UA146741U - METHOD OF TREATMENT OF BETACORONAVIRUS INFECTION - Google Patents

Abstract

A method of treating a beta-coronavirus infection comprises administering to a person in need thereof, at least at one stage of treatment, a medicament comprising as active pharmaceutical ingredient a mixture of a chemical compound of structural formula (1) and a chemical compound of structural formula (2). , in which a person is administered the drug, is determined by the manifestation in humans of at least two symptoms of beta-coronavirus infection, or when a person is diagnosed with a pathogen of beta-coronavirus infection, the person is administered the drug in the amount necessary to achieve the concentration of active from 30 to 100 ng / ml.

Description

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(2) moreover, the stage of treatment at which a person is administered a drug is determined by the manifestation of at least two symptoms of betacoronavirus infection in a person or when the pathogen of betacoronavirus infection is detected in a person by a diagnostic method, while the person is administered a drug in an amount, necessary to reach the concentration of the active pharmaceutical ingredient in human blood plasma from 30 to 100 ng/ml.

The utility model relates to the field of medicine, in particular to methods of treating viral diseases caused by viruses of the orthocoronavirus family, in particular betacoronaviruses.

Betacoronaviruses are single-stranded RNA viruses, the surface of which is covered with needle-like appendages. Betacoronaviruses are one of four genera of viruses belonging to the orthocoronavirus subfamily.

Betacoronaviruses are of greatest clinical importance to humans because they cause a wide range of diseases of varying severity. In the body, betacoronaviruses primarily affect the respiratory tract, digestive system, and nervous tissues, while organs such as the liver, kidneys, heart, and eyes are also often affected. Diseases are transmitted by airborne mechanisms, the spread of betacoronavirus infections occurs mostly in the autumn-winter period, and the source of infection is a sick person.

In the past, betacoronaviruses were one of the most frequent pathogens of mild lesions of the upper respiratory tract of humans, and severe diseases were registered mainly in the presence of an immunodeficient state in the patient. However, in the 21st century the situation changed dramatically as a result of outbreaks of very severe diseases caused by previously unknown betacoronaviruses, such as MEKZ-Som and ZAK5Z-Sou-2.

Thus, the new betacoronavirus BAKZ-Sou-2, at the end of 2019, caused an outbreak of an infectious disease, which was named coronavirus disease (SOMIO-19). SOMIO-19 can be asymptomatic in a person, in a mild form or in a severe form, or with the risk of death. The incubation period of the disease is 1-14 days. Symptoms, on average, develop 5-6 days after infection. Infection caused by ZAKZ-Sou-2 manifests itself in three main clinical forms: 1) mild acute respiratory viral infection; 2) pneumonia without a threat to life; and 3) severe pneumonia with acute respiratory distress syndrome.

Due to the peculiarities of the course of the disease (a long incubation period, a significant number of asymptomatic cases, and a large index of contagiousness), as well as the lack of effective means and methods of treatment, individual outbreaks of SOMIU-19 increased and later acquired the status of a global pandemic.

The special danger of SOMIO-19 lies in a large number of serious consequences, such as for

From infected people and their environment, as well as for the health care system. Risk groups that are more susceptible to SOMIU-19 include smokers, the elderly, men, people of Asian ethnicity, people with impaired immune systems, and people with chronic or severe underlying diseases (eg, diabetes). This list shows that a significant percentage of the world's population is in the risk group, and when infected with SOMIO-19, there is a high probability of developing a particularly severe form of the disease, up to fatal consequences.

Among the complications in people suffering from SOMIO-19, the following have been recorded so far: 1) the development of strong inflammatory processes that lead to fatal pneumonia and acute respiratory distress syndrome; 2) the development of inflammatory processes that have a long-term effect on the health of the cardiovascular system, in particular, that lead to arrhythmias, myocarditis, cardiomyopathy, etc.;

C) development of acute heart, kidney or respiratory failure; 4) a high probability of a fatal outcome.

The negative impact of the pandemic on the global economy and the health care system is associated with a significant increase in the number of people requiring hospitalization (due to the simultaneous infection of a large number of people). As a result, there is an overburdened system characterized by shortages of medical personnel, hospital beds, specialized equipment (eg, ventilators), and general complications in administration, logistics, and financing. The result is, among other things, an increase in overall mortality among the population.

