Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1998-01-08
2000-03-07
Tsang, Cecilia J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530328, A61K 3808, C07K 706
Patent
active
060340649
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD OF THE INVENTION
The present invention relates to peptides or derivatives thereof. The peptides or derivatives thereof according to the present invention are useful for the antigen non-specific suppressive treatment of abnormally augmented immunoreaction in autoimmune diseases. Having an anti-inflammatory effect, it is also useful for the treatment of the inflammation.
Accordingly, the present invention relates to the fields concerned with peptides or derivatives thereof and also with pharmaceuticals containing the same.
1. Background of the Invention
Autoimmune diseases are induced by the continuous production of an antibody or lymphocyte which reacts with a component of the own tissue. In the autoimmune diseases, described specifically, the break-down of immunologic tolerance heightens immune response to own organic components, which causes the reaction between an autoantibody or autoreactive T cell so produced and an autoantigen or cell corresponding thereto, thereby causing cellular dysfunction or tissue damages. At present, 50 or more types of autoimmune diseases are known and according to the spreading degree of a lesion over the organs, they can be classified into organ specific autoimmune diseases and organ nonspecific autoimmune diseases.
Examples of the former diseases include insulin-dependent diabetes mellitus in which a lesion is caused by the selective destruction of B cells in pancreatic island of Langerhans, Basedow disease and Hashimoto disease in which thyroid dysfunction is caused by the antibody against a thyroid stimulating hormone receptor, myasthenia gravis which has muscle contraction lowered by an antibody against an acetylcholine receptor of the striated muscle, and autoimmune hemolytic anemia in which hemolysis is caused by the antibody against the erythrocyte.
Examples of the latter diseases include chronic rheumatoid arthritis in which generalized disorders in the osseous or cartilaginous tissue are considered to occur, triggered by the aggregation of IgG and anti-IgG antibodies (rheumatoid factors), systemic lupus erythematosus in which a disturbing reaction is caused by the deposition of antibodies against DNA or nuclear components to the kidney, joint or skin, SjUgren syndrome in which dysfunction occurs owing to the lymphocytic infiltration into the salivary gland or lacrimal gland and systemic organolesion such as interstitial nephritis occurs concurrently at certain frequency, and multiple sclerosis in which disseminated demyelination nidi and gliosis appear in the substantia alba of the central nervous system and they cause systemic motor paralysis, ophthalmopathy, paresthesia or the like.
2. Prior Art
For the treatment of autoimmune diseases, it is the common practice to administer an immunosuppressant typified by a gluco-steroid preparation, cyclosporin A or FK 506. The treatment using such a preparation is, however, accompanied by the drawback such as serious side effects, for example, infectious diseases, nephrotoxicity of the drug itself or carcinogenesis, which result from wide spectrum of immunosuppression [Sadao Kashiwazaki, Sogo Rinsho, 43 (9), 1725-1729 (1994)].
In recent years, there have been some attempts to treat autoimmune diseases without using such an immunosuppressant with wide spectrum.
Upon reaction with an antigen, B cells recognize the antigen itself, while T cells recognize the complex of an MHC molecule on the surface of the antigen presenting cell and an antigen peptide fitted in the groove of the MHC molecule. The MHC molecule differs with individuals and human T cells having MHC congenial to a certain antigen shows good response to this antigen. This is one of the reasons why some human beings are likely to be reactive to a certain antigen. On the other hand, T-cell antigen receptors (T cell receptors: TcR) can be classified into several families. There is a substance which activates T cells, binding with one or some of the TcR families and the substance is called a superantigen. The superantigen activates a larger number of T
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Ogata Kenji
Takanashi Hitoshi
Wagatsuma Masako
Yamagata Nobuyuki
Gupta Anish
Hoechst Pharmaceuticals & Chemicals K.K.
Tsang Cecilia J.
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