RU2719376C1 - Sedative and muscle relaxant action drug - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to pharmacology, and can be used as a sedative and muscle relaxant drug containing hydroxyzine or its pharmaceutically acceptable salt - 0.00001–2.00002 wt. %, menthol solution in menthyl isovalerate- 0.99001–2.01106 wt. %, peppermint oil - 0.09807–0.14215 wt. %, Spanish hop oil - 0.017–0.020 wt. % and ethanol and purified water in weight ratio of 1.2:1–1.7:1 is the rest, made in the form of drops for oral administration, for therapy of functional disorders of cardiovascular system, tachycardia, neuroses and neurosis-like conditions accompanied by high excitability and irritability, anxiety, fear, difficulty falling asleep and sleep, as well as excitation conditions accompanied by manifested vegetative reactions and intestinal spasms.

EFFECT: therapeutic agent provides combination (synergetic) sedative and muscle relaxant action with reduced amount of active substances and fast provision of therapeutic effect.

3 cl

Description

Technical field

The invention relates to the field of medicine and pharmaceuticals, namely, a sedative and muscle relaxant drug that does not contain components that can cause the development of dependence or chronic poisoning, which can be used for the symptomatic treatment of functional disorders of the cardiovascular system, tachycardia (including tachycardia caused by nervous disorder), neurosis and neurosis-like conditions, accompanied by increased irritability and irritability, anxiety, fear, difficulty falling asleep and sleeping, as well as excitement conditions, accompanied by severe vegetative reactions and intestinal cramps.

State of the art

Various sedative and muscle relaxant drugs are widely known from the prior art, which are used, in particular, for the treatment of functional disorders of the cardiovascular system, including cardialgia, cardialgic syndrome and sinus tachycardia, neuroses accompanied by irritability, anxiety, fear, difficulty falling asleep, states of agitation, accompanied by severe vegetative reactions. Among these drugs, the most famous drugs are Valocordin and Corvalol, produced respectively by Krevel Moiselbach GmbH (Germany) and Pharmstandard - Leksredstva OJSC (Russia), described in the reference book “Modern Medicines. The Latest Reference” / / I.A. Pavlov, O.A. Borisova, A.E. Half; comp. I.I. Pavlova, AST, Sova, St. Petersburg, 2002 (hereinafter - I.A. Pavlov, OA Borisova et al., 2002) on pages 149 - 150, and also issued by Moskovskaya Closed Joint-Stock Company pharmaceutical factory "(Russia) drug" Valoserdin "(online reference" Register of medicines of Russia. Encyclopedia of medicines ", 09/12/2013, URL: https://www.rlsnet.ru/tn_index_id_5638.htm).

The drug "Valocordin" is made in the form of drops for oral administration and contains, per 1 ml of the drug, 18.4 mg of phenobarbital, 18.4 mg of ethyl bromisovalerianate, excipients - 1.29 mg of peppermint oil, 0.18 mg of hop oil, ethanol 96% - 469.75 mg; purified water - 411.97 mg. Hop oil (oregano oil) is an oil obtained from plants of the genus Origanum, including Origanum vulgare L. and Origanum cretici, which has a complex composition and contains complexes of substances that have a sedative, antispasmodic, hypnotic and vasodilating effect (EA Ladynina. Herbalist for all. // M., "Moscow City Printing", pp. 160-162, 1993). (Hereinafter, the terms “ethyl bromosovalerianate” and “ethyl ester of α-bromisovalerianic acid” are used interchangeably.)

The drug "Corvalol" is also made in the form of drops for oral administration and contains, per 1 ml of the drug, 1.96 g of phenobarbital, 2.15 g of ethyl bromisovalerianate, peppermint oil - 0.15 g, sodium hydroxide (sodium hydroxide) - 0.34 g; rectified ethyl alcohol 96% (ethanol) - 50.30 g; purified water - up to 100.00 g.

The drug "Valoserdin" is also made in the form of drops for oral administration and contains, per 100 g of the drug, the active substances: phenobarbital - 2 g, ethyl bromisovalerianate (ethyl ester of α-bromisovalerianic acid) - 2 g, and also excipients: peppermint oil pepper - 0.14 g, Spanish hop oil (oregano oil) - 0.02 g, ethanol (ethyl alcohol) 96 vol. % - 52.00 g, purified water - 43.84 g.

