RU2749968C2 - Method for viral infection control - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine, namely to virology, and can be used to treat herpesvirus infection. To do this, an antiviral drug is applied topically to the target surfaces, including benzydamine hydrochloride with a concentration of benzydamine hydrochloride on the target surface of at least 10 μg /ml.EFFECT: invention makes it possible to increase the effectiveness of herpesvirus infection treatment while reducing the treatment duration and preventing relapses due to the additional anti-inflammatory, analgesic, antibacterial and antifungal effects of benzidamine hydrochloride.6 cl, 4 ex

Description

The field to which the invention relates

The invention relates to medicine, veterinary medicine, agriculture and can be used for the prevention, treatment, prevention of clinical manifestations of viral infections of various origins when using benzydamine hydrochloride in various forms. The method can be especially effective in the treatment of herpesvirus infections, influenza virus, cytomegalovirus infection.

State of the art

In 2009, the World Health Organization (WHO) website published the first report of an outbreak in Mexico and the United States of a new variant of influenza A (H1N1), which was associated with higher mortality than seasonal influenza. In addition, there was an older age of patients compared to the traditional age of children and adolescents who suffer from seasonal flu [1].

The gateway for influenza viruses is the epithelium of the respiratory tract. Infection with the flu occurs through coughing, sneezing, close contact with the sick person. Outbreaks of the disease most often occur in organized groups - kindergartens, schools, military contingents, at work. The usual classic flu develops rapidly, the incubation period ranges from several hours to three days (usually 1-2 days). Symptoms of intoxication instantly increase - weakness, headache, pain in muscles, joints, cramps in the eyes. Then the symptoms of respiratory tract damage join - cough, sore throat, nasal congestion.

Herpes simplex viruses (HSV), including herpes types 1 and 2, are widespread in the human population and can cause a number of conditions in the human body, ranging from asymptomatic forms to severe generalized forms of the disease [2]. The reason for this clinical variation is, on the one hand, the genetic predisposition to HSV infection and the state of the human immune system, on the other hand, the properties of the virus. The most common forms of herpes infection are lesions of the skin and mucous membranes (herpes labialis, herpes genitalis, herpesvirus stomatitis), the treatment of which causes significant difficulties. One of the reasons for the ineffectiveness of therapy is the formation of HSV strains with altered properties that are resistant to traditional methods of treatment and drugs [2].

Traditionally, local agents in various dosage forms are used to prevent complications and improve clinical symptoms.

Such local agents used in the infectious and inflammatory process of various etiologies include hexethidine, benzyldimethyl [3- (myristoylamino) propyl] ammonium chloride monohydrate, cetylpyridinium chloride and others [3]. However, their use has a number of disadvantages, in particular, they have only an antiseptic effect against viruses, but do not have their own anti-inflammatory, analgesic effect. In this case, anesthetics are added to them, relieving only pain, discomfort and other symptoms of inflammation, on the inflammatory process itself, respectively, without affecting.

In addition, the local antiviral action of these agents also has a number of important features. In particular, the antiviral effect of hexetidine in vitro was previously shown; this agent neutralized the herpes simplex virus while it was only on the cell surface. In this case, as a rule, clinical symptoms and the spread of a viral infection are associated with the penetration of the virus inside the cell, for the replication process. In the course of this study, it was shown that hexetidine does not affect the replication of the herpes simplex virus, and therefore does not stop its process of reproduction and spread of its copies [4].

Another local remedy used for many local infectious and inflammatory processes and having only antiseptic properties is benzyldimethyl [3- (myristoylamino) propyl] ammonium chloride monohydrate. Also, in the course of in vitro studies, its antiviral properties against H3N2, H5N1 viruses are declared. In the course of this study, data were also obtained that after infection with a virus of a cell, after 12 hours, this agent did not limit the effect of the virus [5].

Cetylpyridinium chloride is also widely used in Russia and worldwide. It is noted for its antiviral action against H3N2 and several H1N1 strains. The results indicate an increase in the life and survival of cells infected with the virus after the use of cetylpyridinium chloride. However, this agent has been studied only in relation to the influenza virus, as there is information in the publication and patent, and the effect on herpes simplex viruses is not known. In addition, this agent does not have its own anti-inflammatory and analgesic properties [6].

