公开(公告)号：JPH07330618A

公开(公告)日：1995-12-19

申请号：JP14553394

申请日：1994-06-03

Applicant: AGENCY IND SCIENCE TECHN

Inventor： ITO SHOJI ,  MATSUMARU YUJI ,  HIRANO TAKASHI ,  OHASHI SHINICHI

IPC: A61K31/785 ,  A61K49/00 ,  A61P9/00

Abstract: PURPOSE:To obtain a vascular embolic agent, excellent in the safety such as neither adverse side effect nor danger caused by organic solvents and suitably usable in intravascular operation. CONSTITUTION:This vascular embolic agent comprises an aqueous solution containing a heat-sensitive polymeric compound, constituted of at least one recurring unit of an N-substituted (meth)acrylamide represented by the formula (R is H or methyl; R is H, an alkyl or an alkoxyalkyl; R is an alkyl or an alkoxvalkyl) and having a molecular weight corresponding to 0.01-6.0dl/g intrinsic viscosity [eta] in a tetrahydrofuran solution at 27 deg.C and 10-37 deg.C transition temperature in water at 0.5-50wt.% concentration. A homopolymer of the N- substituted (meth)acrylamide, a copolymer of two or more thereof and a copolymer of the N-substituted (meth)acrylamide and other monomers are cited as the heat-sensitive polymeric compound. The vascular embolic agent is capable of emerging from a catheter, thereby increasing the temperature, convertible into a solid form and blocking blood vessels.

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：JPH04351607A

公开(公告)日：1992-12-07

申请号：JP12333591

申请日：1991-05-28

Applicant: SANKYO CO ,  AGENCY IND SCIENCE TECHN

Inventor： KANEKO MASAKATSU ,  KAMOGARI MAKOTO ,  KOBAYASHI TOMOO ,  HIRANO TAKASHI ,  OHASHI SHINICHI ,  TANAKA YOSHIO

IPC: A61K31/70 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7064 ,  A61K31/7072 ,  A61K47/48 ,  A61P35/00 ,  C07H19/067 ,  C08F8/12 ,  C08F8/30 ,  C08F16/32 ,  C08F216/12 ,  C08F220/04 ,  C08F222/06

Abstract: PURPOSE:To obtain a polymer complex having good sustained release properties and strong anti-tumor activity against tumor cells by reacting a divinyl ether- maleic anhydride copolymer with a 5-fluorouridine derivative. CONSTITUTION:The title complex is obtained by reacting a divinyl ether-maleic anhydride copolymer represented by formula I (wherein n is 10 to 30) with a compound represented by formula II (wherein m is 1 to 19) and hydrolyzing the acid anhydride moieties remaining unreacted. It has a structural unit selected from those represented by formulae III to V, and has a -CONH-/-COO- ratio of 0.01-1.0. Preferred examples of the complex include one obtained from a copolymer of formula I (wherein n is an integer of 18 to 23), one having a -CONH-/-COO- ratio of 0.1-0.4, one obtained using a compound of formula II (wherein m is an integer of 2 to 15), one having an average molecular weight of 6,000-26,000, and one containing a structural unit represented by formula IV.

公开(公告)号：JPS6322803A

公开(公告)日：1988-01-30

申请号：JP31283586

申请日：1986-12-26

Applicant: AGENCY IND SCIENCE TECHN

Inventor： HIRANO TAKASHI ,  OHASHI SHINICHI ,  MORIMOTO SATOSHI ,  SHIRAKI MASARU ,  TSUDA KEISHIRO ,  KOBAYASHI TOMOO ,  TSUKAGOSHI SHIGERU

IPC: A61K31/765 ,  A61K45/00 ,  A61K47/48 ,  A61P35/00 ,  C08F8/30

Abstract: PURPOSE:To obtain a copolymer having excellent slow-releasing property of a carcinostatic substance, low toxicity and improved carcinostatic effect, by reacting a carcinostatic substance to a divinyl ether-maleic anhydride copolymer and hydrolyzing the reaction product. CONSTITUTION:A divinyl ether-maleic anhydride copolymer of formula I (n is a value corresponding to the copolymer molecular weight of 2,000-15,000) is made to react with a carcinostatic substance having hydroxyl group or amino group (e.g. 5-fluorouridine, 1-beta-D-arabinofuranosylcytosine) in the presence of an organic solvent (e.g. N-methylpyrrolidone) at a rate to give a content of usually 5-40wt%. The reaction product is hydrolyzed and optionally converted to a salt to obtain the objective copolymer of formula II (R is residue obtained by removing one H atom from the hydroxyl group or amino group of the above carcinostatic substance). EFFECT:The carcinostatic activity is promoted by the synergistic effect with the carcinostatic activity of the copolymer.