Although phenobarbital, which is part of Valocordin, Corvalol, and Valoserdin, has a sedative, muscle relaxant, and vasodilating effect, with regular use it can cause inhibition of central nervous system activity in patients associated with impaired memory and attention, leading to development mental and physical dependence, as well as cause other unwanted effects that are not associated with inhibition of the central nervous system: lowering blood pressure, allergic reactions (cutaneous b, etc.), changes in the blood formula, ataxia, impaired coordination of movements, increased body temperature, etc. It is shown that with prolonged use of drugs containing phenobarbital and other derivatives of barbituric acid, the metabolism of many drugs changes due to the induction of microsomal liver enzymes which is also undesirable.

The use of phenobarbital, as well as other barbiturates, has also been shown to cause hematologic dose-related side effects from the central nervous system and respiratory organs (1. Wyllie E., editor. The treatment of epilepsy: principles and practices. - Philadelphia: Lea & Febiger, 1993 2. AV Astakhov et al. Adverse Reactions Caused by Anticonvulsants in Children, Federal Center for the Study of Side Effects of Medicines, Russian Bulletin of Perinatology and Pediatrics, No. 1, 1999, pp. 1–55) . It is also shown that in children phenobarbital can cause mental retardation (Bayanov A.A., Shiryaeva I.V., Koroleva S.A. // Independent Psychiatric Journal, 2001, No. 2, pp. 31–34). It is also shown that phenobarbital is a potential promoter of carcinogenesis (Abanobi S., Lombardi B., Shinozuka H. // "Cancer Research", v. 42, pp. 412 - 415; Lukienko P.I., Zavodnik L.B., Bushma MI // "Experimental and Clinical Pharmacology", vol. 58, No. 1, pp. 68 - 73, 1995). According to a report by the World Health Organization (1995), 8% of patients treated with phenobarbital for a long time had various forms of oncopathology. The mechanism of this action of phenobarbital is associated with the induction of hepatic cytochromes P450, involved in the metabolic activation of carcinogens and carcinogens to reactive products (Bayanov A.A. // "FASEB J", v. 11, No. 9, p. 295, 1997).

Due to the presence of such serious undesirable side effects in phenobarbital and other derivatives of barbituric acid, in a number of countries, including the USA, UAE, EU countries, etc., the import and use of drugs containing phenobarbital are prohibited, and in those countries where drugs containing phenobarbital are still approved for use, their long-term use is not recommended. Especially dangerous is the use of drugs containing phenobarbital and other derivatives of barbituric acid in pediatrics and epileptological practice.

It should also be noted that the simultaneous use of phenobarbital with other sedative drugs leads to an increase in the sedative-hypnotic effect and may be accompanied by respiratory depression. It should also be noted that the dispensers used in the bottles in which Valocordin, Corvalol and Valoserdin are produced have a rather low dosage accuracy, and therefore there is a high risk of accidental overdosing of these drugs.

In addition to phenobarbital, Valocordin, Corvalol and Valoserdin also contain α-bromisovalerianic acid ethyl ester, whose molecule contains a bromine atom. Due to the cumulative effect of bromine compounds due to their slow elimination from the body, with regular use of Valocordin, Corvalol and Valoserdin, patients may develop chronic bromine poisoning - bromism, which is manifested, in particular, by depression of the central nervous system, confusion consciousness, drowsiness, memory loss, depression, apathy, ataxia, rhinitis, lacrimation, conjunctivitis, acne, hemorrhagic diathesis and impaired coordination of movements. Similar disadvantages associated with the presence of α-bromisovalerianic acid ethyl ester in the preparation are also characteristic of another sedative and hypnotic drug known from Ukrainian patent UA 77909 C2, 01/15/2007, A61K 36/00, A61K 31/19, A61P 25 / 20, A61K 31/223, A61K 36/534, A61K 31/191, A61K 31/045, comprising:

ethyl ester of α-bromisovalerianic acid - 1.8 to 2.8 wt. %

a solution of menthol in menthyl ester of isovalerianic acid - 5.06 - 8.0 wt. %

peppermint oil - 0.1 - 0.2 wt. %

hop oil - 0.01 - 0.04 wt. %

sodium acetate trihydrate - 0.4 - 0.8 wt. %

diluted acetic acid - 0.1 - 0.5 wt. %

ethyl alcohol - 60.0 - 80.0 wt. %

purified water - the rest.