гидрохлорид - лекарственное средство, обладающее сразу несколькими фармакодинамическими свойствами: антибактериальным и фунгицидным, обезболивающим, противовоспалительным (см. например, патенты RU 2695217, RU 2410123). Это принципиально отличает данное средство от других, применяемых при схожих показаниях, с заявленными in vitro антимикиробными свойствами, так как бензидамин влияет на уровень медиаторов воспаления, что останавливает воспалительный процесс, снижая риск развития опасных осложнений, например, абсцессов, паратонзиллитов, при этом оказывая местное обезболивание. В итоге вместо нескольких средств используется одно.

hydrochloride is a drug that has several pharmacodynamic properties at once: antibacterial and fungicidal, analgesic, anti-inflammatory (see, for example, patents RU 2695217, RU 2410123). This fundamentally distinguishes this drug from others used for similar indications, with declared in vitro antimicrobial properties, since benzydamine affects the level of inflammatory mediators, which stops the inflammatory process, reducing the risk of developing dangerous complications, for example, abscesses, paratonsillitis, while providing local anesthesia. As a result, instead of several means, one is used.

In addition, the benzydamine molecule also has serious pharmacokinetic advantages, in particular, it penetrates better into the inflammation focus, where infection and inflammation products are directly concentrated, in comparison with hexetidine, benzyldimethyl [3- (myristoylamino) propyl] ammonium chloride monohydrate, cetylpyridinium chloride and other analogous means.

This is reflected in the safety profile, since the other listed agents are combined with symptomatic agents, and by the combination of contraindications and side effects, they carry greater risks compared to benzydamine.

The antiseptic effect of benzydamine has been studied in in vitro studies using several different types of culture media and a variety of microorganisms. Benzydamine inhibited various bacteria and fungi in culture media infected with the studied microorganisms. In these experiments, benzydamine inhibited gram-positive and gram-negative cocci, gram-negative bacilli, yeasts, and other fungi. Until now, the antiseptic antiviral effect of benzydamine has not been studied.

RF patent No. 2410123 discloses a composition for the prevention of viral infection by topical application, comprising antiviral agents and benzydamine hydrochloride used as an exclusively anti-inflammatory agent. This composition is impregnated with wipes that are used on targeted areas of the skin and mucous membranes. The wipes to a greater extent limit the penetration of viruses from the external environment onto the surface areas, while due to the creation of insignificant and unstable concentrations of antiviral agents over time, they do not affect the viral load in the subcutaneous tissue layers.

They can be used only on open surfaces, which limits their use in the most frequent sites of herpesvirus infection: the mucous membrane of the oral cavity and the border of the lips, nose and conjunctiva of the eyes, as well as the mucous membranes of the genital organs [7].

Wipes as a drug carrier involves the creation of conditions for the retention of the drug in its structure, which means a slower release of the drug, compared to a solution applied to a surface or a gel, ointment or cream form, which is evenly and faster distributed on the outer surfaces, which determines an increase the rate of creation of the maximum concentration of the substance on the surface.

Biological creatures with wound surfaces, including as a manifestation of a viral infection, lose their normal sensitivity. Thus, additional contact of the napkin with the wound surface can lead to discomfort and discomfort.

According to the conditions of their antimicrobial action, wipes must be constantly wet while they are on the surface, which creates difficulties with prolonged use, as well as the lack of control over the incoming concentration of active substances. That is, in the case of applying a cream, ointment, gel, it is possible to calculate, albeit with an error, the amount of the agent applied to the surface area in grams, which prevents the creation of ineffective concentrations of active substances on the surface. The lack of timely moistening of the napkin leads to a change in its physical properties, namely, it becomes hard and dries to the wound.

For a uniform long exposure of the napkin on the surface, it is necessary to use special additional fixing means, for example, bandages or a plaster.

With a reduction in the residual amount of an active antiviral substance, wipes can be a factor in the absorption of microbes, which will accelerate their colonization on the surface and unwanted secondary infection of an already affected area, which can aggravate the condition.

In order to increase the effectiveness of the antiviral and anti-inflammatory action on skin surfaces, including wound surfaces, in addition to forms of solutions, creams, gels and ointments, it is proposed to use benzydamine, as well as benzydamine in combination with other substances that have an excellent mechanism of action or enhance the effect of benzydamine in the form of medical patches or transdermal patches. Unlike wipes, this type of carriers of an active substance or a combination of active substances allows them to be delivered not only to the skin and to the subcutaneous tissues, where the inflammatory focus is usually concentrated.

