Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1994-02-04
1995-05-16
Rose, Shep K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
A61K 3115
Patent
active
054161207
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to a vascular hypertrophy inhibitor and more particularly to a vascular hypertrophy inhibitory composition comprising a compound of formula (I) ##STR2## or a pharmaceutically acceptable salt thereof as an active ingredient.
BACKGROUND ART
It is known that angioplasty, arterial bypass surgery, organ transplantation, etc. frequently entail a hypertrophy and occlusion of the blood vessel owing to, inter alia, proliferation of vascular smooth muscle cells. Though much study is undergoing for finding a useful drug for the prevention and cure of the condition (e.g. J P Kohyo H3-500660), no effective drug has been discovered as yet.
Inspired by this demand for drugs effective for the prevention and cure of vascular hypertrophy, the inventors of this invention did much research and discovered that a compound of the above formula (I), which is already known to have vasodilatory and antithrombotic activities, is capable of inhibiting vascular hypertrophy. Further research has culminated in the perfection of this invention.
DISCLOSURE OF INVENTION
The vascular hypertrophy inhibitory composition of this invention comprises a compound of the above formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.
The vascular hypertrophy inhibitory composition of the invention finds application as a prophylactic/therapeutic drug for vascular hypertrophy, that is to say the thickening and occlusion of blood vessels owing, inter alia, to the proliferation of vascular smooth muscle cells which occur frequently following various operations in man and animals.
The pharmaceutically acceptable salt of compound (I) for use as the active ingredient in this invention includes salts with inorganic or organic bases such as alkali metal salts, e.g. sodium salt, potassium salt, etc., alkaline earth metal salts, e.g. calcium salt etc., ammonium salt, and organic amine salts such as ethanolamine salt, triethylamine salt, dicyclohexylamine salt and so on.
While the compound (I) for use as the active ingredient in this invention includes its stereoisomers, the representative species is (.+-.)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (which is hereinafter referred to as FK409).
The vascular hypertrophy inhibitory composition of this invention is of value as an inhibitor of the hypertrophy (e.g. which can be a cause for restenosis after percutaneous coronary angioplasty) and obstruction of the blood vessel which occur owing, in the main, to the proliferation of vascular smooth muscle cells following angioplasty (e.g. percutaneous coronary angioplasty), arterial bypass procedure, organ transplantation and other operations or a prophylactic/therapeutic drug for vascular hypertrophy and obstruction (or an inhibitor of vascular smooth muscle cell proliferation). The effectiveness of this invention is now shown by way of experimental data. catether-associated carotid artery endothelial injury in rats al. (Lab. Invest. 49, 208, 1983), as follows.
Male SD rats weighing 400-500 g were used. Each rat was anesthetized with pentobarbital sodium and the cervical region was opened. A balloon catheter (Fogarty, 2F) was inserted from the left external carotid artery to the orgin of the common carotid artery. The balloon was then inflated with physiological saline until a slight resistance was felt. The inflated balloon was pulled back as it was to the external carotid artery so as to injure the arterial intima. This operation was repeated 3 times, after which the catheter was withdrawn and the external carotid artery was ligated. After 14 days, the chest was opened under pentobarbital anesthesia and following perfusion with heparin-containing physiological saline (20 units/ml) from the left ventricle, the left common carotid artery was excised and fixed in neutralized formalin. The fixed carotid artery was orcein-stained and microphotographed and the sectional area of the media and that of the hypertrophic portion of the intima were measured by means of an image analyzer (LUZEX2D
REFERENCES:
Yamada et al Medline abstract of Br. J. Pharmacol. 103(3): 1713-8 Jul. 1991.
Shibata et al Medline Abstract of J. Cardiovasc. Pharmocol. 17(3):508-518 Mar. 1991.
Hino et al (I) Cell. Sci. (9):704-709(1990) GA. 115:21440B.
Hino et al (II) J. Antibiot (Tokyo) 42 (11):1578-1583 Nov. 1989 Medline Abstract.
Okamoto et al E.P. 113106 (Jul. 11, 1984) GA. 101:170730J.
Fujisawa Pharm. Co. Ltd JP 60/68390 (Aug. 31, 1985) Derwent Abstract.
Eur. J. Pharmacol., vol. 183, No. 4, pp. 1292-1293, (1990), M. Ohtsuka, et al., "Cardiovascular Activity of FK409, A New Drug For Ischemic Heart Diseases, On Dog In Vitro And In Vivo Preparations".
Kato Yasuko
Sado Mie
Seki Jiro
Fujisawa Pharmaceutical Co. Ltd.
Rose Shep K.
LandOfFree
Vascular hypertrophy inhibitor does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Vascular hypertrophy inhibitor, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Vascular hypertrophy inhibitor will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-638093