WO2019180635A1

WO2019180635A1 - Composition fo use for the treatment of respiratory and oropharyngeal diseases

Info

Publication number: WO2019180635A1
Application number: PCT/IB2019/052256
Authority: WO
Inventors: Umberto DI MAIO
Original assignee: Neilos SRL
Current assignee: Neilos SRL
Priority date: 2018-03-21
Filing date: 2019-03-20
Publication date: 2019-09-26
Anticipated expiration: 2020-09-21
Also published as: IT201800003804A1

Abstract

The present invention relates to a composition including Propolis, extract of Matricaria recutita and β-glucans for the prevention and/or the treatment of the respiratory and oropharyngeal diseases. Such invention is based upon the synergic action of the above-mentioned active principles.

Description

COMPOSITION FO USE FOR THE TREATMENT OF RESPIRATORY AND OROPHARYNGEAL DISEASES

FIELD OF THE INVENTION

The present invention relates to a composition including Propolis, extract of Matricaria recutita and b-glucans for the prevention and/or treatment of the respiratory and oropharyngeal diseases. Such invention is based upon the synergic action of the above-mentioned active principles.

STATE OF ART

The respiratory apparatus consists of several anatomic structures which are useful for the function thereof.

In fact, it is assigned to the exchange of gas, oxygen and carbon dioxide, between the tissues and the outer environment which is fundamental for all cellular processes of the organism and that is for its life.

Anatomically two macro areas are distinguished which are the upper and the lower respiratory tracts. The first ones consist of nose, pharynx and associated structures, whereas the second ones consist of larynx, trachea, bronchi and lungs, the real respiratory surface is constituted by the alveoli. This complex system of organs is useful to prepare air to enter the lungs, by means of filtration by possible particulate, heating and humidification. At the level of the nasal cavities the particles bigger than 10-15 micron can be locked, this thanks to whiskers and the presence of mucus entrapping these particles apart from precipitation by turbolence, mediated by the turbinates deviating the air direction. The mucus stratifies above the peri- ciliary liquid, wherein the vibritile cilia of the epithelium cells are dipped. Particles of about 10 micron reach trachea, they are entrapped in the mucus and then removed by the ciliary motion. Particles of 2-5 micron settle in the terminal bronchioles by gravitational precipitation, whereas those having sizes lower than 2 microns are removed by the alveolar macrophages and taken away by the pulmonary lymphatic system.

The whole respiratory tract consists of epithelial cells differing by type and function along the tracheobronchial tree. The ciliary columnar cells characterize the respiratory tracts from trachea as far as the terminal bronchioles. From their apical surface cilia protrude having the purpose of moving with cleaning effect on mucus and on possible inhaled particles .

The mucoid calcium-like cells which are assigned to the mucus secretion, useful to keep the correct humidity of epithelium and to entrap particulate. They are present in the widest tracts of the respiratory tracts below the small bronchi but they were not found in the bronchioles.

All components of the respiratory apparatus can be exposed to a series of diseases, of different aetiology, often sustained by different pathogenic microorganisms which, by becoming preponderant in the microenvironment and on the normally existing flora, determine the disease and, consequently, cause a reduced functionality.

The object of the present invention is to provide a composition for use in the prevention and/or treatment of the respiratory and oropharyngeal diseases .

SUMMARY OF THE INVENTION

The present invention is based upon the search for and identification of a new combination of active principles which exert both effects for preventing and treating the respiratory and oropharyngeal diseases .

The present invention relates to compositions comprising or consisting of a mixture of Propolis, extract of Matricaria recutita and b-glucans and to the use thereof in the treatment of the respiratory and/or oropharyngeal diseases. The compositions according to the present invention allow to obtain at the same time:

• Anti-inflammatory effect;

• Antimicrobial effect;

• Immuno-stimulant effect;

• Antioxidant effect.

Other advantages and features of the present invention will result evident from the following detailed description.

