WO2023285984A1

WO2023285984A1 - Glutahtione c4 against airway affections

Info

Publication number: WO2023285984A1
Application number: PCT/IB2022/056453
Authority: WO
Inventors: Rocco Crimi; Enrico Garaci
Original assignee: Redox-Co S.R.L.
Priority date: 2021-07-14
Filing date: 2022-07-13
Publication date: 2023-01-19
Also published as: CN117693352A

Abstract

The present invention relates to the compound glutathione C4 (GSH-C4) for use in the treatment of respiratory airways pathologies as well as to a composition comprising said compound, optionally combined with at least one additional active substance for said use.

Description

GLUTAHTIONE C4 AGAINST AIRWAY AFFECTIONS

The present invention relates to the GSH-C4 compound for use in the treatment of respiratory tract diseases as well as to a composition comprising said compound, optionally in combination with at least one further active substance for said use.

STATE OF THE ART

It is known that the respiratory system is one of the districts with the highest incidence and prevalence of diseases caused by pathogens but also by environmental agents given its easy and wide access to foreign agents.

Among the most frequent affections of the airways there are for example, affecting the upper airways, rhinopathy, rhinosinusitis, colds, pharyngitis, laryngitis, rhinitis, tonsillitis, etc., and affecting the lower airways, chronic and non-chronic cough, tracheitis, bronchitis, pneumonia etc.

In all these pathologies, the mucous membranes suffer more or less serious damage, starting from irritation to actual lesions such as, for example, in the case of crusty haemorrhagic rhinopathies, chronic cough.

Currently, the therapies of choice for the treatment of disorders related to the airways include corticosteroid therapies, optionally in combination with antibiotics, emollients, vasoconstrictors or others.

However, it is known that corticosteroid drugs have numerous side effects both when inhaled and when taken systemically (in the latter case the damage is greater) including mucosal damage, superimposed fungal infections, bleeding, weight gain, osteoporosis, increased blood sugar, skin alterations etc.

It is therefore always of interest to identify further compounds or compositions that can be used in the treatment or to assist in the treatment of airway diseases capable of providing clinical results comparable to those obtained with currently preferred therapies and which show a better tolerability and a lower incidence of side effects.

The 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 is reported in the art (Palamara et al. Evidence of antiviral activity of GSH: in vitro inhibition of HSV type 1 replication . 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).

SUMMARY OF THE INVENTION The authors of the present invention have discovered that the GSH derivative, GSH- C4, can be used effectively, in the treatment or in adjuvating treatment of airway diseases, including post-operative trauma, when administered by inhalation solution to a concentration (w/w) from 0.1 to 1.5%; optionally in combination with 0.05-0.5% (w/w) of hyaluronic acid. The authors of the invention have in fact shown that GSH-C4 is effective in the treatment of upper and lower respiratory tract diseases without causing side relevant effects. Unlike cysteine, which freely enters cells and undergoes oxidation processes, becoming toxic and activating inflammatory responses, or reduced glutathione, which is unable to penetrate the cell membrane, GSH-C4 is able to inhibit inflammatory pathways, restore the cellular redox state, and is expelled from the cells once oxidized.

The following are therefore the object of the invention:

- The GSH-C4 compound for use in the treatment or to assist in the treatment of airway diseases; - A composition comprising GSH-C4 at 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 in the adjuvant treatment of diseases of the airways.

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

GLOSSARY

In the present description, the term GSH-C4 alias butanoyl glutathione or n-butanoyl y- glutamylcysteinylglycine indicates the molecule having the formula

and can be prepared as described in example 2 of the patent application W02005063795 and/or as described in the examples of the patent application WO2019102397A1

The term hyaluronic acid has the meaning commonly used in the art and defines a natural polysaccharide, formed by a linear chain of glucuronic acid and N- acetylglucosamine particles. It has anti-inflammatory, mucoregulatory, anti-oedema and restructuring functions and also performs a bacteriostatic function through the creation of a protective patina on the mucosa, hinders the penetration of pathogens and reduces the proliferation of already existing ones.

