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31. 发明专利

JPS6256898B2 失效
公开(公告)号：JPS6256898B2
公开(公告)日：1987-11-27
申请号：JP10436280
申请日：1980-07-31
申请人： TEIJIN LTD
发明人： KATO YOSHINORI , FUKUSHIMA HISASHI , HARA TAKESHI
IPC分类号： C08G69/00 , A61K38/00 , A61P35/00 , C07K1/00 , C07K14/00 , C08G69/10 , C08G69/48

32. 发明专利

JPS62267240A PRODUCTION OF STABLE CYTOTOXIC PROTEIN COMPLEX 失效
公开(公告)号：JPS62267240A
公开(公告)日：1987-11-19
申请号：JP10953886
申请日：1986-05-15
申请人： TEIJIN LTD
发明人： ENDO NORIAKI , TAKEDA YUMIKO , KATO YOSHINORI , HARA TAKESHI
IPC分类号： A61K39/395 , A61K38/16 , A61K45/00 , A61P35/00
摘要： PURPOSE:To obtain the titled complex, by reacting immunoglobulin having introduced functional groups reactive with thiol group with a thiol group- containing cytotoxic substance and treating the unreacted functional groups reactive with the thiol group with a thiol group-containing low-molecular compound. CONSTITUTION:Immunoglobulin having introduced functional groups reactive with thiol group, e.g. maleimide group, or a fragment containing the antigen linking part thereof is reacted with a thiol group-containing cytotoxic substance, e.g. low-molecular carcinostatic agent, and the unreacted functional groups reactive with thiol group in the resultant complex are treated with a thiol group-containing low-molecular compound, e.g. L-cysteine, and sealed to afford the aimed cytotoxic protein complex. Conventional problems in which the residual unreacted functional groups reactive with thiol group initiate unfavorable reaction in purification, preservation or the living bodies are removed by the above-mentioned method and the aimed complex having high safety can be obtained.

33. 发明专利

JPS6238368B2 失效
公开(公告)号：JPS6238368B2
公开(公告)日：1987-08-18
申请号：JP9166180
申请日：1980-07-07
申请人： TEIJIN LTD
发明人： KATO YOSHINORI , FUKUSHIMA HISASHI , HARA TAKESHI
IPC分类号： C08G69/00 , A61K31/795 , A61K39/395 , A61P35/00 , C07D263/44 , C08G69/10 , C08G69/42 , C08G69/48

34. 发明专利

JPS59134734A Cytocidal modified immunoglobulin and its preparation 失效
标题翻译： CYTOCIDAL修饰的免疫球蛋白及其制备
公开(公告)号：JPS59134734A
公开(公告)日：1984-08-02
申请号：JP580783
申请日：1983-01-19
申请人： Teijin Ltd
发明人： KATOU YOSHINORI , UMEMOTO NAOJI , TAKEDA YUMIKO , HARA TAKESHI
IPC分类号： A61K39/395 , A61K47/48 , A61P35/00 , A61P43/00
CPC分类号： A61K47/6881 , A61K47/6809 , Y10S530/809 , Y10S530/83
摘要： NEW MATERIAL:A cytocidal modified immunoglobulin shown by the formula I (Ab is immunoglobulin or its fragment; R is bifunctional organic group; n is 1W20).
EXAMPLE: A modified immunoglobulin of 1a-(4-succinimidyloxycarbonylbutyryl)- 7-amino-9a-methoxymitosan shown by the formula II and mouse monoclonal antibody IgG2b of anti MM46.
USE: A carcinostatic agent showing specifically inhibitory activity against propagation of the target cell to be killed.
PROCESS: A mitomycin C derivative shown by the formula III (X is residue of active ester, derived from alcohol) is reacted with immunoglobulin or its fragment to give a modified immunoglobulin shown by the formula I . The reaction is carried out by adding a compound shown by the formula III dissolved in a small amount of a solvent (e.g., acetone) at 0W40°C to a buffer solution at 5W 8pH.
COPYRIGHT: (C)1984,JPO&Japio
摘要翻译：新物质：式I所示的杀细胞变性免疫球蛋白（Ab为免疫球蛋白或其片段; R为双功能有机基团; n为1-20）。实施例：由式II表示的1a-（4-琥珀酰亚氨基氧羰基丁酰基）-7-氨基-9a-甲氧基淀粉和抗MM46的小鼠单克隆抗体IgG2b的修饰的免疫球蛋白。用途：对待杀死的靶细胞的增殖具有特异性抑制活性的制癌剂。方法：将式III表示的丝裂霉素C衍生物（X是衍生自醇的活性酯的残基）与免疫球蛋白或其片段反应，得到式I所示的经修饰的免疫球蛋白。通过将溶于少量溶剂（例如丙酮）的式III化合物在0-40℃下加入到5-8pH的缓冲溶液中进行反应。