The essence of the invention

Thus, there was a need to solve the problem of combating a localized viral infection, eliminating its clinical symptoms, as well as eliminating the disadvantages characteristic of known methods of combating localized viral infection.

The objective of the invention is to create a method of combating a viral infection that would reliably and in a short time exert a local suppressive effect on viruses, while having its own anti-inflammatory effect and having pharmacokinetic parameters that would allow it to penetrate into the focus of inflammation. In addition, it had its own analgesic effect, since the clinical manifestation of a viral infection is often combined with pain and other discomfort, for example, a sore throat with a flu-like viral infection, as well as inflammatory skin phenomena and pain with a herpesvirus infection.

For the first time, the inventors discovered the antiviral effect of benzydamine hydrochloride and were able to develop a method to combat viral infection using a monopreparation that has antiviral, antibacterial, antifungal, anti-inflammatory and analgesic effects.

The technical result, which is achieved by the invention, consists in providing a reliable and effective treatment of a localized viral infection, combining anti-inflammatory, analgesic, antibacterial and antifungal effects, while not causing unwanted systemic reactions of the body.

An additional technical result is to increase the local antimicrobial action.

An additional technical result is to reduce the severity and duration of symptoms caused by various viral infections.

An additional technical result consists in the reduction of the treatment time, the convenience of the treatment, and the prevention of disease recurrence.

An additional technical result consists in the possibility of combined topical application of benzydamine with other antiviral agents.

An additional technical result consists in the possibility of combined topical application of benzydamine with other anti-inflammatory and antimicrobial agents.

An additional technical result consists in the possibility of using benzydamine as the main active ingredient, or as an additional active ingredient in various dosage forms for topical use: dosed, non-dosed, mixed type, solid, soft, liquid, gaseous.

The task is solved, and the achievement of the technical result is ensured by the fact that in the method of combating respiratory viruses, viruses that infect the skin and mucous membranes, including the local application of an antiviral drug to target surfaces, benzydamine hydrochloride is used as an antiviral drug.

An additional technical result is provided by the fact that the preparation, in addition to benzydamine hydrochloride, includes antimicrobial agents.

An additional technical result is provided by the fact that the preparation, in addition to benzydamine hydrochloride, includes anti-inflammatory agents.

An additional technical result is achieved due to the fact that benzydamine hydrochloride is used in solid, soft, liquid or gaseous form, with a final concentration of benzydamine hydrochloride on the target surface of at least 10.0 μg / ml.

An additional technical result is provided by the fact that a solution of benzydamine hydrochloride is sprayed onto the surface of the respiratory tract or the surface of the mucous membrane. Benzydamine hydrochloride is applied to the surface of the skin and mucous membranes with an applicator. Benzidamian hydrochloride is used in powder form.

Benzydamine hydrochloride is known to have anti-inflammatory, analgesic, antibacterial and antifungal properties. The inventors have proven its antiviral effect against several viruses at once - the influenza virus and herpes simplex viruses, and also confirmed the possibility of its use to fight viruses as a mono-agent.

The antiviral effect against the H1N1 influenza virus was determined using a standardized method. Antiviral activity was assessed by monitoring viral reproduction in MDCK tissue culture cells. For these purposes, the method of enzyme-linked immunosorbent assay (ELISA) was applied. The panels were incubated in a CO2 incubator for 24 hours at 37 ° C. After incubation, the cells were fixed with 80% acetone in phosphate buffer for ELISA, carrying out sequential adsorption of specific reagents - monoclonal antibodies, conjugate, and substrate (tetramethylbenzidine). The reaction was taken into account by optical density (OD) at 450 nM on a spectrophotometer manufactured by Biotek, Synergy NT.

Each virus dilution was examined in 6 replicates, so the average optical density was calculated. The percentage inhibition was defined as the ratio between the difference between the OD of the experiment and the OD of the cell control divided by the difference between the OD of the viral control and the OD of the cell control, multiplied by 100%. The minimum concentration of a substance (compound) that suppresses the activity of the virus by 50.0% (IC50) was also calculated.

