CN117693352A

CN117693352A - Glutathione C4 against airway diseases

Info

Publication number: CN117693352A
Application number: CN202280049985.XA
Authority: CN
Inventors: 罗科·克里米; 恩里科·加拉奇
Original assignee: Redox Science&technology Co ltd
Current assignee: Redox Science&technology Co ltd
Priority date: 2021-07-14
Filing date: 2022-07-13
Publication date: 2024-03-12
Also published as: EP4370144A1; WO2023285984A1

Abstract

The present invention relates to the compound glutathione C4 (GSH-C4) for use in the treatment of respiratory disorders and to compositions comprising said compound optionally in combination with at least one further active substance for said use combination.

Description

Glutathione C4 against airway diseases

Technical Field

The present invention relates to GSH-C4 compounds for use in the treatment of respiratory diseases, and to compositions comprising said compounds, optionally in combination with at least one other active substance for said use.

Background

It is well known that the respiratory system is one of the most frequent and ill areas of disease caused by pathogens and environmental factors, as it is easily and widely exposed to extraneous factors.

Among the most common airway diseases are, for example, rhinopathy affecting the upper respiratory tract, sinusitis, cold, pharyngitis, laryngitis, rhinitis, tonsillitis, etc., and chronic and non-chronic cough, tracheitis, bronchitis, pneumonia, etc. affecting the lower respiratory tract.

In all these conditions, the mucous membrane is subjected to more or less severe lesions, from irritation to actual lesions, for example in the case of crusting hemorrhagic rhinopathy, chronic coughing.

Currently, the first-choice therapies for treating airway-related diseases include corticosteroid therapy, optionally in combination with antibiotics, soothing agents (emollients), vasoconstrictors, or other drugs.

However, it is well known that corticosteroid drugs produce many side effects (the latter being more damaging) upon inhalation and systemic ingestion, including mucosal injury, superimposed fungal infections, bleeding, weight gain, osteoporosis, elevated blood glucose, skin changes, and the like.

It is therefore always of interest to identify further compounds or compositions useful in the treatment or co-treatment of airway diseases which are able to provide clinical results comparable to those obtained with currently preferred therapies and which show better tolerability and lower incidence of side effects.

Antiviral and antioxidant activity of GSH has been described in the art.

In particular, the anti-inflammatory activity of GSH derivatives in anti-inflammatory models has been described and reported in the art (Palamara et al Evidence of antiviral activity of GSH: in vitro inhibition of HSV type 1replication.Antiviral research 27-1995, 237-253)) (Limongi et al "GSH-C4 acts as anti-inflammatory drug in different models of canonical and cell autonomous inflammation trhough NFkB inhibition" Frontiers in immunology 05.02.2019).

Disclosure of Invention

The authors of the present invention have found that the GSH derivative GSH-C4, when administered by inhalation solution to a concentration (w/w) of 0.1 to 1.5%, optionally in combination with 0.05-0.5% (w/w) hyaluronic acid, is effective for the treatment or co-treatment of airway diseases, including post-operative wounds. Indeed, the authors of the present invention have demonstrated that GSH-C4 is effective in the treatment of upper and lower respiratory tract diseases without causing side effects. Unlike cysteine, which freely enters cells and undergoes oxidation processes, produces toxicity, and activates inflammatory reactions, or reduced glutathione, which cannot penetrate cell membranes, GSH-C4 is capable of inhibiting inflammatory pathways, restoring the redox state of cells, and is excreted from cells after oxidation.

Accordingly, the object of the present invention is as follows:

-GSH-C4 compounds for use in the treatment or co-treatment of airway diseases;

-a composition comprising GSH-C4 in a concentration of 0.1% to 1.5% (w/w) and one or more excipients and/or pharmaceutically acceptable additives for use in the treatment or co-treatment of an airway disease.

A device for delivery by inhalation or by nasal or oronasal spray comprising a composition according to any of the embodiments described/claimed.