Hyaluronic acid has excellent viscoelasticity, high moisture retention capacity, high biocompatibility and hygroscopic properties (Gupta, 2019). In aqueous solution, hyaluronic acid is negatively charged and forms salts generally referred to as hyaluronan or hyaluronate (Laurent, 1989), which are highly hydrophilic and, consequently, surrounded by water molecules. In particular, low molecular weight sodium hyaluronate is able to hydrate itself and can reach a level of water mobilization up to 1000 times its own weight. Its physico-chemical characteristics allow the aggregation of polymer chains with the formation of an extended network (Scott, 1991). Due to the rigidity of the molecule and its ability to attract water, hyaluronate occupies a large volume, forming a gel, resisting mechanical pressure. With increasing molecular weights (MW) and concentration, hyaluronic acid networks are strengthened and, as a result, hyaluronic acid solutions show progressively increased viscosity and viscoelasticity (Kobayashi, 1994). Hyaluronic acid solutions are characterized by a non- Newtonian, thinning-cutting (pseudoplastic) and viscoelastic behaviour. This unique rheological behaviour is peculiar and extremely important, as it determines many physiological roles and pharmaceutical, medical, food and cosmetic applications of hyaluronan (Fallacara, 2018).

DETAILED DESCRIPTION OF THE FIGURES

Figure 1 A-B.

Images obtained by nasal video-endoscopy from a patient suffering from crusted haemorrhagic rhinopathy before treatment with GSH-4 based spray.

Figure 2 A-B. Images obtained by nasal video-endoscopy from a patient suffering from crusted haemorrhagic rhinopathy after 15 days of treatment with a GSH-4 based spray having a composition as shown in Table 1.

Figure 3. Images obtained by nasal video-endoscopy from a patient suffering from perforation of the septum with blood serum diffuse crustiness, before treatment with a GSH-4 based spray.

Figure 4. Images obtained by nasal video-endoscopy from a patient suffering from perforation of the septum with diffuse blood serum crustiness, after 15 days of treatment with a GSH-4 based spray having a composition as shown in Table 1.

Figure 5 A-B.

Images obtained by nasal video-endoscopy from a patient suffering from iatrogenic rhinopathy from abuse of nasal sprays with vasoconstrictors, before treatment with GSH-4 based nasal spray.

Figure 6 A-B. Images obtained by nasal video-endoscopy from a patient suffering from iatrogenic rhinopathy from abuse of nasal sprays with vasoconstrictors, after 15 days of treatment with GSH-4 based spray having a composition as shown in Table 1.

Figure 7 A-C. Computed tomography (CT) images of patient 1, A.P. Female, 62 years old, smoker, suffering from acute bronchitis, cough. Period 4-10 November 2019. SEA: start 6, end 3.

Figure 8 A-C. CT images of patient 2, P.F. Male, 80 years old, former smoker, suffering from right fibrothorax, diffuse bronchiectasis, cough. Period 11-17 November 2019. SEA: start 8, end 2.

Figure 9 A-C. CT images of patient 3, L.R. male, 66 years old, former smoker, suffering from idiopathic pulmonary fibrosis, cough. Period 11-17 November 2019. SEA: start 8, end 6.

Figure 10 A-C. CT images of patient 4, N.E. male, 71 years old, smoker, suffering from pulmonary emphysema, bronchiectasis, cough. Period 14-21 November 2019. SEA: start 5, end 3.

Figure 11 A-C.

CT images of patient 5, M.L. Female, 71 years old, non-smoker, suffering from bronchiectasis, chronic bronchitis, cough. Period 18-24 November 2019. SEA: start 8, end 4.

DETAILED DESCRIPTION

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

In one embodiment, said affections comprise pathologies affecting the upper and / or lower airways, irritations, lesions, inflammation of the mucous membranes. A non- limiting example of such conditions comprises, but is not limited to, rhinopathy, post operative injury, cough, acute bronchitis, diffuse bronchiectasis, idiopathic pulmonary fibrosis, pulmonary emphysema.

According to the present invention, the compound is preferably administered by inhalation or intra-nasal route or by nebulization to an individual in need thereof.

