RU2823588C2 - Pharmaceutical composition 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione for therapy of respiratory diseases - Google Patents

Abstract

FIELD: pharmacology; medicine.

SUBSTANCE: group of inventions relates to pharmacology, medicine and chemical-pharmaceutical industry, namely to a pharmaceutical composition for treating and / or preventing respiratory diseases, containing 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione and excipients, use of such a composition and a medicinal agent based thereon. Disclosed pharmaceutical composition contains 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione, wt.%: 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 20–35; anhydrous lactose 60-75; sodium carboxymethyl starch 0.5–5; talc and/or sodium stearate 0.1–2.5. Also disclosed is a medicinal agent for treating and/or preventing respiratory diseases, containing said composition, and use of said composition for preparing a medicinal agent.

EFFECT: wider range of antiviral agents and agents for treating and/or preventing respiratory diseases; high long-term stability of the drug preparation containing 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione; creation of a pharmaceutical composition providing a high level of release of the active ingredient; creation of a mixture for tabletting and a finished dosage form having improved mechanical properties compared to the prototype.

9 cl, 2 tbl, 3 ex

Description

The invention relates to pharmacology, medicine and the chemical-pharmaceutical industry, namely to the pharmaceutical composition of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione or its pharmaceutically acceptable salts for the treatment and/ or prevention of respiratory diseases.

Currently, there is a need to develop new agents and affordable therapeutic forms for the treatment and prevention of influenza and ARVI.

The compound 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazin-2,6-dione (synonym: 1-(2-(1-methyl-1H-imidazol-4-yl)) is known from the prior art ethyl)piperidine-2,6-dione).

The compound 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione is known and described in the application for invention WO 2014/168522 (published 10/16/2014). This patent application discloses a method for producing this compound, and also studies its antiviral activity and use for the treatment of rhinoviruses and other upper respiratory tract diseases.

Application WO 2015/072893 (published May 21, 2015) describes the use of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazin-2,6-dione for the treatment of diseases associated with the development of eosinophilic inflammation, including eosinophilic asthma.

One of the disadvantages of many drugs is the lack of stability of the active substance during shelf life. However, solid state stability and shelf life of the active components are very important factors. The drug and pharmaceutical compositions must be able to be stored for significant periods of time without showing a significant change in the physicochemical properties of the active component.

In the creation of modern drugs, not only the properties of a particular drug are of great importance, but also the scientifically based choice of excipients. This is especially important in the industrial production of drugs with a long shelf life. Excipients are intended for the formation and design of dosage forms and therapeutic systems, and to impart stability to drugs. In the light of the biopharmaceutical concept, excipients must provide the appropriate pharmacological effect and pharmacokinetic parameters of the drug [1].

When developing a pharmaceutical composition, the authors of the present invention were faced with the problem of stability of the active component, as well as difficulties in creating a durable solid dosage form that provides a high level of bioavailability of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazin-2 ,6-dione.

It was unexpectedly discovered that the key factor allowing to achieve stability of the active component when obtaining a medicinal product, and, as a result, stability of the medicinal product throughout the entire shelf life, and a sufficient level of bioavailability, is the residual water content in the pharmaceutical composition in an amount of no more than 0. 1-10 wt. % by weight of the composition.

Considering that other piperidine dione compounds are stable at high humidity, including in aqueous suspensions, we have discovered that the moisture level of the final composition is critical to maintaining the stability and bioavailability of 1-[2-( 1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione.

Thus, the object of the present invention is to provide a stable pharmaceutical composition providing a high level of release of the active component.

The technical result of the claimed invention is:

- expansion of the arsenal of antiviral agents and agents for the treatment and/or prevention of respiratory diseases;

- increasing the long-term stability of a medicinal product containing 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione or its pharmaceutically acceptable salts, solvates, hydrates;

- creation of a pharmaceutical composition that provides a high level of release of the active component;

- creation of a mixture for tableting and a finished dosage form with increased mechanical properties.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 10 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 9 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 8 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 7 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 6 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 5 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 4 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 3 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 2 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 1 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 0.5 wt. % by weight of the composition.

In one embodiment of the present invention, the residual water content in the pharmaceutical composition is preferably no more than 0.1 wt. % by weight of the composition.

The following are definitions of terms that are used in the description of the present invention.