To date, there are no drugs to prevent SOMIO-19, nor approved drugs to treat it. Basically, patients receive symptomatic or supportive therapy, which is not able to overcome the cause of the disease. In severe cases of SOMIO-19, the treatment process is, for the most part, aimed at maintaining the vital functions of the patient's body, when the organs are no longer able to function independently and need external support.

All this leads to an extremely urgent need to find new ways to treat betacoronavirus infections, in particular those caused by the causative agent ZAKZ-Soukh-2.

To date, a number of methods of treatment of betacoronavirus infections, in particular SOMIO-19, have already been proposed. Yes, according to the information from the Order of the Ministry of Health of Ukraine dated April 2, 2020

762 "On the approval of the protocol "Providing medical assistance for the treatment of coronavirus disease (SOMIO-19)", the following method of treatment of SOMIO-19 was approved.

A known method of treatment of the SOMIO-19 coronavirus disease is that a person is injected with a medicine containing as an active pharmaceutical ingredient (API) the chemical substance hydroxychloroquine, chloroquine or chloroquine phosphate (depending on availability in the hospital). The drug with hydroxychloroquine is administered to a person in the amount of AFI 400 mg upon suspicion/diagnosis, again 400 mg after 12 hours, and then 200 mg twice a day for up to 5 days. The drug with chloroquine is administered to a person in the amount of AFI 600 mg (1Omg/kg of human body weight) at diagnosis, repeated 300 mg in a dosage of 5 mg/kg after 12 hours, and in the future 300 mg in a dosage of 5 mg/kg twice a day until 5 days. The medicine with chloroquine phosphate is administered to a person in the amount of API 1000 mg at diagnosis, again 500 mg after 12 hours, and then 300 mg twice a day during the day.

Disadvantages of the known method of treatment are that the treatment is stopped if the observation of the patient continues at home. Thus, the known method of treatment involves only the use for clinical treatment in the conditions of hospitalization.

Another disadvantage of the known method of treatment is that the use for treatment of compositions with the indicated APIs (hydroxychloroquine, chloroquine and chloroquine phosphate) can lead to the development of adverse reactions in humans, characteristic of these chemical compounds. In addition, the increase in the dosage of AFI, which is provided by the known methods of treatment, leads to an increase in the risk of side effects and a decrease in the degree of safety of the specified methods of treatment, which are especially intensified when the specified methods of treatment are used in combination with other methods that include the introduction of additional drugs (for example based on azithromycin or oseltamivir).

Possible adverse reactions can be manifested from the organs of vision, skin, gastrointestinal tract, nervous system, musculoskeletal system, cardiovascular system, blood, hepatobiliary system and immune system. Among the most serious side effects, such as irreversible maculopathy and macular degeneration, long-term myopathy of skeletal muscles, exacerbation of psoriasis and porphyria, etc. are known, which, in combination with the general serious condition of the patient, can lead to a significant complication of the recovery process.

In addition, the results of a number of studies, according to the known methods of treatment of SOMIO-19, are very contradictory. Some studies show that the use of chloroquine and hydroxychloroquine is effective in treating pneumonia caused by betacoronavirus infection. Other studies have shown that treatment with known methods often contributes to the development of ventricular arrhythmia and increases the risk of death for a hospitalized patient infected with betacoronavirus.

Thus, there is a critical need to develop new ways to treat coronavirus infections such as COVID-19.

The objective of the utility model is to create an effective and safe way to treat betacoronavirus infection, which is simple to implement and can be used for clinical or non-clinical human treatment, and allows to achieve a reduction in the mortality rate of hospitalized people diagnosed with betacoronavirus infection, and is cost-effective to implement .

The task is solved by creating a method of treatment of betacoronavirus infection, which consists in the fact that a person who needs it, at least at one stage of treatment, is administered a medicine containing as an active pharmaceutical ingredient a mixture of a chemical compound of the structural formula (1) and a chemical compound of the structural formula ( 2)

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Oti: es She (2, moreover, the stage of treatment at which a person is administered a drug is determined by the manifestation in a person of at least two of the following symptoms of betacoronavirus infection, such as fever, fatigue, cough of various types, loss of appetite, change or loss of the sense of taste and smell, shortness of breath, sputum discharge, general malaise, confusion, headache, muscle pain, sore throat, expectoration of blood, sputum discharge, difficulty breathing, runny nose, diarrhea, nausea, vomiting, symptoms of gastroenteritis, symptoms pneumonia, symptoms of respiratory infection of varying degrees of severity, symptoms of respiratory distress syndrome, respiratory failure, symptoms of sepsis or septic shock, or when the causative agent of betacoronavirus infection is detected in a person by a diagnostic method, while the person is administered the drug in the amount necessary to reach the concentration of the active pharmaceutical ingredient in human blood plasma from 30 to 100 ng/ml.

