RU2817652C1 - Use of preparation containing ammonium glycyrrhizinate as active ingredient in anti-inflammatory therapy of polypous rhinosinusitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to anti-inflammatory therapy of polypous rhinosinusitis, namely to application of an oral preparation containing ammonium glycyrrhizinate as an active ingredient in anti-inflammatory therapy of polypous rhinosinusitis.

EFFECT: invention provides a wider range of agents for the anti-inflammatory therapy of polypous rhinosinusitis, the pathogenetic target of which is the effective counteraction to the pro-inflammatory effects of HMGB1, that is clinically determined by reduction of the main symptoms of the disease (congestion, nasal discharge, et cetera), swelling of the nasal mucosa, absence of further growth and/or reduction of the size of polyps, improved control over the course of the disease.

5 cl, 7 tbl, 3 ex, 7 dwg

Description

Technical field

The invention relates to the field of anti-inflammatory therapy for polypous rhinosinusitis, namely to the use of a drug containing ammonium glycyrrhizinate as an active component in anti-inflammatory therapy for polypous rhinosinusitis.

State of the art

Polyposis rhinosinusitis is a multifactorial disease that results from a complex interaction between the host and the environment and multiple mechanisms leading to chronic inflammation. Its feature is a long-term inflammatory state that occurs without an identifiable trigger. Although there are many theories about its etiopathogenesis, the cause of the disease remains unclear [1]. Although Th2-type inflammation is the central characteristic of an active pathological process, since in the Russian Federation in 81.69% the eosinophilic type of nasal polyps is noted, regardless of gender characteristics, climatic conditions, region of residence of patients [2], it is not known what primarily triggers local cytokine production and infiltration of lymphocytes and eosinophils.

When treating patients with polypous rhinosinusitis, it is necessary to take into account two parallel problems: relapse of polyp growth and exacerbation of the chronic inflammatory process, which is accompanied by complaints of increased nasal congestion, the appearance of copious mucopurulent discharge from the nose and its flow down the back wall of the pharynx, and increased unproductive cough [3]. ]. In addition, these patients experience fatigue, sleep disturbances, anxiety and an increased likelihood of developing depression, since the presence of the above symptoms dictates that they need to spend some time visiting medical facilities and undergoing medical activities, such as nasal irrigation. This lost leisure time likely leads to frustration and potential depression, which impairs patients' quality of life [4]. However, there is no connection between the severity of the disease, computed tomography data of the paranasal sinuses (SNS) and endoscopy of the nasal cavity and the level of impairment of quality of life in these patients [5].

To prevent relapse of polyp growth, basic therapy with intranasal glucocorticosteroids is used, methods of targeted treatment with monoclonal antibodies at different levels of pathogenetic links are being developed [6], but at the same time, the problem of exacerbation of polypous rhinosinusitis also requires active resolution. While analyzing outpatient records for the treatment of polypous rhinosinusitis in Moscow, antibiotics were prescribed in 28.2% of cases, of which 73% were from the macrolide group [7]. On the other hand, a Cochrane review on the use of antibiotics in chronic rhinosinusitis found no evidence of their clinical effectiveness [8], and a bacteriological study of nasal discharge during exacerbation of polypous rhinosinusitis reveals representatives of normal flora, and Staphylococcus aureus is the leader among opportunistic flora, with In this case, its amount, as a rule, is also close to normal; accordingly, infectious agents are not the key factors in the occurrence of this condition [3].

Considering the heterogeneity of the disease and the presence of several clinical phenotypes of polypous rhinosinusitis with a proven difference in the inflammatory mechanism in each of them, the search for alternative anti-inflammatory treatments for certain groups of patients is also very significant for clinical practice [7, 9, 10].

From UA 15178 (Kharkiv Medical Academy of Postgraduate Education), 06/15/2006, a method of treating polypous allergic rhinosinusitis in patients with bronchial asthma is known and involves the administration of the drug “Diprospana” with the active ingredient betamethasone through puncture of the maxillary sinus in a volume of 1 ml once every three months in throughout the year.

Proinflammatory cytokines are important factors mediating inflammation and can potentially initiate and maintain nasal mucosal and SNP responses to various triggers [11], they regulate phagocytic activity and arachidonic acid production [12]. The development of polypous rhinosinusitis is a consequence of persistent inflammatory and remodeling processes. Current treatments improve symptoms but do not eliminate the high relapse rate, highlighting the need for specific studies linking new molecular targets, inflammation and nasal mucosal function [6,7].

Alarmins or endokines are a group of endogenous factors that interact with membrane receptors of immune cells after release into the extracellular space, activating an inflammatory response [13]. The pro-inflammatory cytokine amphoterin is classified as a so-called high-mobility group protein B1 (HMGB1) due to its mobility during electrophoresis. It is a protein from the group of nuclear non-histone proteins that are present in the nucleus of all cells and play a key role in maintaining nuclear homeostasis. HMGB1 plays a role in the pathogenesis of chronic inflammatory diseases of the upper respiratory tract (URT), such as allergic rhinitis, chronic rhinosinusitis and polyposis rhinosinusitis, ensuring the survival of eosinophils and a number of other key cells involved in allergic and non-allergic immune disorders of the nasal mucosa and SNP [14]. .

Belonging to the class of “alarmins,” it is involved in recombination, transcription, repair and other key processes that ensure the functioning of DNA in the cell nucleus [15]. Under normal conditions, this protein is located in the cell nucleus, where it performs certain structural and metabolic tasks; upon extracellular release, it becomes an activator of innate immunity and a powerful inflammatory factor [16].

The main components of the innate immune system are cellular elements (monocytes, macrophages, antigen presenting cells, NK cells) and various pattern recognition receptors (PRRs, pattern recognition receptors), including Toll-like receptors (TLRs) [17]. Under the influence of certain triggers, which include infectious agents, allergens, endogenous peptides released from damaged cells, proinflammatory cytokines are released [18]. The initial phase of HMGB1 secretion by epithelial cells, monocytes or macrophages requires a signal in the form of lipopolysaccharides, interleukin (IL)-1 or tumor necrosis factor (TNF, tumor necrosis factor)-α. A component of the outer membrane of gram-negative bacteria, lipopolysaccharide is involved in the interaction and activation of immune cells, in which it moves nuclear HMGB1 into the cytoplasm and extracellular space, which causes activation, proliferation and release of cytokines involved in subsequent stages of the pathogenesis of polyposis rhinosinusitis [19]. The mechanism of HMGB1 transfer from nuclei to secretory lysosomes, which are special cytoplasmic organelles, is associated with acetylation of specific lysine residues [20]. Next, HMGB1 is located in the cytoplasm with a blocked return to the nucleus and is released into the extracellular environment, where it binds to its receptors for advanced glycation end products (RAGE, receptor for advanced glycation end products), TLR-2, TLR-4 and TLR-9 [21 ,22]. Further, through activation of nuclear factor kB (NF-kB, nuclear factor kappa), amphoterine causes the release of pro-inflammatory mediators, cytokines and chemokines. RAGE is a multiligand type I transmembrane glycoprotein, a member of the immunoglobulin superfamily of cell surface receptors found on smooth muscle cells, macrophages, endothelial cells, and astrocytes. RAGE binds directly to DNA and RNA and promotes their uptake into cells by lowering the immune recognition threshold for TLR9, the major DNA recognition transmembrane signaling receptor [23]. Increased amounts of HMGB1 bind to RAGE receptors expressed by endothelial cells, which promotes the recruitment of eosinophils to the nasal mucosa and SNP, creating conditions for their survival and the release of eosinophil cationic protein and eosinophil basic protein with subsequent damage to the epithelial barrier [24].