The term “medicinal principle”, “medicinal substance”, “medicinal substance” means a physiologically active substance (active substance) of synthetic or other (biotechnological, plant, animal, microbial and other) origin, possessing pharmacological activity and being the active principle of the pharmaceutical composition used for the production and manufacture of a medicinal product (medicine). In the present invention, the active substance is 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione or pharmaceutically acceptable salts, solvates or hydrates thereof.

The term “drug” means a substance (or combination of substances) that comes into contact with the human or animal body, penetrates the organs and tissues of the human or animal body, and is intended to restore, correct or change physiological functions in humans and animals, as well as for treatment and prevention of diseases. Medicines include pharmaceutical substances and drugs.

The term “pharmaceutical substance” means an active substance with pharmacological activity, which is intended for the production, manufacture of drugs and determines their effectiveness.

The term “medicinal product”, “drug” means a medicinal product in the form of a dosage form used for the treatment and prevention of a disease.

The term “dosage form” means the state of the drug corresponding to the methods of its administration and use and ensuring the achievement of the required therapeutic effect.

The term "pharmaceutical composition" means a composition comprising 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione or pharmaceutically acceptable salts, solvates, hydrates, and at least one of the components selected from the group consisting of pharmaceutically acceptable and pharmacologically compatible excipients, solvents, diluents, carriers, auxiliaries, dispensing agents, delivery agents such as preservatives, stabilizers, excipients, disintegrants, humectants, emulsifiers, suspending agents, thickeners, sweeteners, flavorings, flavors, antibacterial agents, fungicides, lubricants, prolonged delivery regulators, the choice and ratio of which depends on their nature, method of administration of the composition and dosage.

The pharmaceutical composition of the present invention may be in dosage form in the form of a tablet, preferably a film-coated tablet, capsule, granule or powder.

The term "solvate" is used to describe a molecular complex containing a compound of the invention and one or more molecules of a pharmaceutically acceptable solvent, for example, ethanol. The term "hydrate" is used when the specified solvent is water.

The term "pharmaceutically acceptable salts" or "salts" includes salts of the active compounds that are prepared with relatively non-toxic acids. Examples of pharmaceutically acceptable non-toxic salts include those formed by inorganic acids such as hydrochloric, hydrobromic, phosphoric, sulfuric and perchloric acids, or organic acids such as acetic, oxalic, maleic, tartaric, succinic, citric or malonic acids, or prepared by others. methods used in this field. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentane propionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanate, hexanate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate (mesylate), 2-naphthalene sulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, hemifumarate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate (tosylate), undecanate, valerate and the like.

The terms “comprising” and “comprising” mean that the specified combinations, compositions and sets include the listed components, but do not exclude the inclusion of other components.

The terms “treatment” and “therapy” cover the treatment of pathological conditions in mammals, preferably in humans, and include: a) reduction, b) blocking (suspension) of the course of the disease, c) alleviation of the severity of the disease, i.e. induction of disease regression, d) reversal of the disease or condition to which the term applies, or one or more symptoms of the disease or condition.

The term “prophylaxis” or “prevention” includes the elimination of risk factors, as well as prophylactic treatment of subclinical stages of the disease in mammals, preferably in humans, aimed at reducing the likelihood of the occurrence of clinical stages of the disease. Patients for prophylactic therapy are selected based on factors known to increase the risk of clinical stage disease compared with the general population. Preventive therapy includes a) primary prevention and b) secondary prevention. Primary prevention is defined as preventive treatment in patients who have not yet reached the clinical stage of the disease. Secondary prevention is the prevention of recurrence of the same or similar clinical condition or disease.

The term "excipient" or "diluent" means excipients used to give solid dosage forms a given volume or weight. Starch, glucose, sucrose, lactose (milk sugar), anhydrous lactose, lactose monohydrate, basic magnesium carbonate, magnesium oxide, sodium chloride, sodium bicarbonate, white clay (kaolin), gelatin, microcrystalline cellulose (MCC) can be used as fillers. , methylcellulose (MC), sodium salt of carboxymethylcellulose (Na CMC), calcium carbonate, disubstituted calcium phosphate, glycine (aminoacetic acid), dextrin, amylopectin, ultraamylpectin, sorbitol, mannitol, pectin, etc. The group is not limited to this list.

The term “binders” means substances included in the tablet mass to give it the necessary viscosity. As binders: carboxymethylcellulose (CMC), hydroxyethylcellulose (OEC), hydroxypropylmethylcellulose (OPMC); polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginic acid, sodium alginate, gelatin, etc. The group is not limited to this list.

