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.

公开(公告)号：JPH0698766A

公开(公告)日：1994-04-12

申请号：JP15557591

申请日：1991-05-30

Applicant: AGENCY IND SCIENCE TECHN

Inventor： HIRANO TAKASHI ,  TODOROKI TAKESHI ,  OHASHI SHINICHI

IPC: A61K38/44 ,  A61P29/00 ,  C12N9/02

Abstract: PURPOSE:To obtain a polymer derivative having high activity and excellent anti-inflammatory action by adding a dimethylmaleic acid anhydride solution to a superoxide dismutase solution, reacting the components and bonding the reaction product to a divinylethyl ether-maleic anhydride copolymer, etc. CONSTITUTION:A superoxide dismutase(SOD) is dissolved in a weakly basic inorganic buffer solution, an organic solvent solution of dimethylmaleic acid anhydride of formula I is dropped to the above solution and made to react with each other, the reaction product is incorporated and bonded with an organic solvent solution of a polymer such as a divinylethyl ether-maleic anhydride copolymer (DIVEMA) expressed by formula II (m is integer of 20-500) or a polyethylene glycol derivative (PEG2) expressed by formula III (n, is integer of 10-700) and the reaction solution is adjusted to weakly acidic state. The precipitated dimethylmaleic acid is separated and the reaction product is purified to obtain an SOD-polymer derivative expressed by formula IV [Polymer is group of formula V (m is integer of 20-500; the group is bonded to the amino group of SOD at the position of X through amide bond); (i) is integer of 1-22].

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.