DETAILED DESCRIPTION OF THE INVENTION

The present invention describes a composition comprising as main active principles, Propolis, extract of Matricaria recutita and b-glucans.

Propolis is a resinous substance which bees collect from the plants' exudate and which they use to seal the holes in the hive. Propolis mainly consists of resin (50%), wax (30%), essential oils (10%), pollen (5%) and other organic compounds (5%) . The main organic compounds existing in Propolis are phenolic compounds, esters, flavonoids in all forms (flavonols, flavons, flavonons, dihydroflavonons , chalcones), terpenes, beta-steroids, alcohols and aromatic aldeydes, sesquiterpenes and stilbenes. The chemical composition of Propolis varies based upon several factors, such as the source of exudates, the climate and the environmental conditions. The Caffeic Acid Phenetyl Ester (CAPE) is a biologically active ingredient with several interesting properties, thereamong induction of apoptosis of tumour cells and the prevention of metastasis. The polyphenols are chemical compounds associated to several pharmacological properties: antioxidant, antibacterial, antiviral, anti-inflammatory. From a chemical point of view, the phenols can be defined as substances having an aromatic ring thereto one or more hydroxyl groups are bound. The presence of phenols in food can modify their oxidative and microbiological stability: the interest in the extraction of these compounds as antioxidant and antimicrobial natural substances derives therefrom. In Propolis the phenolic compounds are present mainly as flavonoids, the concentration thereof depends upon several factors, such as the plants' species, the season and the environmental factors. The antioxidant capability of Propolis is mainly due to polyphenols and flavonoids it includes and there is a high level of correlation between these chemical compounds and the antioxidant capability of this substance. Other compounds which could contribute in the antioxidant action of Propolis belong to the classes of terpenes, steroids, aldehydes and ketones and it is not excluded that all these chemical compounds could synergize to determine the overall antioxidant effect of Propolis. The action mechanisms contributing in the antioxidant capability of Propolis are the following ones: seizure of free radicals, hydrogen donation, chelation of metal ions or the action thereof, the interference with the propagation reactions and the inhibition of enzymatic systems involved in the initiation reactions. The higher the amount of hydroxyl groups of these compounds is, the higher the reactivity and the capability of being subjected to oxidation reactions will be.

Propolis has also a good anti-inflammatory activity. Among the several compounds existing in Propolis, the most interesting one is surely galangin, which is capable of inhibiting cyclo-oxygenase, lipoxygenase and of inhibiting the expression of COX-2. Another compound, the caffeic acid phenetyl ester (CAPE) has the capability of inhibiting the release of arachidonic acid from the cellular membrane. Chrysin is capable of suppressing the activity of COX-2 and of iNOS, by further contributing to the anti-inflammatory mechanism of Propolis. Propolis further has antimicrobial activities. It has the capability of locking propagation of viruses. Several studies have demonstrated Propolis capability of inhibiting the propagation of several viruses, thereamong Herpes simplex of type 1 and 2, the vesicular stomatitis virus and poliovirus of type 2. Moreover, Propolis has an anti-bacterial activity, mainly against Gram negative bacteria. The chemical compounds responsible for this activity are pinocembrin, galangin, CAPE and other acids and phenol esters. In the compositions of the present invention Propolis prepared according to the procedures known to the person skilled in the art or the products available on the market could be used. According to an embodiment Propolis enriched with one or more of the above-mentioned compounds could be used. The composition could include for example an amount of Propolis ranging between 1 mg and 1000 mg, preferably between 400 and 800 mg.

Camomile (common name of Matricaria recutita) is one of the plants most used by man since ancient times, thereto a variety of beneficial effects on health were attributed. Such plant belongs to the family of Asteraceae and it is commonly represented by two types of main varieties such as German camomile (Chamomilla recutita) and Roman camomile (Chamaemelum nobile) .