MDCK cells, grown in 96-well panels to a complete monolayer, were washed from the growth medium, after which the test substance was added to the monolayer at 6 selected concentrations in six repeat wells in a mode simultaneously with cell infection. After introducing the test substance into the corresponding rows, the virus dilutions were added at working doses of 100-1000 TCID50 / ml.

In the mode of assessing the prophylactic effect of the substance Benzydamine, the drug in 6 selected concentrations was introduced into six repeat wells two hours after infection of the cells with virus dilutions at working doses of 100-1000 TCID50 / ml. To study the specific activity of the drug to suppress viral reproduction in the MDCK cell culture, concentrations of 0.5; 1.0; 2.5; 5.0; 7.5 and 10.0 μg / ml.

A series of experiments was carried out to achieve average values of the drug activity when the drug was added simultaneously with cell infection and two hours after cell infection with two doses of influenza virus, which amounted to 100-1000 TCID50 / ml.

As a result, at a concentration of only 10 μg / ml benzydamine (finished local dosage forms contain from 900 μg / ml) with the simultaneous administration of the virus and the agent per cell, the percentage of suppression of the reproduction of the influenza virus was 97.7%. When benzydamine was introduced at the same concentration of 10 μg / ml 2 hours after infection, the percentage of suppression of the reproduction of the influenza virus was also high, and amounted to 78%. Thus, with the simultaneous administration of the virus and benzydamine, the IC50 (μg / ml) is 1.4, the IC50 (μg / ml) 2 hours after infection is 4.2.

Antiviral action against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) was carried out in accordance with the requirements of the Pharmacological State Committee of the Russian Federation for experimental (preclinical) study of new pharmacological substances. For this, the substance benzydamine was used and its antiviral activity against herpesvirus infection caused by HSV-1, HSV-2 in a VERO-B cell culture was studied. The system for assessing the antiviral action of Benzydamine in cell culture included the study of the suppression of the cytopathic effect of the virus (HSV-1, HSV-2) in the cell culture (cytopathic effect (CPE) reduction assay), as well as the effect on the reproduction of the virus (HSV-1, HSV -2) in cell culture.

A one-day monolayer of cell culture was used in the work. The lysate of an infected HSV-1 or HSV-2 culture of VERO-B cells with a biological activity of 6.0 ± 0.5 lg TCID50 / 0D ml and 5.62 ± 0.3 lg TCID50 / 0.1 ml was used as an infectious drug, respectively. VERO-B cells were infected with a single dose of the virus at the rate of 100 TCID50 per monolayer. The study of the antiviral activity of benzydamine was carried out according to the classical scheme - 1 hour after infection.

Experiments were accompanied by appropriate controls. As a positive control, cell cultures infected with test viruses were used, to which a support medium without the drug was added, as a positive control of virus inhibition, cell cultures infected with test viruses, to which acyclovir was added as part of a support medium 1 hour after infection.

As a negative control, non-infected cell cultures were used, to which a maintenance medium without preparation was added; as a negative control of cytotoxicity, non-infected cell cultures, into which various concentrations of benzydamine were added as part of the support medium.

The results were taken into account when the level of accumulation of test viruses in the control samples reached a maximum and a pronounced (100%) CPP was noted.

The virus inhibiting effect of the drug was assessed according to generally accepted indicators - a decrease in the level of virus accumulation under the influence of the drug (Δ, lg) and the inhibition coefficient (Ki,%). The chemotherapeutic index (CTI) was calculated as the ratio of CTK50 to the minimum effective virus inhibitory concentration, which, according to regulatory requirements, reduces HSV-1 / -2 titers by at least 1.5 lg TCID50.

As a result, the maximum statistically significant decrease in HSV-1 infectious titers by 3.6 lg TCD50 was observed under the influence of benzydamine at a concentration of 62.5 μg / ml (CI-60%), a minimum by 1.5 lg TCD50 at a concentration of 5.0 μg / ml (CI-25%).

The benzydamine concentration of 5.0 μg / ml was considered as the minimum effective virus-inhibiting drug concentration, which, according to regulatory requirements, reduces HSV titers by at least 1.5 lg TCD50. HTI was 16.25.

It should also be noted that the use of benzydamine 1 hour after virus adsorption led to a delayed appearance of virus-mediated CPP in cell culture. If in control cultures infected with HSV-1, incubated in a medium without adding a substance, the appearance of virus-induced CPP was noted already 24 hours after infection, then in cultures infected with HSV-1 incubated in a medium with the addition of benzydamine at concentrations from 5.0 to 50, 0 μg / ml - 48 hours after infection.