According to one of the variants of the implementation of the useful model, the administration of the medicinal product to a person who needs it is carried out within 24 hours to 72 hours after the manifestation of symptoms of a betacoronavirus infection in a person.

According to some variants of the implementation of the useful model, a person in need of it is administered a drug made in a dosage form intended for oral, parenteral or inhalation administration.

According to still other variants of the implementation of the useful model, a person in need of it is administered a medicine made in a solid dosage form, a semi-solid dosage form, a soft dosage form, a liquid dosage form, or a dosage form for inhalation.

According to one of the variants of the implementation of the useful model, a person who needs it is administered a medicinal product made in a dosage form.

According to another variant of the implementation of the useful model, a person in need of it is administered a medicinal product made in undosed dosage form.

According to one of the variants of the implementation of the useful model, the administration of the medicinal product to a person in need is carried out on an empty stomach with water.

According to another embodiment of the useful model, the administration of the medicinal product to a person in need is carried out before eating a meal with a high fat content.

According to some variants of the implementation of the useful model, the ratio of the chemical compound of the structural formula (1) and the chemical compound of the structural formula (2) in the medicinal product is from 70:30 to 95:5 parts by mass.

According to some variants of the implementation of the useful model, a person in need of it is administered a medicine that is made in a dosage dosage form and contains from 1 mg to 5 mg of an active pharmaceutical ingredient in a unit dosage dosage form.

According to other variants of the implementation of the useful model, a person in need of it is administered a medicinal product made in a dosage dosage form and containing 3 mg of the active pharmaceutical ingredient in a unit of dosage dosage form.

According to one embodiment of the utility model, the medicine is administered to a person in need by a medical professional.

According to another embodiment of the useful model, a person takes the medicine independently.

According to one variant of the implementation of the useful model, the betacoronavirus infection is the coronavirus disease KOVID-19.

The active pharmaceutical ingredient in the method according to the useful model is the drug ivermectin, which is a mixture of the chemical compound of the structural formula (1) and the chemical compound of the structural formula (2). and | shi

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Ivermectin is a white to yellowish crystalline powder, practically insoluble in water, well soluble in methanol, 95% ethanol and acetone.

After oral administration, ivermectin reaches the average concentration in the blood plasma after about 4 hours. Ivermectin is in the liver, and is excreted unchanged or as metabolites in the feces for about 12 days.

Ivermectin is an antiviral agent with a potentially broad spectrum of action. Ivermectin significantly inhibits the accumulation of integrase, non-structural proteins of the virus and large tumor antigen in the nucleus of human cells due to the inhibition of transport dependent on

Itra/B1. In general, ivermectin reduces the accumulation of all cargo proteins in the nucleus of human cells that contain the cellular signal of intranuclear localization, which is recognized by Itra/B1, which accounts for the broad spectrum of antiviral activity of ivermectin, since nuclear transport of viral proteins is critically important for many RNA viruses.

The authors of this utility model unexpectedly discovered that ivermectin exhibits activity against betacoronavirus pathogens such as the BZAK5-Soum-2 virus and can be used in methods for the treatment of people suffering from such betacoronavirus infections as

SOMIUO-19.

The terms "person in need of treatment", "person in need" should be understood, unless otherwise specified, as a person suffering from a certain disease. According to the essence of this useful model, a person who needs treatment is a person who is sick with a betacoronavirus infection, in particular, in whom distinctive signs and symptoms of a betacoronavirus infection (at least two) were recorded, and/or in whom the causative agent was detected by one or more diagnostic methods betacoronavirus infection.

The term "drug" should be understood, unless otherwise specified, to mean a single chemical compound or a mixture of chemical compounds, at least one of which is an active pharmaceutical ingredient.

According to the essence of this useful model, the API is capable of showing activity against the causative agents of betacoronavirus infections. According to the essence of this utility model, the drug can be ivermectin or a mixture of ivermectin and at least one pharmaceutically acceptable active or excipient.