In camomile several bioactive components were insulated and characterized thereto the several uses in preparations for medical or cosmetic use are owed. About 128 secondary metabolites were identified in this plant and in particular about 28 compounds which can be classified as terpenes and 36 as flavonoids. The main components of the essential oil extracted from flowers are terpenes such as -bisabolol and the azulenes such as chamazulene. Apart from these main components, sesquiterpenes lactones, glycosides, hydrocoumarins , flavonoids, coumarins and mucilages constitute classes of compounds abundantly present in camomile flowers.

Among flavonoids apigenin is the most interesting compound and in the flowers it is present mainly not in free form but in glycosylated form. Other flavonoids existing in camomile are luteolin, patuletin and quercetin.

Traditionally anti-inflammatory properties are attributed to camomile which can be traced back to the presence of a-bisabolol and flavonoids. Such compounds could determine the inhibition of the release of prostaglandin E2 induced by lipopolysaccharides (LPS) and attenuation of the inducible isoform of cyclooxygenase (COX-2) without acting on the constitutive isoform COX-1.

In particular, from in vitro studies on the single components it resulted that apigenin is capable of reducing adhesion of leucocytes to the human endothelial cells and of inhibiting synthesis of prostaglandins, tumour necrosis factor, interleukin- 1 and nitric oxide. On the contrary, chamazulene was found to be capable of inhibiting synthesis of leukotriene B4 and peroxidation of the arachidonic acid .

As shown in the monography of the European Medical

Agency (EMA) , the ethanol and aqueous extracts of camomile have antimicrobial activity. More in details the first ones have more effectiveness on bacteria such as Pseudomonas aeruginosa, beta hemolytic Streptococci, Enterobacter agglomerans, Escherichia coli and Staphylococcus aureus, whereas the aqueous extracts are more active against moulds and yeasts.

Other important components in the extract of camomile flowers are mucilages, hydrophile components existing in most part of plants wherein they are fundamental for the preservation of water, nutrients, for germination of seeds and thickening of the membranes.

Camomile has a high amount of mucilages which, thanks to their mucoadhesive properties, could guarantee a physical protection at the level of the throat and the pharynx by alleviating the inflammatory symptoms in patients with cough and colds. The beneficial action of camomile as adjuvant treatment in inflammatory and infective syndromes of upper respiratory tracts could be expressed thanks to its anti-inflammatory, antimicrobial and lenitive and emollient properties of mucilages . In the compositions of the present invention an extract of camomile could be used prepared according to the procedures known to the person skilled in the art or the products available on the market. According to an embodiment an extract could be used enriched with one or more of the above-said compounds. The composition could include for example an amount of extract ranging between 0.1 mg and 150 mg, preferably between 10 and 50 mg.

b-glucans are a class of long-chain polysaccharides constituted by a chain of b-D-glucopyranosyl units joined by bonds of b— ( 1—3 ) type and with side chains joined by b— ( 1—4 ) and b— ( 1— 6 ) bonds. They are polymers which can be found abundantly in nature, mainly in cereals such as barley and oat, but even in the wall of bacteria and yeasts such as Saccharomyces cerevisiae. They are provided with different pharmacological activities, thereamong protection from infections, decrease in the plasmatic concentrations of lipids, development inhibition and tumour metastasis. It is believed that asthma and allergies are associated to an excessive Th2 response, b-l , 3-glucans can stimulate macrophages, which produce prostaglandin E2, factor of tumour necrosis and IL-10 and they can inhibit Th2 response.

b-glucans are known modifiers in the biological response. Their effects were investigated after administration through several routes: these polymers are capable of carrying out a good pharmacological activity even when administered by oral route and show a strengthened effect when administered with other immunological therapies. These polymers act by activating the whole immune system.

b-glucans can be derived from several sources and show structural differences and their pharmacological activities are determined by their molecular structure, by the chain length, by the level of branches, by possible structural modifications, by shape and solubility.