Inhibition of HMGB1 may be an effective and innovative therapeutic target for patients with chronic URT diseases. Due to its pathogenetic significance, much effort has been devoted to exploring the possibilities of counteracting the proinflammatory effects of HMGB1. Inhibition of the action of any cytokine, including HMGB1, can be achieved in several ways:

1) Blocking the release of HMGB1 by activated immune cells. But because it inhibits the physiological homeostatic function of the protein in all cells, it can be associated with serious side effects.

2) Blocking of RAGE, TLR2, TLR9 receptors with antagonist drugs. But, due to the fact that these HMGB1 receptors also induce antibacterial activity and other immune effects, this mechanism is also therapeutically disadvantageous.

3) Inactivation of HMGB1, which is the most effective and safe strategy.

Although various drugs have been proposed at the preclinical level, almost none of them have reached clinical application with rare exceptions [25].

The low molecular weight HMGB1 inhibitor glycyrrhizin is a triterpene saponin, consists of one molecule of glycyrrhetinic acid in the form of an aglycone (the active component of the molecule) connected to two molecules of glucuronic acid, and is part of Glycyrrhiza glabra (licorice glabra, licorice smooth, lacryil, licorice) [26] . In structure, it is similar to the phenanthrene part of glucorticosteroids. At the same time, unlike traditional herbal medicine, glycyrrhizin should not be considered as a plant extract, but as a specific chemical compound isolated from the licorice plant. Glycyrrhizin has an anti-inflammatory effect, inhibits the chemotactic and mitogenic function of HMGB1 by binding to their hydrophobic residues, without significantly distorting their secondary structure and without interfering with their DNA binding ability, while interfering with the ability of the HMGB1 protein to bind to its cognate receptors and exert pro-inflammatory and chemotactic effects [ thirty]. Since HMGB1 promotes the survival of eosinophils [31], glycyrrhizin selectively induces their death. In addition, glycyrrhizin has an antiviral effect against human cytomegalovirus, herpes simplex virus, influenza virus, increases the proliferation of lymphocytes, acts as a promoter of late signal transmission by T lymphocytes for the production of IL-2, and through activation of NF-κB enhances the production of IL-2 induced by lipopolysaccharides. 12 macrophages, synthesis of IFN-γ and IL-10 by NK (Natural killer) cells [26]. Glycyrrhizin has an antioxidant effect and significantly reduces reactive oxygen species (ROS) produced by neutrophils in a dose-dependent manner [27,28], the formation of which may cause a more severe course of the disease [29].

There is data on the successful use of the nasal spray “Narivent”, containing dipotassium glycyrrhizinate, for polypous rhinosinusitis in relation to the relief of symptoms of inflammation and nasal congestion. The use of the topical drug “Narivent” led to persistent clinical positive dynamics in the form of a decrease in the severity of nasal congestion, as well as an objective decrease in the content of HMGB1 in the nasal fluid, which was comparable to the effect of treatment with intranasal budesonide [14].

As of today, the data of A.Yu. Ovchinnikov has been published. et al. on the effective use of Reglisam in patients with prolonged rhinosinusitis after SARS-CoV-2 infection. The inclusion of the drug Reglisam in treatment regimens for prolonged rhinosinusitis promotes effective relief of edema and inflammation in the nasal mucosa, improvement of mucociliary transport and drainage of the SNP, which objectively allows by the seventh day of therapy to significantly reduce the severity of local inflammatory symptoms (edema, hyperemia, discharge) and postnasal drip , normalize nasal breathing with minimal use of decongestants, improve the quality of life of this group of patients.

However, the prior art does not know the use of a drug containing ammonium glycyrrhizinate as an active component, in particular the drug Reglisam, in the anti-inflammatory therapy of polypous rhinosinusitis.

Disclosure of the invention

The objective of the claimed invention is to expand the arsenal of drugs for anti-inflammatory therapy of polypous rhinosinusitis, which would be highly effective and accessible.

The technical result of the claimed invention is to expand the arsenal of drugs for anti-inflammatory therapy of polypous rhinosinusitis, the pathogenetic target of which is to effectively counteract the pro-inflammatory effects of HMGB1, which is clinically determined by a decrease in the main symptoms of the disease (stuffiness, nasal discharge, etc.), swelling of the nasal mucosa, the absence of further growth and/or reduction in the size of polyps, increasing control over the course of the disease.

The technical result is achieved through the use of a drug containing ammonium glycyrrhizinate as an active component in the anti-inflammatory therapy of polypous rhinosinusitis.

Glycyrrhizic acid is hydrolyzed in the body to glycyrrhetinic acid, the chemical structure of which is similar to steroid hormones, it can bind to glucocorticoid receptors and has a weak glucocorticoid-like effect [32, 33]. In the course of numerous studies, it was found that the active substance ammonium glycyrrhizinate effectively inactivates the cytokine HMGB1, inhibits transforming growth factor-β (TGF-β, transforming growth factor β)-1 [34], which is involved in the development of tissue fibrosis of nasal polyps, activates the synthesis and promotes the accumulation of extracellular matrix components while simultaneously reducing their destruction by matrix metalloproteinases, and the amount of which is increased in polypous rhinosinusitis [35]. Glycyrrhizin causes a decrease in GATA-3, resulting in a decrease in the number of Th2 and a shift in the Th1/Th2 ratio, which is also important for the treatment of polypous rhinosinusitis. In addition, glycyrrhizin increases the expression level of FoxP3, which is a key marker of T-regulatory lymphocytes. The transcription factor FoxP3 is able to reduce the expression of pro-inflammatory cytokines TNFα, IL-2, IL-17, IFNγ, as well as IgE and IL-4 [36,37], which contributes to regression of the inflammatory process.

In addition, glycyrrhizin has an antioxidant effect and significantly reduces reactive oxygen species (ROS) produced by neutrophils in a dose-dependent manner [20,21], the formation of which may cause a more severe course of the disease [22].

Thus, there are several therapeutic points of application of the active substance ammonium glycyrrhizinate for use in polypous rhinosinusitis, which makes its study and use in this disease relevant.

In particular cases, a drug containing ammonium glycyrrhizinate as an active component is used in solid dosage form, preferably tablets.

The drug Reglisam in a dosage of 50 mg, registered in the Russian Federation, is used in studies as a drug containing ammonium glycyrrhizinate.

