CS270604B1 - Physiologically perfused bloodstream enhancing agent - Google Patents

Abstract

Physiologically effective preparation increasing cerebral blood flow and regulating brain cell metabolism. It is usable as a geriatric and antimigraine agent. It consists of the active ingredients beta raimetik in an amount of 1.75 to 7 wt. %, preferably etophylline or pentoxifylline, and alpha sympatholytic in an amount of 0.01 to 0.2 wt. %, preferably dihydroergocristine or dihydroergocryptine or dihydroergocornine or their mixture in a ratio of 1 to 1:1.

Description

The invention relates to a composition of a novel physiologically active preparation for increasing cerebral blood flow. and regulating brain cell metabolism. It is in the form of a solution to be used in the form of drops. Dosing is guaranteed by a drip insert. It contains a betamimetic, preferably etophylline or pentoxifylline, and an alpha-sympatholytic in addition to pharmaceutical excipients. !

A large number of substances and additives are known in the world, which are termed therapeutics for the treatment of CNS ischemia. One of the longest used is aminophyllin, which is not very effective due to irregular absorption from the gastrointestinal tract. The bronchodilator effect is most marked, it has no effect on the regulation of CNS cell metabolism. The possible formation of nitrosamines in the acidic content of the stomach is not negligible either, as the numerous literature reports. .

Xanthinol nicotinate has well-marked peripheral vasodilatory effects, while the central effect is clinically insignificant. In the acute ischemic phase, it can worsen the perfusion of the ischemized area by the mechanism of steel syndrome, it can also cause headaches by the mechanism of vasodilation. This substance is not suitable for the treatment of headaches. '

Nitroglycerin is a prominent coronary vasodilator, but vasodilation of CNS vessels is likely. It can be used successfully in the treatment of migraine in the aura phase. CNS ischemia is likely to cause steel syndrome. ·

Cynaririne is a central and peripheral vasodilator, due to the possibility of steel syndrome it is not suitable for acute CNS ischemia. It worsens hypotension in hypotonics and causes dizziness. Due to its strong vasodilating effect, it can cause headaches, so it is not suitable for the treatment of cephalgia. .

Vinpocetine is an effective central vasodilator. also suitable for the treatment of some headaches, not suitable for the treatment of acute CNS ischemia. '

Naphthidrofuryl is an effective central and especially peripheral vadodilator, suitable for the treatment of chronic ischemia and CNS sclerosis. It is not suitable for the treatment of acute ischemia, where oxygen perfusion is worsened by steel syndrome. Vincamine is an effective vasodilator of peripheral and central vessels. Caution should be exercised when treating acute CNS ischemia. Semi-synthetic ergot alkaloids of the ergotoxin series, especially dihydroergocristine, dihydroergocornine, dihydroergocryptine, mostly in the form of salts with methanesulfonic acid, are very suitable for their alpha-sympatholytic effect, without local vasoconstrictive effect for the treatment of headaches and chronic CNS ischemia. It is not suitable for the treatment of acute CNS ischemia due to the possibility of steel syndrome.

The above-mentioned drawbacks and problems are eliminated by the fact that in the preparation according to the invention the substances are used exactly in pharmacy and by precisely defined their properties, which makes it possible to predict with certainty the final effect of the preparation. clinical trials.

The combination of beta mimetics and alpha sympatholytics significantly improves cerebral perfusion, without the risk of Steel syndrome, because the beta mimetic component etophylline induces relative hyporvontilation and tospiratory alkalinity, which causes partial vasoconstriction in the nonischemic area of the CNS vascular system and in the ischemized area. vasoactive substances do not show up and therefore perfusion is improved. There is no vasoconstriction in the ischemized area, but relative congestion from the surrounding areas where vasoconstriction has occurred. Said combination of both substances is suitable for the treatment of vasomotor headaches, both acute CNS ischemia or their forms of transient ischemic attacks - migraine acompagne, as well as chronic cerebrovascular insufficiency.

CS 270 604 Bl

The preparation contains a combination of an alpha sympatholytic component, preferably dihydroergicin methanesulfonate 0.01% to 0.2% by weight, and a beta mimetic, preferably etophylline 1.75% to 7% by weight, substances which ensure the stability of the preparation, both chemical and microbiological, so good bioavailability.

The subject matter of the invention is further elucidated in 2 examples, without being limited thereto.

Example 1 ' ¹

Aethophyllinum 3.50% mass DH-ergocristinum mesylium 0.10% mass Propylene glycol 50,00% mass Spiritus (95% by weight) . 22.00% mass Aqua demineralized to 100.00% mass

Example 1 - Method of preparation.

Alcohol and propylene glycol are charged to the homogenizer at room temperature, then both active ingredients are added in succession and the mixture is completely homogenized. After dissolving the two active ingredients, the required amount of water is added and homogenized again. The solution is then filtered and filled into vials.

Example 2

Pentoxyphyllium 3.50 wt.

DH-ergotoxinium mesylicum 0.10 wt.

To glycerins 5.00% by weight.

Propylene glycol 20.00% by weight

Spiritus (95% by weight) 11.00% by weight

Aqua demineralized to 100.00% by weight. .

Example 2 - Method of preparation

Alcohol, propylene glycol and glycerin are charged to the homogenizer at room temperature and both active ingredients are added in succession. After dissolving them, the required amount of water is added and the mixture is completely homogenized. The solution is then filtered and filled into vials.

Pharmacology of the preparation according to the invention

Acute toxicity was determined in mice and rats, toxicity was determined after 60 days of administration, and the organs of the animals tested were subjected to macroscopic and histological examination. All tests performed confirmed the safety of the product.

Clinical experience with the preparation according to the invention

It has been tested in patients with migraine, vasomotor headache, Horton's syndrome, migraine acompagne, cerebrovascular insufficiency and organic psychosyndrome in involution. ·

There was a regression of subjective problems as well as an objective neurological finding. The advantage is the minimal occurrence of side effects even with long-term administration. The preparation according to the invention does not increase blood pressure. With the prescribed method of use, irritation in the area of the gastrointestinal tract is also significantly reduced.

Claims (1)

OBJECT OF THE INVENTION A physiologically active preparation for increasing cerebral blood flow and regulating the metabolism of brain cells in the form of a solution containing a mimetic in an amount of 1.75% to 7% by weight, preferably etophylline or pentoxifylip. a vehicle of propylene glycol, glycerin, ethanol and water, characterized in that it contains a sympatholytic alpha component in an amount of 0.01% to 0.2% by weight, preferably dihydroergocrisrin or dihydroergocryptine or dihydroergocornine or a mixture thereof in a ratio of 1: 1: 1. . ,.