Co-administration of S-adenosyl-L-methionine to reduce the nephr

Details Co-administration of S-adenosyl-L-methionine to reduce the nephr Co-administration of S-adenosyl-L-methionine to reduce the nephr

1994-04-07

1995-11-14

Robinson, Douglas W.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

536 2731, 424649, A61K 3170

Patent

active

054666783

DESCRIPTION:

BRIEF SUMMARY
Field of Industrial Application

The present invention relates to a pharmaceutical composition containing S-adenosyl-L-methionine or a salt thereof as an active ingredient. More particularly, this invention relates to a pharmaceutical composition for use as a nephrotoxicity alleviator capable of alleviating the nephrotoxicity caused by a drug administered to the living organism, which composition contains S-adenosyl-L-methionine or a salt thereof (hereinafter referred to as SAMes), and also to a pharmaceutical composition for use as an antitumor activity potentiator capable of potentiating the antitumor activity of a platinum complex compound, which composition contains SAMes as an active ingredient.


Background Art

A variety of drugs have currently been in use for the treatment of different malignant tumors. Cisplatin (cis-diamine-dichloroplatinum: CDDP), above all, is an excellent drug with which an increase in life span can be expected, and has shown a significant Life span-extending effect, in particular in the treatment of testicular tumor, bladder cancer, ureteral tumor and ovarian cancer. While CDDP has excellent antitumor activity, it produces serious toxicity and, above all, its nephrotoxicity is considered as a dose-regulating factor. In order to alleviate such toxicity, such measures as the simultaneous use of diuretics upon administration of CDDP and hydration have been taken, although the toxicity-alleviating effects of these measures are not satisfactory in some patients. In particular where CDDP is repeatedly administered, its accumulated toxicity tends to grow to a point where in certain patients with manifested nephrotoxicity its dose is obliged to be reduced or the drug has to be replaced, with the result that the otherwise possible life span extension is lost. The nephrotoxicity is a serious problem in other therapies as well, for example, in the treatment of ovarian cancer wherein the dose of CDDP is increased, while making administration intervals as short as possible, to enhance the dose intensity. In order to overcome such problems, many attempts to search for compounds capable of alleviating CDDP's nephrotoxicity have been made. Thus, for example, such compounds as sodium thiosulfate, acetazolamide, selenium dioxide, sodium selenate, cysteine, 3-aminobenzamide, phosphomycin and bismuth subnitrate have been reported to show nephrotoxicity-alleviating activity, although these compounds have yet to be put into practical use clinically. Furthermore recent years have seen extensive developments of drugs possessing nephrotoxicity-alleviating activity, as demonstrated, for example, by the recent approval of glutathione in Italy, application for approval of amifostin in the United States of America and clinical investigation of ulinastin now going on in Japan.
On the other hand, it is also known that when CDDP is administered in combination with the above mentioned toxicity alleviator or the like for the suppression of side effects like nephrotoxicity, the antitumor activity of CDDP itself is suppressed. Accordingly, it has been a technical problem in this field to achieve the desired effects without lowering the antitumor activity.


Objects of Invention

The objects of the present invention are to provide a pharmaceutical composition for use as a drug to alleviate the nephrotoxicity caused by a drug administered to the living organism, which composition contains S-adenosyl-L-methionine (hereinafter referred to as SAMe), and also to provide a pharmaceutical composition for use as an antitumor activity potentiator capable of potentiating the antitumor activity of platinum complex compounds, which composition contains SAMe as an active ingredient.


Disclosure of Invention

In order to achieve the above described objects, the present inventors have made extensive studies on SAMe, focusing attention on the fact that glutathione or the like SH-compounds produced in the living organisms detoxicate active oxygen or chemically reactive toxicants through reaction therewith. As a result, the afor

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