This drug in its various dosage forms shows positive results in the treatment of exudative and purulent otitis media [38], bronchial asthma, obstructive bronchitis, pneumonia [39,40,41], acute respiratory tract infections, including COVID-19, allergic rhinitis [42].

This application discloses the use and effectiveness of the drug Reglisam in the complex treatment of exacerbation of polypous rhinosinusitis.

In preferred embodiments, Reglisam is used in combination with intranasal administration of mometasone furoate and irrigation of the nasal mucosa with isotonic saline solution. If necessary, local vasoconstrictors can also be used for no more than 5 days, while the oral drug Reglisam in tablets (50 mg per tablet) is taken daily, 2 tons, 2-3 times a day for 90 days (3 months).

Blueprints

The invention will be more clearly understood from the non-limiting description given with reference to the accompanying drawings, which show:

Figure 1 - Endoscopic picture of the nasal cavity of patient O. (example 1) a - upon admission (before therapy), b - upon admission after 90 days of therapy with the inclusion of the drug Reglisam.

Figure 2 - Dynamics of severity according to the visual analogue scalevisual analogue scale of the main symptoms of polypous rhinosuinusitis of patient O. (example 1).

Figure 3 - Endoscopic picture of the nasal cavity of patient P. (example 2) a - upon admission (before therapy), b - upon admission after 90 days of therapy with the inclusion of the drug Reglisam.

Figure 4 - Dynamics of severity on a visual analogue scalevisual analogue scale of the main symptoms of polypous rhinosuinusitis of patient P. (example 2).

Figure 5 - Dynamics of severity according to the visual analogue scalevisual analogue scale of the main symptoms of polypous rhinosuinusitis.

Figure 6 - Dynamics of the number of patients complaining of various symptoms of polypous rhinosuinusitis against the background of therapy.

Figure 7 - Assessment of the presence and severity on a visual analog scale of edema and mucous discharge according to endoscopy of the nasopharynx over time during therapy.

Carrying out the invention

The use of a drug containing ammonium glycyrrhizinate as an active component in the anti-inflammatory therapy of polypous rhinosinusitis was investigated and illustrated in this application using the example of the use of the oral drug Reglisam in tablets (50 mg per tablet), registered in the Russian Federation.

The drug can be used for the treatment of polypous rhinosinusitis in a comprehensive manner:

- mometasone furoate two doses (100 mcg in 1 dose) twice a day intranasally for 3 months,

- daily irrigation of the nasal mucosa with isotonic saline solution

- if necessary, local vasoconstrictors for no more than 5 days,

- as a systemic anti-inflammatory therapy, the oral drug Reglisam in tablets (50 mg per tablet) daily, 2 tablets 2-3 times a day for 90 days (3 months).

When using a drug containing ammonium glycyrrhizinate as an active component, in particular the drug Reglisam, in the anti-inflammatory therapy of polypous rhinosinusitis, the arsenal of drugs for anti-inflammatory therapy of polypous rhinosinusitis is expanded. Positive clinical dynamics of the symptoms of polypous rhinosinusitis are ensured, a decrease in swelling of the nasal mucosa and mucous discharge, no further growth of polyps and a decrease in the size of existing polyps.

Examples of implementation

Below are examples of the implementation of the claimed invention, confirming the achievement of a technical result in the implementation of the claimed invention, namely, when using a drug containing ammonium glycyrrhizinate as an active component, using the example of the drug Reglisam, in the anti-inflammatory therapy of polypous rhinosinusitis.

Clinical example No. 1 . Patient O., 50 years old,

History of the disease. He considers himself sick since 2012, when he first began to notice congestion and copious mucous discharge from the nose. He was consulted by an otolaryngologist, polypous rhinosinusitis was diagnosed, and in the same year surgical treatment was performed in the scope of FESS (functional endoscopic sinus surgery). A year after the operation, a recurrence of polypous rhinosinusitis occurred; he constantly uses intranasal glucocorticosteroids (InGCS).

In 2019, a lingering cough appeared; an examination revealed bronchial asthma and allergic rhinitis; based on the results of skin prick tests, sensitization to house dust mites was detected, and therefore allergen-specific immunotherapy (ASIT) was recommended, which has not been carried out to date.

Patient observation methodology. At the visits, complaints and objective signs during endoscopic examination of the nasal cavity were assessed using a 4-point visual analogue scale (VAS) (“0” – absent, “1” – slightly expressed, “2” – moderately, “3” – pronounced manifestations), during an endoscopic examination of the nasal cavity, the presence and severity of swelling of the nasal mucosa and the presence of mucous discharge were objectively assessed according to VAS.

On the first visit:

The patient actively complained of symptoms of nasal congestion, nasal discharge/decreased sense of smell, postnasal drip, sleep disturbance, sneezing and coughing. The scores for the initially recorded complaints are presented in Table 1.

Table 1. Initial score of complaints and endoscopy data of patient O. before inclusion of Reglisam in therapy.

Complaints Points Sneezing 2 Nasal congestion 3 Nasal discharge, decreased sense of smell 3 Postnasal drip (feeling of mucus running down the back of the throat) 3 Cough 2 Sleep disturbance 2 Endoscopy Edema 3 Discharge 3 The severity of polypous vegetations 2

Objectively, during endoscopy (Fig. 1a), nasal breathing is moderately difficult, the mucous membrane is edematous and of normal color, polypous vegetations of the 2nd degree are determined on the right and left. The tissue of nasal polyps is edematous and covered with copious mucous discharge. Nasopharynx – without pathological changes. Pharynx - upon pharyngoscopy, the palatine tonsils are intact, the mucous membrane of the posterior wall of the pharynx is slightly hyperemic due to the viscous mucous discharge flowing from the nasopharynx.

Diagnosis: Polypous rhinosinusitis. Allergic rhinitis, persistent form. Sensitization to household allergens. Allergic bronchial asthma.

The patient was prescribed treatment: Reglis, 2 tablets of 50 mg 3 times a day (course - 90 days), mometasone furoate, 2 doses (100 mcg) 2 times a day in each half of the nose, irrigation with isotonic saline solution of the nasal mucosa 3- 4 times a day.

Dynamics after 45 days:

Against the background of the prescribed therapy, by the 45th day of treatment, stable positive dynamics were obtained in the form of regression of the severity according to VAS of the initially recorded main symptoms of the disease: nasal congestion, nasal discharge/decreased sense of smell, postnasal drip, sleep disturbance. Symptoms of sneezing and coughing were completely relieved. Table 2.

Table 2. Score of complaints and endoscopy data of patient O. after 45 days of therapy with the inclusion of the drug Reglisam.

