Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-04-23
2000-03-21
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514510, 514557, 514898, A61K 3134, A61K 3121, A61K 3119
Patent
active
060403365
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP96/03481, filed Aug. 6, 1996.
The invention relates to the use of prostane derivatives in the preparation of a medicament for the treatment of bacterially induced meningitis and also to the combination of prostane derivatives with antibiotics.
Despite great advances in antimicrobial therapy, mortality in the case of bacterial meningitis is high (M. N. SCHWARTZ (1984) Bacterial meningitis: more involved than just the meningitis. N. Engl. J. Med., 311: 912-914).
Pneumococci are aetiologically the most frequent causes of meningitis in adults and result in death in from 25% to 30% of cases. Clinical observations would suggest that an increase in the intracranial pressure (ICP), the formation of cerebral oedemas and cerebral vasculitis determine the fatal course of the meningitis (H.-W. PFISTER (1989): Complicated purulent meningitis of the adult: persisting high mortality caused by vasculitis and increased intracranial pressure, Nervenarzt, 60: 249-254). The inflammatory changes in bacterial meningitis are mediated by cytokines such as TNF. TNF can be detected in humans with pneumococcal meningitis. (K. J. TRACEY (1994) Tumor necrosis factor--alpha: In: The cytokine handbook A. THOMSON, eds. Academic Press London, pp. 289-304, and also: T. P. LEIST et al. (1988) Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients. J. Exp. Med., 167 (5): 1743-1748). CSF pleocytosis and cerebral oedema occur after the intracisternal increase in TNF (K. SAUKKOMEN et al. (1990) The role of cytokines in the generation of inflammation and tissue damage in experimental gram positive meningitis. J. Exp. Med. 171 (2): 439-448). That points to a transmigration of leucocytes and a breakdown of the blood/brain barrier.
EP 0 011 591 describes prostane derivatives and their preparation. Those prostane derivatives are compounds that are derived from prostacyclin (PGI.sub.2). They contain a methylene group instead of the 9-ether-oxygen atom in the prostacyclin. Prostane derivatives are used in the treatment of various diseases, the cardiovascular and thrombo-aggregation-inhibiting action being especially important.
The use of prostane derivatives as medicaments is known from EP 0 011 591. That Application describes the lowering of peripheral, arterial and coronary vascular resistance, the inhibition of thrombocyte aggregation and breaking down of platelet thrombi, myocardial cytoprotection and therewith a lowering of the systemic blood pressure without at the same time reducing cardiac output and coronary blood supply; treatment of stroke, prophylaxis and treatment of coronary heart diseases, coronary thrombosis, cardiac infarction, peripheral arterial diseases, arteriosclerosis and thrombosis, treatment of shock, inhibition of broncho-constriction, inhibition of gastric acid secretion and cytoprotection of the gastric mucous membrane and intestinal mucous membrane; anti-allergic properties, lowering of pulmonary, vascular resistance and of pulmonary blood pressure, promotion of renal blood flow, use instead of heparin or as an adjuvant in haemofiltration dialysis, storage of blood plasma stocks, especially of blood platelet stocks, inhibition of labour pains, treatment of toxaemia of pregnancy, anti-proliferative action and increase of cerebral blood flow.
EP 0 055 208, EP 0 099 538 and EP 0 119 949 describe carbacyclin derivatives that have similar indications to those of the above-mentioned prostane derivatives.
EP 0 084 856 describes further prostane derivatives which have been proposed for use in inhibiting thrombocyte aggregation, in lowering the systemic blood pressure or in the treatment of gastric ulcers, with beraprost being given special mention.
The use of prostane derivatives in the treatment of immune responses is described in various publications. For example, the treatment of anti-allergic properties is mentioned, inter alia, in EP 0 011 591.
EP 0 055 208 describes, inter alia the anti-allergic a
Angstwurm Klemens
Scholz Peter
Weber Jorg
Jordan Kimberly
Schering Aktiengesellschaft
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