The compound can be formulated into a pharmaceutical composition. The object of the present invention is therefore a composition comprising GSH-C4 at a concentration from 0.01% to 1.5% (w/w) and one or more excipients and/or pharmaceutically acceptable additives for use in the treatment or in adjuvating the treatment of airway diseases.

GSH-C4 can be at any concentration w/w in the range indicated above, such as 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, said GSH-C4 has a concentration from 0.4% to 1.2% w/w, or from 0.6% to 1% w/w, or 0.8% w/w. In one embodiment, the composition as described and claimed herein may comprise other pharmacologically active compounds suitable for the treatment of the airways, such as for example 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 excipients, such as polysaccharides, including hyaluronic acid, which exert a protective action on the oropharyngeal and/or nasopharyngeal mucosa and a mechanical action useful for administering the active ingredient GSH-C4. In a preferred embodiment, the composition may comprise, in addition to excipients commonly used by those skilled in the art in the preparation of pharmaceutical compositions, GSH-C4 at a concentration from 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). GSH-C4 can be at any concentration w/w in the range indicated above, such as 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, said GSH-C4 has a concentration from 0.4% to 1.2% w/w, or from 0.6% to 1% w/w, or 0.8% w/w.

Hyaluronic acid or its pharmaceutically acceptable salt may be at any w/w concentration within the above range. In one embodiment, hyaluronic acid or its pharmaceutically acceptable salt may be at a concentration between 0.8 and 0.3% w/w.

In one embodiment, the composition will therefore consist of GSH-C4 at a concentration from 0.1% to 1.5% (w/w) and hyaluronic acid or a pharmaceutically acceptable salt thereof at a concentration of 0.05. 0.5% (w/w) and suitable excipients. The excipients may vary according to the type of formulation chosen according to what is commonly used by those skilled in the art.

Hyaluronic acid or its salt suitable to be used for the preparation of the composition of the invention may be hyaluronic acid or its high, medium or low molecular weight salt; whose molecular weights are respectively included within the following ranges: 1 ,800- 2,200 KDa, 1000-1800 kDa, 100-500 KDa.

For the preparation of the composition, in any of the forms indicated in the present description, hyaluronic acid and/or any salt of hyaluronic acid suitable for use by inhalation, such as for example the sodium salt of hyaluronic acid (sodium hyaluronate).

According to an embodiment, the present invention refers to a composition formulated in liquid form according to the qualitative-quantitative composition reported in Table 1. Table 1:

According to a further embodiment, the present invention refers to a composition formulated in liquid form according to the qualitative-quantitative composition shown in Table 2.

Table 2:

Preferably, the liquid composition indicated in table 2 can be administered to an individual in need thereof in a dose equal to 3 ml_, every twelve hours, morning and evening, for a total duration of 7 days. According to a further embodiment, the present invention refers to a composition formulated in liquid form according to the qualitative-quantitative composition reported in Table 3.

Table 3:

According to a further embodiment, the present invention refers to a composition formulated in liquid form according to the qualitative-quantitative composition reported in Table 4.

Table 4:

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

According to the invention, the composition as described and claimed can be used for the treatment and/or to adjuvate the treatment of diseases affecting the upper and/or lower airways, irritation, injury, inflammation of the mucous membranes. A non-limiting example is given by rhinopathies, post-operative injuries, cough, acute bronchitis, diffuse bronchiectasis, idiopathic pulmonary fibrosis, pulmonary emphysema.

In a particular embodiment, the composition of the invention can be used for the treatment of those pathologies in which the nasal mucosa is affected by infectious- inflammatory, dysreactive, granulomatous and neoplastic pathologies.

In the first two cases, with different pathogenetic mechanisms, we witness changes in the normal production of secretions that normally cover the nasal mucosa, the onset of congestive states with consequent hypertrophy and oedema of the nasal mucosa, possibly associated with serum-blood crustiness. Conversely, some forms can lead to a sub-atrophy of the mucosa itself, with a qualitative-quantitative modification in the production of secretions. The drugs for topical use currently available are represented by various molecules of cortisones associated or not with antihistamines, vasoconstrictors, antibiotics, and a series of products with various components ranging from blackcurrant to turmeric, from propolis to garlic, from aloe vera to the viburnum. All these last components are characterized by anti-inflammatory, emollient, astringent, immunomodulating properties, etc. Another relevant aspect is then represented by the treatment of the nasal mucosa following rhinological surgery. This therapeutic approach aims to restore, in the shortest time possible, the anatomical-functional integrity of the mucosa itself and in particular conditions, both attributable to the clinical characteristics of the patient and to the type of intervention undergone, is of fundamental importance.

