Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1993-05-20
1994-11-01
Wityshyn, Michael G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530350, 514 21, A61K 3702
Patent
active
053607899
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a therapeutic agent for skin or corneal diseases, and more specifically to a therapeutic agent for skin or corneal diseases, which contains CPB-I or recombinant CPB-I as an active ingredient and is useful for treating a skin or corneal disease such as a wound or psoriasis.
BACKGROUND ART
There have hitherto been provided a number of substances having a therapeutic effect on skin and corneal diseases, in particular, wounds. For example, growth factors (BIO/Technology, 135-140, 1985) such as an epidermal growth factor (EGF) (Exp. Cell Res., 164, 1-10, 1986), acid and basic fibroblast growth factors (acid and basic FGFs). (J. Surg. Res., 45, 145-153, 1988), transforming growth factors (TGF-.alpha. and TGF-.beta.) (Japanese Patent Application Laid-Open No. 167231/1990; Science, 233, 532-534, 1986) and insulin-like growth factors (IGF-I and IGF-II), adhesion factors such as fibronectin, laminin and vitronectin (Ann. Rev. Biochem., 52, 961, 1983), and chemical substances such as retinoids and analogous compounds thereof (Am. J. Ophthalmol., 95, 353-358, 1983; Ann. Ophthal., 19, 175-180, 1987) have been known. The healing process of the skin wound is accompanied by granulation tissue formation, angiogenesis and re-epithelization. In these processes, fibroblasts, vascular endothelial cells and epidermal cells (keratinocytes) proliferate and migrate, respectively. The above-mentioned factors and other chemical substances have been known to be effective to the skin healing.
The healing process of the epithelia, parenchyma and endothelia of the cornea is accompanied by the migration and proliferation of epithelial cells, the phagocytosis of waste matter and the production of extracellular matrix by parenchymal cells, and the migration of endothelial cells, respectively.
In recent years, damages of endothelial cells have become recognized after cataract surgery, keratoplasty and wearing of contact lenses. Therefore, the importance of the endothelial cells has been pointed out. Human endothelial cells are said not to proliferate or to be hard to do. In their healing process, their migration and adhesion might be important. Up to the present, it has been reported that use of rabbit cultured endothelial cells which has proliferating ability revealed the fact that EGF and FGFs promote their proliferation. However, any effective remedy has not been yet reported. There is hence a demand for development of such an agent as promote the migration and adhesion of the endothelial cells.
On the other hand, as clinical pictures of skin diseases, in particular, psoriasis which is a chronic skin disease, there have been leukocyte infiltration (J. Invest. Dermatol., 68, 43-50, 1977), the hyperplasia of epidermis (J. Invest. Dermatol., 50, 254-258, 1968) and aberrant terminal differentiation (J. Invest. Dermatol., 70, 294-297, 1978), and as biochemical findings, there have been known, from the investigation on the mouse skins applied with a phorbol ester (TPA) which is a carcinogen, exhibiting psoriasis-like findings, the activation of protein kinase C (PKC) (J. Invest. Dermatol., 93, 379-386, 1989), increase in release of arachidonic acid and prostaglandin (Biochem. Biophys. Res. Commun., 92, 749-756, 1980), induction of ornithine dehydrogenase and transglutaminase activity (Cancer Res., 39, 4183-4188, 1979; Biochem. Biophys. Res. Commun., 97, 700-708, 1980) and increase in interleukin 1 (J. Invest. Dermatol., 88, 499A, 1987).
Steroid ointments and PUVA therapy have been used in local treatment for psoriasis, and dietetic therapy, vitamin D.sub.2, vitamin B.sub.12, etretinoids, etc. in general treatment. In recent years, TGF-.beta. having an antiproliferative effect on keratinocytes (Japanese Patent Application Laid-Open No. 167231/1990) and cyclosporin A having an antiinflammatory effect (JAMA, 256, 3110-3116, 1986) have also been studied as therapeutic agents for psoriasis. However, action mechanisms thereof have not yet been clear.
Although the above-mentioned factors and chemic
REFERENCES:
patent: 4873222 (1989-10-01), Arai et al.
patent: 4937324 (1990-06-01), Fujikawa et al.
patent: 5116942 (1992-05-01), Inoue et al.
patent: 5179081 (1993-01-01), Iwasaki et al.
Nagoya Takao
Nakao Hiroshi
Saino Yushi
Kowa Co. Ltd.
Sayala C.
Wityshyn Michael G.
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