Complaints Points Sneezing 0 Nasal congestion 2 Nasal discharge, decreased sense of smell 1 Postnasal drip (feeling of mucus running down the back of the throat) 1 Cough 0 Sleep disturbance 1 Endoscopy Edema 2 Discharge 2 The severity of polypous vegetations 2

Objectively, during endoscopy of the nasal cavity, positive dynamics are noted in the form of a decrease in swelling of the nasal mucosa and the severity of mucous discharge, polypous vegetations of the 2nd degree are determined. Pharynx - upon pharyngoscopy, the palatine tonsils are intact, the mucous membrane of the posterior pharyngeal wall is clean and normal in color, all inflammatory phenomena have regressed.

During the observation period, the course of therapy with Reglisam was completed in full, no adverse reactions were noted, and no additional conservative treatment was added.

Dynamics after 90 days:

Against the background of the prescribed therapy, by the 90th day of treatment, the symptoms of nasal congestion, postnasal drip and sleep disturbance were only slightly disturbing, the remaining symptoms were completely relieved. Table 3.

Table 3. Score of complaints and endoscopy data patient O. after 90 days of therapy with the inclusion of the drug Reglisam.

Complaints Points Sneezing 0 Nasal congestion 1 Nasal discharge, decreased sense of smell 0 Postnasal drip (feeling of mucus running down the back of the throat) 1 Cough 0 Sleep disturbance 1 Endoscopy Edema 1 Discharge 1 The severity of polypous vegetations 2

Objectively, during endoscopy (Fig. 1b) of the nasal cavity, positive dynamics are noted in the form of a decrease in swelling of the nasal mucosa and the severity of mucous discharge, polypous vegetations of the 2nd degree are determined. Pharynx - upon pharyngoscopy, the palatine tonsils are intact, the mucous membrane of the posterior pharyngeal wall is clean and normal in color.

During the observation period, the course of therapy with Reglisam was completed in full, no adverse reactions were noted, and no additional drugs were prescribed.

The patient has polypous rhinosinusitis, accompanied by respiratory allergies (allergic rhinitis and allergic bronchial asthma). The patient was on constant basic therapy with intranasal corticosteroids. When Reglisam was added to pathogenetic therapy at the end of the course of treatment, there was a complete regression of the main complaints of sneezing, nasal discharge, and cough; a significant reduction in the severity of symptoms of nasal congestion, postnasal drip and sleep disturbances (Figure 2). Positive dynamics were confirmed by endoscopic examination of the nasal cavity.

Clinical example No. 2 . Patient P., 37 years old,

History of the disease. He considers himself sick since 2018, when he first began to notice congestion and copious mucous discharge from the nose. He was consulted by an otolaryngologist, polypous rhinosinusitis was diagnosed, and surgical treatment was performed in 2020, including endoscopic nasal polypotomy. A year after the operation, a recurrence of polypous rhinosinusitis occurred, and he constantly uses InGCS. Since 2016, he has been suffering from non-allergic bronchial asthma.

On the first visit:

The patient actively complained of symptoms of sneezing, nasal congestion, nasal discharge/decreased sense of smell, postnasal drip, cough, and sleep disturbance. The score for the patient’s initially recorded complaints is presented in Table 4.

Table 4. Initial score of complaints and endoscopy data of patient P. before inclusion of Reglisam in therapy.

Complaints Points Sneezing 2 Nasal congestion 3 Nasal discharge, decreased sense of smell 3 Postnasal drip (feeling of mucus running down the back of the throat) 3 Cough 2 Sleep disturbance 2 Endoscopy Edema 3 Discharge 3 The severity of polypous vegetations 3

Objectively, during endoscopy (Fig. 3a), nasal breathing is moderately difficult, the mucous membrane is edematous and of normal color, polypous vegetations of the 3rd degree are determined on the right and left. The tissue of nasal polyps is edematous and covered with copious mucous discharge. Nasopharynx – without pathological changes. Pharynx - upon pharyngoscopy, the palatine tonsils are intact, the mucous membrane of the posterior wall of the pharynx is slightly hyperemic due to the viscous mucous discharge flowing from the nasopharynx. In Fig. 3a on the left, swelling of the mucous membrane is indicated on the nasal septum, change

Diagnosis: Polypous rhinosinusitis. Non-allergic bronchial asthma.

The patient was prescribed treatment: Reglisam 2 tablets 3 times a day (course - 90 days), mometasone furoate spray 2 doses (100 mcg) 2 times a day in each half of the nose, irrigation of the nasal mucosa with isotonic saline solution 3-4 times in a day.

Dynamics after 45 days:

Against the background of prescribed therapy, by the 45th day of treatment, stable positive dynamics were obtained in the form of regression of the severity of the initially recorded main symptoms of the disease according to VAS. Table 5.

Table 5. Score of complaints and endoscopy data of patient P. after 45 days of therapy with the inclusion of the drug Reglisam.

Complaints Points Sneezing 1 Nasal congestion 2 Nasal discharge, decreased sense of smell 2 Postnasal drip (feeling of mucus running down the back of the throat) 2 Cough 1 Sleep disturbance 1 Endoscopy Edema 2 Discharge 2 The severity of polypous vegetations 2

Objectively, during endoscopy of the nasal cavity, positive dynamics are noted in the form of a decrease in swelling of the nasal mucosa and the severity of mucous discharge, polypous vegetations of the 2nd degree are determined. Pharynx - upon pharyngoscopy, the palatine tonsils are intact, the mucous membrane of the posterior pharyngeal wall is clean and normal in color, all inflammatory phenomena have regressed.

During the observation period, the course of therapy with Reglisam was completed in full, no adverse reactions were noted, and no additional drugs were prescribed.

Dynamics after 90 days:

Against the background of the prescribed therapy, by the 90th day the symptoms of nasal congestion and postnasal drip were only slightly disturbing, the remaining symptoms were completely relieved. Table 6.

Table 6. Score of complaints and endoscopy data of patient P. after 90 days of therapy with the inclusion of the drug Reglisam.

Complaints Points Sneezing 0 Nasal congestion 1 Nasal discharge, decreased sense of smell 0 Postnasal drip (feeling of mucus running down the back of the throat) 1 Cough 0 Sleep disturbance 0 Endoscopy Edema 1 Discharge 1 The severity of polypous vegetations 2

Objectively, during endoscopy (Fig. 3b) of the nasal cavity, positive dynamics are noted in the form of a decrease in swelling of the nasal mucosa and the severity of mucous discharge, polypous vegetations of the 2nd degree are determined. Pharynx - upon pharyngoscopy, the palatine tonsils are intact, the mucous membrane of the posterior pharyngeal wall is clean and normal in color.

During the observation period, the course of therapy with Reglisam was completed in full, no adverse reactions were noted, and no additional drugs were prescribed.

Comment: the patient has polypous rhinosinusitis, accompanied by non-allergic asthma. This phenotype of polypous rhinosinusitis is characterized by a more severe course, in contrast to the combination of polypous rhinosinusitis with respiratory allergies. In this case, a decrease in all key clinical signs (Figure 4) and the severity of polyposis vegetations (from 3rd to 2nd degree) indicate a good clinical response to the ongoing anti-inflammatory therapy. Of particular note is the objective reduction in swelling of the nasal polyp tissue during endoscopic examination already at the second visit (45th day of treatment).

