Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1991-12-23
1993-11-30
Schenkman, Leonard
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514825, 514885, A61K 31685
Patent
active
052665640
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
The invention concerns a process for the preparation of a pharmaceutical composition for the treatment of autoimmune diseases with derivatives of lysolecithin.
From DE-OS 20 09 342 and DE-OS 20 09 343 it is already known that synthetic lysolecithin compounds can be used as immunological adjuvants and for the increase of resistance. Furthermore, from DE-OS 26 19 686, it is known that such alkyl-lysophospholipids are effective as antitumorur agents. In addition, it is known that, after administration of lysophosphatides, it results in the formation of activated cells which can increase the resistance of the body against undesired influences. Finally, in U.S. Pat. No. 4,778,788 is described the use of synthetic lysolecithin compounds for the treatment of multiple sclerosis.
In all immunological reactions of the organism, T-lymphocytes play a central part. Their function and their method of working can thereby be divided up into two important working mechanisms, namely:
1. the direct defence against a foreign body, such as bacteria, viruses, parasites and other substances displaying an antigen, whereby the T-lymphocytes participate directly by an effector mechanism, and
2. the regulation of the immune response in order that this does not overshoot.
In both cases, it is characteristic for the manner of working of the T-lymphocytes that these display a high specificity, i.e. that these cells have the property of being able to recognise a single, quite specific antigen. However, before the T-cells show this property, it is necessary that they are first activated from a dormant state, which presupposes a proliferation and a differentiation.
T-lymphocytes can now be divided up into two large sub-groups on the basis of definite membrane structures which are formed by proteins, namely, the CD4.sup.+ and the CD8.sup.+ T-cells. The CD4are designated as helper or as inducer T-cells and, inter alia, are responsible for the recognition of foreign proteins and the initiation of defence reactions against antigens. The CD8.sup.+ cells, which are designated as suppressor or as cytotoxic T-cells, are responsible, inter alia, for the recognition and the destruction of virus-infected cells.
It has now been shown that, especially in the case of more highly developed species of the animal kingdom, T-cells appear which display auto-reactive properties. This means that such T-lymphocytes are directed against body-inherent structures of the organism and thus are pre-programmed to attack the body's own materials and cells. Normally, these auto-reactive T-cells remain inactive due to the regulating actions of other cells or factors so that an equilibrium for the protection of the organism results. However, if this equilibrium is disturbed, then auto-immune diseases can thereby be induced. This leads to the formation of auto-aggressive cells or auto-antibodies which finally initiate the auto-immune disease. However, hitherto it has not been known which antigens are responsible in the case of humans for the initiation of these symptoms.
Such auto-immune diseases have previously been treated with immune-suppressive substances, such as corticosteroids, cyclophosphamides, cyclosporin A and the like. However, it has been shown that these substances not only inhibit the whole immune system but, in addition, also display considerable side effects, such as a suppression of the bone marrow, carcinogeneity, as well as high toxicity.
The task forming the basis of the invention is to make available a further agent for the treatment of auto-immune diseases which does not display the above-mentioned disadvantages.
R. Andreesen and P. Munder (New Trends Lipid Mediators Res. Basel, Karger, 1988, Vol. 1, pages 16 to 29 and Immunobiol. (1979) 156, 498-508) have already been able to show that alkyl-lysophospholipids are able to inhibit the non-specific proliferation of lymphocytes.
Surprisingly, it has now been found that the proliferation of precisely those specific auto-reactive T-cells which are responsible for the auto-immune reactions ca
REFERENCES:
patent: 4778798 (1988-10-01), Munder
Modolell Manuel
Munder Gerhard
Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E. V.
Schenkman Leonard
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