括以下步骤：（a）破坏细菌以获得细胞提取物，其中所述破坏是机械和化学破坏中的至少一种; （b）将所述细胞提取物暴露于含有乙酸和盐酸的酸混合物中，其中所述酸混合物包含浓度为0.01至10M的乙酸和浓度为1至100mM的盐酸，以产生酸水解产物; 和（c）从所述酸水解产物中纯化具有选自Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg（SEQ ID No：1）的氨基酸序列的肽， Gly-Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr（SEQ ID No：2）和Ala-Tyr-Ile-Ala-Ser-Lys-Gly-Leu（SEQ ID No：3）。

2. 发明授权

US5098887A Angiotensin converting enzyme inhibitor 失效
标题翻译： ANGIOTENSIN转化酶抑制剂
公开(公告)号：US5098887A
公开(公告)日：1992-03-24
申请号：US659432
申请日：1991-02-26
申请人： Tsutomu Mimura , Yasuhiro Kohama , Kazuhiko Nagata , Ryoichi Tsurutani
发明人： Tsutomu Mimura , Yasuhiro Kohama , Kazuhiko Nagata , Ryoichi Tsurutani
IPC分类号： C12N9/99 , A61K38/00 , A61K38/55 , A61P9/12 , C07K1/20 , C07K7/06 , C07K14/195 , C07K14/41 , C07K14/81 , C12N9/04 , C12P21/02 , C12R1/07
CPC分类号： C12N9/0006 , A61K38/00
摘要： An angiotensin converting enzyme inhibitor containing Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg (SEQ ID No: 1) Gly-Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr (SEQ ID No: 2) or Ala-Tyr-Ile-Ala-Ser-Lys-Gly-Leu (SEQ ID No: 3) as an active component.

3. 发明授权

US5071955A Octopeptide exhibiting antimypertensive activity 失效
标题翻译： OCTOPEPTIDE展示抗生素活性
公开(公告)号：US5071955A
公开(公告)日：1991-12-10
申请号：US363772
申请日：1989-06-09
申请人： Tsutomu Mimura , Yasuhiro Kohama , Mikio Satake , Yasukazu Nagase
发明人： Tsutomu Mimura , Yasuhiro Kohama , Mikio Satake , Yasukazu Nagase
IPC分类号： A61K38/00 , A61K38/55 , A61P9/12 , A61P29/00 , C07K1/02 , C07K1/04 , C07K1/14 , C07K1/16 , C07K1/20 , C07K7/06 , C07K14/81 , C12N9/04
CPC分类号： C12N9/0006 , A61K38/00
摘要： A novel peptide possessing excellent antihypertensive activity is disclosed. The peptide has the formula:Pro-Thr-His-Ile-Lys-Trp-Gly-Asp (I)and can be prepared by purifying a fluid extracted from fish tissues or by combining constituting amino acids by a peptide synthesis method. It exhibits excellent ACE inhibitory activity, low toxicity, and good stability, and is thus an extremely useful and effective antihypertensive substance.

4. 发明授权

US4775743A Peptide derivatives 失效
标题翻译：肽衍生物
公开(公告)号：US4775743A
公开(公告)日：1988-10-04
申请号：US905815
申请日：1986-09-10
申请人： Tsutomu Mimura , Yasuhiro Kohama , Chikara Fukaya , Masahiro Watanabe , Kazumasa Yokoyama
发明人： Tsutomu Mimura , Yasuhiro Kohama , Chikara Fukaya , Masahiro Watanabe , Kazumasa Yokoyama
IPC分类号： A61K38/00 , A61P7/02 , A61P9/06 , C07K5/06 , C07K7/06 , C07K7/18
CPC分类号： C07K7/06 , C07K5/06026 , C07K7/18 , A61K38/00 , Y10S514/821
摘要： New peptide derivatives represented by the following general formulaR.sub.1 -Pro-Hyp-R.sub.2wherein R.sub.1 is a hydrophobic radical, R.sub.2 is a hydrophilic radical, Pro is prolyl and Hyp is hydroxyprolyl show more powerful inhibitory action against platelet agglutination than conventional drugs and have potential use as anti-agglutination agent. The peptide derivative can be prepared by condensing a peptide containing a hydrophobic radical with a carboxylic acid containing a hydrophilic radical. The peptide derivative can be used in the form of parenteral injections, tablets, capsules or powder, the typical daily dose being in the range from 1 mg to 500 mg for adults.
摘要翻译：由以下通式R1-Pro-Hyp-R2表示的新肽衍生物，其中R1是疏水基团，R2是亲水基团，Pro是脯氨酰基，Hyp是羟基脯氨酸，比常规药物显示更强大的抗血小板凝集抑制作用，并具有潜力用作抗凝集剂。肽衍生物可以通过将含有疏水基团的肽与含有亲水基团的羧酸缩合而制备。肽衍生物可以以肠胃外注射，片剂，胶囊或粉末的形式使用，成人的典型日剂量范围为1mg至500mg。

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