Glossary of terms

In the present specification, the term GSH-C4 alias Ding Xiangu glutathione or n-butyryl gamma-glutamylcysteinyl glycine denotes a molecule having the formula

And may be prepared as described in example 2 of patent application WO2005063795 and/or as described in example of patent application WO2019102397 A1.

The term hyaluronic acid has the meaning commonly used in the art and defines a natural polysaccharide formed from linear glucuronic acid and N-acetylglucosamine particles. It has anti-inflammatory, mucosal regulatory, anti-oedema and recombinant functions, and also functions to inhibit bacteria by forming a protective oxide layer on the mucosa, impeding penetration of pathogens and reducing proliferation of existing pathogens.

Hyaluronic acid has excellent viscoelasticity, high moisturizing ability, high biocompatibility and hygroscopic properties (Gupta, 2019). In aqueous solution, hyaluronic acid is negatively charged and forms a salt commonly known as hyaluronic acid or hyaluronate (Laurent, 1989), which is highly hydrophilic and is therefore surrounded by water molecules. In particular, low molecular weight sodium hyaluronate is capable of self-hydration and can reach levels of water operators up to 1000 times its own weight. Its physicochemical properties allow the polymer chains to aggregate and form an extended network (Scott, 1991).

Because of the rigidity of the molecule and its ability to absorb water, hyaluronate occupies a large volume, forming a gel, against mechanical pressure. As Molecular Weight (MW) and concentration increase, the hyaluronic acid network is strengthened, and thus, the hyaluronic acid solution shows gradually increasing viscosity and viscoelasticity (Kobayashi, 1994). Hyaluronic acid solutions are characterized by non-newtonian, thin-cut (pseudoplastic) and viscoelastic behaviour. This unique rheological behavior is peculiar and extremely important, as it determines many of the physiological roles of hyaluronic acid as well as pharmaceutical, medical, food and cosmetic applications (farlagara, 2018).

Drawings

FIGS. 1A-B.

Patients with crusted hemorrhagic rhinopathy were imaged by nasal video endoscopy prior to treatment with GSH-4 based sprays.

Figures 2A-b images obtained by nasal video endoscopy of patients with crusted hemorrhagic rhinopathy after 15 days of treatment with GSH-4 based sprays having the composition shown in table 1.

Fig. 3.

Patients with perforation of the nasal septum and diffuse crusting of serum were imaged by nasal video endoscopy prior to treatment with GSH-4 based sprays.

Figure 4. Images obtained by nasal video endoscopy of patients with diaphragmatic perforation with diffuse serum crusting after 15 days of treatment with GSH-4 based sprays having the composition shown in table 1.

Fig. 5A-B.

Patients with iatrogenic rhinopathy due to abuse of nasal sprays containing vasoconstrictors were imaged by nasal video endoscopy prior to treatment with GSH-4 based sprays.

Figures 6A-b images obtained by nasal video endoscopy of patients suffering from iatrogenic rhinopathy due to abuse of nasal sprays containing vasoconstrictors after 15 days of treatment with GSH-4 based sprays having the composition shown in table 1.

Fig. 7A-c. Computed Tomography (CT) images of patient 1, a.p.: women, 62 years old, smoked, had acute bronchitis and cough. Cycle 2019, 11 months 4 to 10 days. SEA: start 6, end 3.

Fig. 8A-c. CT images of patient 2, p.f.: men, 80 years old, had smoked, had right fiber chest, diffuse bronchiectasis, and coughs. Cycle 2019, 11 months 11 to 17 days. SEA: start 8, end 2.

Fig. 9A-c. CT images of patient 3, l.r.: men, 66 years old, had smoking with idiopathic pulmonary fibrosis and cough. Cycle 2019, 11 months 11 to 17 days. SEA: start 8, end 6.

Fig. 10A-c. CT images of patient 4, n.e.: men, 71 years old, smoked, had emphysema, bronchiectasis, and coughing. Cycle 2019, 11, 14 to 21. SEA: start 5, end 3.