As the mammal cells do not synthetize b-glucans, they are recognized as PAMPs (Pathogen Associated

Molecular Patterns, molecular profiles associated to the pathogens) by the receptors of the innate immunity PRR (Pattern Recognition Receptors) existing on the surface of the cells of the immune system. PRR which recognize b-glucans include the toll-like receptors (TLR) , Lectine with domain of type C ( CLR) such as dectin-1, receptors of the complement system (CR3), lactosylceramide and scavenger receptors. The receptors for b-glucan were identified on the surface of the cells of the immune system, thereamong neutrophils, eosinophils, Natural Killer cells, endothelial cells, alveolar epithelial cells and various types of macrophages, as well as cells not belonging to the immune system, thereamong epithelial cells, vascular endothelium cells, fibroblasts, b-glucans are powerful activators of macrophages, monocytes and neutrophils and they are mainly responsible for the stimulation of the reticuloendothelial system. The recognition of the b-glucans as not-self molecules by the mammal cells induces the innate and adaptive immune response. The initial response to b-glucans takes place through the innate immunity. This response is rapid and not specific and mainly involves the phagocytic cells, such as macrophages and neutrophils. b-glucans interact with the mucosal immune system at intestinal level (Peyer plates) and this induces the production of cytokines and the resistance to infections. b-glucans are transported by the intestinal macrophages to the organs of the immune system (spleen, lymph nodes, bone marrow, etc.) through the lymphatic system. In the bone marrow, the b-glucans having the highest molecular weight are degraded into smaller fragments by the macrophages. The signalling mechanism induced by b- glucans does not derive from internalization of these macromolecules, b-glucans induce phagocytosis, they stimulate bactericidal mechanisms such as the respiratory burst and induce the production of components of the innate immune system, such as TNF- ci, Interleukin-1, protein MIP-2 (macrophage inflammatory protein 2-alpha), eicosanoids. Other cells are employed at the infection site and they activate the adaptive immune response. In the compositions of the present invention b-glucans prepared according to the procedures known to the person skilled in the art or the products available on the market could be used. The composition could include for example an amount of b-glucans ranging between 0.1 mg and 2000 mg, preferably between 10 and 500 mg.

The compositions according to the present invention could be formulated in any form suitable to the designated administration and associated to any other suitable component, in a variety of ways, for example they will be formulated for the nasal or inhalatory administration such as liquids, solutions, suspensions, solutions in bottles for nebulization, aerosol, creams, ointments. The compositions could be formulated with excipients and/or diluents. Such excipients can be selected for example among those usually known in the state of art and include, but they are not limited thereto: a) carriers, b) fillers c) moistening agents d) disintegrating agents e) binders etc. In the formulations according to the present invention in liquid forms diluents, carriers, excipients known to the person skilled in the art, could be used.

According to an embodiment the compositions will be formulated for oral use for example as capsules, soft capsules, tablets, pills, gelatines, powders or granules. Such excipients can be selected for example among those usually known in the state of art and they include, but they are not limited thereto: a) carriers, such as for example sodium citrate and calcium phosphate, b) fillers such as for example starch, lactose, microcrystalline cellulose, sucrose, glucose, mannitol and colloidal silica, c) moistening agents, such as for example glycerol, d) disintegrating agents, such as alginates, calcium carbonate, starches, derivatives of starch, of cellulose and of polyvinylpyrrolidone, silicates and sodium carbonate e) binders such as carboxymethylcellulose, alginates, gelatine, polyvinylpyrrolidone, sucrose, polymeric derivatives of cellulose, starch derivatives f) retarding agents such as paraffin, cellulose polymers, esters of fatty acids g) absorption accelerators, such as compounds of quaternary ammonium, h) wetting agents and surfactants such as cetyl alcohol and glycerol monostearate, i) adsorbents, such as bentonite clays and kaolin, k) lubricants such as talcum, calcium stearate, magnesium stearate, polyethylene glycol, sodium lauryl sulfate, sodium stearyl fumarate j) glidants such as talcum, colloidal silica. The forms of solid dosage, such as tablets, capsules, soft capsules, gelatines, pills and granules, could be coated with enteric, gastric coatings or of any other type known in the state of art. They can include opacifiers and can be of the type to allow the release of the active ingredients only or preferably in a certain tract of intestine, in case, in delayed way. Substances which can allow such delayed use include, but they are not limited thereto, polymers and waxes. The soft capsules could house the antioxidant active substances in liquid form alone or in solutions, suspensions or emulsions of the active substances in a liquid solvent. The soft capsules could be characterized by a casing qualitatively similar to that of the hard ones, but thicker and softer.

