Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-07-17
2002-06-04
Spivack, Phyllis G. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06399650
ABSTRACT:
FIELD OF THE INVENTION
The present invention concerns the use of a cyclic gamma-aminobutyric acid (GABA) derivative, namely N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, as a drug for improving disturbances of the Activities of Daily Living (ADL) after a stroke or for recovering, or at least for improving the recovery of, a post-stroke patient.
BACKGROUND OF THE INVENTION
Cyclic GABA derivatives, more particularly 2-oxopyrrolidine derivatives, are compounds extensively used in pharmaceutical compositions for the improvement of memory and attention and are known as mnemotonic or nootropic agents. Typical drugs of this class include 2-oxo-1-pyrrolidineacetamide (piracetam), 1-(4-methoxybenzoyl)-2-pyrrolidinone (aniracetam) and 4-hydroxy-2-oxo-1-pyrrolidineacetamide (oxiracetam).
DESCRIPTION OF THE PRIOR ART
It is known (BE 883791U.S. Pat. No. 4,341,790) that anilides of 2-oxo-1-pyrrolidineacetamide show central vasoactive and tranquillizing properties as well as the ability of regulating the metabolism and inhibiting thrombocyte agglutination. Thus, said compounds are deemed to be useful for the treatment of cerebro-ischemic or atrophic diseases, brain irrigation disorders, brain atrophic crises as well of brain aging processes. Among these anilides of 2-oxo-1-pyrrolidineacetamide, the 2,6-dimethylanilide, i.e. N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, known and hereinafter referred to as nefiracetam, represented by the formula (A)
has been reported to be effective in prolonging the survival time upon a decrease in blood oxygen level and in relieving failure of memory due to cerebropathy.
The literature extensively discloses (see for example E. Ohtomo et al., J Clin. Exp. Med., Suppl., 1994, 170/9, 777-816) the usefulness of nefiracetam in improving psychiatric disorders associated with cerebrovascular diseases such as stroke (cerebral infarction or cerebral hemorrhage), this activity being a consequence of the favorable action of nefiracetam on the cerebral irrigation, as suggested by BE 883791.
It is also known (K. Hirata et al., Brain Topography 1996, 8/3, 279-284) that nefiracetam acts as a cerebral metabolic enhancer in improving the mental function impairment in stroke patients, thus confirming the suggestion of BE 833791 which disclosed the metabolism-regulating properties of the compound.
Moreover, it is known (U.S. Pat. No. 5,886,023) that nefiracetam improves symptoms of cerebrovascular or Alzheimer's type dementia due to a decline in mental function.
All these documents indicate that the efficacy of nefiracetam in the symptomatic treatment of impaired mental function is due to its ability in improving the cerebral irrigation or to its metabolism-regulating properties. Psychiatric symptoms and cognitive impairment are frequently observed following stroke and negatively affect both the patient and the caregiver.
In the above-cited article of Ohtomo et al., the global results of a clinical study, conducted in two groups of patients to which nefiracetam and, respectively, placebo were administered after a stroke (celebral infarction or celebral hemorrhage), showed that the compound improves the psychiatric symptoms but concluded that there was no significant difference between the two groups as far as the activities of daily living were concerned. Thus, according to these results nefiracetam appeared as inactive in improving the disturbances of the activities of daily living in post-stroke patients.
On the other hand, no drug is known for a positive effect in this indication. Such an effect could suggest a curative use of a drug for the recovery from a stroke or, at least, for an improved recovery from stroke.
SUMMARY OF THE INVENTION
It has now surprisingly been found that, if nefiracetam is administered to a patient, suffering from the consequences of a stroke, early after the event or at least within the first six months after the stroke, a significant improvement with regard to the global disturbances of the activities of the daily living is obseved.
More particularly, it has been found that nefiracetam is able to induce an improvement in the recovery of post-stroke patients, provided that said nefiracetam is administered early after the event at the most within the first six months after said event.
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Apomorphine-induced hypoa
Otomo Eiichi
Takasu Yoshiyuki
Daiichi Pharmaceutical Co. Ltd.
Spivack Phyllis G.
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