Also, the use of benzydamine led to a significant decrease in the reproduction of HSV-2, as evidenced by the indicators of infectious virus titers. The maximum statistically significant decrease in HSV-2 infectious titers by 3.06 lg TCD50 (CI-54.45%) was observed when using the substance at a concentration of 62.5 μg / ml (p <0.05). The minimum decrease by 1.5 lg TCD50 (CI 26.69%) - against the background of the use of the substance at a concentration of 15.75 μg / ml. MIC - 15.75 μg / ml. HTI was 5.15.

For the reference drug acyclovir MIC in relation to HSV-1 was 0.2 μg / ml, CTK50 - 500 μg / ml, CTI - 2500; MIC in relation to HSV-2 was 0.5 μg / ml, CTI - 1000.

Implementation of the invention

As a result of the studies carried out, it was found that benzydamine has antiviral activity against infection caused by the H1N1 influenza virus, HSV-1 / -2, in vitro, both with simultaneous infection with the cell virus and the introduction of benzydamine, and some time after infection. It should be noted separately that the technique was standardized, and a control drug was also used, in particular acyclovir with known antiherpetic properties.

Example 1. To study the antiviral action of benzydamine when it was simultaneously introduced with the H1N1pdm09 influenza virus, its concentration of 10 μg / ml was used. The effectiveness of suppressing the reproduction of the virus was 97.7%.

Example 2. To study the antiviral effect of benzydamine when it was introduced 2 hours after infection with the H1N1pdm09 influenza virus, its concentration of 10 μg / ml was used. The effectiveness of suppressing the reproduction of the virus was 78%.

Example 3. To study the antiviral action of benzydamine when it was introduced 1 hour after infection with HSV-1, its concentration of 62.5 μg / ml was used. The effectiveness of suppressing the reproduction of the virus was 60%.

Example 4. To study the antiviral effect of benzydamine when it was introduced 1 hour after infection with HSV-2, its concentration of 62.5 μg / ml was used. The effectiveness of suppressing the reproduction of the virus was 54.45%.

The minimum concentration of the substance (a compound) which suppresses the activity of influenza virus at 50,0% (IC _50): the following formula was used to calculate the minimum concentration of the substance that suppresses the activity of influenza virus at 50,0% (IC50),.

The calculation of the decrease in the level of accumulation of the virus under the influence of the drug (Δ, lg) was carried out in accordance with the following relationship: The decrease in the level of accumulation of the virus under the influence of the drug (Δ, lg) was determined by the formula 1:

where Ak is the level of accumulation of the virus during cultivation without introducing the studied drug into the nutrient medium (lg TCID50 / 0.1 ml); Ao - the level of accumulation of the virus during cultivation with the introduction of the studied drug into the nutrient medium (lg TCID50 / 0D ml).

The inhibition coefficient (Ki,%) was calculated as follows: The inhibition coefficient (Ki,%) was calculated using the formula:

where Akontr is the level of accumulation of the virus during cultivation without introducing the studied drug into the nutrient medium (lg TCID50 / 0.1 ml);

Aop - the level of accumulation of the virus during cultivation with the introduction of the studied drug into the nutrient medium (lg TCID50 / 0.1 ml).

The drug can be used in several pharmaceutical forms with the following formulation:

Cream for external use, per 100 g:

Benzydamine g / x 3

Water 51

Olive oil 20

Paraffin 15

Stearic acid 5

Tocopherol acetate 1

Polaxamer 40

Ear drops 100 mg:

Benzydamine g / x 20 mg

Glycerin 30 mg

Olive oil 30 mg

Water 20 mg

Solution for use on the mucous surfaces of the respiratory tract, 30 ml:

Benzydamine g / x 45 mg

Glycerol 3 g

Ethanol 6 g

Water 30 ml

As shown by standardized in vitro studies, the invention has the following advantages over the methods currently used in medicine and veterinary medicine for the treatment and prevention of localized viral infection: namely:

Expanding clinical areas for topical application of benzydamine in dosage forms to combat influenza and herpes viruses.

Improving the effectiveness of treatment where local agents with antiviral properties are needed, since benzydamine stops viral replication already in infected cells, which is not available for most similar local agents with declared antiviral properties in vitro.

