Title:  Method for improving disturbances of activities of daily living after stroke

United States Patent:  6,399,650

Assignee:    Daiichi Pharmaceutical Co., Ltd. (Tokyo, JP)

Filed:  July 17, 2001

A method for improving the disturbances of Activities of Daily Living in post-stroke patients by early administration of nefiracetam after the stroke is disclosed. This method of treatment allows an improvement in the recovery from stroke.

DETAILED DESCRIPTION OF THE INVENTION

Thus, it is an object of the present invention to provide a method for improving the disturbances of the Activities of Daily Living (ADL) in a post-stroke patient which comprises administering to said patient an effective dose of nefiracetam, said administration being initiated within the first six months after the event.

In order to display the best activity, nefiracetam will be administered early or at least as soon as possible, advantageusly within three month, preferably within one month after the stroke.

Nefiracetam can be administered in various manner to achieve the desired effect. The compound can be administered alone or in the form of pharmaceutical preparations to the patient to be treated, preferably orally. The oral amount of nefiracetam administered will vary and can be any effective amount according to the physician's prescription. Normally, depending upon the patient and the mode of administration, the quantity of compound administered orally may vary over a wide range to provide from about 1 mg/kg to about 20 mg/kg, usually 1.5 mg/kg to 15 mg/kg of body weight of the patient per dose. Unit doses of nefiracetam can contain, for example, from about 50 mg to about 1200 mg, usually from 100 to 600 mg of the compound and may be administerd orally 1 to 4 times daily.

The activity of nefiracetam to improve the disturbancies of ADL has been discovered during a controlled clinical trial against placebo. The compound has been administered orally (450 mg/day) to 32 post-stroke patients within six months after the event whilst, concurrently, 27 patients received placebo. The two groups of patients were followed during at least 8 weeks and followed up at the end of week 4 and at the end of week 8 on a symptom scale measuring Activities of Daily Living. The nefiracetam-treated patients showed a moderate or remarkable improvement, whereas no patient in the group treated with placebo showed an improvement. Among the above 59 patients, 19 received nefiracetam and 10 received placebo within three months after stroke. Some 70% of the nefiracetam-treated patients showed a moderate or remarkable improvement whilst no improvement has be noted in the patients who received placebo. The difference was significant (p=0.035, .chi.² test). Thus, unlike what the literature seemed to suggest, it has been discovered that nefiracetam has the surprising and unique property of showing a dramatically good activity when given early after stroke. According to the results of this study, the early treatment with nefiracetam after stroke objectively improves the recovery from stroke, as shown by the fact that, beside psychiatric symptoms such as emotional disturbance and reduced spontaneity, also intellectual dysfunction dramatically improved in a high percent of nefiracetam-treated patients whilst no improvement was noted in the placebo-treated patients. Moreover, nefiracetam surprisingly tends to improve neurological signs and incontinence of urines. Thus nefiracetam, when administered early after the event, appears to be the first drug which is able to induce a recovery from stroke or, at least, to improve the recovery from stroke.

The mechanism of action of nefiracetam for this indication, which is not bound to the nootropic activity of the drug, is unknown, but it is believed that its surprising effect in improving the disturbancies of ADL after a stroke or in the recovery of, or at least in improving the recovery of, a post-stroke patient, is due to a true brain repair.

Thus, it is a second object of the present invention to provide a method for recovering, or at least for improving the recovery of, a post-stroke patient which comprises administering to said patient an effective amount of nefiracetam, said administration being initiated within three months from the stroke.

It is a third object of the present invention to provide a pharmaceutiacal composition for the improvement of the disturbancies of ADL in post-stroke patients comprising, as active ingredient, an effective amount of nefiracetam.

It is a fourth object of the present invention to provide a pharmaceutical composition for the recovery of, or at least for improving the recovery of, a post-stroke patient, comprising, as active ingredient, an effective amount of nefiracetam.

It is a fifth object of the present invention to provide the use of nefiracetam for the preparation of a medicament for improving the disturbancies of ADL in a post-stroke patient.

It is a sixth object of the present invention to provide the use of nefiracetam for the preparation of a medicament for the recovery, or at least for improving the recovery, of a post-stroke patient.

It is a seventh object of the present invention to provide the use of nefiracetam for the preparation of a medicament for the early treatment of stroke.

The pharmaceutical formulations in which form nefiracetam will normally be utilized, are prepared in a manner well known per se in the pharmaceutical art and usually comprise nefiracetam in admixture or otherwise in association with a pharmaceutically acceptable carrier or diluent thereof. For making those formulations the active ingredient will usually be mixed with a carrier, or diluted with a diluent, or enclosed or encapsulated in a capsule, sachet, cachet, paper or other suitable container. Suitable carriers and diluents are known per se.

The formulations may be administered to the post-stroke patient for example in the form of tablets, capsules, dragees, suppositories, syrups or suspensions.

Claim 1 of 18 Claims

What is claimed is:

1. A method for improving the Activities of Daily Living (ADL) in a post-stroke patient which comprises administering to said patient a composition comprising an effective amount of nefiracetam, said administering being initiated within six months after a stroke.

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