Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ketone doai
Reexamination Certificate
1998-11-09
2001-08-07
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ketone doai
Reexamination Certificate
active
06271266
ABSTRACT:
BACKGROUND OF THE INVENTION
1. FIELD OF THE INVENTION
The present invention relates to a cytoprotectant composition and more particularly to an anti-&bgr;-amyloid protein-induced cytotoxicity composition.
2. BACKGROUND ART
It is known that the cells constituting a living matter are under constant exposure to many various unfavorable factors, endogenous and exogenous, with the result that they are sometimes prevented from functioning normally or physically injured, thus undergoing degeneration and even apoptosis. Moreover, the various diseases caused by such cytological changes are serious contemporary social concerns.
The most important neuropathological feature of the brain of patients with Alzheimer's disease is senile plaques. The senile plaque contains a variety of substances but its dominant contents are &bgr;-amyloid proteins of 40 to 43 amino acid residues in length [Cell, 52, 307-308, 1988 and Neuron, 6, 487-498, 1991].
It has been demonstrated in experiments using cultured nerve cells that &bgr;-amyloid as such shows neuronal toxicity [Brain Research, 533, 315-320, 1990 and Science, 25, 279-282, 1990] and is regarded as an etiologic factor in Alzheimer's disease. Moreover, recent research has shown that aggregation of &bgr;-amyloid proteins is essential to the expression of their toxicity [Neurobiology of Aging, 1, 587-590, 1992 and Journal of Molecular Biology, 218, 149-163, 1991].
Meanwhile, it is disclosed in JP-A-3-81218 and its corresponding U.S. Pat. No. 5,059,627 that substituted 1,4-benzoquinone derivatives and the corresponding substituted 1,4-hydroquinone derivatives have potent nerve growth factor secretion-inducing activity and are, therefore, effective in the treatment of Alzheimer's disease.
According to JP-A-7-61923 and its corresponding EP-A-629400, administration of idebenone as a therapeutic agent in high doses (270 mg-360 mg day per adult) is clinically effective in Alzheimer type senile dementia.
Arch. Gerontol. Geriatr., 15, 249-260, 1992, also, reports the efficacy of idebenone by administering 90 mg daily to adult patients with Alzheimer type senile dementia.
The Journal of pharmacology and Experimental Therapeutics, 250, 1132-1140, 1989 reports that in the rat retinal neuron-neuroblastoma hybrid N18-RE-105 cells, idebenone suppresses glutamate-induced neuronal death and exerts the neuroprotection by the reactive oxygen species scavenging activity of the compound.
REFERENCES:
patent: 5059627 (1991-10-01), Goto et al.
patent: 0 629 400 A1 (1994-12-01), None
patent: 629400 (1994-12-01), None
G. Weyer et al., “Efficacy and Safety of Idebenone in the Long-Term Treatment of Alzheimer's Disease: A Double-Blind, Placebo Controlled Multicentre Study”, Human Psychopharmacology, vol. 11, pp. 53-65, (1996).
N. Ranen et al., “A Controlled Trial of Idebenone in Huntington's Disease”, Movement Disorders, vol. 11, No. 5, pp. 549-554, (1996).
U. Senin et al., “Idebenone in Senile Dementia of Alzheimer Type: A Multicentre Study”, Arch. Geront. Geriatr, vol. 15, pp. 249-260, (1992).
T. Nabeshima, “Nerve Growth Factor Strategy and Preparation of Animal Model for Alzheimer-Type Senil Dementia”, Yakugaku Zasshi, vol. 115, No. 7, pp. 499-512, (1995).
Abstract to Canonico et al., “The role of free radicals and brain aging”, G. Gerontol. 42(2), pp. 71-75, 1994.*
Abstract to FR 2,703,591 A1, Oct. 14, 1994.
Goto Giichi
Hirai Keisuke
Miyamoto Masaomi
Jones Dwayne C.
Takeda Chemical Industries Ltd.
Wenderoth , Lind & Ponack, L.L.P.
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