公开(公告)号：JPS6377824A

公开(公告)日：1988-04-08

申请号：JP21943486

申请日：1986-09-19

Applicant: TOSOH CORP

Inventor： KATSUURA KIMIO ,  NIWA KUNIHIRO ,  IGARASHI TATSUO ,  SAITO MITSUTAKA

IPC: A61K38/44 ,  A61K9/06 ,  A61K9/127 ,  A61P17/00

Abstract: PURPOSE:To obtain a gelatinized preparation for external use having specific pH, viscosity and improved percutaneous absorption, comprising a specific amount of superoxide dismutase-containing liposome as an active ingredient, a carboxyvinyl polymer and a specific amount of a water-soluble basic substance. CONSTITUTION:A gelatinized preparation for external use which consists of 0.01-5.00wt% superoxide dismutase-containing liposome as an active ingredient, (0.1-3.0wt%) carboxyvinyl polymer, a water-soluble basic substance (e.g. alkylamine, dialkylamine, etc.) in an amount required for neutralizing the carboxyvinyl polymer and the rest of water and has pH 4-10 and 10,000-100,000 centipoise viscosity. The preparation may be mixed with

公开(公告)号：JP2000026454A

公开(公告)日：2000-01-25

申请号：JP19394698

申请日：1998-07-09

Applicant: TOSOH CORP

Inventor： TOKUNAGA TAKUMI ,  YAMAMOTO TAKASHI ,  ITO HIROYUKI ,  KONO KAZUHISA ,  HANAZAKI YASUAKI ,  KATSUURA KIMIO

IPC: C07D333/20 ,  C07D333/36

Abstract: PROBLEM TO BE SOLVED: To obtain a new triamine derivative useful as an organic intermediate, etc., of a medicine, an agrochemical material or the like. SOLUTION: This new triamine derivative is a compound of formula I [R1 is H, a lower alkyl or a lower cycloalkyl; R2 is H, a lower acyl or the like; R3 is H or a lower alkyl; R4 is H, a lower alkyl or a lower acyl; R3 and R4 form a ring by bonding each other; X, Y and Z are each H, a lower alkyl, a lower alkoxy or the like; (m), (n) are each 0, 1; E is carbonyl, CR5R6 (R5, R6 are each H or a lower alkyl); F is carbonyl or the like; provided that E and F can not be carbonyl simultaneously], e.g. 2-[3-(formylamino)phenylamino]- N-methyl-N-(3-thienylmethyl)acetamide. Further the compound the formula I is obtained by reacting a compound of formula II (E' is CR5R6; E7 is H, a lower alkyl or a lower acyl; V is a halogen) with a compound of formula III (R9 is H or a lower alkyl) in an inert solvent in the presence of a base.

公开(公告)号：JP2000026432A

公开(公告)日：2000-01-25

申请号：JP19394798

申请日：1998-07-09

Applicant: TOSOH CORP

Inventor： TOKUNAGA TAKUMI ,  YAMAMOTO TAKASHI ,  ITO HIROYUKI ,  KONO KAZUHISA ,  HANAZAKI YASUAKI ,  KATSUURA KIMIO

IPC: C07D239/34 ,  C07F7/10

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful as a synthetic intermediate of a thiocarbamate derivative expected as medical and agricultural chemicals and an organic intermediate, especially as a treating agent for hyperlipidemia. SOLUTION: This compound is expressed by formula I (R1 is H, a lower alkyl or a lower alkoxyalkyl; R2 and R3 are each a lower alkyl; X is O or S; Y is C or Si; V is a halogen), e.g. (2-tert-butylpyrimidin-5-yl)= chlorothioformate. The compound of formula I is obtained by reacting a compound of formula II (e.g. 2-tert-butylpyrimidin-5-ol) with a halocarbonylation agent such as thiophosgene in a solvent such as cyclohexane in the presence of a base such as sodium hydroxide preferably at from -5 deg.C to 40 deg.C for 2-10 hrs.