Example 3 (with a wide sample).

In the clinical diagnostic department of the State Budgetary Healthcare Institution MONIKI named after. M. F. Vladimirsky for the period from June 2022 to February 2023 observed 33 patients over 18 years of age with a diagnosis of exacerbation of polypous rhinosinusitis in combination with allergic or non-allergic BA. Polypous rhinosinusitis was confirmed using endoscopic examination, data from multislice computed tomography (MSCT) of the SNP and histological examination of the tissue of nasal polyps; BA was confirmed by spirometry; a bronchodilator test was performed according to indications. The allergic examination included collecting an allergic history and performing prick tests with diagnostic water-salt allergens (NPO Microgen) to determine the type of sensitization. Exacerbation of polypous rhinosinusitis was established on the basis of the clinical picture and the results of an endoscopic examination of the nasal cavity (swelling, hyperemia and the presence of mucopurulent discharge on the nasal mucosa). Patients complained of sneezing, nasal congestion, nasal discharge/decreased sense of smell, postnasal drip, headache/facial pain, lacrimation, cough, and sleep disturbance. The criteria for non-inclusion of patients into the study were: suspicion of acute respiratory infection, indications of intolerance/hypersensitivity and contraindications to any components of the study drug; severe, uncontrolled form of arterial hypertension, chronic heart failure; the inability of the study participant to comply with the requirements of the protocol and doctor’s orders; pregnancy and breastfeeding; age under 18 and over 65 years.

All patients were prescribed complex conservative treatment of polypous rhinosinusitis: two doses of mometasone furoate (100 mcg in 1 dose) twice a day intranasally for 3 months, daily irrigation with an isotonic saline solution of the nasal mucosa, and, if necessary, local vasoconstrictors no more than 5 days, as a systemic anti-inflammatory therapy, the oral drug “Reglisam” in tablets (50 mg per tablet) daily in a dosage according to the instructions for use for 90 days (3 months).

The observation period for patients was 90 days (3 months) and included 3 visits: 1st visit (1st day) - start of treatment, 2nd and 3rd visits were carried out on the 45th and 90th days from start therapy accordingly. At the 1st, 2nd and 3rd visits, complaints were assessed (sneezing, nasal congestion, nasal discharge/decreased sense of smell, postnasal drip, headache/facial pain, lacrimation, cough, sleep disturbance) on a 4-point scale visually -analog scale (VAS) (“0” – absent, “1” – slightly expressed, “2” – moderate, “3” – pronounced manifestations), during endoscopic examination of the nasal cavity, the presence and severity of swelling of the mucous membrane was objectively assessed according to VAS nose and the presence of mucous discharge.

The results obtained during the observational program were processed using the Statistica for Windows 10.0 package (Statsoft Inc. USA). Data are presented depending on the type of distribution: in the form of the mean (M) and its standard deviation (±σ); as the median and upper and lower quartiles Me [Q25; Q75]. Qualitative parameters are presented in the form of absolute numbers and relative quantities (%). The statistical significance of differences when comparing unrelated groups by proportion (frequency of a trait) was calculated using a two-sided Fisher exact test; differences in the results of unrelated samples by quantitative trait were determined using the Mann-Whitney test; related samples were determined by the Friedman test. Differences were considered statistically significant at p<0.05.

Research results and discussion

All 33 patients completed the observation program in accordance with the protocol, of whom 25 (76%) were women and 8 (24%) men; the average age of the patients was 53.5 ± 1.74 years. All patients had a history of bronchial asthma (BA), 27% (n=9) suffered from allergic rhinitis, three patients had occupational hazards (stone industry, metal mining enterprise, gasoline fumes). At the time of inclusion in the study, the average duration of the disease was 9.4±1.2 years, 2 patients had not previously been operated on due to polyposis, the remaining patients had a history of nasal polypectomy.

During therapy, persistent positive, reliable dynamics were obtained in the form of regression of the severity according to VAS of the initially recorded main symptoms of the disease: sneezing, nasal congestion, nasal discharge/decreased sense of smell, postnasal drip, headache/facial pain, lacrimation, cough, sleep disturbance (Table 7. , Fig.5).

Table 7. VAS score for the severity of polyposis symptoms over time by visit .

Symptom Average score in the group, M±σ P
(visits 1-3) Visit 1
1st day Visit 2
Day 45 Visit 3
90th day Sneezing 1.45±0.2 0.27±0.3 0 p<0.05 Nasal congestion 2.9±0.5 1.9±0.3 1.09±0.3 p<0.05 Nasal discharge/decreased sense of smell 2.81±0.2 1.72±0.5 0.81±0.4 p<0.05 Postnasal drip 2.72±0.2 1.59±0.3 0.68±0.3 p<0.05 Head/facial pain 0.68±0.5 0.04±0.2 0 p<0.05 Tearing 0.59±0.3 0.04±0.3 0 p<0.05 Cough 1.04±0.1 0.31±0.1 0 p<0.05 Sleep disturbance 1.09±0.5 0.54±0.3 0.36±0.3 p<0.05

The severity of symptoms of sneezing, headache/facial pain, lacrimation and cough decreased to minimal values by the 45th day of treatment and were completely relieved by the 90th day of treatment. The intensity of symptoms of nasal congestion, nasal discharge/reduced sense of smell, and sleep disturbances steadily decreased during the therapy; by the 90th day of observation, the score for the severity of these symptoms was more than 2.5 times lower than the initial one and the percentage of its reduction reached 62-75 % (p<0.05).

By the 90th day of treatment, in comparison with the first visit, the number of patients complaining of nasal discharge/decreased sense of smell and postnasal drip decreased by more than 2 times (decrease by 52% and 58%, respectively, p<0.05) , the proportion of patients with sleep disturbances decreased by 28%, complaints of sneezing, headache/facial pain, lacrimation and cough were not observed in the observed group of patients by the 3rd visit (Fig. 6). With regard to the frequency of the symptom of nasal congestion, a similar significant decrease in dynamics was not observed (1st visit - 100%, 3rd visit - 96%), but despite the fact that by the 3rd visit this symptom still persisted in a significant proportion of patients , in contrast to the 1st visit, its severity, in accordance with the results of the VAS score, decreased by 62% during therapy (Table 7.).

When assessing the presence and severity of local inflammatory symptoms according to VAS according to the endoscopic picture of the nasopharynx during treatment, statistically significant differences in dynamics were also obtained (Fig. 7). Initially, in all patients, edema and mucous discharge were detected during endoscopy, the degree of their severity was significant and amounted to 3 points. On the 90th day of treatment, mucous discharge was absent in more than half of the patients (55% (n=18)); the severity of the symptom by the 45th and 90th days of treatment decreased by 57% and 83%, respectively (p<0. 05) On the 90th day of treatment, edema was not recorded in 21% (n=7) of patients, while the severity of the symptom decreased significantly by the 45th and 90th treatment by 40% and 79%, respectively (p<0. 05).