In connection with the indicated shortcomings of the preparations “Valocordin”, “Corvalol”, “Valoserdin” and the preparation according to the patent of Ukraine UA 77909 C2, limiting the possibilities of their medical use, the task of creating a safe and effective for the treatment of functional disorders of the cardiovascular system (cardialgia, cardialgic syndrome and sinus tachycardia), neurosis, accompanied by irritability, anxiety, fear, difficulty falling asleep and excitement conditions, accompanied by a pronounced autonomic reaction E means containing no components having a cumulative effect or can cause dependence, but provides a pronounced sedation.

When solving this problem, an important alternative to anxiolytic drugs containing phenobarbital or other barbiturates is anxiolytic drugs containing hydroxyzine as the active substance. Hydroxyzine ((±) - 2- (2- {4 - [(4-chlorophenyl) phenylmethyl] piperazin-1-yl} ethoxy) ethanol) is a non-benzodiazepine anxiolytic, which is a diphenylmethane derivative of structural formula (I)

(I).

(I).

In clinical practice, hydroxyzine has been used since the mid-1950s. and is used both in the form of a hydroxyzine base and in the form of a pharmaceutically acceptable acid addition salt - hydroxyzine hydrochloride.

Hydroxyzine has an anxiolytic, antihistamine, antipruritic and antiemetic effect. By lowering the concentration of histamine at a central level, hydroxyzine has the ability to reduce anxiety, reduce aggressiveness and cause a persistent anxiolytic effect (Krebs MO. // La Revfue des Entretiens de Bichat 2001; 2 (5)). Unlike phenobarbital, hydroxyzine is not addictive. Hydroxysin acts already 15-30 minutes after ingestion, the maximum concentration of hydroxyzine in blood plasma (C _max ) is observed 2 hours after taking the drug. The action of hydroxyzine lasts for 6-8 hours. The main advantages of hydroxyzine are the rapid onset of action, its good tolerance, the absence of the phenomenon of "rebound", physical and mental dependence, withdrawal symptoms and a positive effect on cognitive function, as well as the fact that hydroxyzine in therapeutic doses does not have a depressing effect on respiration, makes it more preferable for use in the composition of sedative, vasodilator, hypnotic and antispasmodic drugs, in comparison with phenobarbital - the active substance of the drugs "Valoco Din "and" Corvalol ".

Currently, considerable experience has been gained with the use of hydroxyzine for various indications, in particular, as a means of controlling smoking (Turle G. // "Brit J Psychiat" 1958; 104: 82 p. 33), in pediatric dentistry (Lang L. // “J – Dent – Child” 1965; 32, 4: 253–8), as a treatment for anxiety neurosis and “mild” depression (Middlefell R., Edwards K. // “Brit J Psychiat” 1959; 105: 792-4), as well as violations of behavior and learning in children (Segal L., Tansley A. // "J Mental – Science; Br J Psychiat" from 1963; 1957; 103: 677–81). In addition, hydroxyzine is also successfully used to treat itching (Rhoades R., Leifer K. et al. // "J Allergy Clin Immunol", 1975 Mar .; 55, 3: 180–5), with pigmented urticaria (mastocytosis) in children (Kettelhut B., Berkebile C. et al. // "J Allergy Clin Immunol" 1989 May; 83, 5: 866–70), in oncology (Broder L., Lean N. et al. // "PROC– AM – ASSOC – CANCER – RES "; 1982; 23: 514), in burn patients (Vitale M. et al. //" J burn care & rehabilitat "1991; 12, 4: 330–3), in narcology (Kaim S., Klett C. et al. // Agressologie: revue internationale de physio – biologie et de pharmacologie appliquees aux effets de l'agression, 1968; 9, 2: 305–8) and in many other conditions. In a study by Samuelian J, Billardon M, Guillou N. // L’encephale 1995; 21: 147 it was also shown that hydroxyzine also positively affects cognitive function: hydroxyzine, having the same anxiolytic activity as the reference drug, restored cognitive function to normal limits.

