Preventive and therapeutic agent for kidney diseases

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

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A61K 3155

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active

058246754

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP96/02341, filed Aug. 22, 1996.


TECHNICAL FIELD

The present invention relates to a preventive and therapeutic agent for kidney diseases and more particularly, to a preventive and therapeutic agent for kidney diseases typified by acute renal failure.


BACKGROUND ART

Renal failure is a state in which renal functions are damaged severely such that internal environment of the living body can no longer be maintained in normal conditions. In particular, acute renal failure--which involves sharp aggravation of renal functions that leads to a loss of homeostasis of body fluid, permitting accumulation of nitrogen metabolites--shows high lethality even with today's advanced dialysis therapy, and is a pathological condition with poor prognosis.
Therapeutic agents for acute renal failure include loop diuretics and osmotic diuretics, which are used in expectation of recovery of renal functions by increasing the flow in kidney tubules so as to wash away casts formed in the tubules and thereby prevent obstruction of the tubules. However, depending on the manner of use, these agents present the risk of inviting hearing disorders and the even more severe adverse side effects of heart failure and pulmonary edema. Therefore, there is demand for development of more effective and safe preventive or therapeutic drugs for acute renal failure.
Accordingly, an object of the present invention is to provide a preventive and therapeutic agent for kidney diseases, particularly, renal failure.


DISCLOSURE OF THE INVENTION

Under the above circumstances, the present inventors conducted careful studies so as to solve the above-mentioned problems, and found that the compounds represented by the following formula (1), their acid addition salts, or hydrates of the formula (1) compounds or of their acid addition salts exhibit potent preventive and therapeutic effects against kidney diseases, particularly renal failure, and moreover, these compounds strongly suppress formation of edemas generated through ischemia-reperfusion, thus leading to completion of the invention.
Accordingly, the present invention provides a preventive and therapeutic agent for kidney diseases comprising as its active component a compound of the following formula (1): ##STR2## (wherein each of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6, which may be identical to or different from one another, represents a lower alkoxyl group, and each of A and A', which may be identical to or different from each other, represents a lower alkylene group); an acid addition salt thereof; or a hydrate of the compound of formula (1) or of the acid addition salt thereof.
The present invention also provides a preventive and therapeutic composition for kidney diseases containing a compound of the above formula (1), an acid addition salt thereof, or a hydrate of the compound of formula (1) or of the acid addition salt thereof, in admixture with a pharmaceutically acceptable carrier.
The present invention also provides use of a compound of the above formula (1), an acid addition salt thereof, or a hydrate of the compound of formula (1) or of the acid addition salt thereof, in the preparation of a preventive and therapeutic agent for kidney diseases.
The present invention also provides a method for the prevention and treatment of kidney diseases characterized by administering an effective amount of a compound of the above formula (1), an acid addition salt thereof, or a hydrate of the compound of formula (1) or of the acid addition salt thereof.


BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the suppressive effect of the compound against the increase of plasma creatinine in a rat acute renal failure model.
FIG. 2 shows the suppressive effect of the compound against the formation of edemas caused by ischemia-reperfusion of the rat kidney.


BEST MODE FOR CARRYING OUT THE INVENTION

The compounds represented by formula (1) (hereinafter referred to as compounds (1)) which are used in the present invention are known and are described in, for ex

REFERENCES:
1992 Conn's Current Therapy, edited by Robert E. Rakel, W.B. Saunders Company, 1992.
The Merck Manual, Fourteenth Edition, edited by Robert Barkow, Merck Sharp & Dohme Research Laboratories, 1982.

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