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    HIGH-MOLECULAR MITOMYCIN C DERIVATIVE AND PRODUCTION THEREOF
    21.
    发明专利
    HIGH-MOLECULAR MITOMYCIN C DERIVATIVE AND PRODUCTION THEREOF 失效

    公开(公告)号：JPH04288304A

    公开(公告)日：1992-10-13

    申请号：JP7719591

    申请日：1991-03-18

    Applicant: AGENCY IND SCIENCE TECHN

    Inventor： HIRANO TAKASHI ,  TODOROKI TAKESHI ,  OHASHI SHINICHI

    IPC: A61K31/785 ,  A61K47/48 ,  A61P35/00 ,  C08F8/30 ,  C08F16/32 ,  C08F20/02 ,  C08F216/12 ,  C08F220/02

    Abstract: PURPOSE:To prepare the title deriv. having a low toxicity and improved anticancer effects by reacting a specific divinyl ether-maleic anhydride copolymer with an aminocarboxylic acid and then with mitomycin C. CONSTITUTION:The title deriv. comprising 10-500 repeating units of formulas III and IV (wherein R is a mitomycin C residue of formula V; and n is 1-11) in a molar ratio of (0:100)-(90:10) or a salt thereof is produced by reacting a divinyl ether-maleic anhydride copolymer of formula I (wherein m is 10-500) having a mol.wt. of 100,000 or lower with an aminocarboxylic acid of formula II (wherein n is 1-11) in an org. solvent and then with mitomycin C, if necessary converting the reaction product into a pharmacologically acceptable salt, filtering the product by ultrafiltration, and freeze-drying it.

    NOVEL RECOMBINANT PLASMID PGRFM44-6
    23.
    发明专利
    NOVEL RECOMBINANT PLASMID PGRFM44-6 失效

    公开(公告)号：JPH02142476A

    公开(公告)日：1990-05-31

    申请号：JP29420488

    申请日：1988-11-21

    Applicant: AGENCY IND SCIENCE TECHN

    Inventor： IWAKURA MASAHIRO ,  OHASHI SHINICHI ,  TANAKA YOSHIO

    IPC: C12N15/09 ,  C07K14/00 ,  C07K14/575 ,  C07K14/60 ,  C07K19/00 ,  C12N1/21 ,  C12N15/18 ,  C12N15/62 ,  C12P21/02 ,  C12R1/19

    Abstract: NEW MATERIAL:A recombinant plasmid pGRFM44-6 stably replicated in Esherichia coli, capable of giving trimethoprim resistance and amplicillin resistance to the Escherichia coli as a host and coding the fused protein of a bovine growth hormone-releasing factor derivative having an amino acid sequence of the formula with a dihydrofolic acid reductase. USE:For the production of a bovine growth hormone-releasing factor (GRS) and a dihydrofolic acid reductase(DHFR). PREPARATION:For example, a recombinant plasmid pSG1-12 coding DHFR and the sequence of Np.1-29 amino acids of bovine GRF is treated with a restriction enzyme. The produced DNA fragment is combined with a synthetic DNA coding the sequence of No.29-44 amino acids of the GRF and subsequently inserted into an Escherichia coli, followed by culturing the Esherichia coli and screening the cultured colony thereof the select a clone producing DHFR-GRF, thereby providing the pGRFM44-6.

    HIGH-MOLECULAR LINK BETWEEN METHOTREXATE DERIVATIVE AND PYRAN COPOLYMER AND ITS PRODUCTION
    24.
    发明专利
    HIGH-MOLECULAR LINK BETWEEN METHOTREXATE DERIVATIVE AND PYRAN COPOLYMER AND ITS PRODUCTION 失效