The efficacy of hydroxyzine in the treatment of generalized anxiety disorder (Ferreri M, Hantouche EG. Recent clinical trials of hydroxyzine in generalized anxiety disorder. // "Acta Psychiat Scand" 1998; 98 Suppl. 393, pp. 102 - 108; E. Hantouche, M. Ferreri, The Effectiveness of Hydroxyzine in Generalized Anxiety (Translation: AE Bobrov, MD) // "Psychiatry and Psychopharmacotherapy", 2000, Volume 2, No. 4, pp. 124 - 126). In particular, it was shown that hydroxyzine statistically significantly, quickly and significantly reduced anxiety symptoms at the end of the 1st week of treatment, and this effect persisted for another 1 week after stopping treatment (Ferreri M, Hantouche T, Billardon M. // " L'encephale "1994; 20: 785–91), and after the drug was discontinued, the patients did not experience a rebound phenomenon or a return of anxiety.

From the prior art from the patent of Ukraine for utility model UA 89626 U, 04/25/2014, A61K 31/21, the sedative and hypnotic drug, proposed in the form of tablets or hard capsules containing hydroxyzine in an amount of up to 4, is proposed as the closest analogue of the present invention. 5 wt. %, as well as ethyl ester of α-bromisovalerianic acid in an amount of up to 7 wt. %, peppermint oil or a mixture of peppermint oil with hop oil - up to 0.25 wt. %, β-cyclodextrin - up to 50 wt. %, excipients, including bound water, - the rest. Specific examples of the implementation of the technical solution according to UA 89626 U reveal a quantitative content of hydroxysine of 3.33 - 4.29 wt. % (see tables 1 - 3 on page 2 - 3 of the description of UA 89626 U).

The ethyl ester of α-bromisovalerianic acid, which is part of tablets according to UA 89626 U, is an unstable volatile liquid, inconvenient for the production of solid dosage forms. In this regard, within the framework of UA 89626 U, it turned out to be necessary to additionally use substances that retain α-bromisovalerianic acid ethyl ester in a tablet. In addition, α-bromisovalerianic acid ethyl ester, as mentioned above, as well as other pharmaceutically acceptable bromine compounds, has a cumulative effect, i.e. when it is used, there is a gradual accumulation of bromine in the body, as a result of which chronic bromine poisoning develops.

Finally, the implementation of the drug according to UA 89626 U in the form of tablets or hard capsules can adversely affect the bioavailability (hereinafter - the bioavailability) of hydroxyzine, since it is known that the bioavailability of drugs in solid dosage forms is generally lower than in solutions.

The objective of the invention, therefore, is to create an effective sedative, devoid of the undesirable properties inherent in known analogues, in which, thanks to the synergistic (super-cumulative) action of components selected in optimal quantities, without the use of barbiturates, the specified sedative effect would be provided.

The technical results achieved in the framework of the invention include:

(a) the implementation of the sedative and muscle relaxant effects of the drug while reducing the amount of active substances of the specified drug (due to the synergistic action of the active components),

(b) the achievement of a sedative and muscle relaxant effect in the absence of barbiturates and with a smaller, in comparison with the closest analogue, amount of hydroxyzine,

(c) rapid provision of the therapeutic effect of the drug (from the moment the drug enters the oral cavity),

(d) the possibility of effective treatment of tachycardia caused by a nervous disorder

and

(e) the expansion of the arsenal of sedative, vasodilator, hypnotic, muscle relaxant and antispasmodic drugs, applicable for the treatment of functional disorders of the cardiovascular system (cardialgia, cardialgic syndrome and sinus tachycardia), neurosis, accompanied by irritability, anxiety, fear, and difficulty falling asleep accompanied by severe vegetative reactions.

