公开(公告)号：EP0058993B1

公开(公告)日：1990-05-09

申请号：EP82101407.3

申请日：1982-02-24

申请人： THE GREEN CROSS CORPORATION

发明人： Ohmura, Takao ,  Hirao, Yutaka ,  Funakoshi, Satoshi

IPC分类号： A61K37/04

CPC分类号： C07K14/78 ,  A61K35/16 ,  A61K38/00 ,  A61K39/395 ,  A61L2/0023 ,  A61L2/04

摘要： Cold insoluble globulin which may have hepatitis virus activity can be virus-inactivated with keeping at a minimum the damage of the cold insoluble globulin by heating its aqueous solution at 50 DEG to 80 DEG C. for 5 to 20 hours in the presence of 10% (W/V) or more of at least one principal stabilizer of neutral amino acids, monosaccharides, disaccharides, and sugar alcohols with or without 10% (W/V) or more of at least one auxiliary stabilizer of salts of hydrocarbon carboxylic acids or hydroxyhydrocarbon carboxylic acids both having 3 to 10 carbon atoms.

公开(公告)号：EP0278422A3

公开(公告)日：1990-04-04

申请号：EP88101689.3

申请日：1988-02-05

申请人： GREEN CROSS CORPORATION

发明人： Hirao, Yutaka ,  Takechi, Kazuo ,  Uriyu, Katuhiro ,  Uemura, Yahiro

IPC分类号： A61K39/395

CPC分类号： A61K9/0019 ,  A61K39/39591 ,  A61K47/26 ,  A61K2300/00

摘要： An intravenously injectable solution of chemically unmodified γ-globulin having a complete molecular structure is disclosed, said solution containing sorbitol as a stabilizer and having a low electrical conductivity and a pH of about 5.5 ± 0.2. The injectable solution does not cause an increase of γ-globulin polymer, a rise of anticomplement titer, or impairment of the activities of the γ-globulin, either during preservation or upon administration to a living body.

公开(公告)号：EP0106608A3

公开(公告)日：1986-03-26

申请号：EP83305940

申请日：1983-09-30

申请人： GREEN CROSS CORPORATION

发明人： Ohmura, Takao ,  Hirao, Yutaka ,  Hanamura, Takuji ,  Ohmizu, Akimasa ,  Funakoshi, Satoshi

IPC分类号： A61K37/04

CPC分类号： A61K38/39

摘要： A lyophilized cold insoluble globulin preparation can be prepared in a stable condition and in a short time by lyophilizing an aqueous solution of a cold insoluble globulin in the presence of albumin and a neutral amino acid, a monosaccharide, a disaccharide or a sugar alcohol. The preparation dissolves in water without occurrence of turbidity and is usable for injection.

公开(公告)号：EP0278422B1

公开(公告)日：1994-06-08

申请号：EP88101689.3

申请日：1988-02-05

申请人： GREEN CROSS CORPORATION

发明人： Hirao, Yutaka ,  Takechi, Kazuo ,  Uriyu, Katuhiro ,  Uemura, Yahiro

IPC分类号： A61K39/395

CPC分类号： A61K9/0019 ,  A61K39/39591 ,  A61K47/26 ,  A61K2300/00

公开(公告)号：EP0246579B1

公开(公告)日：1993-08-04

申请号：EP87107112.2

申请日：1987-05-16

申请人： GREEN CROSS CORPORATION

发明人： Uemura, Yahiro ,  Uriyu, Katuhiro ,  Takechi, Kazuo ,  Hirao, Yutaka ,  Suyama, Tadakazu

IPC分类号： A61K39/395

CPC分类号： C07K16/00 ,  A61K38/00 ,  A61K39/395 ,  A61L2/0023

摘要： A method of producing immunoglobulin preparations for intravenous injection which starts with an immunoblobulin-containing fraction and comprises the treatment steps of: (a) treating said fraction with 4-l0 weight/volume percent of polyethylene glycol having a molecular weight of l,000-l0,000 under conditions of pH 4-6, ion strength 0.000l-0.l M and temperature 0-4 DEG C and recovering the supernatant, (b) treating the supernatant obtained in step (a) with l0-l5 weight/volume percent of polyethylene glycol having a molecular weight. of l,000-l0,000 under conditions of pH 6-9, ion strength 0.000l-0.l M and temperature 0-4 DEG C and recovering the resulting precipitate, and (c) heat-treating, in any desired step, said immunoglobulin in the presence of a stabilizer under conditions sufficient to inactivate contaminant viruses. The preparations obtained according to the invention retain immunoglobulins without substantial inactivation thereof, and are substantially free of such contaminants as anti-human blood group substance antibodies. With contaminant viruses inactivated as a result of the heat treatment, said preparations have good solubility and are sufficiently low in anticomplement activity.

公开(公告)号：EP0253313B1

公开(公告)日：1992-09-30

申请号：EP87109927.1

申请日：1987-07-09

申请人： GREEN CROSS CORPORATION

发明人： Hirao, Yutaka ,  Uriyu, Katuhiro ,  Takechi, Kazuo ,  Uemura, Yahiro

IPC分类号： A61K39/395

CPC分类号： A61L2/0023 ,  Y10S530/83

公开(公告)号：EP0179477B1

公开(公告)日：1992-01-22

申请号：EP85113535.0

申请日：1985-10-24

申请人： GREEN CROSS CORPORATION

发明人： Hirao, Yutaka ,  Ohmura, Takao ,  Takechi, Kazuo ,  Nakajima, Tsunetaka ,  Nishida, Masayuki

IPC分类号： A61K37/04

CPC分类号： A61K47/42 ,  A61K9/0048 ,  A61K38/39 ,  A61K47/10 ,  A61K47/26

公开(公告)号：EP0196761B1

公开(公告)日：1991-07-10

申请号：EP86301196.1

申请日：1986-02-20

申请人： GREEN CROSS CORPORATION

发明人： Hirao, Yutaka ,  Uriyu, Katuhiro ,  Uemura, Yahiro

IPC分类号： A61L2/04

CPC分类号： A61L2/0023 ,  A61K39/39591 ,  A61K2300/00

公开(公告)号：EP0106608B1

公开(公告)日：1989-12-06

申请号：EP83305940.5

申请日：1983-09-30

申请人： GREEN CROSS CORPORATION

发明人： Ohmura, Takao ,  Hirao, Yutaka ,  Hanamura, Takuji ,  Ohmizu, Akimasa ,  Funakoshi, Satoshi

IPC分类号： A61K37/04

CPC分类号： A61K38/39

公开(公告)号：EP0196761A3

公开(公告)日：1986-10-22

申请号：EP86301196

申请日：1986-02-20

申请人： GREEN CROSS CORPORATION

发明人： Hirao, Yutaka ,  Uriyu, Katuhiro ,  Uemura, Yahiro

IPC分类号： A61L02/04

CPC分类号： A61L2/0023 ,  A61K39/39591 ,  A61K2300/00

摘要： A gramma-globulin aqueous solution can be subjected to sterile heat-treatment without losing its activity when the treatment is conducted in the presence of at least one stabilizer which is a monosaccharide, disaccharide or sugaralcohol added to the solution. The stabilizer serves to decrease the harmful polymer or anticomplement activity of the gamma-globulin before the treatment but to maintain the titer of a wide variety of antibodies to various viruses and bacteria, while the infectivity of viruses possibly contained is completely removed. An additional stabilizer, which is a neutral amino, a neutral inorganic salt, an organic carboxylic acid salt or a surface active agent, assists the abovementioned stabilizer when used together with it.