    公开(公告)号：JPH07173080A

    公开(公告)日：1995-07-11

    申请号：JP13287393

    申请日：1993-05-11

    Applicant: AGENCY IND SCIENCE TECHN

    Inventor： HIRANO TAKASHI ,  TODOROKI TAKESHI ,  OHASHI SHINICHI ,  KOKUBU TOMOKUNI ,  TANAKA HIDEAKI

    IPC: A61K31/505 ,  A61K47/48 ,  A61P35/00

    Abstract: PURPOSE:To obtain the subject new low toxic high-molecular link or a salt thereof having excellent carcinostatic activity. CONSTITUTION:This high-molecular link is made up of 10-500 recurring units of formula I and formula II (R is a methotrexate residue of formula III or IV; (n) is 1-12) with the molar ratio of formula I to formula II of (0:100) to (90:10). The high-molecular link is obtained by the following processes: methotrexate is reacted with an alkyldiamine to synthesize and isolate a methotrexate derivative, which is, in turn, reacted with a pyran copolymer in a water-soluble organic solvent. The high-molecular link gradually releases the methotrexate derivative as a carcinostatic substance in the serum, having markedly excellent carcinostatic activity as compared to the single use of methotrexate, owing to the synergistic effect between carcinostatic methotrexate and carcinostatic pyran copolymer.

    ANGIOTENSIN II
    27.
    发明专利
    ANGIOTENSIN II 失效

    公开(公告)号：JPH01252288A

    公开(公告)日：1989-10-06

    申请号：JP7967988

    申请日：1988-03-31

    Applicant: AGENCY IND SCIENCE TECHN

    Inventor： IWAKURA MASAHIRO ,  OHASHI SHINICHI ,  SAKAI TSUKASA ,  TANAKA YOSHIO

    IPC: C12N15/09 ,  C07K1/14 ,  C07K1/22 ,  C07K7/14 ,  C07K14/00 ,  C07K19/00 ,  C12N1/20 ,  C12N1/21 ,  C12N9/06 ,  C12P21/02 ,  C12R1/19

    Abstract: PURPOSE:To obtain a large amount of dihydrofolic acid reductase-angiotensin II fused protein, by manifesting a fused gene in which an angiotensin II gene is included in a plasmid vector pTP 70-1 with a colon bacillus. CONSTITUTION:A newly recombined plasmid pANG2-11, which is replicated in stable with a colon bacillus, imparting resistance to trimethoprim and resistance to ampicillin to a colon bacillus as a host, having a size of 4651 basic pairs and having a bonded structure of chemically synthesized DNA of 43 basic pairs containing a conformation coding angiotensin II at BamHI site of pTP 70-1, is produced. A colon bacillus introduced of the plasmid pANG2-11 (FERM BP-1815) produces a large amount of dihydrofolic acid reductase-angiotensin II fused protein.

    PRODUCTION OF BRADYKININ
    28.
    发明专利
    PRODUCTION OF BRADYKININ 失效

    公开(公告)号：JPS6471497A

    公开(公告)日：1989-03-16

    申请号：JP22612787

    申请日：1987-09-09

    Applicant: AGENCY IND SCIENCE TECHN

    Inventor： IWAKURA MASAHIRO ,  OHASHI SHINICHI ,  SAKAI TSUKASA ,  TANAKA YOSHIO

    IPC: C12N15/09 ,  C07K1/12 ,  C07K7/06 ,  C07K7/18 ,  C07K19/00 ,  C12N1/21 ,  C12P21/02 ,  C12R1/19

    Abstract: PURPOSE:To obtain bradykinin having hypotensive action, by separating bacterial cell from E.coli C600 strain containing pBLAK1, treating the cell with cyanogen bromide and separating the objective compound by high-performance liquid chromatography. CONSTITUTION:E.coli C600 strain containing recombinant plasmid pBLAK1 is cultured in a medium, the bacterial cells are collected after cultivation and centrifuged to obtain a protein composed of dihydrofolic acid reductase-reductase fused to bradykinin. The protein is mixed and treated with cyanogen bromide and subjected to high-performance liquid chromatography to obtain bradykinin useful in the fields of medical and pharmaceutical industries, etc.

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