Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Patent
1999-06-09
2000-12-12
Ambrose, Michael G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
A61K 3121, A61K 31155, A61P 902, A61P 3900
Patent
active
061600083
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to S-alkylisothiouronium salts with phosphorus-containing acids which affect arterial blood pressure and possess oxygen protective activity, and to the use of such compounds in cases of acute and chronic hypotension (hemorrhage, trauma, shock, poisoning), especially for first aid, as well as in cases of oxygen poisoning.
BACKGROUND OF THE INVENTION
Most medicaments affecting arterial blood pressure act either via the stimulation of alpha-adrenergic receptors or directly on the visceral muscles of the vascular wall. Adrenomimetics, e.g. adrenaline, noradrenaline, adrianol, phenylephrine (mezaton) ephedrine, ethylephrine, etc., and polypeptides, e.g. glucogon, angiotensin, octapressin, etc. are most often used.
Mezaton is a well known adrenomimetic drug (M. D. Mashkovsky, Medicines, 12-th edd., Moscow., Medicine, 1993, Part I, p. 303), having a pharmaceutical activity related to that of the compounds of the present invention. Mezaton (1-(m-hydroxyphenyl)-2-methylaminoethanol hydrochloride) selectively stimulates .alpha.1-adrenoreceptors, causes arterial constriction and increase in systolic and diastolic pressure (with possible reflectoral bradycardia). Mezaton practically does not have cardiostimulating effect. Unlike adrenaline and noradrenoline, mezaton is not a catecholamine (it contains only one hydroxyl group in aromatic nucleus) and is not influenced by the enzyme--catechole-O-methyltransferase, therefore it is more stable and has a prolonged effect. Mezaton's anti-hypotensive effect usually lasts for approximately 20 minutes after a single intravascular injection.
Adrenomimetics, among them mezaton, have some common shortcomings, as they increase tissue oxygen consumption, cause metabolic acidosis, may cause arrhythmia (especially during general anesthesia), and exert exciting influence on the central nervous system (O. M. Avakyan, Adrenoreceptor function pharmacological regulation, M., Medicine, 1988, p. 8; V. G. Kulinsky, A. N. Kovalevsky, Bulletin of Experimental Biological Medicine, 1984, p. 9). The appearance of secondary hypotension is characteristic of them. Adrenomimetics do not correct arterial hypotension caused by adrenergic blocking agents, and have only a slight anti-hypotensive effect in case of metabolic acidosis (C. Kortanje, V. I. Mathy, R. Charldorp, Haunyn-Gchinedeleg in Arch. Pharmacol., 330:3, 187-192 (1985)).
Medicaments with polypeptide structure have a short adrenomimetic effect. To achieve prolonged effect they are injected in the form of perfusion (I. M. Autkunson, S. I. Dusting, V. I. Rand, Aust. J. Exp. Biol. Med., 50:847-859 (1972)).
In the pathogenesis of oxygen poisoning, the main function belongs to the adrenoreceptors .beta..sub.1 and .beta..sub.2 which affect the metabolism of catecholamines. A known compound used in hyperoxia experiments on animals is etyron (S-ethylisothiouronium bromide). Etyron was described in the literature (E. A. Mukhin et al., Hypertensive medicines 1983, 118-122) as having a protective activity under increased oxygen pressure.
S-Alkylisothiouronium salts with phosphorus containing acids, among them Difetur (S-ethylisothiouronium diethylphosphate) are described in the art as having distinct radioprotective effect and their toxicological characteristics have been studied (P. G. Zherebchenko, Yu. D. Zilber, G. P. Pospekhov, et al., Radiobiologya, 8:582-587 (1968); Zh. A. Goloschapova, T. N. Tuzhilkova, L. I. Mizrakh, Radiobiology, 21:521-525 (1981)).
OBJECT OF THE INVENTION
The object of the present invention is to provide new medicaments having an effect of increasing arterial blood pressure. In addition, it is the object of the present invention to provide a new medicament having oxygen protective effect.
SUMMARY OF THE INVENTION
The above object is achieved by the use of S-alkylisothiouronium salts with phosphorus containing acids of formula I: ##STR1## wherein R is a straight or branched alkyl, optionally substituted by halogen, and X is an anion derived from a phosphorus contai
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Arzamastsev Evgeni
Bondareva Galina
Darchuk Victor
Gikavy Victor
Jashounsky Vladimir
Ambrose Michael G.
Meditor Pharmaceuticals Ltd.
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