Improving the effectiveness of treatment where topical antiviral agents are needed, since benzydamine can be used in combination, for example, with acyclovir and other topical antiviral agents.

Increase in overcoming the resistance of resistant viral strains, since benzydamine has shown its activity against the H1N1pdm09 influenza virus strain resistant to rimantadine.

An increase in the clinical significance of the use of benzydamine due to the discovery of antiviral properties, since benzydamine can be more widely used in viral infection, which is accompanied by unpleasant painful sensations, in particular with a sore throat (influenza virus) and pain on the mucous membrane (herpesvirus infection). The use of benzydamine as a local antiviral agent for various viral infections will be combined with a local anesthetic effect, which was previously revealed in benzydamine.

An increase in the clinical significance of the use of benzydamine due to the discovery of antiviral properties, since it is known that benzydamine has local anti-inflammatory properties, and therefore has a positive effect on the attenuation of the local inflammatory process. With herpesvirus infection or sore throat against the background of the influenza virus, an increase in the level of pro-inflammatory cytokines associated with the development of a local inflammatory process is often noted. The use of benzydamine as a local antiviral agent for various viral infections will be combined with a local anti-inflammatory effect, which was previously revealed in benzydamine.

An increase in the clinical significance of the use of benzydamine due to the discovery of antiviral properties, since it is known that benzydamine has local antibacterial and antifungal properties, which means it has a positive effect on the prevention of complications of secondary infection after the action of a viral infection. With herpesvirus infection or with the influenza virus, an increase in the activity of bacterial and fungal infections is often noted, for example, due to the immunosuppressive action of viruses. The use of benzydamine as a local antiviral agent for various viral infections will be combined with a local antibacterial and antifungal effect, which was previously revealed in benzydamine.

An increase in the clinical significance of the use of benzydamine due to the discovery when used in various topical dosage forms (dosed, non-dosed, mixed type, solid, soft, liquid, gaseous) for various viral infections.

Literature

1. World Health Organization, the WHO,

http://www.euro.who.int/ru/health-topics/communicable-diseases/influenza/data-and-statistics/seasonal-influenza-ah1n1-key-issues.

2. Kukhanova M.K., Korovina A.H., Kochetkov C.H. Human herpes simplex virus: life cycle and search for inhibitors. Advances in Biological Chemistry, vol. 54, 2014, p. 457-494.

3. State Register of Medicines of the Russian Federation, www.http: //grls.rosminzdrav.ru.

4. Deryabin P.G., Galegov G.A., Andronova V.A., Botikov A.G. Study of the antiviral properties of Hexoral in vitro against a number of viruses that cause acute respiratory infections and herpes // Bulletin of Experimental Biology and Medicine, 2015; 160 (9): 339.

5. Agafonov A.P. In vitro study of the antiviral properties of Miramistin against influenza virus subtypes H3N2 and H5N1. Antibiotics and chemotherapy. 2005. T. 50, No. 12. P. 911.

6. Popkin DL, Zilka S, Dimaano M, et al. Cetylpyridinium Chloride (CPC) Exhibits Potent, Rapid Activity Against Influenza Viruses in vitro and in vivo. Pathog Immun. 2017; 2 (2): 252-269. doi: 10.20411 / pai.v2i2.200.

7. Dyudune A.D. Herpesvirus infection: modern aspects of clinical presentation, diagnosis and treatment. Clinical immunology. Allergology. Infectology. - 2007. - No. 2, - S. 150-154.

Claims (6)

1. A method of combating herpesvirus infection, including the local application of an antiviral drug to target surfaces, characterized in that the antiviral drug used is a drug comprising benzydamine hydrochloride with a concentration of benzydamine hydrochloride on the target surface of at least 10.0 μg / ml. 2. The method according to claim 1, wherein the antiviral preparation further comprises antimicrobial agents. 3. A method according to claim 1 or 2, characterized in that benzydamine hydrochloride is used in solid, soft, liquid or gaseous form. 4. A method according to claim 3, characterized in that a solution of benzydamine hydrochloride is sprayed onto the surface of the respiratory tract or the surface of the mucous membrane. 5. The method according to claim 3, characterized in that benzydamine hydrochloride is applied to the surface of the skin and mucous membrane with an applicator. 6. The method according to PP. 1 and 2, characterized in that benzydamine hydrochloride is used in powder form.