35. 发明专利

JPS5993096A 5-FLUORO-2'-DEOXYURIDINE DERIVATIVE AND ITS PREPARATION 失效
公开(公告)号：JPS5993096A
公开(公告)日：1984-05-29
申请号：JP20184782
申请日：1982-11-19
申请人： TEIJIN LTD
发明人： WATANABE KENZOU , KATOU YOSHINORI , SAITOU MASAHIKO , OOBA TAKEO , FUKUSHIMA HISASHI , HARA TAKESHI
IPC分类号： C07H19/10 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61K31/7072 , A61P35/00
摘要： NEW MATERIAL:The compound of formula I [A is 1-30C bivalent aliphatic hydrocarbon group; n is 0 or 1; when n is 0, Y is bonded directly to O; Y is H or (substituted) phenyl, provided that when Y is H, n is 1; R is H or OH-protecting group] and its salt. EXAMPLE:5-Fluoro-2'-deoxyuridine-5'-docosyl phosphate. USE:Antitumor agent for oral administration. PROCESS:The objective compound can be prepared by reacting the 3'-substituted- 5-fluoro-2'-deoxyuridine (e.g. 3'-acetyl-5-fluoro-2'-deoxyuridine) with the phosphoric acid monoester (e.g. docosyl phosphate) in the presence of a condensation agent such as p-toluenesulfonyl chloride, and if necessary, removing the protecting groups.

36. 发明专利

JPS58167519A CYTOTOXIC COMPLEX AND PREPARATION THEREOF 失效
公开(公告)号：JPS58167519A
公开(公告)日：1983-10-03
申请号：JP4998082
申请日：1982-03-30
申请人： TEIJIN LTD
发明人： KATOU YOSHINORI , UMEMOTO NAOJI , FUKUSHIMA HISASHI , HARA TAKESHI
IPC分类号： C07K16/00 , A61K38/00 , A61K38/16 , A61K39/395 , C07K1/113 , C07K14/00 , C07K19/00
摘要： NEW MATERIAL:A cytotoxic complex expressed by formulasIand II (Ab is immunoglobulin linkable specifically to a specific antigen or a fragment thereof; B1, B2 and B3 and W are bifunctional organic group; t1 and t2 are 0 or 1; v is an integer 1-10; S1 and S2 are S; Y is amino group or reaction residue of amino group or imino group of a cytotoxic substance containing the amino group or imino group; Z is H or monovalent cation; R1 is H or 1-4C alkyl; R2 is side chain at the alpha-position of an alpha-amino acid, etc.; m is an integer 1-4; n is 5-1500; p and q are 0-1500). USE:An antitumor agent capable of linking specifically to a specific antigen in the target cells, and selectively reacting a cytotoxic substance, e.g. actinomycin D, with tumorous cells. PROCESS:An antibody expressed by formula III or a fragment thereof is reacted with a polymer expressed by formula IV (X is a group capable of forming an active disulfide with the adjacent S) to give a cytotoxic complex expressed by formulaIin which t2 is 1.

37. 发明专利

JPS5718727A REACTIVE POLYMER AND ITS PREPARATION 失效
公开(公告)号：JPS5718727A
公开(公告)日：1982-01-30
申请号：JP9166180
申请日：1980-07-07
申请人： TEIJIN LTD
发明人： KATOU YOSHINORI , FUKUSHIMA HISASHI , HARA TAKESHI
IPC分类号： C08G69/00 , A61K31/795 , A61K39/395 , A61P35/00 , C07D263/44 , C08G69/10 , C08G69/42 , C08G69/48
摘要： PURPOSE:To prepare a reactive polymer having high reactivity and effective to combine an antitumor antibody having bonding capability to tumor cells, etc. with a cytotoxic substance such as carcinostatic agent, by introducing an active group to the terminal carboxyl group of the main chain of a polymer composed of specific constituent units. CONSTITUTION:The objective reactive polymer having a degree of polymerization of 5-3,000 is obtained by introducing an active group of formula II (X is H or a group capable of forming together with S an active disulfide group; W is bi-valent organic group; R1 is H or 1-4C alkyl) to the terminal carboxyl group of a polymer wherein pref. >=60mol% of the constituting units of the polymer is an alpha-amino acid of formula I (Z is H or uni-valent cation; m is 1-4), e.g. glycine. USE:A cytotoxic substance having amino group or imino group in the molecule, e.g. carcinostatic agent, is made to react with said polymer and introduced into the side chain of the polymer. A target-oriented drug can be obtained by reacting an anti- tumor immunogloblin with the active group at the terminal of the molecule.