Fig. 11A-c. CT image of patient 5, m.l.: women, 71 years old, do not smoke, suffer from bronchiectasis, chronic bronchitis, cough. Cycle 2019, 11, 18 to 24 days. SEA: start 8, end 4.

Detailed Description

The present invention relates to GSH-C4 compounds for use in the treatment or co-treatment of airway diseases.

In one embodiment, the disease includes a disease affecting the upper and/or lower airways, irritation, injury, inflammation of the mucosa. Non-limiting examples of such conditions include, but are not limited to, rhinopathy, postoperative injury, cough, acute bronchitis, diffuse bronchiectasis, idiopathic pulmonary fibrosis, emphysema.

According to the invention, the compounds are preferably administered to an individual in need thereof by inhalation or intranasal route or by nebulization.

The compounds may be formulated into pharmaceutical compositions. Accordingly, the object of the present invention is a composition comprising GSH-C4 in a concentration of 0.01% to 1.5% (w/w) and one or more excipients and/or pharmaceutically acceptable additives, for use in the treatment or co-treatment of airway diseases.

GSH-C4 may be any concentration w/w within the above range, for example 0.1;0.2;0.3;0.4;0.5;0.6;0.7;0.8;0.9;1.0;1.1;1.2;1.3;1.4;1.5.

according to some preferred embodiments, the concentration of GSH-C4 is 0.4% to 1.2% w/w, or 0.6% to 1% w/w, or 0.8% w/w. In one embodiment, the compositions described and claimed herein may comprise other pharmacologically active compounds suitable for treating airways, such as antibiotics; antibacterial, antifungal or other agents.

However, in one embodiment GSH-C4 is the only pharmacologically active ingredient present in the composition.

The composition may then comprise adjuvants, such as polysaccharides, including hyaluronic acid, which exert a protective effect on the oropharyngeal and/or nasopharyngeal mucosa, as well as mechanical effects useful for administering the active ingredient GSH-C4. In a preferred embodiment, the composition may comprise GSH-C4 at a concentration of 0.01% to 1.5% (w/w) and hyaluronic acid or a pharmaceutically acceptable salt thereof at a concentration of 0.05 to 0.5% (w/w), in addition to adjuvants commonly used by those skilled in the art in the preparation of pharmaceutical compositions. GSH-C4 may be any concentration w/w within the above range, for example 0.1;0.2;0.3;0.4;0.5;0.6;0.7;0.8;0.9;1.0;1.1;1.2;1.3;1.4;1.5.

according to some preferred embodiments, the concentration of GSH-C4 is 0.4% to 1.2% w/w, or 0.6% to 1% w/w, or 0.8% w/w.

Hyaluronic acid or a pharmaceutically acceptable salt thereof may be at any w/w concentration within the above-mentioned range. In one embodiment, the concentration of hyaluronic acid or a pharmaceutically acceptable salt thereof may be 0.8% w/w to 0.3% w/w.

Thus, in one embodiment, the composition will consist of GSH-C4 at a concentration of 0.1% to 1.5% (w/w) and hyaluronic acid, or a pharmaceutically acceptable salt thereof, at a concentration of 0.05 to 0.5% (w/w) and suitable excipients. The excipients may vary according to the type of formulation that one skilled in the art chooses depending on the usual use.

The hyaluronic acid or salt thereof suitable for use in preparing the compositions of the invention may be hyaluronic acid or a high, medium or low molecular weight salt thereof; their molecular weights are included in the following ranges, respectively: 1,800-2,200kDa, 1000-1800kDa, 100-500kDa.

For preparing any of the forms of composition shown in this specification, hyaluronic acid and/or any hyaluronate salt, such as sodium hyaluronate (sodium hyaluronate), suitable for use by inhalation.

According to one embodiment, the present invention relates to a composition formulated in liquid form according to the qualitative-quantitative composition reported in table 1.

Table 1:

according to another embodiment, the invention relates to a composition formulated in liquid form according to the qualitative-quantitative composition shown in table 2.