Liquid forms suitable to an oral administration for example are emulsions, solutions, prepared or extemporaneous suspensions, syrups and elixirs. Excipients suitable to the formulations according to the present invention in liquid forms for oral use include, but they are not limited thereto, diluents such as water or other solvents, solubilizing agents, and emulsifiers selected from ethyl alcohol, polyalcohols, propylene glycol, glycerol, polyethylene glycol and sorbitan esters. These formulations can even include sweeteners and aroma. The compositions could be for example a medical device, food supplement, a nutraceutical , dietary, nutritional composition, food product, a beverage, a neutraceutical product, a medicament, medicated food, food for special medical purposes, food. The compositions mainly will be intended to be used by human beings, but they could also be used on animals. The combination of above-mentioned active ingredients could be used formulated in one single composition according to the various above-described embodiments or in a kit including the several separate ingredients, for example in single compositions such as capsules, pills, tablets for sequential or contemporary administration of the different ingredients. According to an embodiment the compositions according to the present invention will be in form of a spray comprising for example a bottle, a dosing pump and a dispenser.

Preferably, independently from the used type of formulation, the combination of active ingredients according to the present invention will be administered with a daily dosage regime according to the above-mentioned concentrations, that is Propolis in an amount between 1 mg and 1000 mg, the extract of Matricaria recutita in an amount between 0.1 mg and 150 mg and b-glucans are present in an amount between 0.1 mg and 2000 mg.

The compositions according to the present invention will be used for the prevention and/or treatment of the respiratory or oropharyngeal diseases, in particular for a disease selected from rhinitis, sinusitis, pharyngitis, epiglottitis, laryngitis, bronchiolitis, cystic fibrosis, bronchiectasis.

Hereinafter a brief description of some of the specific diseases will be shown which can be treated with the combination of the three active ingredients according to the present invention.

Diseases of the Upper Respiratory Tracts

Rhinitis

Rhinitis is an inflammatory process relating the mucosa of the nasal cavities and it is distinguished in acute and chronical. Acute rhinitis generally are sustained by viruses, thereamong Rhinovirus, Coronavirus, influenza and parainfluenza viruses, RSV, Coxsackie virus, ECHO virus and adenovirus. The contagion takes place by direct contact with the ill subject who, in the peak of maximum infectivity (generally on the first day) , has 500-1000 virions per ml of secretion, which he/she emits through cough and sneezing. Bacterial superinfections are possible which cause complications such as otitis and sinusitis. The common cold by Rhinovirus determines acute symptoms in the first 3-4 days, whereas for 7- 10 days cough and other symptoms persist. There is an excess in mucous secretions which are fluid and transparent, and become purulent and evil-smelling in case of bacterial superimposition. The chronical form generally is secondary to sinusitis, deviations of the nasal septum, hypertrophic adenoids. The allergic rhinitis is due to the exposure by the subject to substances which cause him/her a mediated IgE reaction, characterized by an excessive production of fluids, intranasal pruritus, sneezing and obstruction. IgE, in fact, bind to the mastocytes which release huge amounts of histamine, responsible for all morbid manifestations. Recent studies have highlighted that the allergic rhinitis and asthma are concurrent and to be considered as two manifestations of the whole respiratory tract, rather than place them one in the upper tract and the other one in the lower tract of the respiratory tree. In fact, it results that between 20 and 50% of patients with allergic rhinitis have asthma too and that 30 to 90% of patients with asthma have concomitant rhinitis. Therefore, the allergic rhinitis could be a factor predisposing to the development of allergic asthma, and in the specific case the sensibilization to aeroallergens (pollen or animal hair) would appear to be an important risk factor in the association of asthma and rhinitis. Sinusitis

