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31. 发明专利

JPH02273697A PEPTIDE AND ANTIDEMENTIAL AGENT CONTAINING THE SAME 失效
公开(公告)号：JPH02273697A
公开(公告)日：1990-11-08
申请号：JP9591989
申请日：1989-04-15
申请人： NIPPON CHEMIPHAR CO , FUJIREBIO KK
发明人： MAZAKI MITSUO , UEHARA MASAKI , HIRATE KENJI , ISOWA YOSHIKAZU , SATO YOSHIAKI , NAKAJIMA YOSHIHARU
IPC分类号： A61K38/00 , A61K38/095 , A61P25/28 , C07K5/113 , C07K5/117 , C07K7/06 , C07K7/16
摘要： NEW MATERIAL:The peptide of formula A-Ser-Pip-Arg (A is Pro-Asn, Asn or Pro; Pip is pipecolic acid), its derivative or their salt. EXAMPLE:The compound of formula I. USE:An antidemential agent useful for the prevention and treatment of Alzheimers disease, etc. It exhibits strong nootropic action and has extremely low toxicity. PREPARATION:The exemplified compound can be produced e.g. by reacting a compound of formula II (Boc is t-butoxycarbonyl; Bzl is benzyl; OBzl is benzyl ester) with a compound of formula Z-Pro-OSn (Z is benzyloxycarbonyl; OSu is N-hydroxysuccinimide ester) in a mixture of hydrochloric acid and ethyl acetate in the presence of triethylamine and demasking the resultant compound of formula III by reducing with Pd-carbon, etc.

32. 发明专利

JPH02218621A SUSTAINED RELEASE PREPARATION 失效
公开(公告)号：JPH02218621A
公开(公告)日：1990-08-31
申请号：JP3818089
申请日：1989-02-20
申请人： NIPPON CHEMIPHAR CO
发明人： YAMASAKA HEINOJIYOU , SAKAMOTO YOSHIOMI , YOSHIDA YOSHIYUKI , SAITO KATSUMI
IPC分类号： A61K31/19 , A61K9/16 , A61K9/22 , A61K31/195 , A61K47/36
摘要： PURPOSE:To obtain a sustained release preparation advantageously obtainable by a simple method, capable of reducing the amount of additive used by blending a readily water-soluble component with a water-soluble polymer having hydrogel formation ability and a water-insoluble polymer. CONSTITUTION:(A) A readily water-soluble component such as metallic salt of organic acid such as valproic acid, aspartic acid or citric acid is blended with (B) a water-soluble polymer having hydrogel formation ability such as sodium alginate, natural gum, carrageenan, hydroxypropyl cellulose or methyl cellulose and (C) a water-insoluble polymer such as ethyl cellulose in the ratios of 1 pt.wt. component A, 0.05-0.5 pt.wt. component B and 0.02-0.2 pt.wt. component C. The amount of the component A blended is >=0.4 pt.wt., especially preferably >=0.6 pt.wt. based on 1 pt.wt. preparation. The preparation shows excellent behavior close to 0-order elution.

33. 发明专利

JPH02138263A IMIDAZOLE DERIVATIVE, PRODUCTION THEREOF AND ANTI-ULCER AGENT CONTAINING THE SAME DERIVATIVE 失效
公开(公告)号：JPH02138263A
公开(公告)日：1990-05-28
申请号：JP29785688
申请日：1988-11-24
申请人： NIPPON CHEMIPHAR CO
发明人： OKABE SUSUMU , MAZAKI MITSUO , YAMAKAWA TOMIO , MATSUKURA HITOSHI , NOMURA YUTAKA
IPC分类号： A61K31/415 , A61K31/4166 , A61K31/4184 , A61K31/47 , A61P1/04 , C07D233/84 , C07D233/86 , C07D233/88 , C07D233/90 , C07D233/92 , C07D235/28 , C07D401/12
摘要： NEW MATERIAL:A compound expressed by formula I (R and R are H, alkyl, cycloalkyl or aryl, etc.; R -R are H, halogen, alkoxy, aralkyloxy, alkyl, NO2 or NH2, etc.; R is H, alkyl, aryl or hetero-ring group containing S, etc.; R and R are H, halogen, alkoxy, alkyl, NO2, NH2, acyl or aryl, etc.; n is 0 or 1). EXAMPLE:2-(2-methylaminobenzylthio)-4,5,6,7-tetrahydro-1H-benzimidazole. USE:An anti-ulcer agent having excellent gastric inhibitory action and also having cell-protecting action for stomach and intestines. PREPARATION:For instance, a compound expressed by formula II (X is eliminating group) is reacted with a compound expressed by formula III to obtain the compound expressed by formula I as n is 0.