38. 发明专利

JPS5686189A HEXAHYDRONAPHTHO 1**2* 4*5 IMIDAZO 2*11B THIAZOLE DERIVATIVE AND ITS PREPARATION 失效
公开(公告)号：JPS5686189A
公开(公告)日：1981-07-13
申请号：JP16351279
申请日：1979-12-18
申请人： TEIJIN LTD
发明人： HARA TAKESHI , SHIKAYAMA YASUKATA
IPC分类号： C07D513/04 , A61K31/425 , A61P29/00 , A61P35/00 , A61P37/00
摘要： NEW MATERIAL:The titled derivative of formula I [X1 and X2 are H or halogen; n is an integer 1,2 or 3; the steric configuration of rings B and C is trans] and an acid addition salt thereof. EXAMPLE:6a,11a-trans-9-Carboxymethyl-8-( 4-chlorophenyl )-5,6,6a,8,9,11a-hexahydro-8-hydroxynaphtho[1',2':4,5]imidazo[2,1-b]th iazole hydrobromide. USE:An immunological activator, an immunological regulating agent and a veterinary anthelmintic agent effective for treating cancer and rheumatic arthritis. PROCESS:A compound of formula II is reacted with a compound of formula III (X3 is halogen) to give the compound of formula I. The reaction is carried out in a solvent, e.g. ethanol, at room temperature to the boiling point of the system.

39. 发明专利

JPS55151590A HEXAHYDRONAPHTHO 2**1* 4*5 IMIDAZO 2*11B THIAZOLE AND ITS PREPARATION 失效
公开(公告)号：JPS55151590A
公开(公告)日：1980-11-26
申请号：JP5798679
申请日：1979-05-14
申请人： TEIJIN LTD
发明人： SHIKAYAMA YASUKATA , HARA TAKESHI , SAITOU MASAHIKO , SUZUKI YOUJI
IPC分类号： C07D513/04 , A61K31/425 , A61P29/00 , A61P35/00
摘要： NEW MATERIAL:The title compound shown by the formula I (R is lower alkyl, lower alkoxy, or halogen; n is 0 or 1-4; B and C rings are cis or trans form). EXAMPLE:Trans-5,6,6a,9,10,11a-hexahydronaphtho[ 2',1':4,5 ]imidazo[ 2,1-b ] thiazole. USE:A drug useful for treatment of cancer and autoimmune disease, e.g., rheumatoid arthritis having immuization or immunosuppression. PROCESS:A tetrahydronaphtho[1,2-d]imidazoline-2-thione is reacted with a compound shown by the formula [Y or Z is halogen, arylsulfonyloxy or alkanesulfonyloxy) to give a compound shown by the formula I. The compound shown by the formula II is also novel one.

40. 发明专利

JPS55147501A PREPARATION OF ANTIINFLAMMATORY POLYSACCHARIDE 失效
公开(公告)号：JPS55147501A
公开(公告)日：1980-11-17
申请号：JP5480679
申请日：1979-05-07
申请人： TEIJIN LTD
发明人： SUZUKI YOUJI , KOMORIYA KEIJI , KUROZUMI SEIJI , HARA TAKESHI
IPC分类号： C08B37/00
摘要： PURPOSE:To prepare a polysaccharide having antiinflammatory action, by supersonic decomposition of succinoglucan. CONSTITUTION:An aqueous solution of succinoglucan obtained by the aeration culture of Alcaligenes faecalis var. myxogenes 10C3 (FERM-P 2068) is decomposed, by use of a supersonic disintegrator, in such a manner that the viscosity of a 1% aqueous solution of its calcium salt is 50-400 CP at 30 deg.C, and then an antiinflammatory polysaccharide is crystallized out with addition of a precipitant such as alcohols, ketones or surfactants. No difference is recognized between the 1R spectrum of the polysaccharide and that of the raw material, succinoglucan. It has absorption at 890cm assigned to the beta-glucoside linkage and at 1730cm assigned to the ester linkage.

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