Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-01-19
1998-02-03
Tsang, Cecilia J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 12, 514 21, 530350, 530380, 530397, 530399, 435 691, 435 694, A61K 3816, C07K 100, C12P 2106
Patent
active
057144613
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to medicinal compositions for the normalization of blood coagulation or treatment of abnormal blood coagulation, comprising a glycoprotein produced by human fibroblast cells, TCF-II (tumor cytotoxic factor-II), more particularly agents for the treatment of disseminated intravascular coagulation (DIC) syndrome, increase of platelet count and prevention of thrombocytopenia.
DESCRIPTION OF THE PRIOR ART
Biologically active substances produced by human derived fibroblast cells, for example, .beta.-interferon as a tumor cytotoxic factor, have been well known. Biologically active substances produced by fibroblast cells other than .beta.-interferon such as a tumor cytotoxic glycoprotein called CBF is disclosed in Japanese Patent Laid-open Publication No. 146293 (1983). A tumor growth inhibitory factor (INF) with molecular weight of 35,000-48,000, which is purified from culture broth of fibroblasts derived from human tissue, is disclosed in Japanese Patent Laid-open Publication No. 33120 (1986). Furthermore, a tumor necrosis factor-like substance which is purified from the culture broth of fibroblasts, a fibroblast-derived necrosis factor, FNF, and a physiologically active substance with cytotoxic activity, which is produced by animal-derived fibroblasts and has a molecular weight of 40,000 to 60,000 and an isoelectric point of pH 5.0.+-.0.5, are disclosed in Japanese Patent Laid-open Publication No. 1872 (1986) and Japanese Patent Laid-open No. 103021 (1987), respectively. In addition, all the primary amino acid sequence and cDNA encoding the amino acid sequence of a tumor cytotoxic factor, which is obtained from the culture broth of human-derived fibroblasts, with a molecular weight of 36,000.+-.1,000 and an isoelectric point of pH 10.5 or higher are disclosed in Japanese Patent Laid-open No. 10988 (1989). The inventors have been investigating antitumor substances derived from human fibroblast cells and found a new antitumor protein, which is different from antitumor proteins hitherto reported. Furthermore, the inventors successfully cloned a cDNA encoding the protein, determined its all the primary amino acid sequence, and confirmed usefulness of the protein. The new antitumor protein and its gene were disclosed in the inventors' International Patent Publication No. 10651 (1990). The new antitumor protein was called as TCF-II.
TCF-II has both potent antitumor activity and proliferation stimulative activity for normal cells and is a member of the HGF (hepatocyte growth factor) group. Molecular weight determination of TCF-II with SDS electrophoresis showed a common band, A chain, with 78,000.+-.2,000 and two bands, B and C chains, with 30,000.+-.2,000 and 26,000.+-.2,000, respectively.
TCF-II may be used for the regeneration of liver after the hepatectomy due to its proliferation stimulative effect on hepatocytes. However, no effect of TCF-II on diseases related to abnormal blood coagulation such as DIC and thrombocytopenia has been known.
DIC accompanies with various basal diseases and frequently causes blood clotting in systemic fine blood vessels. It impairs functions of many organs and tends to result in marked hemorrhages due to consumption coagulopathy and hyperfibrinolysis. The basal diseases causing DIC include malignant tumor, leukemia, sepsis, infectious diseases, obstetric diseases such as placental abruption and amniotic fluid embolism, and shock in a descending order. Diseases frequently accompanied with DIC include leukemia, malignant lymphoma, myeloma, collagen disease, and liver diseases in. descending order. In addition to risk factors such as surgical invasion, administration of an antitumor agent, infectious diseases and shock may accelerate the onset of DIC. During the onset of DIC, coagulation factors such as blood coagulation factors I, II, V, VIII and XIII are consumed and their blood level decrease. Platelets are consumed in thrombus of systemic fine blood vessels by adhesion and coagulation in damaged subcutaneous tissues and incorporation
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Fujise Nobuaki
Masunaga Hiroaki
Mohamed Abdel A.
Snow Brand Milk Products Co. Ltd.
Tsang Cecilia J.
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