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Therapeutic agent for renal failure

a technology of renal failure and therapeutic agents, which is applied in the direction of biocide, drug composition, and elcosanoid active ingredients, etc., can solve the problems of not yet recognized that such derivatives have therapeutic activities on renal failure, reduce the excretion of nitrogenous metabolic products, and fail to maintain the homeostasis of the biological environmen

Inactive Publication Date: 2003-05-15
TORAY IND INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has not yet recognized that such derivatives have therapeutic activities on renal failure.
Renal failure is a condition characterized by decreased number of functional nephrons, resulting in reduced excretion of nitrogenous metabolic products and eventually causing the failure to maintain homeostasis in the biological environment.
However, such dietary therapy and the treatment with an antihypertensive agent as mentioned above produce unsatisfactory effects.
However, there still remain problems in that the patients are unavoidable to visit the hospital twice or three times a week, that defects of erythrocyte production or maturation may occur, that complications will follow which may caused by the accumulation of aluminum and .beta.2-microglobulin in a body occurring after the long-term dialysis, and so on.

Method used

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  • Therapeutic agent for renal failure
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  • Therapeutic agent for renal failure

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0096] Effect of beraprost sodium on 5 / 6 nephrectomized rat model:

[0097] The effect of beraprost sodium on a 5 / 6 nephrectomized rat model, which has been widely used as a model animal for renal failure, was examined. Two-thirds of the left kidney was removed from each of 4-week-old male Wistar rats (Charles River Japan Inc.) with a razor, and all of the right kidney was then removed therefrom one week after. Three weeks after the initial surgery, blood was collected from each rat through the tail vein and serum creatinine and BUN levels were determined from the blood. At this point of time, the urine was also collected for 24 hours to determine the mass of proteins in the urine. The rats were allocated to one of the treatment groups by the stratifying continuous randomization method based on the mass of proteins in the urine and the body weight (n=8 per group). There was observed little difference in the initial values of blood creatinine and BUN values among the rats. Three weeks a...

example 2

[0100] Renal failure rat models of which the primary disease was glomerulonephritis were used to examine the effect of different 4,8-inter-m-phenylene prostaglandin I.sub.2 derivatives including beraprost sodium on the models. Eight-week-old male WKY rats (Charles River Japan Inc.) were administered intravenously with rabbit anti-rat glomerular basement membrane antiserum to induce glomerulonephritis. Two weeks after the induction, blood was collected from each rat through the tail vein to determine blood creatinine and BUN levels. The blood creatinine and BUN levels in the glomerulonephritis-induced rats were remarkably higher than those in the non-induced rats, which indicated that the conditions of the rats progressed into renal failure. Four types of 4,8-inter-m-phenylene prostaglandin I.sub.2 derivatives in total, including beraprost sodium, were individually administered subcutaneously to the rats from the back continuously with an osmotic pump (ALZET) for one week, beginning ...

example 3

[0103] Glomerulonephritis rat models were used to examine the effect of beraprost sodium on the rat models both in a stage where renal failure had not been found (i.e., the inflammatory stage) and a stage where BUN level was increased and the conditions were progressed into renal failure (i.e., the renal failure stage). Eight-week-old male WKY rats (Charles River Japan Inc.) were administered intravenously with rabbit anti-rat glomerular basement membrane antiserum to induce glomerulonephritis. Each of beraprost sodium, captopril (SIGMA) and prednisolone (Shionogi & Co., Ltd.) was orally administered to the rats everyday either for one week from day 1 through day 7 after induction of glomerulonephritis (i.e., during the inflammatory stage) or for two weeks beginning two weeks after the induction through four weeks after the induction (i.e., during the renal failure stage). The frequency of the administration was twice a day for beraprost sodium and captopril and once a day for predn...

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Abstract

The present invention relates to a therapeutic agent for renal failure comprising, as an active ingredient, a 4,8-inter-m-phenylene prostaglandin I2 derivative, and also relates to a method of treatment of renal failure using the same.

Description

[0001] The present invention relates to a therapeutic agent for renal failure comprising, as an active ingredient, a 4,8-inter-m-phenylene prostaglandin I.sub.2 derivative or a pharmacologically acceptable salt thereof.[0002] Prostaglandins (PGs) are a class of naturally occurring compounds with a wide variety of physiological activities, which have a common prostanoic acid skeleton. Naturally occurring PGs are classified into PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs, PGIs and PGJs according to the structural characteristics of the 5-membered ring in the skeleton. It is and also classified into subclasses 1, 2, 3 and so on according to the ansaturation and oxidation. Various synthetic analogues of these PGs are known. Among these, PGI.sub.2, which is a typical PGI derivative, is called prostacycline (see Nature, vol. 268, p. 688, 1976). PGI.sub.2 is known as a substance having potent platelet aggregation inhibiting activity and peripheral vasodilator activity. Japanese Examine...

Claims

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Application Information

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IPC IPC(8): A61K31/558
CPCA61K31/558A61K31/343A61P13/12
Inventor KURUMATANI, HAJIMUSUZUKI, MOTOHIRO
Owner TORAY IND INC
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