Table 2:

chemical name	CAS	Concentration% w/w
			Sodium hyaluronate	9067-32-7	0,05
Reduced L-glutathione	70-18-8	0,8
			Sodium chloride 0.9% solution		q.b.a 100

Preferably, the liquid composition shown in table 2 can be administered every twelve hours in the morning and evening at a dose equal to 3mL for a total duration of 7 days to an individual in need thereof.

According to another embodiment, the invention relates to a composition formulated in liquid form according to the qualitative-quantitative composition reported in table 3.

Table 3:

according to another embodiment, the invention relates to a composition formulated in liquid form according to the qualitative-quantitative composition reported in table 4.

Table 4:

chemical name	CAS	Concentration% w/w
			Reduced L-glutathione	70-18-8	0,8
Sodium chloride 0.9% solution		q.b.a 100

Preferably, the liquid composition shown in table 4 can be administered every twelve hours in the morning and evening at a dose equal to 3mL for a total duration of 7 days to an individual in need thereof.

According to the invention, the described and claimed compositions are useful for the treatment and/or co-treatment of diseases affecting the upper and/or lower airways, irritation, damage, inflammation of the mucous membranes. Non-limiting examples given are rhinopathy, postoperative injury, cough, acute bronchitis, diffuse bronchiectasis, idiopathic pulmonary fibrosis, emphysema.

In a specific embodiment, the compositions of the invention may be used to treat those conditions in which the nasal mucosa is affected by infectious inflammation, abnormal response, granuloma and neoplastic pathologies.

In the first two cases, with different pathogenesis, we observe that the normal production of secretions, which normally cover the nasal mucosa, is altered, with consequent hyperemic conditions and leading to hypertrophy and oedema of the nasal mucosa, possibly associated with serum blood crusting. Conversely, some forms can lead to sub-atrophy of the mucosa itself and to qualitative-quantitative changes in secretion production. The drugs currently available for topical administration are represented by various cortisone molecules, associated or not with antihistamines, vasoconstrictors, antibiotics, and a range of products with different compositions, from blackcurrants to turmeric, from propolis to garlic, from aloe vera to podiata. All of these last ingredients are characterized by anti-inflammatory, soothing, astringent, immunomodulatory properties, and the like. Another related aspect is the treatment of the nasal mucosa following a nasal operation. This treatment method aims at restoring the anatomical functional integrity of the mucous membrane itself in the shortest possible time and is critical under specific conditions (due to both the clinical characteristics of the patient and the type of intervention performed).

As reported in the examples section below, the authors of the present invention have shown that nasal sprays containing GSH-C4 and hyaluronic acid based compositions as reported in Table 1 can be effective in the treatment of nasopharyngeal diseases requiring tissue repair due to mechanical trauma (nasal surgery) or due to viral or bacterial infection.

The authors also demonstrated that the compositions of the present invention as shown in table 2 are effective in treating cough, in particular chronic cough.

Cough is known to be a reflex of evolutionary choice, aimed at protecting the airways, mainly against inhalation of foreign bodies. As a protective reflex, it has an intrinsic resemblance to pain: both have a conserved purpose in the acute case, more or less a major psychological component, and become pathological when they occur chronically.

However, when cough is chronic, this is not just a problem affecting quality of life. In fact, such reflections are constantly induced, possibly affecting the body of the affected person, sometimes with little effect, sometimes even causing serious or possibly fatal damage.

Mild complications are more common and have less risk to patient health. However, the definition "mild" does not correspond to a low impact on quality of life, which is more severe for patients with these complications. The most common are: muscle pain, depression, fatigue, insomnia, headache, gastroesophageal reflux and vomiting. Serious complications are those events that may immediately cause permanent damage or constitute a life hazard to the patient. These symptoms are not common and chronic cough patients never see them normal, including rib fractures, pneumothorax and mediastinal emphysema, syncope, arrhythmia, urinary incontinence.