In the framework of the present invention, this problem is solved, and technical results (a) - (e) are achieved by creating a sedative and muscle relaxant drug, made in the form of an oral solution containing

hydroxysine or its pharmaceutically acceptable salt is 0.00001 - 2.00002 wt. %

a solution of menthol in menthylovalerate - 0.99001 - 2.01106 wt. %

peppermint oil - 0.09807 - 0.14215 wt. %

Spanish hop oil (oregano oil) - 0.01961 - 0.02031 wt. %

as well as

ethanol 96% and purified water in a mass ratio of 1.2: 1 - 1.7: 1 - the rest.

The medicine according to the invention can be used for a wide range of indications, including stressful situations accompanied by psychoemotional stress, functional disorders of the cardiovascular system, neurosis and neurosis-like conditions accompanied by increased excitability and irritability, disturbances in falling asleep and sleep, tachycardia, arousal states with severe vegetative manifestations and intestinal cramps, while ensuring the realization of a synergistic sedative and muscle relaxant Procedure, at a lower, in comparison with the conventional art, an amount of active ingredient. The drug according to the invention provides a sedative effect in the absence of components that can cause the development of addiction, while the sedative synergistic effect of the drug appears from the moment the drug enters the oral cavity.

In a preferred embodiment of the invention, but not limited to this embodiment, the sedative and muscle relaxant drug of the invention comprises:

2.00 wt. % hydroxyzine or its pharmaceutically acceptable salt,

2.00 wt. % menthol solution in menthyl valerate,

0.14 wt. % peppermint oil,

0.02 wt. % Spanish hop oil

as well as

ethanol and purified water in a mass ratio of 1.227: 1 - the rest.

As a pharmaceutically acceptable salt of hydroxyzine, the drug of the invention may most preferably contain hydroxyzine hydrochloride. In alternative embodiments, other pharmaceutically acceptable hydroxyzine salts may be used in place of hydroxysine hydrochloride, for example (without limitation), sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, acid phosphate, isonicotinate, lactate, salicylate , acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, fumarate, gluconate, glucuronate, sugar, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzosulfonate, n-toluenesulfate or hydroxyzine moate. A specific list of pharmaceutically acceptable salts of hydroxyzine, preferred for use in the composition of the medicinal product according to the invention, can be determined by a person skilled in the art, based on general considerations that determine the choice of a pharmaceutically acceptable salt in each case (see, for example: Berge SM Pharmaceutical Salts. // Journal of Pharmaceutical Sciences, January 1977, vol. 66, No. 1, pp. 1-19; Gupta D., Bhatia D., et al. Salts of Therapeutic Agents: Chemical, Physicochemical and Biological Considerations . // "Molecules", 2018, 23, 1719, pp. 1-15).

Peppermint oil containing menthol and its esters, as well as various flavonoids (luteolin-7-glucoside, hesperidin, etc.), as menthol, have a calming effect, as well as reflex vasodilator and antispasmodic effects. Mentilizalerate reduces the excitability of the central nervous system, enhances the effect of sleeping pills, and also has a weak antispasmodic effect. In turn, Spanish hop oil (oregano oil) has a reflex vasodilating and antispasmodic effect. In the present description, peppermint oil and hop oil, taken together, are hereinafter also referred to as an “oil component”.

In the framework of the present invention, it was unexpectedly found that a decrease in the quantitative content of the oil component, as well as a decrease in the quantitative content of hydroxysine, does not adversely affect the sedative properties of the drug according to the invention, while at the same time reducing the risk of accidental overdose of the drug.

Also in a preferred embodiment of the invention, but also without limitation, ethyl alcohol is at least 90%, more preferably at least 95%, most preferably at least 96% ethyl alcohol. Also more preferably, but not limited to, the drug of the invention is taken orally dropwise. In a preferred, but also not limiting embodiment of the invention, the dose of the drug per dose is 5 to 25 drops, most preferably 15 to 20 drops. The maximum daily dose of a medicament according to the invention is preferably 30 to 50 drops, more preferably 30 to 40 drops, most preferably 40 drops.

The drug according to the invention can, without limitation, be used in stressful situations accompanied by psychoemotional stress, with functional disorders of the cardiovascular system, with neurosis and neurosis-like conditions, accompanied by increased irritability and irritability, with disturbances in falling asleep and sleep, with tachycardia, as well as in conditions excitement with pronounced autonomic manifestations and intestinal cramps.