The authors of the invention have shown, as reported in the examples section below, that a nasal spray containing a composition based on GSH-C4 based and hyaluronic acid as reported in Table 1 is effective in the treatment of nasopharyngeal diseases in which there is a need for a tissue repair, either as a result of a mechanical-traumatic injury (nasal surgery) or due to an infection, viral or bacterial. The authors also demonstrated that the composition of the invention as shown in table 2 is effective in the treatment of cough, in particular chronic cough.

It is known that cough is a reflex selected by evolution in order to protect the airways, primarily from the inhalation of foreign bodies. As a protective reflex, it has intrinsic analogies with pain: both have conservative purposes in acute, have a more or less predominant psychological component and become pathological when they occur in chronic.

However, when cough is chronic, it is not a problem that affects only the quality of life. In fact, the continuous afinalistical eliciting of this reflex, can have consequences on the body of the affected person, sometimes of little entity, other times, instead, up to serious and potentially fatal damage.

Mild complications are more frequent and of low risk to the patient's health. Nevertheless, the definition "mild" does not correspond to a low impact on the quality of life, which is however more compromised in patients who manifest these complications. The most frequent are: muscle aches, depression, fatigue, insomnia, headache, gastroesophageal reflux and vomiting. Serious complications are those events that can cause immediate permanent damage or pose a life risk to the patient. They are not common events and are never perceived as normal by people with chronic cough, including rib fractures, pneumothorax and pneumomediastinum, syncope, arrhythmias, urinary incontinence.

When the cough is chronic, it actually stops being a symptom and becomes more like a syndrome involving potential injury to various organs and functions. The clinician's attention must be aimed at investigating all these aspects, considering them as possible and serious complications in patients suffering from chronic cough. The impact on quality of life, on access to the emergency room and hospitalization, on the use of sometimes improper drugs is difficult to estimate, but it is certainly important. A satisfactory result, if it is not possible to obtain cough control, is certainly the prevention and control of these complications.

The authors of the invention have surprisingly discovered that the GSH-C4 compound can be used with benefit for the treatment of chronic cough and for the protection of the respiratory tract. The examples section shows experiments carried out with a liquid composition as reported in Table 2 according to the invention, with the dosage of a 3 ml vial, every 12 hours for 7 consecutive days, on patients suffering from cough and various pulmonary diseases, which demonstrated the effectiveness of the composition of the invention. Advantageously, therefore, the composition for use according to the present invention is a composition suitable for administration by inhalation or intra-nasal route or by nebulization.

According to an embodiment, hence, said composition is in a form selected from aerosol, nasal spray, solution, suspension, nasal drops, powder for inhalation.

The composition object of the invention offers the advantage of being able to be administered by inhalation, by aerosol, nebulization, or spray, therefore in a simple and easy way, even at home, directly into the respiratory tract of patients in need thereof. Thanks to the presence of the highly vascularized nasal mucosa, the inhaled administration of the composition object of the invention allows the action of GSH-C4 at the mucosa level.

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

Some examples of pharmaceutically acceptable carriers include, for example, water, saline, phosphate buffered saline, glycerol, mixture of water and ethanol and the like, as well as combinations thereof. In some cases, it is preferable to include in the composition object of the invention also isotonic agents, for example sugars or poly alcohols, such as mannitol or sorbitol.

Agents capable of increasing the shelf life of the composition can also be used in the composition object of the invention and include wetting agents, emulsifiers, preservatives or buffers.

The composition object of the invention in any of the embodiments described here may also contain stabilizing agents of the microbial load, such as benzalkonium chloride or the like.