The method of treatment of betacoronavirus infection according to a useful model is carried out in such a way that a person in need of it is administered a drug embodied in a pharmaceutically acceptable dosed or undosed dosage form that, as an API, contains ivermectin in an amount necessary to achieve a therapeutically effective concentration of ivermectin in human blood plasma.

The authors of this useful model, as a result of conducting practical research, found that the administration of a medicinal product in a dosage dosage form containing from 1 mg to 5 mg of ivermectin to a person in need of treatment, preferably with 3 mg of ivermectin in a dosage dosage unit, allows to ensure the optimal concentration indicator

APfI in human blood plasma, necessary for the manifestation of antiviral activity of ivermectin against causative agents of betacoronavirus infections, e.g. 5 AKZ-Sou-2. As a result of research, it was established that the concentration of ivermectin in human blood plasma should be in the range of values from 3 to 100 ng/ml. This range is optimal, and is therapeutically effective for SOMI-19 cases, which can be individual, depending on the severity of the disease and the general condition of the person.

For greater effectiveness of the claimed method of treatment, it is suggested to start the process of treating the patient as soon as possible, preferably within the first 72 hours after diagnosing a person with a coronavirus infection and/or showing symptoms of a betacoronavirus infection (at least two). The further scheme of treatment is determined by a medical specialist on the basis of individual indicators of the state of each individual person and features of the course of the disease.

According to the essence of the utility model, the method of treatment may involve administering to a person in need of drugs embodied in various dosage forms to provide

From the maximum therapeutic effect and safety in each specific case of the disease. In particular, the medicine can be made in a dosed dosage form or undosed dosage form, as well as in a solid dosage form, a semi-solid dosage form, a soft dosage form and / or a dosage form for inhalation. Thus, liquid dosage forms, according to the method according to the useful model, include solutions for infusion or injection, syrups, drops, etc. Semi-solid dosage forms, according to the method according to the useful model, include gels, creams, ointments, liniments, pastes, suppositories, plasters, transdermal and film therapeutic systems, film-forming and foam therapeutic systems, etc. Solid dosage forms, according to the method according to the useful model, include tablets, capsules, dragees, pills, lollipops, etc. Dosage forms for inhalation, according to the method according to the useful model, include solutions, suspensions, emulsions and powders for inhalation systems (dosed aerosol inhalers, powder inhalers, nebulizers and spacers).

Reception of the medicinal product, according to the method according to the useful model, embodied in a dosage form for oral use can be carried out on an empty stomach or immediately before eating. In particular, the introduction of the medicinal product before eating a meal with a large amount of fat allows you to significantly increase the bioavailability of ivermectin (given the chemical structure of the compound, because ivermectin practically does not dissolve in water). One or another preferred method of administering a medicinal product to a person in need of treatment is determined by a medical specialist, according to the person's individual needs for treatment.

The drug, according to the method of the utility model, can be prepared using pharmaceutically acceptable excipients, such as carriers, fillers, excipients, propellants, glidants, wetting agents, lubricating agents, binding agents, disintegrating agents, thickeners, stabilizers , solubilizers, extenders, preservatives, pH regulators, surface-active substances, taste correctors, odor correctors, dyes, pigments, which ensure the delivery of ivermectin to the human body at a level sufficient for the manifestation of antiviral activity against the causative agents of betacoronavirus infections.

A number of preclinical and clinical studies were conducted to prove the effectiveness of the method of treating betacoronavirus infection using a useful model. Some of the results of these studies are presented below, but these results are not exhaustive, as research is currently (516) still ongoing.

EXAMPLE 1

Study of the antiviral effectiveness of the method according to a useful model.

Human neck adenocarcinoma cells were cultured in Dulbecco's modified Eagle's medium, which contained 10 95 vol. fetal bovine serum, 1 mM I-glutamate, 1 mM penicillin/streptomycin and 20 mM HEPES, at 37 "C in 595 CO". 24 hours before transfection, cells were seeded on coverslips. Recombinant proteins were expressed in the cells, which contained cellular intranuclear localization signals recognized by different types of importins 1 h before microscopic analysis, cells were treated with ivermectin at a final concentration of 25 μM for 1 h or left untreated.

The results of the study showed that ivermectin inhibited only human cytomegalovirus and TSI 54 polymerase, which contained cellular signals of intranuclear localization recognized by importins Itra/B1. At the same time, no effect was found on the sex-determining factor, peptide related to parathyroid hormone, histone H2B and thyrotropin-releasing hormone, which are transported into the nucleus using only Ytrp1. Similarly, no effect is observed on BIMO-conjugating enzyme, which is transported by Ytr13.