The invention is illustrated by the following examples, intended solely to illustrate the invention, but not to limit the scope of claims.

Example 1

Peppermint oil (14 g), a solution of menthol in menthylisovalerate (100 g) and Spanish hop oil (2 g) are mixed at room temperature, then hydroxyzine hydrochloride (0.001 g) is added, the mixture is brought to the required volume using ethanol and purified water in a mass ratio of 1.45: 1, respectively. The resulting mixture is poured into dark glass bottles, hermetically sealed, information on the name and quantitative and qualitative composition of the drug is applied to the bottles, then the bottles are placed in the secondary packaging.

Example 2

Peppermint oil (10 g), a solution of menthol in menthylisovalerate (150 g) and Spanish hop oil (11 g) are mixed at room temperature, then hydroxyzine hydrochloride (1.01 g) is added, the mixture is brought to the required volume using ethanol and water purified in a mass ratio of 1.7: 1, respectively. The resulting mixture is poured into dark glass bottles, hermetically sealed, information on the name and quantitative and qualitative composition of the drug is applied to the bottles, then the bottles are placed in the secondary packaging.

Example 3

Peppermint oil (12 g), menthol solution in menthylisovalerate (200 g) and Spanish hop oil (20 g) are mixed at room temperature, then hydroxyzine hydrochloride (201 g) is added, adjusted to the required volume using ethanol and purified water in bulk 1.2: 1 ratio, respectively. The resulting mixture is poured into dark glass bottles, hermetically sealed, information on the name and quantitative and qualitative composition of the drug is applied to the bottles, then the bottles are placed in the secondary packaging.

Example 4

Investigated the sedative and muscle relaxant properties of the claimed drug containing 2.00 wt. % hydroxyzine hydrochloride, 2.00 wt. % menthol solution in menthyl valerate, 0.14 wt. % peppermint oil, 0.02 wt. % Spanish hop oil, ethanol and purified water in a mass ratio of 1.227: 1 - the rest, with a single intragastric administration of the specified medicinal product to experimental animals.

As a comparison drug, the drug “Valoserdin” (drops for oral administration) manufactured by Moscow Pharmaceutical Factory was used. The study was performed on 50 rats (males) of the Wistar outbred line. Before the start of the study, rats were divided into groups of 10 animals in such a way that there were no statistically significant differences in age, body weight and other indicators between animals of different groups. The test drug was administered intragastrally to experimental animals of the experimental groups using a probe, while the doses of the drug in the experimental groups were 43.5 mg / kg, 87 mg / kg and 174 mg / kg of body weight, 10 rats per dose (hereinafter, doses are calculated based on hydroxyzine hydrochloride). The comparison group (10 rats) was administered intragastrically with the drug “Valoserdin”; control animals (10 rats) were injected with an intragastric aqueous-alcoholic solution.

When choosing the doses, they were guided by the coefficient for the recalculation of doses with the intragastric method of administration relative to the parenteral, amounting to 6.9, proposed by I.V. Berezovskaya (IV Berezovskaya. Classification of chemicals according to the parameters of acute toxicity with parenteral routes of administration. - "Chemical and Pharmaceutical Journal", t. 37, No. 3, 2003, p. 32 - 34). When choosing the volume of the drug for intragastric administration, it was taken into account that it is planned to use 30-40 drops of the drug diluted with water in the clinic. The volume of the test drug and the comparison drug was adjusted with distilled water to 10 ml of solution per 1 kilogram of the animal’s body weight, and then the animals were administered in accordance with their body weight.