When a cough is chronic, it is no longer actually a symptom, but rather becomes more like a syndrome involving potential damage to various organs and functions. The clinician's attention must be focused on investigating all of these aspects, considering that they may be a serious complication in chronic cough patients. The impact on quality of life, on entering emergency rooms and hospitalization, and on sometimes misuse drugs is difficult to estimate, but certainly important. If cough cannot be controlled, a satisfactory result is certainly to prevent and control these complications.

The authors of the present invention have surprisingly found that GSH-C4 compounds may be advantageously used for the treatment of chronic cough and the protection of the respiratory tract. The examples show in part experiments performed on patients suffering from cough and various pulmonary diseases using the liquid compositions reported in table 2 according to the invention, with a dose of 3ml vials, once every 12 hours, for 7 consecutive days, demonstrating the effectiveness of the compositions of the invention.

Thus, advantageously, the composition used according to the invention is a composition suitable for administration by inhalation or intranasal route or by nebulization.

Thus, according to one embodiment, the composition is in a form selected from the group consisting of aerosols, nasal sprays, solutions, suspensions, nasal drops, inhalation powders.

The composition of interest of the present invention provides the advantage of being able to be administered by inhalation, aerosol, nebulization or spraying and therefore in a simple and easy way, even at home, directly into the respiratory tract of a patient in need thereof. Inhalation administration of the compositions of interest of the present invention allows GSH-C4 to function at the mucosal level due to the presence of highly vascularized nasal mucosa.

In one embodiment, the composition may comprise adjuvants, carriers, solvents, dispersion media, diluents, tackifiers, salts, adjuvants or surfactants, provided that they are physiologically compatible.

Some examples of pharmaceutically acceptable carriers include, for example, water, saline, phosphate buffered saline, glycerol, mixtures of water and ethanol, and the like, and combinations thereof. In some cases, it is preferred to further include an isotonic agent, for example, a sugar or a polyalcohol such as mannitol or sorbitol in the composition of interest of the invention.

Agents that increase the shelf life of the composition may also be used in the compositions of interest of the present invention and include wetting agents, emulsifying agents, preservatives, or buffers.

The subject compositions of the present invention in any of the embodiments described herein may also comprise a microbial load stabilizer, such as benzalkonium chloride and the like.

The pharmaceutical composition according to any of the embodiments described herein is sterile and stable under storage conditions.

Advantageously, according to one aspect of the present invention, the pharmaceutical composition according to any of the preceding embodiments may be administered by inhalation and/or intranasally and/or oronasally. The pharmaceutical composition according to the invention is dispersed in very fine droplets facilitating its delivery through the respiratory tract, increasing the bioavailability of the active ingredient at the mucosal level.

According to one aspect of the invention, the composition of interest of the invention may be prepared in any form, provided that it is suitable for administration of the inhaled and/or intranasal and/or oronasal type, and in particular in a form selected from aerosols and/or nasal or oronasal sprays, nebulized formulations, solutions, emulsions, suspensions, nasal drops, powders. The compositions of interest of the present invention may also be packaged in multi-dose containers and single-dose containers, for example in vials in the case of liquid compositions.

Non-limiting examples of generating devices that can be used for aerosol administration of pharmaceutical compositions according to the present invention include nebulizers (or small volume nebulizers, SVN), metered dose inhalers (or pressurized metered dose inhalers, pmdis), or Dry Powder Inhalers (DPIs).

According to one embodiment, GSH-C4 may be administered to an individual in need thereof in the form of a liquid or powder composition for aerosol, by means of a nebulizer activated from a suitable dispenser or by classical ultrasonic electric devices or pistons. The most suitable dispensing device for administering the composition of interest of the present invention may be selected according to the type of patient, the increased convenience of use, or the frequency of administration. Thus, an inhalation delivery device or a delivery device by means of a nasal or oronasal spray comprising a pharmaceutical composition according to any of the preceding embodiments is also an object of the present invention.

According to one embodiment of the invention, the nasal or oronasal spray delivery device may comprise a bottle and/or vial containing the pharmaceutical composition to be administered and a nebulizer system connected to a terminal injector (e.g. in the form of a nozzle) to allow the delivery of an optimal volume of the composition per dose directly into the nasal or oronasal cavity.