The term "disintegrant" means substances used to improve disintegration or dissolution, providing mechanical destruction of tablets in a liquid medium, which is necessary for the rapid release of the active substance. The baking powder can be one or more of microcrystalline cellulose, croscarmellose sodium, crospovidone, sodium starch glycolate, starch, pectin, gelatin, amylopectin, ultraamylopectin, agar-agar, alginic acid, potassium and sodium alginate, Tween-80, etc. The group is not limited to this list.

The term "glidant" refers to auxiliary substances used in the tablet manufacturing process at the compression stage to improve the flow of granules or powder by reducing friction between particles. The sliding substance can be represented by one or more of starch, talc, polyethylene oxide-4000, stearic acid, calcium and magnesium stearate, etc. The group is not limited to this list.

The term “lubricant” or “lubricant” means auxiliary substances that help reduce the friction force between the surface of the tablet and the walls of the punch cuvette in which the tablet is formed, used in the technological process of producing tablets at the pressing stage. The lubricant can be represented by one or more of magnesium stearate, calcium stearate, sodium stearyl fumarate, polyethylene glycol (with a molecular weight greater than 3350), sodium lauryl sulfate, talc, mineral oil, leucine and poloxamer, etc. The group is not limited to this list.

The term “respiratory tract diseases” means diseases selected from the group consisting of rhinitis, sinusitis, rhinosinusitis, pharyngitis, nasopharyngitis, tonsillitis, diseases of the vocal folds and larynx, vasomotor and allergic rhinitis, bronchitis, bronchiolitis, pneumonia, bronchial asthma, chronic obstructive disease lungs, cystic fibrosis, coronavirus infection COVID-19, diseases caused by a virus selected from the group consisting of rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, adenovirus, metapneumovirus, coronavirus, including SARS-CoV-2, Coxsackie virus, enterovirus, rotavirus, herpes virus. The group is not limited to this list.

The examples presented below illustrate, but do not cover all possible embodiments of the invention and do not limit the invention.

Example 1. Preparation of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione tablets

1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione, filler, leavening agent, sift through a sieve with a specified mesh diameter. The sifted substances are placed in a mixer, where they are mixed for the time necessary to obtain a homogeneous mixture.

Lubricants, glidants and other powdering substances are added to the resulting mixture and mixing is carried out.

The resulting tablet mass is tabletted on a rotary pressing machine. The tablets must be white or off-white with a creamy tint, with solid edges, a smooth and uniform surface, without cracks or chips.

Additionally, the tablets are coated with a film coating.

As a filler, it is preferable to use anhydrous lactose, lactose monohydrate and combined fillers, which include lactose, microcrystalline cellulose, mannitol or mixtures thereof.

The disintegrant is selected from crospovidone, povidone, copovidone, sodium carboxymethyl starch, and mixtures thereof.

The lubricant is selected from talc, stearic acid salts, steryl fumarate salts, colloidal silicon dioxide and mixtures thereof.

Below are the pharmaceutical compositions according to the present invention.

Table 1. Pharmaceutical compositions of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione.

Composition 1 Composition 2 Composition 3 Composition 4 Components wt. % Components wt. % Components wt. % Components wt. % 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 20 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 40 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione thirty 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 35 Lactose anhydrous 75 Lactose anhydrous 55 MCC 65 MCC 60 sodium carboxymethyl starch 3.5 sodium carboxymethyl starch 2.5 Crospovidone 2.5 Crospovidone 4 Talc 0.5 Talc 1 Talc 1 Talc 0.5 Magnesium stearate 1 Magnesium stearate 1.5 Colloidal silicon dioxide 1.5 Colloidal silicon dioxide 0.5 Residual moisture, wt.% by weight of the composition 2 Residual moisture, wt.% by weight of the composition 2 Residual moisture, wt.% by weight of the composition 03 Residual moisture, wt.% by weight of the composition 2.7

Composition 5 Composition 6 Composition 7 Composition 8 Components wt. % Components wt. % Components wt. % Components wt. % 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 25 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 40 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 20 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 35 Lactose anhydrous 70 Lactose anhydrous 55 MCC 75 MCC 59 Crospovidone 4.5 Crospovidone 3 Povidone 3.5 Povidone 5 Talc 0.25 Talc 1.5 Talc 0.5 Talc 0.5 Colloidal silicon dioxide 0.25 Colloidal silicon dioxide 0.5 Magnesium stearate 1 Magnesium stearate 0.5 Residual moisture, wt.% by weight of the composition 1.5 Residual moisture, wt.% by weight of the composition 2.4 Residual moisture, wt.% by weight of the composition 2.8 Residual moisture, wt.% by weight of the composition 1.8