Two days before the start of the experiment, a catheter was implanted into the carotid artery for all animals. On the day of the experiment, all animals were connected through the indicated catheter to the PowerLab unit in order to register blood pressure (hereinafter - BP) and heart rate (hereinafter - heart rate) directly. Within 10 minutes, baseline blood pressure and heart rate values were recorded, then the study drug (experimental group) or comparison drug (comparison group) was administered, after which blood pressure and heart rate were recorded over 30 minutes. At the same time, constant monitoring of the general condition of the animals was carried out, noting all changes in their behavior. After registering blood pressure and heart rate in the experimental groups, the comparison group and the control group, the locomotor activity of animals was studied using the ATM3 Auto System and the ATM3 Auto System counting system using an Optovarimex instrument manufactured by Columbus Instruments. The muscle strength of animals was measured in the "Grip Strength Meter" test. Within two days from the moment of drug administration, survival and general condition and motor and research behavior of animals were observed; also studied the muscle relaxant effect of the study drug and the comparison drug. The behavior of animals was studied in the Open Field test, which is a standard test for assessing motor and research activity and anxiety under conditions of emotional stress (Prut L., Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review // Eur J Pharmacol 2003 Feb 28; 463 (1-3): 3-33). The muscle relaxant effect of the study drug and the comparison drug was evaluated by muscle relaxation of the front limbs of the animals of the experimental group and the comparison group.

At the end of the study, on the third day after drug administration, all animals were euthanized.

As a result of the study, it was found that the studied drug in doses of 43.5 mg / kg and 87 mg / kg did not cause a significant decrease in the level of systemic blood pressure and heart rate relative to the initial values; Thus, it is shown that the preparation according to the invention in the therapeutic dose range does not have a toxic effect on the activity of the cardiovascular system. At a dose of 174 mg / kg in animals, tachycardia was detected, which, apparently, is due to an overdose of hydroxyzine.

In the Open Field test, the preparation according to the invention at a dose of 87 mg / kg showed a sedative effect comparable to that of the comparative preparation, which was manifested by a decrease in locomotor and orientational research activity of animals. Significant changes in some indicators of the Open Field test were also found when using a dose of 43.5 mg / kg.

The muscle relaxant effect of the preparation according to the invention was observed both with the introduction of the smallest dose of hydroxyzine (43.5 mg / kg) and the largest (174 mg / kg), while in the experimental group, in comparison with the group treated with hydroxyzine, this effect was more pronounced , which, apparently, is associated with the presence in the preparation according to the invention of peppermint oil, Spanish hop oil and a solution of menthol in menthylisovalerate.

As a result of the study, it was found that the muscle relaxant effect of the drug according to the invention was comparable with that of the comparison drug.

Thus, in the framework of the present invention, a sedative and muscle relaxant drug is obtained that does not contain components that can cause addiction or have cumulative properties, which, when administered orally, provides a quick therapeutic effect of the drug, which makes it possible to effectively treat tachycardia caused by a nervous disorder, expanding arsenal of sedative, vasodilator, hypnotic and antispasmodic drugs applicable for the treatment of functional disorders of the cardiovascular system, tachycardia, neurosis and neurosis-like conditions, accompanied by increased excitability and irritability, anxiety, fear, difficulty falling asleep and sleep, as well as excitement conditions, accompanied by severe vegetative reactions and intestinal cramps.

Claims (10)

1. A sedative and muscle relaxant drug intended for the treatment of functional disorders of the cardiovascular system, tachycardia, neurosis and neurosis-like conditions, accompanied by increased irritability and irritability, anxiety, fear, difficulty falling asleep and sleep, as well as excitement conditions, accompanied by severe vegetative reactions and intestinal cramps containing: hydroxysine or its pharmaceutically acceptable salt is 0.00001 - 2.00002 wt. % a solution of menthol in menthylovalerate - 0.99001 - 2.01106 wt. % peppermint oil - 0.09807 - 0.14215 wt. % Spanish hop oil - 0.017 - 0.020 wt. % and ethanol and purified water in a mass ratio of 1.2: 1–1.7: 1 - the rest, made in the form of drops for oral administration. 2. Sedative and muscle relaxant drug according to claim 1, characterized in that it contains 2.00 wt. % hydroxyzine or its pharmaceutically acceptable salt, 2.00 wt. % menthol solution in menthyl valerate, 0.14 wt. % peppermint oil, 0.02 wt. % Spanish hop oil, ethanol and purified water in a mass ratio of 1.227: 1 - the rest. 3. Sedative and muscle relaxant drug according to any one of p. 1, 2, characterized in that the pharmaceutically acceptable salt of hydroxysine is hydroxyzine hydrochloride.