公开(公告)号：JP2000026419A

公开(公告)日：2000-01-25

申请号：JP19394898

申请日：1998-07-09

Applicant: TOSOH CORP

Inventor： TOKUNAGA TAKUMI ,  YAMAMOTO TAKASHI ,  ITO HIROYUKI ,  KONO KAZUHISA ,  HANAZAKI YASUAKI ,  KATSUURA KIMIO

IPC: C07D213/64

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound comprising a specific pyridine derivative and useful as an intermediate for medicines and agrochemicals and an organic intermediate. SOLUTION: This new compound is represented by formula I (R1 and R2 are each a lower alkyl; X is O or S; Z1 is a group CR3 or a group SiR4; R3 and R4 are each H, a lower alkyl, a lower alkoxy or the like; V1 is a halogen), e.g. (5-trimethylsilylpyridin-2-yl) chlorothioformate. The compound represented by formula I is obtained by reacting a compound represented by formula II [e.g. 5-trimethylsilyl-2(1h)-pyridinone] with a halocarbonylating agent such as thiophosgene in the presence of a base such as sodium hydroxide without or in a solvent such as water, preferably at -10 to +100 deg.C for several min to 24 h.

公开(公告)号：JPH11158198A

公开(公告)日：1999-06-15

申请号：JP32319597

申请日：1997-11-25

Applicant: TOSOH CORP

Inventor： IDE TERUHIKO ,  MURAYAMA KEIICHI ,  NAKAMURA MAKOTO ,  KATSUURA KIMIO

IPC: G01N30/96 ,  C07K1/18 ,  C07K14/715 ,  C12N1/19 ,  C12N5/10 ,  C12P21/00 ,  C12R1/645 ,  C12R1/91

Abstract: PROBLEM TO BE SOLVED: To purify the subject substance for expressing IL-6 physiological action, etc., on an industrial scale by bringing a solution containing an interleukin 6 (IL-6) receptor and impurities into contact with an ion exchanger and separating the adsorbed substance. SOLUTION: In this method for purifying an interleukin 6 receptor (IL-6R) from a culture solution of a gene recombinant fungus comprising a yeast belonging to the genus Pichia or the like or a gene recombinant animal cell as a solution containing IL-6R and impurities, the solution is brought into contact with an ion exchanger in a fluidized bed composed of the ion exchanger comprising a cation exchanger having an ion exchange group containing a cation exchange group such as a sulfopropyl group, etc., to adsorb IL-6R, which is separated from the ion exchanger by using an alkali buffer solution, etc., to purify a large amount of the objective IL-6R essential for expressing various physiological actions, useful for clinical applications, etc., on an industrial scale.

公开(公告)号：JPH10101633A

公开(公告)日：1998-04-21

申请号：JP25615596

申请日：1996-09-27

Applicant: TOSOH CORP

Inventor： KATSUURA KIMIO ,  IRINO SHIGEAKI ,  TOKUDA AKIRA

IPC: C07C231/20 ,  C07C237/12 ,  C07K1/14

Abstract: PROBLEM TO BE SOLVED: To provide a method for effectively producing an optically active amino acid ester having a high optical purity and useful as a raw material for a medicine in high yield by treating a D-isomer of a specific ester additive of an amino acid in a specified condition. SOLUTION: This method for producing an optically active amino acid ester having a high optical purity comprises a step for obtaining a D-isomer of an amino acid additive of a compound of the formula by mixing and reacting an optically active amino acid ester such as (homo) phenylalanine and phenylglycine containing the D- isomer with a N-substituted-α-Laspartyl-L-phenylalanine alkyl ester of the formula [R1 is a (substituted) phenyl; R2 is an aliphatic oxycarbonyl or a (substituted) benzyloxycarbonyl; R3 is an alkyl] in an aqueous solution to provide an adduct of the D-isomer of the amino acid ester with the compound of the formula, (i) a step for separating the adduct from the aqueous phase by using a water-incompatible solvent and extracting the adduct, (ii) a step for purifying the separated adduct by washing an organic solvent layer containing the adduct as the slurry, (iii) a step for recovering the D-amino acid ester having high optical purity as an acidic solution by performing acidolysis of the adduct with an acid aqueous solution to provide the objective optically active amino acidester.

公开(公告)号：JPH1025284A

公开(公告)日：1998-01-27

申请号：JP18051496

申请日：1996-07-10

Applicant: TOSOH CORP

Inventor： HANAZAKI YASUAKI ,  KATSUURA KIMIO

IPC: C07D285/10 ,  B01J31/24 ,  C07B61/00

Abstract: PROBLEM TO BE SOLVED: To industrially advantageously obtain the subject compound useful as an organic intermediate and an intermediate for medicines and agrochemicals by reacting a specific 1,2,5-thiadiazole derivative with an organotin reactant in the presence of a palladium compound catalyst. SOLUTION: A 1,2,5-thiadiazole derivative of formula I [R is H, a 1-6C alkyl which may be substituted with (F or a 1-3C alkoxy group) or phenyl which may be substituted with (F, Cl, trifluoromethyl, a 1-6C alkyl or a 1-3C alkoxy); X is Cl or CF3 SO3 ] (e.g. 3-chloro-4-phenyl-1,2,5-thiadiazole) is reacted with an organotin reactant of formula II [R is phenyl which may be substituted with (F, Cl, CF3 , a 1-6C alkyl or a 1-3C alkoxy)] [e.g. tributyl(4-chlorophenyl)tin, etc.] in the presence of a palladium compound [e.g. tetrakis(triphenylphosphine) palladium to give the objective 1,2,5-thiadiazole derivative of formula III.