Thus, the results of the study showed that ivermectin inhibits nuclear transport mediated by Itra/B1 and may be effective against RnNKC viruses that are transported by Itra/p1. Therefore, the method according to the useful model is effective for the treatment of human RNA viruses used by Itra/B1.

EXAMPLE 2

A preclinical study was conducted to determine the effectiveness of the method based on a useful model in suppressing the causative agent of the SOMIO-19 coronavirus disease.

Mego/15I AM cells were cultured in minimally enriched medium containing 7 95 fetal bovine serum, 2 mM I-glutamine, 1 mM sodium pyruvate, 1500 mg/L sodium bicarbonate, 15 mM HEPES, and 0.4 mg/mL geneticin, at 37 "С and 5595 СО". 24 hours before infection with 5АК5З-СоМ-2 cells were seeded in a 12-well plate for tissue cultures.

Infection occurred in an infectious environment for 2 hours. The medium containing the seed culture was removed and replaced with 1 ml of fresh medium containing the active pharmaceutical ingredient at a concentration of 5 µM, DMSO medium and incubated

From within 0-3 days. At the given time, the cell supernatant was collected and centrifuged for 10 min. The supernatant obtained after centrifugation was collected in tubes for analysis. Cell monolayers were collected by scraping and re-dispersed in 1 ml of fresh medium. The effectiveness of ivermectin was determined in the supernatant and cell sediment by the rate of replication of ZAKZ-CoU-2 RNA by polymerase chain reaction with reverse transcription. The control was Mego/15I AM cells infected with ZAK5-SouM-2, which were treated with DMSO.

On day 0, the amount of viral RNA in the supernatant and cell pellet was 100 95.

On day 1, the amount of viral RNA in the supernatant was approximately 8 95, and in the cell sediment - approximately 0.2 95. That is, after 24 hours, almost complete destruction of the pathogen SOMIO-19 was observed. On subsequent days of the study, the amount of viral RNA in the supernatant and cell sediment was no more than 0.01 95 of the initial amount.

Thus, the method according to the useful model, successfully destroys clinically isolated ZAKZ-SomM-2 ip miito.

EXAMPLE Z

A multicenter, observational, pseudorandomized case-control study was conducted by prospectively selecting data from people diagnosed with SOMIO-19.

SOMIO-19 was diagnosed by high-throughput sequencing or real-time reverse transcription-polymerase chain reaction analysis of nasal or pharyngeal swab samples. The result of a person's treatment is discharge from the hospital, successful hospitalization or death during hospitalization. Individuals with a confirmed diagnosis of SOMIA-19 were selected for the study, for the treatment of which a drug was used, according to the method according to the utility model, in the form of an uncoated tablet, containing as an active pharmaceutical ingredient a mixture of a chemical compound of the structural formula (1) and a chemical compound of the structural formula formula (2) (ivermectin) in the amount of 3 mg in one tablet. The drug, according to the method according to the utility model, also contained such auxiliary components as polyvinyl polypyrrolidone, corn starch, magnesium stearate, sodium carboxymethyl cellulose, butylated hydroxyanisole and a flavoring agent. For each person who received the drug according to the method according to the useful model, a suitable control was selected (a person with a diagnosis of coronavirus infection who was not treated according to the method according to the useful model).

The analysis was carried out on the basis of data for 1408 hospitalized people diagnosed with SOMI-19, of which 704 people took the drug in an average daily amount of 125 μg per 1 kg of human weight (group 1), and 704 people who received treatment according to the established protocol for the treatment of SOMIO-19 using hydroxychloroquine (2nd group).

The main measure of effectiveness was the ratio of people who died in both groups.

At the same time, each group was divided into two subgroups: a) persons who received artificial lung ventilation, b) persons who did not receive artificial lung ventilation.

The results of the analysis revealed that the total mortality is lower in the 1st group, which took the drug according to the studied treatment method (1.4 95), compared to the 2nd group, which did not take the indicated composition (8.5 95). At the same time, in the subgroups that required artificial ventilation, death was recorded in 7.3 95 (group 1) and 21.3 95 people (group 2).

Thus, the method of treating betacoronavirus infection according to a useful model contributes to a statistically significant reduction in mortality in patients with SOMIO-19, compared to those individuals who received treatment according to the established protocol for the treatment of SOMIO-19.