Composition 9 Composition 10 Composition 11 Composition 12 Components wt. % Components wt. % Components wt. % Components wt. % 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 40 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 33.33 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 35 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 20 Lactose anhydrous 57 MCC 63.33 MCC 60 Lactose anhydrous 80 Povidone 0.5 Sodium carboxymethyl starch 1.83 Sodium carboxymethyl starch 4.9 Residual moisture % wt. by weight of the composition 0.5 Talc 1.5 Talc 0.5 Talc 0.1 Colloidal silicon dioxide 1 Magnesium stearate 1 Residual moisture % wt. by weight of the composition 2.7 Residual moisture % wt. by weight of the composition 1.0 Residual moisture % wt. by weight of the composition 2.5

Example 2. Study of the storage stability of the pharmaceutical composition of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione

The stability of pharmaceutical compositions of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazin-2,6-dione was assessed by the content of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazin- 2,6-dione and compared with the stability of the prototype (composition 1 with a water content of 15 wt.% by weight of the composition was used as a prototype).

All samples were stored in glass vials sealed with rubber stoppers with aluminum caps in a climate chamber at a temperature of 60°C under accelerated testing conditions. The content of the active substance was determined by HPLC using standards.

The “accelerated aging” method consists of maintaining the test drug at temperatures and humidity levels that exceed the temperature and humidity of its storage during circulation.

The shelf life (C) at storage temperature (t _xp ) is related to the experimental shelf life (S _E ) at an elevated experimental storage temperature (t _e ) by the following relationship:

,

where is the matching coefficient $$K=A^{\frac{t_{\text{uh}}-t_{XR.}}{10}}$$ .

The temperature coefficient of the chemical reaction rate (A) is taken to be 2.5. The given dependence is based on Van't Hoff's rule about a 2-4-fold increase in the rates of chemical reactions with an increase in temperature by 10°C.

In accordance with the general pharmacopoeial article OFS.1.1.0009.15, the value of the coefficient of conformity (K) depending on the selected temperature range ( ), equal to 35°C, is 24.7. The experimental storage period with a selected shelf life of 3 years is 45 days.

As a result of the research, it was found that the resulting compositions (compositions 1-12, respectively) have increased storage stability compared to the prototype. The results are presented below in Table 1.

It was found that after 45 days of storage under the conditions of the accelerated aging method, the compositions of the present invention containing residual water in an amount from 0.1 to 10 wt. % by weight of the composition had a statistically significantly increased stability compared to the prototype (statistical significance level p<0.05). The prototype remained stable for less than 15 days, then the content of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazin-2,6-dione decreased by more than 3%.

Table 2. Assessment of the stability of pharmaceutical compositions of 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione by accelerated aging method in comparison with the prototype

Storage time at (t _e -t _xp ) = 35°C, days The amount of active substance detected by HPLC data in mass. % of theoretical content Composition 1 Composition 2 Composition 3 Composition 4 Composition 5 Composition 6 Composition 7 Composition 8 Composition 9 Composition 10 Composition 11 Composition 12 Prototype 0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 5 99.9±0.1 99.9±0.1 100.0±0.1 100.0±0.1 100.0±0.1 100.0±0.1 99.9±0.1 99.9±0.1 100.0±0.1 99.9±0.1 99.9±0.1 100.0±0.1 99.3±0.1 10 99.8±0.1 99.9±0.1 100.0±0.01 100.0±0.01 99.9±0.1 99.9±0.1 99.8±0.1 99.7±0.1 99.8±0.1 99.9±0.1 99.8±0.1 99.9±0.1 98.4±0.2 15 99.6±0.1 99.7±0.1 99.9±0.1 99.8±0.01 99.8±0.1 99.7±0.1 99.6±0.2 99.6±0.1 99.7±0.1 99.6±0.2 99.6±0.1 99.8±0.1 97.9±0.2 20 99.3±0.1 99.4±0.1 99.6±0.1 99.5±0.01 99.6±0.2 99.4±0.1 99.3±0.2 99.4±0.2 99.5±0.1 99.3±0.2 99.4±0.2 99.6±0.2 96.8±0.3 25 99.0±0.1 99.3±0.1 99.4±0.1 99.3±0.2 99.3±0.2 99.1±0.2 99.0±0.2 99.1±0.2 99.0±0.2 99.1±0.2 99.2±0.2 99.3±0.2 95.0±0.3 thirty 98.8±0.2 98.6±0.2 99.2±0.2 99.2±0.2 98.9±0.3 98.6±0.2 98.9±0.3 99.0±0.3 98.7±0.2 98.9±0.3 99.0±0.3 99.1±0.3 94.3±0.4 35 98.5±0.3 98.3±0.2 99.0±0.2 98.8±0.3 98.5±0.3 98.3±0.3 98.7±0.4 98.8±0.4 98.4±0.2 98.8±0.4 98.7±0.4 98.9±0.4 92.4±0.5 45 98.6±0.4 98.5±0.3 99.0±0.3 98.3±0.3 98.6±0.3 98.1±0.4 98.4±0.5 98.0±0.4 98.3±0.3 98.7±0.5 98.6±0.4 98.5±0.4 90.2±0.6

