Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1997-08-11
1999-09-07
Jarvis, William R. A.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
A61K 3843
Patent
active
059487607
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a novel therapeutic use of superoxide dismutases (SOD).
BACKGROUND
SOD was characterized in 1968 by McCORD and FRIDOVICH; it is an enzyme which promotes removal of the superoxide radical (O.sub.2.sup.-), constitutes a priori a mechanism of protection against the deleterious effects of this radical, is capable of being formed in vivo from atmospheric oxygen and therefore plays a major role in preventing the toxic effects which could result from exposure to an oxygenated atmosphere.
As free radicals derived from oxygen seem to be involved in numerous complaints, the use of SOD in therapeutics has therefore been recommended in inflammatory arthropathy (R. NORDMANN et al., Cah. Nutr. Diet., 1991, 26, 6, 398-402); SOD has also been proposed with a greater or lesser degree of success in pulmonary diseases, more particularly bronchopulmonary dysplasia, or in other toxic conditions associated with the presence of substantial amounts of oxygen (central nervous system, ischaemia, non-vascular gastro-intestinal disorders, ocular disorders (locally in the anterior chamber of the eye) or control of the undesirable effects of anticancer treatments) (GREENWALD R. A., Free Radical Biol. Med., 1990, 8, 201-209).
SOD, in its liposomal bovine Cu/Zn form, has been found to be particularly effective on radiofibrosis in clinical trials (Baillet F. et al., Treatment of radiofibrosis with liposomal superoxide dismutase. Preliminary results of 50 cases, Free Rad. Res. Commun., 1, 387-394, Harwood Academic Publishers GmbH, 1986) and subsequently in experiments on pigs (Lefaix J. L. et al., La fibros cutaneo-musculaire radio-induite: efficacite therapeutique majeure de la SOD Cu/Zn liposomiale (Radioinduced cutaneomuscular fibrosis: major therapeutic efficacy of liposomal Cu/Zn SOD), Bull. Cancer, 1993, 80, 799-807), these results being all the more interesting because there is no product which has an equivalent action.
Of the SODs tested, those which have an extended half-life and a low incidence of immunological illnesses are preferred; the following may be mentioned in particular: Cu/Zn SOD of bovine origin (a homodimer which catalyses the dismutation of the superoxide radical), Mn SOD, Fe SOD, liposomal SODs, SODs conjugated with polyethylene glycol, SOD polymers or copolymers and recombinant human Cu/Zn SOD and Mn SOD.
SUMMARY OF THE INVENTION
The Applicants have found a novel use of SOD-based preparations with an extended duration of action for the production of a drug intended for treating or preventing brain function disorders, preferably cognitive brain function disorders, which are caused by a specific cerebral aggression, damage, stress or insult or by a non-specific aggression.
In terms of the present invention, non-specific aggression is understood as meaning for example an electrical stimulation (plantar shock) and specific cerebral aggression, damage, stress or insult, is understood as meaning for example extended whole-head irradiation.
Unexpectedly, the said SOD preparation with an extended duration of action protects mammals from brain function disorders in both a preventive capacity and a curative capacity.
The SOD preparation with an extended duration of action is preferably selected especially from liposomal SODs, SOD/polyethylene glycol conjugates and SOD polymers or copolymers.
Advantageously, the superoxide dismutase (SOD) is especially mammalian (murine, bovine, human) Cu/Zn SOD, Mn SOD or Fe SOD or a recombinant SOD.
These preparations can be administered either parenterally, preferably subcutaneously, or orally.
The SOD-based preparations as defined above can be used in mammals, and especially in man, for the curative or preventive treatment of the cognitive brain function disorders caused by a specific cerebral aggression, damage, stress or insult, (for example irradiation) or by a non-specific aggression (for example electrical stimulation).
The doses of SOD are effective on the complications of radiotherapy over a wide range of posologies, t
REFERENCES:
Roda et al, Chemical Abstracts, vol. 115, abstract No. 247753, 1991.
Kizuki et al, Biological Abstracts, vol. 92, abstract No. 44946, 1991.
Matsumiya et al, Chemical Abstracts, vol. 115, abstract No. 247930, 1991.
Uyama et al, Chemical Abstracts, vol. 116, abstract No. 143724, 1992.
"Superoxide Dismutase and Catalase as Therapeutic Agents for Human Diseases--A Critical Review", Greenwald, Robert A., Free Radical Biology & Medicine, vol. 8, No. 2, pp. 201-209, 1990.
"Age-related changes in levels of the .beta.-subunit of nerve growth factor in selected regions of the brain: comparison between senescence-accelerated (SAM-P8) and senescence-resistant (SAM-R1) mice", Katoh-Semba et al., Neuroscience Research, vol. 20, No. 3, pp. 251-256, 1994.
Database WPI, Section Ch, Week 9433, Derwent Publications Ltd., London GB; Class B05, AN 94-269367 & JP,A,06 199 690 (Kato K), Jul. 19, 1994.
Baillet Fran.cedilla.ois
Lamproglou Ioannis
Assistance Publique-Hopitaux de Paris
Jarvis William R. A.
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