By creating a thin cloud of topical particles, the delivery device via nasal or oronasal spray is capable of rapidly and effectively delivering an appropriate dose of the subject compositions within the nasal or oronasal cavity. The device may also be equipped with an oronasal mask to allow delivery throughout the oropharyngeal cavity.

Another example of an inhalation delivery device according to the present invention is a metered dose inhaler device (MDI) comprising a pharmaceutical composition to be administered in a suitable dose.

According to any of the embodiments described herein, GSH-C4 or a composition comprising it may be administered every 12 hours in the morning and evening or every 24 hours to an individual in need thereof, preferably for a total duration of 7 days, or even more preferably for a total duration of 15 days.

At any point in the specification and claims, the term "comprising" ("comprises") may be replaced by the term "consisting of.

The examples reported below are intended to illustrate embodiments of the compositions disclosed in this specification and are in no way to be considered limiting of the preceding description and the claims that follow.

Examples

All patients receiving the following test provided informed consent.

9 patients with nasal disorders were recruited during the period of 5 to 6 months 2020, evenly distributed by gender and age. Specifically, 1 had specific vasomotor rhinopathy, 2 had non-specific vasomotor rhinopathy, 2 had iatrogenic rhinopathy (abuse of vasoconstrictors), 2 had crusted hemorrhagic bacterial infectious rhinitis (one of which was accompanied by perforation of the nasal septum), and 2 patients underwent nasal surgery.

Example 1

All enrolled patients were administered a glutathione spray as the sole topical therapy after a preliminary otorhinolaryngological specialist visit, the composition of which is shown in the example of table 1,

each nostril was sprayed twice, once a day, and 15 consecutive days.

Nasal video endoscopy was performed on each patient before and after treatment, and prior and after treatment was collected focusing on the past symptoms of nasal symptoms and satisfaction with treatment.

No patient complained of any significant side effects. Only one patient complained of a slight nasal "burning" and, incidentally, this sensation was of short duration.

Results

The crusted hemorrhagic rhinopathy case showed complete restoration of epithelial integrity. Cases of iatrogenic rhinopathy, particularly those who have abused topical vasoconstrictors, corticosteroids for many years, report significant improvements in symptoms and nasal objectivity. The final observations are relevant; in fact, iatrogenic rhinopathy is often an problematic issue. The antioxidant properties of GSH may determine the re-balance and eutrophication activity of the nasal mucosa in these patients, which, as is evident from the large body of evidence present in the literature, exhibit (in fact) serious alterations such as a marked change and/or disappearance of cilia, a change in gland composition, a change in nerve endings, etc.

Cases of specific and non-specific vasomotor rhinopathy (allergic rhinopathy) show an improvement in symptoms. However, the study samples were too small to evaluate the efficacy of GSH versus topical corticosteroid treatment.

The outcome of the patient receiving the nasal surgery is also relevant. Rapid restoration of mucosal integrity is observed without the use of any other topical drug.

Example 2

After a preliminary otorhinolaryngological specialist visit, all enrolled patients were administered the liquid composition defined in the example of table 2 as the sole topical therapy by aerosol, in 3ml vials, once every 12 hours for 7 consecutive days.

The effect of GSH-C4 based compounds (composition of table 2) at inhalation concentrations of 0.8% on cough symptoms was evaluated in 5 patients presenting with clinical symptoms and various pulmonary diseases (see details of patient-related chest CT images, fig. 7-11). According to the recommendations of the recent guidelines of the European respiratory medical society [14], the tool for quantifying cough symptoms is the Visual Analog Score (VAS) (from 1 to 10). The duration of treatment was empirically defined as approximately one week with 3ml dose aerosol administration every 12 hours.

Results

The results of this pilot study are shown in fig. 7-11 and are summarized in table 5 below:

TABLE 5

Patient(s)

Sex (sex)

Age of

Diagnosis of

Duration of treatment

Pre-treatment VAS

Post-treatment VAS

A.P.