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

Advantageously, according to an aspect of the invention, the pharmaceutical composition according to any of the previously described embodiments, can be administered by inhalation and / or intra-nasal and / or oronasal. The dispersion of a pharmaceutical composition according to the invention in very fine drops facilitates its transport through the respiratory tract, increasing the bioavailability of the active ingredients at the level of the mucosal membranes.

According to an aspect of the invention, the composition object of the invention can be made in any form as long as it is suitable for administration of the inhalation and/or intra-nasal and/or oronasal type, and in particular in a form selected from aerosol and/or nasal or oronasal spray, nebulized formulation, solution, emulsion, suspension, nasal drops, powder. The composition object of the invention can also be packaged both in multi-dose containers and in 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 a pharmaceutical composition according to the invention include a nebulizer (or small volume nebulizer, SVN), a metered-dose inhaler (or pressurized metered-dose inhaler, pMDI), ora dry powder inhaler (DPI).

According to an embodiment, the GSH-C4 can be administered to an individual in need thereof, in the form of a liquid or powder composition for aerosol, from a nebulizer activated by inspiring from the appropriate dispenser or through the classic ultrasonic electric devices or with a piston. The selection of the most appropriate dispensing device for administering a composition object of the invention can be made in relation to the type of patient, the greater ease of use, or the frequency of administration. Therefore, an inhaled delivery device or a delivery device by means of a nasal or oronasal spray comprising a pharmaceutical composition according to any of the previously described embodiments is also object of the invention.

According to an embodiment of the invention, said nasal or oronasal spray delivery device can comprise a bottle and/or vial containing the pharmaceutical composition to be administered and a spray atomizer system connected to a terminal syringe, for example in the form of a spout, to allow the delivery of an optimal volume of the composition per dose directly into the nasal or oronasal cavity.

Through the generation of a thin local cloud of particles, said delivery device by means of a nasal or oronasal spray enables the delivery of an appropriate dose of the composition object of the invention quickly and effectively within the nasal or oronasal cavity. The device can alternatively be equipped with an oronasal mask in order to allow delivery throughout the oropharyngeal cavity.

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

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

At any point in the description and in the claims, the term comprising may be replaced by the term "consisting of". Examples are reported below which have the purpose of illustrating embodiments of the compositions disclosed in the present description, these examples are in no way to be considered as a limitation of the previous description and subsequent claims.

EXAMPLES

All patients subjected to the tests described below provided their informed consent.

Nine patients with rhinological pathologies were recruited in the period May-June 2020, evenly distributed by sex and age. In particular, n.1. suffering from specific vasomotor rhinopathy, n.2 from nonspecific vasomotor rhinopathy, n.2 from iatrogenic rhinopathy (abuse of vasoconstrictors) n.2 from crusted haemorrhagic bacterial infectious rhinitis (one with perforation of the nasal septum) and n.2 patients that underwent nasal surgery.

Example 1

All enrolled patients, after a preliminary ENT specialist visit, were administered, as the only local therapy, the Glutathione spray having a composition as shown in the example of Table 1, with a dosage of two sprays per nostril, morning and evening for 15 consecutive days.

A nasal video-endoscopy was performed in each patient before and after the treatment and an anamnesis focused on the nasal symptoms before and after the treatment as well as the degree of satisfaction with the therapy received was collected.

None of the patients complained of any significant side effects. Only one patient complained of a slight sensation of nasal "burning", which was, by the way, of short duration.

RESULTS

Cases with crusted-haemorrhagic rhinopathy showed a complete restitutio in integrum of the epithelium. The cases with Iatrogenic rhinopathy, in particular the patient who, for years had been abusing topical vasoconstrictors, corticosteroids, reported a marked improvement in symptoms and nasal objectivity. This last observation is relevant; in fact, iatrogenic rhinopathies often represent a difficult problem to solve. The antioxidant properties of GSH, probably, determine a rebalancing and eutrophicating activity on the nasal mucosa of these patients who, as known from the numerous evidences present in the literature, presents (the nasal mucosa in fact) serious alterations such as profound alteration and/or disappearance of cilia, changes in the glandular component, alterations in nerve endings, etc. Cases with specific and non-specific vasomotor rhinopathy (allergic rhinopathy) showed an improvement in symptoms. However, the study sample is too small to evaluate the efficacy of GSH versus topical corticosteroid therapy.

