Use of mono and di inositolphosphates for treating inflammation

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...

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514109, 514129, A61K 3166

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053428323

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BRIEF SUMMARY
The present invention relates to the use of a compound of formula (I): combatting different conditions in mammals including man.
The invention also relates to a pharmaceutical composition comprising as a pharmaceutically active ingredient a specific compound of formula (I).
Inositolphosphates are a group of compounds occuring in different plants, as constituents in cell membranes, etc. The hexaphosphorylated myo-inositol, phytic acid, is present in different grains at varying amounts. It is known that lower inositol phosphate derivatives are formed when the grains are germinated. The end products are inositol and inorganic phosphate.
Some other inositolphosphates exist in the blood of birds, especially the inositol-pentaphosphate. This compound regulates the affinity for oxygen to hemoglobin in the erythrocytes.
Lower inositolphosphates linked to glycerol moities are constituents of plasma membranes in cells.
This is valid for very specific isomers of inositoltrisphosphates, inositol-bisphosphates and inositol-monophosphates. These inositolphosphates are released within the cells and regulate different metabolic pathways.
From C. A., vol. 33 (1939), abstr. no. 7351, no 3/4, the use of phosphates including inositolphosphates as an antirachitic diet has been reported. No reference is made to specific inositolphosphates.
The U.S. Pat. No. 4,473,563 discloses the extra corporal treatment of erythrocytes to incorporate therein inositolphosphates to improve the oxygen supply. Then erythrocytes are separated from the blood, which has been pumped out of the body for that purpose. After complicated treatment of erythrocytes the latter are reintroduced into the blood. There is no disclosure of administering inositol phosphates directly to the body.
In the U.S. Pat. No. 2,723,938 the use of inositolphosphates is disclosed for stabilizing dispersions of an aqueous suspension of penicillin. This ensures that brief simple manual shaking will restore a state of complete and uniform dispersion of the penicillin after prolonged storage.
From the European Patent No. 179.439 a pharmaceutical composition comprising as a pharmaceutically active ingredient at least one isomer of inositol-trisphosphate is known. In said patent the effect of this pharmaceutical composition is shown for different areas such as platelet aggregation.
The invention relates to the use of a compound of formula (I) for the preparing of a medicament for preventing, alleviating or combatting for example the following conditions: Tissue damage such as oedema formation, vascular leakage, burns, thiniris and asthma; diabetes or complications thereof such as cataract formation, retinopathy, neuropathy, nephropathy, vascular complications, hyperglycemia and hyperketonemia; bone disorders such as osteoporosis, Paget's disease, bone erosion, hypercalcemia and osteoarthritis; disorders related to transplantation and graft operations such as rejection; abnormal immunological response; abnormal levels of lipoproteins; cardiovascular diseases; hemorrhage and inflammatory conditions such as rheumatoid arthritis and gout.
The inventions also covers the use of a compound of formula (I) for the preparing of a medicament for preventing, alleviating or combatting damage to cell membranes, metal intoxication, conditions of ischemia and reperfusion, conditions of shock, conditions related to vasculitis, dermatitis, gastrointestinal diseases such as ulcerative colitis and pancreatitis, synovitis, periodontal diseases and cerebral diseases, autoimmune diseases such as multiple sclerosis, eye diseases or damage to the retina or lens, light and oxygen induced diseases or damages and skin damages.
The different isomers of the compound of formula (I) are inositol-monophosphates and inositol-bisphosphates. In one preferred embodiment of the invention the inositol-isomer is myo-inositol but also other inositols, i.e. allo-inositol, epi-inositol, chiro-inositol, muco-inositol, cis-inositol, neo-inositol, scyllo-inositol are to be contemplated to be in the scope of the invention.
The

REFERENCES:
patent: 4562449 (1987-03-01), Ropars et al.
patent: 5019566 (1991-05-01), Siren
Chem Abst. 110: 111342 Mar. 1989.
Chem Abst. 107: 88954, Sep. 1987.

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