Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1997-07-18
1999-01-05
Sayala, Chhaya D.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
530351, 424 851, C07K 118
Patent
active
058564446
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a novel physiologically active substance (thrombocytopoiesis stimulating factor) having activity in acting on cells in the megakaryocyte system, in promoting their differentiation and maturation, and in promoting the formation of platelets, as well as to a medicinal composition containing this physiologically active substance as an active component for the treatment of thrombocytopenia. Since the physiologically active substance (thrombocytopoiesis stimulating factor) of the present invention has activity in acting on the megakaryocyte-platelet system, in promoting differentiation and maturation therein, and in promoting the formation of platelets, it is particularly useful in the medical field as an active component or the like in therapeutics and preventives for thrombocytopenia and thrombocytopenic purpura associated with chemotherapy and marrow grafts, and for various other diseases which are prone to bleeding attributed to thrombocytopenia.
BACKGROUND ART
Blood cells such as erythrocytes, leukocytes, lymphocytes, and platelets are present as material components in the blood, which is an indispensable medium for the somatic cells constituting the body, and these blood cells each have an inherent function in the continual maintenance of the body. Understanding the phenomenon of the differentiation, maturation, proliferation, and the like of these blood cells in the body has long been the subject of research in the field of hematology, but the differentiation and maturation of various blood cells from one type of multifunctional hematopoietic stem cell in the marrow, the roles played by various endogenous humoral factors during the process of differentiation and maturation, and, other facts have recently been elucidated.
In light of such facts, these endogenous humoral factors hold promise as medicinal products such as drugs for the treatment of diseases associated with decreases in the blood cells of the blood cell systems, and a variety of humoral factors, such as erythropoietin, G-CSF, GM-CSF, M-CSF, and interleukin, have thus far been discovered, some of which have been put to actual use as drugs having action in promoting the differentiation and maturation of blood cells such as those in the erythrocyte, leukocyte, and lymphocyte systems.
Platelets, however, are anucleate cells with a diameter of 2 to 3 .mu.m in the blood, and although they are a type of material component in the blood that plays an important role in hemostatis or thrombogenesis in the body, it has become clear that platelets are formed as a result of the fragmentation of the cytoplasm of megakaryocytes which have matured following the transition from multifunctional hematopoietic cells in the marrow to megakaryoblasts by way of megakaryocyte precursor cells.
There have recently been various reports on the results of research on the megakaryocyte-platelet system. For example, it has been reported that IL-6 has action in promoting the maturation of megakaryocytes, which are precursor cells of platelets (Toshiyuki Ishibashi, et al., Proc. Natl. Acad. Sci. USA., Vol. 86, pp. 5953-5957 (1989), and Toshiyuki Ishibashi, et al., Blood., Vol. 74, pp. 1241-1244 (1989)).
Based on research thus far undertaken, two factors having different types of action are believed to exist in the formation of megakaryocyte colonies from bone marrow cells (N. Williams, et al., J. Cell Physiol., 110, 101 (1982)). Specific examples of such factors which have been reported include megakaryocyte colony stimulating factor (Meg-CSF) which forms megakaryocyte colonies on its own, and megakaryocyte potentiator factor (Meg-POT) which has no activity in forming megakaryocyte colonies in itself but does have activity in increasing megakaryocyte colonies in the presence of Meg-CSF and in promoting their maturation.
Examples that have been reported as having Meg-CSF activity in humans include IL-3 (M. Teramura, et al., Exp. Hematol., 16, 843 (1988)), granulocyte-macrophage colony stimulating factor (M. Teramura, et al.
REFERENCES:
Fujimoto et al., Biochem. Biophy. Res. Comm., vol. 174(3), pp. 1163-1168, 1991.
Yoshida et al., Cancer Res., vol. 52, pp. 464-469, 1992.
Higuchi Masato
Kawakita Makoto
Matsuzaki Hiromitsu
Shibuya Kazushi
Takatsuki Kiyoshi
Chugai Seiyaku Kabushiki Kaisha
Sayala Chhaya D.
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