Example 3 Preferred Formulations of 1-[2-(1-Methylimidazol-4-yl)-ethyl]perhydroazin-2,6-dione

A special case of a new pharmaceutical composition is a dosage form characterized by the fact that it includes 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazin-2,6-dione as the active principle, and sodium carboxymethyl starch as excipients , anhydrous lactose, magnesium stearate, talc with the following content of ingredients, mass. %. Additionally, the tablet can be coated with a film coating.

Ingredient Mass. % 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 20-40 Excipients: lactose anhydrous 60-80 Sodium carboxymethyl starch 0.5-5 Talc, magnesium stearate 0.1-2.5 Film casing 3-5

The most preferred composition is the following:

Components wt. % 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 33.33 Lactose anhydrous 63.33 Sodium carboxymethyl starch 1.84 Talc 0.50 Magnesium stearate 1.00

Also, this pharmaceutical composition can be made in the form of capsules placed in a gelatin shell, in the form of granules and powder for dissolution.

Bibliography

1. V.L. Bagirova, N.B. Demina, I.A. Devyatkina, A.I. Tentsova, V.A. Denisov Modern aspects of the use of excipients in the technology of pharmaceuticals Farmateka. - 1998. - No. 6. - P. 34-36.

Claims (18)

1. Pharmaceutical composition for the treatment and/or prevention of respiratory tract diseases, containing 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione and excipients in the following quantities: - 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 20-35 wt.% - Lactose anhydrous 60-75 wt.% - Sodium carboxymethyl starch 0.5-5 wt.% -Talc and/or sodium stearate 0.1-2.5 wt.%. 2. Pharmaceutical composition according to claim 1, containing - 1-[2-(1-methylimidazol-4-yl)-ethyl]perhydroazine-2,6-dione 33.33 wt. % - Lactose anhydrous 63.33 wt. % - Sodium carboxymethyl starch 1.84 wt. % - Talc 0.50 wt. % - Magnesium stearate 1.00 wt. %. 3. Pharmaceutical composition according to claim 1 or 2, characterized in that the residual level of water content in said composition ranges from 0.1 to 10 wt. % by weight of the composition. 4. A medicinal product for the treatment and/or prevention of respiratory tract diseases, containing a composition according to any one of paragraphs. 1-3. 5. The medicinal product according to claim 4, characterized in that the diseases are selected from the group consisting of ARVI, influenza and coronavirus infection COVID-19. 6. The medicinal product according to claim 4, characterized in that the diseases are selected from the group consisting of rhinitis, sinusitis, rhinosinusitis, pharyngitis, nasopharyngitis, tonsillitis, vasomotor and allergic rhinitis, bronchitis, bronchiolitis, pneumonia. 7. The medicinal product according to claim 4, characterized in that the diseases are selected from the group consisting of diseases of the vocal folds and larynx, bronchial asthma, chronic obstructive pulmonary disease, cystic fibrosis. 8. A medicinal product according to claim 4, characterized in that the diseases are caused by a virus selected from the group consisting of rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, adenovirus, metapneumovirus, coronavirus, Coxsackie virus, enterovirus, rotavirus, virus herpes. 9. Use of a pharmaceutical composition according to claims. 1-3 for the preparation of the medicinal product according to claim 4.