F

62

Acute bronchitis

For 7 days

6

3

P.F.

M

80

Chest bronchiectasis with fiber

For 7 days

8

2

L.R.

M

66

Idiopathic pulmonary fibrosis

For 7 days

8

6

N.E.

M

71

Emphysema is accompanied by bronchiectasis

For 8 days

5

3

M.L.

F

71

Diffuse bronchiectasis

For 7 days

8

4

The data show that all patients had reduced cough symptoms intensity after subjective assessment using the VAS scale. The reduction in 3 out of 5 cases compared to the starting value was equal to or greater than 50%. No patients reported side effects after inhalation of GSH-C4.

Although the number of patients studied was small, the results indicate that inhalation of GSH-C4 has a beneficial effect on cough symptoms, and no side effects.

Example 3

All enrolled patients were given glutathione sprays as the sole topical therapy after a preliminary otorhinolaryngological specialist visit, with a composition as shown in the example of table 3 reported in this specification, at a dose of two sprays per nostril, once a day in the morning and at night, for 15 consecutive days.

The authors of the present invention have demonstrated that nasal sprays comprising the compositions reported in table 3 above based on GSH-C4 alone can be effective in the treatment of nasopharyngeal diseases requiring tissue repair, either due to mechanical trauma (nasal surgery) or due to viral or bacterial infection.

Example 4

All enrolled patients were given the liquid composition defined in the examples of table 4 reported in the present specification as the sole topical treatment by aerosol administration, once every 12 hours, in 3ml vials, for 7 consecutive days after a preliminary otorhinolaryngology specialist visit.

The authors have shown that the composition of the invention as shown in table 4 is effective for the treatment of cough, in particular chronic cough. Cough is known to be a reflex of evolutionary choice, aimed at protecting the respiratory tract, mainly against inhalation of foreign bodies.

Claims

1. GSH-C4 compounds for use in the treatment or auxiliary treatment of airway diseases.

2. The compound for use according to claim 1, wherein the airway diseases include diseases affecting the upper and/or lower airways, irritation, damage, inflammation of the mucosa.

3. A compound according to claim 3, wherein the disease is rhinopathy, postoperative injury, cough, acute bronchitis, diffuse bronchiectasis, idiopathic pulmonary fibrosis, emphysema.

4. The compound for use according to claim 1 or 2, wherein the compound is administered to an individual in need thereof by inhalation or intranasal route or by aerosolization.

5. A composition comprising GSH-C4 at a concentration of 0.01% to 1.5% (w/w) and one or more pharmaceutically acceptable excipients and/or additives, said composition being used in the treatment or Used in auxiliary treatment of airway diseases.

6. The composition for use according to claim 5, wherein the concentration of GSH-C4 is 0.4% w/w to 1.2% w/w, or 0.6% w/w to 1% w/w, or 0.8 %w/w.

7. The composition for use according to any one of claims 5 or 6, wherein the airway diseases include diseases affecting the upper airway and/or lower airway, irritation, damage, inflammation of the mucosa.

8. The composition for use according to any one of claims 5 to 7, wherein the disease is rhinopathy, postoperative injury, cough, acute bronchitis, diffuse bronchiectasis, idiopathic pulmonary fibrosis, pulmonary emphysema.

9. The composition for use according to any one of claims 5 to 8, wherein the composition is a composition for administration by the inhalation or intranasal route or by aerosolization.

10. The composition for use according to any one of claims 5 to 9, wherein the composition is in a form selected from the group consisting of aerosol, nasal spray, solution, suspension, nasal drops, inhalation powder .

11. The composition for use according to any one of claims 5 to 10, further comprising hyaluronic acid or a pharmaceutically acceptable salt thereof at a concentration of 0.01% to 1.5% w/w.

12. The composition for use according to any one of claims 5 to 11, wherein the composition comprises, in addition to GSH-C4, one or more additional pharmaceutically active compounds.

13. An inhalation or nasal or oronasal spray delivery device comprising a composition according to any one of claims 5 to 12.