During the observation period, there were no adverse events associated with taking the study drug, including allergic reactions or individual intolerance reactions.

Thus, the data obtained from the studies demonstrated that the inclusion of a drug containing ammonium glycyrrhizinate as an active component, in particular the anti-inflammatory drug Reglisam, in the treatment of polypous rhinosinusitis effectively helps relieve sneezing, headache/facial pain, lacrimation and cough, as well as regression of symptoms of nasal congestion, nasal discharge/decreased sense of smell, sleep disturbances, which significantly improves the quality of daily life of patients. Also, according to endoscopy data, a decrease in the severity of local inflammatory symptoms (edema and mucous discharge) was recorded over time during therapy, which objectively confirmed the effectiveness of the treatment and determined the restoration of nasal breathing in a significant proportion of patients.

The invention has been described above with reference to a specific embodiment thereof. Other embodiments of the invention may be obvious to those skilled in the art but do not change its essence as disclosed in the present description. Accordingly, the invention is not to be limited in scope by the description and examples provided.

Bibliography

1. Biggs TC, Hayes SM, Harries PG, Allan RN, Walls AF, Pender SLF, Salib RJ. Immunological profiling of key inflammatory drivers of nasal polyp formation and growth in chronic rhinosinusitis. Rhinology. 2019;57(5):336-342 https://doi.org/10.4193/Rhin19.167.

2. Savlevich E.L., Gaganov L.E., Gerasimov A.N., Kurbacheva O.M., Egorov V.I., Zurochka A.V. Analysis of the clinical course of polypous rhinosinusitis and the pathomorphological composition of the tissue of nasal polyps in patients living in various regions of the Russian Federation. Head and neck. Head and neck. Russian magazine=Head and neck. Russian Journal. 2021;9(3):15–24. Savlevich E.L., Gaganov L.E., Gerasimov A.N., Kurbacheva O.M., Egorov V.I., Zurochka A.V. Analysis of clinical course of chronic rhinosinusitis with nasal polyp (CRSWNP) and pathomorphological composition of nasal polyp tissue in patients living in different regions of the Russian Federation. Head and neck. Russian Journal. 2021;9(3):15–24 (In Russian). https://doi.org/10.25792/HN.2021.9.3.15–24

3. Savlevich E.L., Egorov V.I., Savushkina E.Yu., Zurochka A.V., Gerasimov A.N., Mitrofanova E.S., Lyubimova E.V. Study of microbial factors during exacerbation of polypous rhinosinusitis. Journal of Microbiology, Epidemiology and Immunobiology. 2022;99(4):445-452. Savlevich E.L., Egorov V.I., Savushkina E.Yu, Zurochka A.V., Gerasimov A.N., Mitrofanova E.S., Lyubimova E.V. Study of microbial factors in exacerbation of chronic rhinosinusitis with nasal polyps. Journal of microbiology, epidemiology and immunobiology. 2022;99(4):445-452. (In Russ.) https://doi.org/10.36233/0372-9311-201

4. Schlosser RJ, Gage SE, Kohli P, Soler ZM. Burden of illness: A systematic review of depression in chronic rhinosinusitis. Am J Rhinol Allergy. 2016;30(4):250-6. https://doi.org/10.2500/ajra.2016.30.4343

5. Alt JA, Smith TL, Mace JC, Soler ZM. Sleep quality and disease severity in patients with chronic rhinosinusitis. Laryngoscope. 2013;123(10):2364-70. https://doi.org/10.1002/lary.24040

6. Savlevich E.L., Kozlov V.S., Kurbacheva O.M. Current trends in diagnostic search and treatment of polypous rhinosinusitis. Russian rhinology. 2018;26(2):41-47. Savlevich EL, Kozlov VS, Kurbacheva OM. The modern trends in the diagnostic search for and the treatment of chronic rhinosinusitis with nasal polyps. Russian Rhinology. 2018;26(2):41-47. (In Russ.). https://doi.org/10.17116/rosrino201826241

7. Savlevich E.L. Egorov V.I. Shachnev K.N. Tatarenko N.G. Analysis of treatment regimens for polypous rhinosinusitis in the Russian Federation. Russian otorhinolaryngology. 2019;18;1(98). Savlevich E.L., Egorov V.I., Shachnev K.N., Tatarenko N.G. The analysis of polypous rhinosinusitis treatment regimens in the Russian Federation. Rossiiskaya otorinolaringologiya. 2019;18(1):124–134. (in Russ.) https://doi.org/10.18692/1810-4800-2019-1-124-134

8. Head K, Chong LY, Piromchai P, Hopkins C, Philpott C, Schilder AG, Burton MJ. Systemic and topical antibiotics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2016;4:CD011994. https://doi.org/10.1002/14651858.CD011994

9. Savlevich E.L., Cherenkova V.A., Molodnitskaya A.Yu. Principles of basic therapy for polypous rhinosinusitis. Medical advice. 2020;(16):73-78. https://doi.org/10.21518/2079-701X-2020-16-73-78 Savlevich E.L., Cherenkova V.A., Molodnitskaia A.Yu. Basic principles for the treatment of chronic rhinosinusitis with nasal polyps. Meditsinskiy sovet = Medical Council. 2020;(16):73-78. (In Russ.) https://doi.org/10.21518/2079-701X-2020-16-73-78

10. Savlevich E.L., Kurbacheva O.M., Zurochka A.V., Mitrofanova E.S., Smolkin Yu.S., Lyubimova E.V. The role of leukotriene receptor blockers in the treatment of allergic rhinitis in combination with polypous rhinosinusitis. Medical advice. 2022;(8):111-116. Savlevich E.L., Kurbacheva O.M., Zurochka A.V., Mitrofanova E.S., Smolkin Yu.S., Lyubimova E.V. The role of leukotriene receptor blockers in the treatment of allergic rhinitis in combination with chronic rhinosinusitis with nasal polyps. Meditsinskiy sovet = Medical Council. 2022;(8):111-116. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-8-111-116

11. Savlevich E.L., Brodovskaya O.B., Remizova I.I., Chistyakova G.N., Ishchenko A.M., Simbirtsev A.S. Clinical and immunological effectiveness of the use of a new aerosol form of recombinant interferon-α2b in the treatment of patients with acute nasopharyngitis. Cytokines and inflammation. 2010;1(9): 49-56. Savlevich E.L., Brodovskaya O.B., Remizova I.I., Chistyakova G.N., Ishchenko A.M., Simbirtsev A.S. Clinical and immunological aspects of application of the new aerosol form of recombinant interferon α2b in the treatment of patients with acute nasopharyngitis. Tsitokiny i vospalenie. 2010;1(9):49-56. (In Russ.)