The following examples are intended to illustrate the utility model only and are not intended to limit the utility model in any way.

The implementation of the useful model allows to achieve the following technical result: - Effective and safe treatment of betacoronavirus infection when applying the method according to the useful model; - The possibility of clinical and non-clinical treatment of betacoronavirus infection, which further facilitates and simplifies the treatment regimen for people with a mild and moderate degree of the disease; - Reduction of mortality among patients with betacoronavirus infection, in particular among people who need artificial ventilation of the lungs, when applying the method according to the useful model; - Reducing the burden on the health care system and medical institutions due to the possibility of using a method based on a useful model for non-clinical treatment, as well as successful treatment and reducing the mortality of hospitalized people.

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Claims (13)

USEFUL MODEL FORMULA 1. The method of treating betacoronavirus infection, which consists in the fact that a pharmaceutical composition is administered to a person in need at least at one stage of treatment, which is characterized by the fact that the pharmaceutical composition contains as an active pharmaceutical ingredient a mixture of a chemical compound of the structural formula (1) and a chemical compounds of structural formula (2): tek I St Y M x X. xx . and she your ode she s ren and bod du same St. - t what and : ! from Osy mon: gentlemen I 5-4 TE () still - I I shk No ZK it and fe ri Y she |y 1 Y ' Go" She I taltayeti o t Z NI ! - Os - on: aa Olyu (2 what and contains at least one pharmaceutically acceptable auxiliary ingredient, wherein the stage of treatment in which the human is administered the pharmaceutical composition is determined by the manifestation in the human of at least two of the following symptoms of betacoronavirus infection such as fever, fatigue, cough of various types, loss of appetite, change or loss sense of taste and smell, shortness of breath, sputum discharge, general malaise, confusion, headache, muscle pain, sore throat, expectoration of blood, sputum discharge, difficulty breathing, runny nose, diarrhea, nausea, vomiting, symptoms of gastroenteritis , symptoms of pneumonia, symptoms of a respiratory infection of varying degrees of severity, symptoms of respiratory distress syndrome, respiratory failure, symptoms of sepsis or septic shock, or when a person is diagnosed with the causative agent of betacoronavirus and other infection, while a person is administered a pharmaceutical composition in the amount necessary to reach the concentration of the active pharmaceutical ingredient in the human blood plasma from 3 to 100 ng/ml. 2. The method according to claim 1, which is characterized by the fact that the introduction of the pharmaceutical composition is carried out within 24 hours to 72 hours after the manifestation of symptoms of betacoronavirus infection in a person. 3. The method according to any of items 1, 2, which is characterized by the fact that the introduction of the pharmaceutical composition is carried out on an empty stomach with water. 4. The method according to any of items 1, 2, which is characterized by the fact that the introduction of the pharmaceutical composition is carried out before eating food with a high fat content. 5. The method according to any of items 1-4, which is characterized by the fact that the ratio of the chemical compound of the structural formula (1) and the chemical compound of the structural formula (2) is from 70:30 to 95:5 parts by mass. b. The method according to claim 5, which differs in that the ratio of the chemical compound of the structural formula (1) and the chemical compound of the structural formula (2) is from 80:20 to 90:10 parts by mass. 7. The method according to any of items 1-6, which is characterized by the fact that a person in need of it is administered a pharmaceutical composition made in a solid dosage form, a semi-solid dosage form, a soft dosage form, a liquid dosage form or a dosage form form for 3 inhalations. 8. The method according to claim 7, which is characterized by the fact that a person in need of it is administered a pharmaceutical composition made in a dosage form. 9. The method according to claim 7, which is characterized by the fact that a person in need of it is administered a pharmaceutical composition made in undosed dosage form. 10. The method according to any one of points 8, 9, which is characterized by the fact that the person in need is administered a pharmaceutical composition made in a dosage form intended for oral, parenteral or inhalation administration. 11. The method according to claim 8, which is characterized by the fact that the person who needs it is administered a pharmaceutical composition made in a dosage dosage form, containing from 1 mg to 5 mg of an active pharmaceutical ingredient in a unit dosage dosage form. 12. The method according to claim 11, which is characterized by the fact that a person in need of it is administered a pharmaceutical composition made in a dosage dosage form containing 3 mg of an active pharmaceutical ingredient in a dosage dosage form unit. 13. The method according to any of items 1-13, which is characterized by the fact that the betacoronavirus infection is COVID-19.