公开(公告)号：JPH1075792A

公开(公告)日：1998-03-24

申请号：JP24888996

申请日：1996-08-30

Applicant: AGENCY IND SCIENCE TECHN

Inventor： ITO HIROKO ,  HIRANO TAKASHI

IPC: C12N15/09 ,  C07H21/04 ,  C12N9/00 ,  C12Q1/68 ,  C12R1/645

Abstract: PROBLEM TO BE SOLVED: To obtain a new primer for amplifying ribozyme gene of Isaria japonica comprising an oligonucleotide having a specific base sequence, used for amplification, etc., of ribozyme gene of the Isaria japonica useful as a treatment, etc., for viral disease, cancer, etc., by an antisense method. SOLUTION: This primer for amplifying ribozyme gene of Isaria japonica is the new one comprising an oligonucleotide having base sequences of formula I and II, respectively, and a nucleic acid sequence usable for an antisense method expected as a new treating method for viral disease and cancer can be constituted based on an information of the basic sequence determined from a group I ribozyme gene derived from the Isaria japonica and amplified by using the primer. The primer is obtained by synthesizing few kinds of oligonucleotides each having 20-25 mer length and, based on the base sequence, etc., of 18S liposome DNA gene of Sclerotenia sclerotiorum belonging to the family Sclerotium of class Ascomycetes, and selecting the primer by confirming the amplification of the gene of the Isaria japonica.

公开(公告)号：JPH05310819A

公开(公告)日：1993-11-22

申请号：JP10592192

申请日：1992-03-31

Applicant: AGENCY IND SCIENCE TECHN

Inventor： HIRANO TAKASHI ,  KOKUBU TOMOKUNI ,  OHASHI SHINICHI

IPC: A61K31/70 ,  A61K31/765 ,  A61P35/00 ,  A61P43/00 ,  C08F8/32 ,  C08F8/42 ,  C08F8/44 ,  C08F16/32 ,  C08F20/02 ,  C08F216/12 ,  C08F222/06

Abstract: PURPOSE:To obtain an arabinofuranosylcytosine having low toxicity and an excellent carcinostatic effect by incorporating an arabinofuranosylcytosine residue into a divinyl ether/maleic anhydride copolymer through the medium of a specific group. CONSTITUTION:A divinyl ether/maleic anhydride copolymer represented by formula II (wherein m is an integer of 10-500) is reacted in an inert organic solvent with an amino acid represented by the formula H2N-(CH2)n-COOH (wherein n is an integer of 1-11) and then with arabinofuranosylcytosine. According to need, the reaction product is converted into a salt form. The obtained derivative contains 10-500 repeating units represented by formula I (wherein R is H or an arabinofuranosylcytosine residue and n is an integer of 1 to 11), at least 10mol% of the units containing an arabinofuranosylcytosine residue as R.

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.

公开(公告)号：JPH0975084A

公开(公告)日：1997-03-25

申请号：JP25450595

申请日：1995-09-07

Applicant: AGENCY IND SCIENCE TECHN ,  HIGETA SHOYU KK

Inventor： ITO HIROKO ,  MATSUI IKUO ,  ISHIKAWA KAZUHIKO ,  HIRANO TAKASHI ,  HOSONO KUNIAKI ,  TAKAGI HIROAKI ,  TANAKA AKIMITSU

IPC: C12N15/09 ,  C12N9/26 ,  C12N15/00 ,  C12R1/07

Abstract: PROBLEM TO BE SOLVED: To obtain a new modified synthetic enzyme in which tyrosine constituting the active center of the region A of a cyclodextrin-synthesizing enzyme is replaced with another amino acid, and which gives the reaction product greatly high in the amount of the synthesized α-cyclodextrin. SOLUTION: This new modified cyclodextrin-synthesizing enzyme wherein the 100-tyrosine constituting the active center of the region A of a cyclodextrin- synthesizing enzyme having an amino acid sequence of the formula is replaced with another amino acid such as tryptophane, phenylalanine, leucine or aspartic acid. The action of the enzyme on a substrate such as starch can give the reaction product greatly high in the content of the α-cyclodextrin. The modified enzyme is obtained by extracting the chromosome from Bacillus macerans IAM 1243, multiplying the chromosome with PCR using a synthesized primer containing the base sequence of the cyclodextrin-synthesizing enzyme, subjecting the multiplied chromosome to a site-specific mutation so as to replace the tyrosine of the active center of the obtained gene with another amino acid.

公开(公告)号：JPH0937797A

公开(公告)日：1997-02-10

申请号：JP21404395

申请日：1995-07-31

Applicant: AGENCY IND SCIENCE TECHN

Inventor： ITO HIROKO ,  HIRANO TAKASHI ,  HOSONO KUNIAKI

IPC: C12N15/09 ,  C07H21/04 ,  C12Q1/68

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new primer consisting of oligonucleotides having specific base sequences respectively, capable of amplifying the 18S ribosome RNA of plant worm, determining and analyzing quickly the base sequence and identifying the plant worm's strain. SOLUTION: This new primer consists of oligonucleotides having base sequences of formula I and formula II, respectively, and has the following advantages: the 18S ribosome RNA gene of plant worm can be amplified by PCR process; the base sequence of the gene can be determined and analyzed quickly; the plant worm's strain capable of producing pharmacologically active substance can be identified based on its genetic characteristics; and exploration efficiency of new physiologically active substance-productive bacteria can be remarkably improved. As the plant worm (e.g. Cordyceps sinensis) belongs to Ascomycetes, this new primer is obtained by the following process: several kinds of partial base sequences are synthesized based on the base sequence of the 18S ribosome RNA gene of a strain (e.g. Sclerotinia sclerotiorum) as other Ascomycetes, and from these partial base sequences, one that enables amplification of the plant worm's gene is selected.

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].