12. Korkmazov M.Yu., Dubinets I.D., Lengina M.A., Korkmazov A.M., Kornova N.V., Ryabenko Yu.I. Selected indicators of immunological reactivity during surgical alteration of ENT organs. Russian immunological journal. 2022; 25(2): 201-206. Korkmazov M.Yu., Dubinets I.D., Lengina M.A., Korkmazov A.M., Kornova N.V., Ryabenko Yu.I. Distinct indexes of immunological reactivity in surgical alteration of ORL organs. Rossiyskiy immunologicheskiy zhurnal = Russian journal of immunology. 2022; 25(2): 201-206. (In Russ.). https://doi.org/10.46235/1028-7221-1121-DIO

13. Dumitriu IE, Baruah P, Manfredi AA, Bianchi ME, Rovere-Querini P. HMGB1: guiding immunity from within. Trends Immunol. 2005;26(7):381–387. https://doi.org/10.1016/j.it.2005.04.009

14. Cavone L, Cuppari C, Manti S, Grasso L, Arrigo T, Calamai L, Salpietro C, Chiarugi A. Increase in the Level of Proinflammatory Cytokine HMGB1 in Nasal Fluids of Patients With Rhinitis and its Sequestration by Glycyrrhizin Induces Eosinophil Cell Death . Clin Exp Otorhinolaryngol. 2015;8(2):123-8. https://doi.org/10.3342/ceo.2015.8.2.123

15. Chikhirzhina E.V., Polyanichko A.M., Starkova T.Yu. Extranuclear functions of the non-histone protein HMGB1. Cytology. 2020;62,(10):716-725. Chikhirzhinaa E. V., Polyanichkoa A. M., Starkova T. Yu. Extranuclear Functions of Nonhistone Protein HMGB1. Cytology. 2020;62,(10):716-725. https://doi.org/10.31857/S0041377120100016

Lotze MT16. , Tracey KJ. High-mobility group box 1 protein (HMGB1):nuclear weapon in the immune arsenal. Nat Rev Immunol 2005;5(4):331–342. (In Russ.) https://doi.org/10.1038/nri1594

17. Egorov V.I., Savlevich E.L. The place of innate immunity in the development of chronic rhinosinusitis and prospects for conservative treatment tactics. Almanac of Clinical Medicine. 2016;44(7):850-856. Egorov V.I., Savlevich E.L. Тhe role of innate immunity in the development of chronic rhinosinusitis and perspectives of its conservative management. Almanac of Clinical Medicine. 2016;44(7):850-856. (in Russ) https://doi.org/10.18786/2072-0505-2016-44-7-850-856

18. Vroling AB, Fokkens WJ, van Drunen CM. How epithelial cells detect danger: aiding the immune response. Allergy. 2008;63(9):1110–1123. https://doi.org/10.1111/j.1398-9995.2008.01785.x

19. Chen D, Bellussi LM, Passali D, Chen L. LPS may enhance expression and release of HMGB1 in human nasal epithelial cells in vitro. Acta Otorhinolaryngol Ital. 2013 Dec;33(6):398-404. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870446/

20. Gardella S, Andrei C, Ferrera D, Lotti LV, Torrisi MR, Bianchi ME, Rubartelli A. The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep. 2002;3(10):995-1001. https://doi.org/10.1093/embo-reports/kvf198.

21. Park JS, Svetkauskaite D, He Q, Kim JY, Strassheim D, Ishizaka A, Abraham E. Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem. 2004 Feb 27;279(9):7370-7. https://doi.org/10.1074/jbc.M306793200

22. Kokkola R, Andersson A, Mullins G, Ostberg T, Treutiger CJ, Arnold B, Nawroth P, Andersson U, Harris RA, Harris HE. RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent macrophages. Scand J Immunol. 2005 Jan;61(1):1-9. https://doi.org/10.1111/j.0300-9475.2005.01534.x

23. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2010;28:367-388. https://doi.org/10.1146/annurev.immunol.021908.132603

24. Bellussi LM, Cocca S, Passali GC, Passali D. HMGB1 in the Pathogenesis of Nasal Inflammatory Diseases and its Inhibition as New Therapeutic Approach: A Review from the Literature. Int Arch Otorhinolaryngol. 2017;21(4):390-398. https://doi.org/10.1055/s-0036-1597665

25. Yang H, Wang H, Czura CJ, Tracey KJ. HMGB1 as a cytokine and therapeutic target. J Endotoxin Res. 2002;8(6):469-72 https://doi.org/10.1179/096805102125001091

26. Bordbar N, Karimi MH, Amirghofran Z. The effect of glycyrrhizin on maturation and T cell stimulating activity of dendritic cells. Cell Immunol. 2012;280(1):44-49. https://doi.org/10.1016/j.cellimm.2012.11.013

27. Dadaev Kh.A., Sadyrova M.A., Akilov D.Kh. Medicinal plant licorice glabra. Biology and Integrative Medicine. 2021. No. 1 (48). pp. 250-263. Dadaev K., Sadyrova M., Akilov J. Medicinal plant Glycyrrhiza Glabra. Biology and integrative medicine. 2021. No. 1 (48). pp. 250-263. https://cyberleninka.ru/article/n/lekarstvennoe-rastenie-solodka-golaya

28. Shamsa F., Ohtsuki K., Hasanzadeh E., Rezazadeh Sh. The anti-inflammatory and anti-viral effects of an ethnic medicine: glycyrrhizin, J. Med. Plants. 2010;9(6):1–28. https://jmp.ir/article-1-504-en.pdf

29. Korkmazov M.Yu., Solodovnik A.V., Korkmazov A.M., Lengina M.A. Prospects for the use of herbal preparations in combination with physical methods in the complex therapy of chronic adenoiditis. Medical advice. 2021;(18):19-27. Korkmazov M.Yu., Solodovnik A.V., Korkmazov A.M., Lengina M.A. Prospects for using herbal preparation in combination with physical methods in complex therapy of chronic adenoiditis. Meditsinskiy sovet = Medical Council. 2021;(18):19-27. (In Russ.) https://doi.org/10.21518/2079-701X-2021-18-19-27

30. Mollica L, De Marchis F, Spitaleri A, Dallacosta C, Pennacchini D, Zamai M, Agresti A, Trisciuoglio L, Musco G, Bianchi ME. Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. Chem Biol. 2007;14(4):431-41. https://doi.org/10.1016/j.chembiol.2007.03.007

31. Lotfi R, Herzog GI, DeMarco RA, Beer-Stolz D, Lee JJ, Rubartelli A, Schrezenmeier H, Lotze MT. Eosinophils oxidize damage-associated molecular pattern molecules derived from stressed cells. J Immunol. 2009;183(8):5023-31. https://doi.org/10.4049/jimmunol.0900504

32. Wang Y, Yang M, Ma Z, Liang Q, Tan H, Xiao C, Gao Y. Effects of 18beta-glycyrrhizic acid and 18alpha-glycyrrhizic acid on mRNA and protein expression of cytochrome P450 3A in cultured rat primary hepatocyte. Zhongguo Zhong Yao Za Zhi. 2009;34(3):307-311.

