RU2560668C2 - Transdermal sedative pharmaceutical gel for treatment of psychoemotional disorders - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, namely to transdermal gel of sedative action. Transdermal gel of sedative action contains dry extract of leonurus, dry extract of St.-John's wort, dry extract ginkgo biloba, propyleneglycol and purified water, in specified quantities.

EFFECT: transdermal gel has sedative and anti-stress action without pronounced effect on motor activity.

1 dwg, 1 tbl

Description

The invention relates to the pharmaceutical industry and medicine, namely to sedatives of plant origin, and can be used to treat functional disorders of the central nervous system.

The pharmaceutical composition of sedative and cerebroprotective action contains motherwort, ginkgo biloba and hypericum extract taken in a specific ratio. The above composition has a prolonged effect and does not cause drowsiness. Plant extracts, unlike synthetic antidepressants, do not impair cognitive function (speed of reaction, short-term memory), and also do not affect the coordination of movements.

The changed lifestyle and nutritional nature of modern man have led to the widespread dissemination of various types of borderline anxiety disorders, manifested in mental, behavioral and somatic disorders. Often people complain of causeless headaches, increased fatigue, fears, anxiety, nervousness, impatience, insomnia, a constant feeling of fatigue, uncontrolled irritation, from which both the person himself and the people around him suffer. Usually, doctors recommend removing such symptoms with herbal sedatives based on alcoholic extracts of valerian root, motherwort and other medicinal plants, but this prevents many motorists from taking it.

Known sedative herbal medicines (drugs of valerian, motherwort, St. John's wort, which have a calming effect on the central nervous system with increased nervous excitability) (MD Mashkovsky, Medicines, M .: "Medicine", 1972, part 1 , pp. 37-40). The use of tablets with dry extracts, such as motherwort, as well as any other, does not allow for rapid relief of neurotic conditions. In addition, the dynamics of absorption of tablets with dry extracts are affected by the fullness of the stomach, the state of the mucous membrane, the amount of fluid taken for drinking, etc.

St. John's wort psychotropic drugs are one of the most famous drugs in the world that successfully combine the properties of an antidepressant and a thymostabilizer. The main factors determining their popularity is the complexity of the mechanisms of action and, accordingly, the breadth of the clinical and pharmacological spectrum, which makes it possible to use St. John's wort preparations for a wide variety of clinical forms of disorders of the psycho-emotional sphere - from dysthymia to severe depressive disorders; high efficiency within the framework of nosological forms; favorable safety features; high degree of compliance; economic accessibility (RF Patent No. 2396878 dated 12/18/2008). However, such features of the pharmacokinetics of drugs as the need for long-term use (14-20 days) for sufficient accumulation of hyperforin in order to provide a therapeutic effect, narrow its practical use.

The pharmacological action of the extract of ginkgo biloba leaves is based on its ability to inhibit the processes of free radical oxidation, which are an important element of tissue damage during ischemia and hypoxia. Due to its antioxidant properties, ginkgo biloba preparations affect the formation of vasoactive mediators and inflammatory mediators, which determines their ability to improve blood circulation and have anti-inflammatory effects. In addition, the biologically active substances of ginkgo biloba have a pronounced effect on the metabolic processes in the tissues, improving metabolism and optimizing energy metabolism. Such a complex effect of ginkgo preparations on tissues explains their high therapeutic efficacy in a wide range of pathological conditions of the nervous system. However, the low lipophilicity of flavonol glycosides reduces the ability to pass through the blood-brain barrier with traditional methods of administration.

A promising direction in this area is the creation of a sedative transdermal gel with the ability to penetrate the blood-brain barrier. This route of administration has several advantages compared to other widely used routes of administration - painlessness, prolonged action, maintaining constant concentrations of the drug substance.