The result in patients undergoing rhinological surgery is also relevant. A rapid restitutio in integrum of the mucosa without using any other topical drug was observed.

Example 2

After a preliminary ENT specialist visit, a liquid composition as defined in the example of Table 2 was administered by aerosol to all enrolled patients, as sole local therapy, with a dosage of a 3 ml vial, every 12 hours for 7 consecutive days.

The effect of inhalation of the compound based on GSH-C4 at a concentration of 0.8% (composition Table 2) on the cough symptom was evaluated in 5 patients who presented the clinical symptom and who were suffering from various lung diseases (see detail of patients with relative chest CT images, Figs. 7-11). The instrument used for the quantification of the cough symptom was the visual analogic scale (VAS) (from 1 to 10), as per the recommendations of the recent guideline of the European Society of Respiratory Medicine [14] The duration of treatment was empirically defined as approximately one week with aerosol administration of a dose of 3 ml every 12 hours. RESULTS

The results of this pilot study are shown in Figures 7-11 and synthetically summarized in Table 5 below:

Table 5

The data show that in all patients there was a reduction in the intensity of the cough symptom, subjectively assessed using the VAS scale. In 3 out of 5 cases this reduction was equal to or greater than 50%, compared to the starting value. No patient reported side effects following the inhalation of GSH-C4.

Despite the small number of patients studied, the results indicate a beneficial effect of the inhalation of GSH-C4 on the cough symptom in the absence of side effects.

Example 3

All enrolled patients, after a preliminary ENT specialist visit, were administered, as the only local therapy, the Glutathione spray having a composition as shown in the example of Table 3 reported in this description, with a dosage of two sprays per nostril, in the morning and evening for 15 consecutive days.

The authors of the invention have demonstrated that a nasal spray containing a composition exclusively based on GSH-C4 as reported in the aforementioned Table 3 is effective in the treatment of nasopharyngeal diseases in which there is a need for tissue repair, both as a consequence of a mechanical-traumatic insult (nasal surgery) or as a consequence of a viral or bacterial infection.

Example 4

All enrolled patients, after a preliminary ENT specialist visit, were administered by aerosol, as the only local therapy, a liquid composition as defined in the example of Table 4 reported in this description, with a dosage of a 3 ml vial, each 12 hours for 7 consecutive days.

The authors have demonstrated that the composition of the invention as shown in Table 4 is effective in the treatment of cough, in particular of chronic cough. It is known that cough is a reflex selected by evolution in order to protect the airways, primarily from the inhalation of foreign bodies.

Claims

1. GSH-C4 compound for use in the treatment or to aid in the treatment of airway affections.

2. The compound for use according to claim 1, wherein said airway affections comprise diseases affecting the upper and/or lower airways, irritations, lesions, inflammations of the mucosa.

3. The compound according to claim 3 wherein said affections are rhinopathies, post-operative lesions, cough, acute bronchitis, diffuse bronchiectasis, idiopathic pulmonary fibrosis, pulmonary emphysema.

4. The compound for use according to claim 1 or 2, wherein said compound is administered by inhalation or intra-nasal route or by means of nebulization to an individual in need thereof.

5. A composition comprising GSH-C4 at a concentration from 0.01% to 1.5% (w/w) and one or more pharmaceutically acceptable excipients and/or additives for use in the treatment or to aid in the treatment of airway affections.

6. The composition for use according to claim 5, wherein said GSH-C4 has a concentration from 0.4% to 1.2% w/w, or from 0.6% to 1% w/w, or at 0.8% w/w.

7. The composition for use according to any one of claims 5 or 6 wherein said airway affections comprise diseases affecting the upper and/or lower airways, irritations, lesions, inflammations of the mucosa.

8. The composition for use according to any one of claims 5 to 7, wherein said affections are rhinopathies, post-operative lesions, 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 said composition is a composition for administration by inhalation or intra-nasal route or by nebulization.

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

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 from 0.01% to 1.5% w/w.

12. The composition for use according to any one of claims 5 to 11 wherein said composition comprises one or more further pharmaceutically active compounds besides GSH-C4.

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