34. 发明专利

JPH0253800A PEPTIDE 失效
公开(公告)号：JPH0253800A
公开(公告)日：1990-02-22
申请号：JP20135888
申请日：1988-08-12
申请人： FUJIREBIO KK , NIPPON CHEMIPHAR CO
发明人： ISOWA YOSHIKAZU , SATO YOSHIAKI , NAKAJIMA YOSHIHARU , MAZAKI MITSUO , MIYAKE MASAHISA , UEHARA MASAKI , HIRATE KENJI
IPC分类号： A61K38/095 , A61K20060101 , A61P25/28 , C07K20060101 , C07K7/16
摘要： NEW MATERIAL:A peptide expressed by formula I or derivative (salt) at functional groups thereof. USE:A preventive and treating agent for senile dementia, cerebrovascular dementia, Alzheimer disease, Pick disease, Huntington chorea, Creutzfeldt.Jakob disease, Parkinson disease, cerebellospinal degeneration, etc. PREPARATION:For example, a C-terminal amino acid having protected carboxyl group is successively bound to amino acids having protected alpha-amino and functional groups in the side chain according to the sequence of a peptide and the alpha-amino-protecting group is then removed. The above-mentioned operation is repeated to synthesize a peptide expressed by formula II (Z is benzyloxycarbonyl; Acm is acetamidomethyl; Mbs is p-methoxybenzenesulfonyl). Cysteine hydrochloride is then added and reacted therewith and protecting groups are subsequently removed to afford the compound expressed by formula I.

35. 发明专利

JPH0253735A AGENT FOR ALLEVIATING DEMENTIA 失效
公开(公告)号：JPH0253735A
公开(公告)日：1990-02-22
申请号：JP20135588
申请日：1988-08-12
申请人： NIPPON CHEMIPHAR CO , FUJIREBIO KK
发明人： YOSHIDA MITSUO , KANAZAWA ICHIRO , MAZAKI MITSUO , MIYAKE MASAHISA , UEHARA MASAKI , HIRATE KENJI , ISOWA YOSHIKAZU , SATO YOSHIAKI , NAKAJIMA YOSHIHARU
IPC分类号： A61K38/22 , A61K38/095 , A61P25/28 , C07K5/10 , C07K7/16 , C07K14/575
摘要： NEW MATERIAL:A peptide shown by the formula (Asn is asparagine; Gys is cysteine; Pro is proline; Arg is arginine), a derivative or a salt thereof. USE:An agent for alleviating dementia having excellently improving action on dementia and low toxicity useful for preventing and treating presbyophrenia, cerebrovascular dementia, Alzheimer's disease, Pick's disease, etc. PREPARATION:A peptide shown by the formula is obtained by an ordinary peptide synthesis by either of liquid phase method or solid phase method. Azide method, acid chloride method or acid anhydride method is used as a condensation method to form azide bond. Before the condensation reaction, carboxyl, amino, etc., not participating in the reaction may be protected and carboxyl, amino, etc., taking part in the reaction may be activated.

36. 发明专利

JPH0160476B2 失效
公开(公告)号：JPH0160476B2
公开(公告)日：1989-12-22
申请号：JP3834379
申请日：1979-04-02
申请人： NIPPON CHEMIPHAR CO
发明人： SEKINE HIROYASU
IPC分类号： C07D499/18 , C07D501/12

37. 发明专利

JPH01226843A TERPENE COMPOUND 失效
公开(公告)号：JPH01226843A
公开(公告)日：1989-09-11
申请号：JP5449088
申请日：1988-03-08
申请人： NIPPON CHEMIPHAR CO
发明人： SHIRAHAMA HARUHISA
IPC分类号： C07C43/215 , A61K31/047 , A61K31/05 , A61K31/09 , A61K31/215 , A61P1/00 , A61P1/16 , A61P3/06 , A61P9/00 , A61P9/10 , A61P27/02 , A61P29/00 , A61P37/00 , A61P43/00 , C07C27/00 , C07C39/19 , C07C41/00 , C07C43/23 , C07C67/00 , C07C69/12 , C07C69/18 , C09K15/14 , C11B5/00
摘要： NEW MATERIAL:A compound shown by formula I [R -R are H, acyl, aralkyl or alkyl; R and R are H or alkyl; substitution position of OR and OR are (b, d), (b, c) and (a, c)]. EXAMPLE:2-(3,7,11,15-Tetramethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihy droxyphe nylacetate. USE:A drug having excellent inhibitory action on formation of peroxide lipid and useful as a remedy for hepatic diseases, anti-inflammatory drug, antirheumatic, remedy for diseases of digestive tube, anti-cataract, antiarteriosclerotic agent, anti-cerebral infarct, remedy for autoimmune disease, especially remedy for hepatic diseases. PREPARATION:For example, a phenolic derivative is reacted with 3,7,11,15- tetramethyl-2,6,10,14-hexadecatetraenyl bromide in a solvent such as DMSO in the presence of NaH, etc. and then subjected to rearrangement reaction in a solvent such as CCl4 in the presence of boron trifluoride ether complex, etc. to give a compound shown by formula I.