33. Li J, Zhao M, Xiang X, He Q, Gui R. A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapeutic efficacy of steroid-resistant nephrotic syndrome. J Nanobiotechnology. 2021;19(1):417. https://doi.org/10.1186/s12951-021-01165-z

34. Yao Z, Fu Y. Glycyrrhizic acid restrains airway inflammation and remodeling in asthma via the TGF-β1/Smad signaling pathway. Exp Ther Med. 2021;21(5):461. https://doi.org/10.3892/etm.2021.9892

35. Savlevich E.L., Zurochka A.V., Kurbacheva O.M., Egorov V.I., Gaganov L.V., Lyubimova E.V. Transforming growth factors TGF-β1, TGF-β2 and TGF-β3 in nasal polyp tissue in different phenotypes of polypous rhinosinusitis. Medical immunology. 2022;24(1):1417-1426. Savlevich E.L., Zurochka A.V., Kurbacheva O.M., Egorov V.I., Gaganov L.E., Lyubimova E.V. Transforming growth factors TGF-β1, TGF-β2 and TGF-β3 in the tissue of nasal polyps in different phenotypes of chronic rhinosinusitis with nasal polyps. Medical Immunology (Russia)/Meditsinskaya Immunologiya. 2022;24(1):147-156. (in Russ.) https://doi.org/10.15789/1563-0625-TGF-2365

36. Eremeeva A.V., Sorokina L.N., Mineev V.N., Lim V.V., Nyoma M.A., Trofimov V.I. Expression of the FoxP3 transcription factor in bronchial asthma. Medical immunology. 2016;18(4):373-378. Eremeeva A.V., Sorokina L.N., Mineev V.N., Lim V.V., Nyoma M.A., Trofimov V.I. Expression of FoxP3 transcription factor in bronchial asthma. Medical Immunology (Russia). 2016;18(4):373-378. (In Russ.) https://doi.org/10.15789/1563-0625-2016-4-373-378

37. Fouladi S, Masjedi M, Ghasemi R, G Hakemi M, Eskandari N. The In Vitro Impact of Glycyrrhizic Acid on CD4+ T Lymphocytes through OX40 Receptor in the Patients with Allergic Rhinitis. Inflammation. 2018;41(5):1690-1701. https://doi.org/10.1007/s10753-018-0813-8

38. Drozdova M.V., Ryazantsev S.V., Bykova A.V. New possibilities for the treatment of exudative otitis media in children. Questions of practical pediatrics. 2022; 17(2): 65–71. Drozdova M.V., Bykova A.V., Ryazantsev S.V. New therapeutic options for otitis media with effusion in children. Vopr. prakt. pediatrician (Clinical Practice in Pediatrics). 2022; 17(2): 65–71. (In Russ). https://doi.org/10.20953/1817-7646-2022-2-65-71.

39. Kamaev A.V., Trusova O.V., Makarova I.V., Korostovtsev D.S. Study of the clinical effectiveness of ammonium glycyrrhizinate in preschool children at high risk of developing bronchial asthma. Questions of practical pediatrics. 2018;13(4):104-11. Kamaev AV, Trusova OV, Makarova IV, Korostovtsev DS. Study of ammonium glycyrrhizinate clinical effectiveness in preschool age children of high risk for asthma. Questions prakticheskoi pediatrii. 2018;13(4):104-11 (in Russ) https://doi.org/10.20953/1817-7646-2018-4-104-111

40. Berezovsky A.S., Nezabudkin S.N., Nezabudkina A.S., Antonova T.I. The place of ammonium glycyrrhizinate (glycyram) in the treatment of mild persistent bronchial asthma in children. Allergology and immunology in pediatrics. 2012;3(30):2-6. Berezovskii AS, Nezabudkin SN, Nezabudkina AS, Antonova TI. Place of Ammonium glycyrrisinate (Glycyram) in the treatment of mild persistent asthma in children. Allergologiia i immunologiia v pediatrii. 2012;3(30):2-6 (in Russ)

41. Revyakina V.A., Larkova I.A., Kuvshinova E.D. Possibilities of preventive anti-inflammatory therapy in the acute period of ARI in children with mild and moderate bronchial asthma. Questions of practical pediatrics. 2020;15(6):35-41. Revyakina VA, Larkova IA, Kuvshinova ED. Preventive anti-inflammatory therapy during the acute respiratory infections in children with mild and moderate bronchial asthma. Questions prakticheskoi pediatrii. 2020;15(6):35-41 (in Russ). https://doi.org/10.20953/1817-7646-2020-6-35-41

42. Geppe N.A., Malakhov A.B., Boytsova E.V., Gaymolenko I.N., Ermakova I.N., Zaitsev A.A., Ivakhnenko E.F., Ilyenkova N.A., Kamaev A.V., Klyukhina Yu.B., Kondurina E.G., Konova O.M., Kulagina V.V., Lev N.S., Lyutina E.I., Megiryan M.M., Melnikova I.M., Meshcheryakov V.V., Mizernitsky Yu.L., Mironova A.K., Mikhalev E.V., Mozzhukhina L.I., Odinaeva N.D., Pavlinova E.B., Pobedinskaya N. S.S., Skachkova M.A., Soroka N.D., Trishina S.V., Tsarkova S.A., Shulyak I.P. Resolution of the Expert Council on the use of the anti-inflammatory drug ammonium glycyrrhizinate in the treatment of acute respiratory tract infections and allergic diseases of the respiratory tract. Pediatrics. Consilium Medicum. 2022;4:317–321. Geppe NA, Malakhov AB, Boitsova EV, Gaimolenko IN, Ermakova IN, Zaitsev AA, Ivakhnenko EF, Il'enkova NA, Kamaev AV, Kliukhina IuB, Kondiurina EG, Konova OM, Kulagina VV, Lev NS, Liutina EI, Megirian MM, Mel'nikova IM, Meshcheriakov VV, Mizernitskii IuL, Mironova AK, Mikhalev EV, Mozzhukhina LI, Odinaeva ND, Pavlinova EB, Pobedinskaia NS, Skachkova MA, Soroka ND, Trishina SV, Tsar'kova SA, Shuliak IP. Resolution of the Expert Council on the use of the anti-inflammatory drug ammonium glycyrrhizinate in the treatment of acute respiratory infections and allergic diseases of the respiratory tract. Pediatrics. Consilium Medicum. 2022;4:317–321. https://doi.org/10.26442/26586630.2022.4.201953

Claims (5)

1. The use of an oral drug containing ammonium glycyrrhizinate as an active component in the anti-inflammatory therapy of polypous rhinosinusitis. 2. Use according to claim 1, in which the drug is used in solid dosage form, preferably tablets. 3. Use according to claim 2, in which the drug Reglisam is used as a drug containing ammonium glycyrrhizinate in a dosage of 50 mg per tablet. 4. Application according to claim 3, in which the drug Reglisam is used in combination, together with the use of mometasone furoate intranasally and irrigation of the nasal mucosa with isotonic saline solution. 5. Application according to claim 3 or 4, in which the drug Reglisam is used for 90 days, 1 tablet 2-3 times a day.