公开(公告)号：JP2000026457A

公开(公告)日：2000-01-25

申请号：JP19394998

申请日：1998-07-09

Applicant: TOSOH CORP

Inventor： YAMAMOTO TAKASHI ,  TOKUNAGA TAKUMI ,  ITO HIROYUKI ,  KONO KAZUHISA ,  HANAZAKI YASUAKI ,  KATSUURA KIMIO

IPC: C07D333/36 ,  B01J23/72 ,  B01J27/122 ,  C07B61/00

Abstract: PROBLEM TO BE SOLVED: To obtain a 3-aminothiophene derivative useful as a synthetic intermediate of a medicine, an agrochemical, etc., by reacting each specific thienyl halide derivative with an amine derivative in the presence of a copper catalyst, simply at a low cost in a high purity and in a high yield. SOLUTION: This new 3-aminothiophene derivative expressed by formula III is obtained by reacting a 3-thienyl halide derivative expressed by formula I (R1, R2 are each H, F, a lower alkyl, a lower alkoxy, a lower alkoxycarbonyl or a lower acyl; X is a halogen) with an amine derivative expressed by formula II (R3 is H or a lower alkyl; R4 is H, a lower alkyl or a lower alkyl substituted with hydroxyl) in the presence of a copper catalyst (amount of use is preferably 0.001-1 equivalent based on the derivative of formula I) consisting of a single substance or a mixture of two or more kinds selected from a metallic copper powder, metallic copper granules, a metallic copper wire, cuprous (I) oxide, cuprous (I) chloride, cuprous (I) bromide and cuprous (I) iodide, under a pressure of normal pressure to 1 MPa.

公开(公告)号：JPH10101628A

公开(公告)日：1998-04-21

申请号：JP25615396

申请日：1996-09-27

Applicant: TOSOH CORP

Inventor： KATSUURA KIMIO ,  IRINO SHIGEAKI ,  TOKUDA AKIRA

IPC: C07B57/00 ,  C07C227/34 ,  C07C229/36

Abstract: PROBLEM TO BE SOLVED: To efficiently obtain an optically active amino acid (derivative) in high optical purity by previously preparing an optically active amino acid (derivative) in an optical purity not lower than a convergent value of mutual solubility between optical isomers and crystallizing an optically active amino acid (derivative) which excessively exists. SOLUTION: One or more kinds of optically active amino acids (derivatives) selected from a group of phenylglycine (derivative), phenylalanine (derivative), homophenylalanine (derivative) and naphthylalanine (derivative) are previously prepared in an optical purity not lower than a convergent value of mutual solubility between optical isomers and an optically active amino acid (derivative) which excessively exists is crystallized to provide the objective optically active amino acid (derivative) having high optical purity. Furthermore, the convergent value of mutual solubility between optical isomers indicates a ratio (optical purity in mother liquid) of target optical isomer to optical isomers in mother liquid equilibrated when crystals of racemic substance and optically active substance simultaneously exist and the value is constant without depending on a ratio of crystals of the racemic substance and the optically active substance.

公开(公告)号：JPH10101626A

公开(公告)日：1998-04-21

申请号：JP25615496

申请日：1996-09-27

Applicant: TOSOH CORP

Inventor： KATSUURA KIMIO ,  IRINO SHIGEAKI ,  TOKUDA AKIRA

IPC: C07B57/00 ,  C07B63/00 ,  C07C227/34 ,  C07C229/36

Abstract: PROBLEM TO BE SOLVED: To provide a method for producing an optically active amino acid having a high optical purity of at least >=99% or its hydrochloride. SOLUTION: In this method for producing an optically active amino acid having high optical purity or its hydrochloride by crystallization from an optically active amino acid containing an optical isomer, crystallization of an optically active substance is carried out in pH region exhibiting an isoelectric point by utilizing pH dependence of convergence of mutual solubility between optical isomers and then, pH of recovered mother liquid is lowered to