Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-01-03
2000-04-04
Weddington, Kevin E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514461, 549456, 549458, A01N 4308, A61K 3134
Patent
active
060462337
DESCRIPTION:
BRIEF SUMMARY
This application is a National Stage filing under 37 U.S.C. .sctn. 371 of PCT/JP96/00443, filed Feb. 27, 1996.
TECHNICAL FIELD
The present invention relates to an agent for treating cor pulmonale comprising a prostaglandin I.sub.2 derivative such as, for example, beraprost, or a salt thereof as an active ingredient.
BACKGROUND ART
Cor pulmonale develops a disease condition in which an increase in the pulmonary vascular resistance due to an organic or functional abnormality of the lungs causes right ventricular pressure overload, resulting in right ventricular hypertrophy and further right ventricular insufficiency. Cor pulmonale is caused by various diseases, the critical mechanism of ventricular hypertrophy is not clarified, and no curative means is established. Although cor pulmonale is treated by causal disease treatment (including oxygen therapy) or using a diuretic and cardiotonic, an effective curative means has not yet been established.
On the other hand, prostaglandin I.sub.2 (PGI.sub.2, prostacyclin) which is known as a substance having the strong actions of inhibiting platelet aggregation and dilating the peripheral vessel (refer to "Nature" Vol. 268, p688, 1976) has an unstable exoenol structure, and thus PGI.sub.2 is very unstable in a neutral aqueous solution and is converted into 6-oxo PGF.sub.1 .alpha. which has substantially no physiological activity. This instability of PGI.sub.2 brings about an important problem in utilizing this compound as a medicine. The PGI.sub.2 is also unstable in vivo and thus has the fault that its physiological action has no persistency. Japanese Examined Patent Publication No. 1-53672 discloses, as compounds in which the faults of PGI.sub.2 are significantly improved, PGI.sub.2 derivatives having a skeleton in which the structure of the exoenol ether portion, that is a characteristic structure of PGI.sub.2, is converted into an inter-m-phenylene type. However, this publication does not suggest the curative effects of those derivatives on cor pulmonale, and it has not yet been known that the PGI.sub.2 derivatives have the curative effects on cor pulmonale.
As a result of extensive research for developing an agent for treating cor pulmonale having excellent efficacy and practicability, the inventors found that the compounds used in the present invention have the significant effect of ameliorating the condition of cor pulmonale, resulting in the achievement of the present invention.
DISCLOSURE OF THE INVENTION
The present invention provides an agent for treating cor pulmonale comprising as an active ingredient a 5,6,7-trinor-4,8-inter-m-phenylene prostaglandin I.sub.2 derivative or a pharmacologically acceptable salt thereof represented by the following formula (I): ##STR2## wherein R.sub.1 is hydrogen, a carboxyl group or a functional derivative thereof, --CH.sub.2 OH, or a pharmacologically acceptable cation;
A is (1) --(CH.sub.2).sub.n --, (2) --(CH.sub.2).sub.m --CH.dbd.CH--(CH.sub.2).sub.p --, (3) --(CH).sub.m --C.tbd.C--(CH.sub.2)p-- or (4) --CH.sub.2 --O--CH.sub.2 -- (wherein n is an integer of 0 to 3, and each of m and p is 0 or 1):
R.sub.2 is (1) a straight chain or branched alkyl group having 5 to 10 carbon atoms, (2) --Ct H2t--OR.sub.3 (wherein t indicates an integer of 1 to 5, and R.sub.3 indicates a straight chain or branched alkyl group having 1 to 5 carbon atoms, or a phenyl group), (3) --Ct H2t--CH.dbd.C (R.sub.4) (R.sub.5) (wherein t indicates the same as defined above, and R.sub.4 and R.sub.5 each indicate hydrogen, a methyl group, an ethyl group, a propyl group or a butyl group); or (4) --Ct H2t--C.tbd.C--R.sub.6 (wherein t indicates the same as defined above, and R.sub.6 indicates hydrogen, a methyl group or an ethyl group), and formula (I) indicates d-, l- and dl-forms.
BEST MODE FOR CARRYING OUT THE INVENTION
The inventors of this invention have already found prostaglandin I.sub.2 derivatives are effective as an antiulcer agent, an anti-thrombogenic agent, an antihypertensive agent, and an antiasthmatic agent (Japanese Examined Pat
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Yuki et al., "Orally administered beraprost sodium inhibits pulmonary hypertension induced by monocrotaline in rats", Tohoku J. Exp. Med. 173(4), pp. 371-5, 1994, see abstract.
Stedman's Medical Dictionary, 24th Edition, pp. 319 and 677, 1983.
Kasukawa Reiji
Koike Hiroshi
Kurumatani Hajimu
Miyata Masayuki
Nishio Shintaro
Jones Dwayne C.
Toray Industries Inc.
Weddington Kevin E.
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