Transdermal therapeutic systems are known for the purpose of sedating the patient (RF Patent No. 2098083 of 12/10/1997). The use of dexmedetomidine by the authors in silicone and acrylic adhesives made it possible to increase the penetration rate of the active substance. However, the methodology for preparing such a therapeutic system is very long and laborious.

The patent of the Russian Federation No. 2383328 of 03/10/2010, in which a transdermal gel containing an extract of stem cells of pig placenta and other components included in organosilicon niosomes is known, is known from the prior art. However, sedative transdermal gels, including plant extracts of motherwort, St. John's wort and ginkgo biloba introduced into the organosilicon niosomes, were not found by us.

The closest in purpose and combination of essential features is the document (Russian scientists suggest that the Czechs fight cancer together: www.vneshmarket.ru/PressRelease/PressReleaseShow.asp ID = 98377), which discloses a gel-like agent for delivery to cells and tissues through skin drug doxorubicin introduced into organosilicon niosomes.

SUMMARY OF THE INVENTION

Transdermal administration of extracts of motherwort, St. John's wort and ginkgo biloba is proposed for a qualitatively high passage of phenolic compounds through the blood-brain barrier in order to achieve a pronounced sedative and cerebroprotective effect.

The combination of extracts with antihypoxic, cerebroprotective and sedative effects allows a comprehensive impact on the prevention and elimination of anxiety and depression.

The development of new solutions for the delivery of biologically active compounds through the blood-brain barrier is one of the ways to increase the effectiveness of the transdermal route of administration of sedatives.

The implementation of the invention

Dry extracts of motherwort, St. John's wort and ginkgo biloba were diluted with propylene glycol 70% in a ratio of 1: 1: 1. Due to the fact that the active substances occupy a small volume relative to other components, their introduction to other components of the emulsion was carried out with vigorous mechanical shaking on a shaker for 5 minutes at room temperature. Then followed by stirring and subsequent introduction into the aqueous phase of the mixture. The final stage of gel formation occurred with vigorous mechanical stirring of the mixture using the reclaimer homogenizer for 10 minutes.

Sedative transdermal gel contained:

Dry motherwort extract 1 g Hypericum extract dry 1 g Ginkgo biloba extract dry 1 g Propylene glycol 70% 22 g Purified water Up to 1000.0 ml

The study of motor and emotional activity using the "open field" method showed that the gel obtained in a therapeutic dose when taken orally does not cause a significant decrease in motor activity. The behavior of intact rats in the "open field", despite the presence of individual characteristics, had common features. After a short adaptation, the animals usually crossed from 18 to 26 peripheral segments and practically did not enter the central ones. They also performed from 12 to 17 uprights. The introduction of saline did not significantly affect the psycho-emotional state of rats. An insignificant deviation of the motor and research activity of animals can be noted, which is probably due to the stressful nature of the injection procedure itself.

The indicator “horizontal locomotor activity” is 37.1 for the gel obtained, 32.5 motherwort tincture; compared to control 28.7. In terms of “vertical locomotor activity” there is a decrease compared with the control in gel 9.6 and in motherwort tincture 12.7. Emotional activity decreased with the use of the gel: transdermal gel significantly increased the mobility of rats, which led to a significant increase in the number of crossed peripheral segments. More often vertical racks were made, reflecting the growth of research activity. Rats that received motherwort tincture also moved faster along the periphery of the open field, crossing a greater number of segments than intact and control animals. Grooming (the number of washings) while taking the gel was 26.5, and the number of bowel movements was 3.5. The comparison drug motherwort tincture grooming also significantly increased 25.3 and 5.8, respectively, the number of bowel movements.

Thus, the technical result is that the transdermal gel has a sedative and antistress effect without a pronounced effect on motor activity (Table 1).

Claims (1)

A sedative transdermal gel containing:
Dry motherwort extract 1 g Hypericum extract dry 1 g Ginkgo biloba extract dry 1 g Propylene glycol 70% 22 g Purified water Up to 1000.0 ml

Images