38. 发明专利

JPH01207277A QUATERNARY SALT OF BENZIMIDAZOLE DERIVATIVE 失效
公开(公告)号：JPH01207277A
公开(公告)日：1989-08-21
申请号：JP3015588
申请日：1988-02-12
申请人： NIPPON CHEMIPHAR CO
发明人： OKABE SUSUMU , MAZAKI MITSUO , YAMAKAWA TOMIO
IPC分类号： C07D235/28 , A61K31/415 , A61K31/4184 , A61K31/445 , A61K31/454 , A61P1/04
摘要： NEW MATERIAL:The quaternary salt of a benzimidazole derivative of formula I (R , R and R are linear or cyclic alkyl, aryl or aralkyl, or R and R form 5-7 membered ring together; R , R , R , R and R are H, halogen, alkoxy, alkyl, trifluoromethyl, alkoxycarbonyl, nitro, amino, acyl or fluorine-substituted alkoxy; X is anion). EXAMPLE:2-[(Benzimidazol-2-ylsulfinyl)methyl]phenyltrimethyl ammonium hydroxide. USE:The salt exhibits an ulcer-resistant action, a gastrointestinal cell-protecting action, etc., and is useful as a drug. PREPARATION:The compound of formula I is obtained by reacting a compound of formula II with a compound of formula III (Y is reactive group), oxidizing the obtained compound of formula IV (Z is anion) and, if necessary, subjecting the product to a cation exchange reaction.

39. 发明专利

JPH01199166A METHOD FOR SIMPLE AND PRECISE DIFFERENTIAL MEASUREMENT OF SACCHARIFIED HEMOGLOBIN IN BLOOD 失效
公开(公告)号：JPH01199166A
公开(公告)日：1989-08-10
申请号：JP2451288
申请日：1988-02-04
申请人： NIPPON CHEMIPHAR CO
发明人： SHIMIZU YOSHIO , KAWAJI HARUHIKO
IPC分类号： G01N33/66
摘要： PURPOSE:To enable the measurement of the concentration of hemoglobin in a short tie, by a method wherein first and second eluents made of buffer solutions having specific cation concentrations respectively are added to elute HbA1(a+b), HbA1c and the absorbances of eluates are measured. CONSTITUTION:An eluent A formed of a buffer solution which contains an acid salt and a basic salt each formed of orthophosphate and is adjusted to be pH7.2-7.5 according to the concentration ratio therebetween and which has a cation concentration of 0.016-0.027M, and an eluent B formed of a buffer solution which contains said salts and is adjusted to be pH6.7 according to the concentration ratio therebetween, wherein the concentration of the orthophosphate is 0.03-0.05M and which has the cation concentration of 0.10-0.11M with a common salt added thereto, are obtained. In addition, a column adjusting solution C which is formed of an orthophosphoric acid and is adjusted to be pH6.5-6.6 according to the concentration ratio and which has a cation concentration of 0.093M preferably, is obtained. Then, hemolyzed blood is added to a column formed by filling up subacid ion- exchange resin equilibrated by the adjusting solution C, the eluent A is added thereto to elute HbA1(a+b), the eluent B is added thereto subsequently to elute HbA1c, and absorbance is measured for each of eluates. Thereby the concentration of hemoglobin can be measured in a short time.

40. 发明专利

JPH0121127B2 失效
公开(公告)号：JPH0121127B2
公开(公告)日：1989-04-19
申请号：JP5040280
申请日：1980-04-18
申请人： NIPPON CHEMIPHAR CO
发明人： SUDO ROKURO , MAZAKI MITSUO , KAMISHIRO TOSHIRO , NISHIOKA KOICHIRO
IPC分类号： A61K31/04 , A61K31/045 , A61K31/05 , A61K31/06 , A61P9/00 , A61P9/08 , A61P25/28

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