Sinusitis is the inflammation of the mucosa coating the paranasal sinuses, bone cavities placed in the facial bones and which are in communication with the nasal fossae, and therefore they can infect for the same causes which determine rhinitis. Sinusitis can be distinguished in viral acute or bacterial acute (up to 4 weeks), chronical (beyond 12 weeks) and acute recurrent (at least 4 episodes per year with resolution) . When sinusitis involves nasal cavity one speaks about rhinosinusitis . Generally, a healthy sinus is sterile, characterized by suitable drainage of the mucus, and free passage of air. Ciliary abnormality or immobility determine an inhibition of the drainage resulting in sinusitis. Factors predisposing to this disease are an immunocompromised state, deviation of the nasal septum, nasal polypuses, tumours , trauma and fractures, cocaine abuse, presence of foreign bodies .

A viral acute form can be subjected to bacterial superinfection. The bacteria commonly responsible for these infections are Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Moraxella catarrhalis. Pseudomonas aeruginosa is most frequently present in sinusitis by HIV infections and cystic fibrosis. Some kinds of fungi such as Candida, Aspergillus, Blastomyces, Coccidioides , Rizophus, Histoplasma, and Cryptococcus can cause sinusitis in immunocompromised patients. The signs and symptoms of acute rhinosinusitis consist in: mucopurulent discharges from the nose, nasal obstruction, congestion, facial pain, pressure to the involved sinuses, hyposmia, anosmia, fever, feel of pressure or "plug" in the ears, teeth pain. Generally in the first 3-5 days one is not capable of distinguishing a viral form from a bacterial form, therefore the use of antibiotics is not recommended.

If the disease persists after 10 days, then very probably it will be sustained by bacteria and the antibiotic treatment is recommended. The chronical forms have a slower onset, longer duration and frequency. The symptoms are similar to those of the acute form with, in addition, bad breath, laryngitis, bronchitis and asthma worsening.

Often sinusitis auto-solves, and the treatment is mainly symptomatic. In particular, the decongestant treatment is useful to reduce oedema, to improve drainage of the excess mucus and keep patency of the sinus apertures. A good result can be obtained from the local application of hypertonic saline solution both in the treatment of the acute bacterial form, and of the recurrent acute one and in the chronical one and even for prevention. The selection of the antibiotics, instead, has to take into consideration the production of beta lactamases and of the presence of pneumococci resistant to drugs.

Pharyngitis ( faringo-tonsillitis )

It is an inflammatory process of pharynx, hypopharynx, uvula and tonsils, which generally transmits by direct contact with the respiratory secretions. It is most common in childhood age (5-

15 years), and, although it is frequently auto- limiting, the swelling of the involved portions can cause a reduced patency of the respiratory tracts or, however, can preclude the swallowing of adequate amounts of liquids with consequent dehydration. The infection can be sustained by viruses (such as Epstein-Barr ) and by bacteria. In particular the beta-haemolytic Streptococcus pyogenes of group A is the most frequent one in the paediatric forms, but even Micoplasma pneumoniae, Clamidia pneumoniae are found in adults and children. The forms transmitted by sexual contact and sustained by Neisseria gonorrhoeae and those by Corynebacterium dyphtheriae (form reduced by the use of vaccine) are further to be considered.

Epiglottis .

It is an inflammation of epiglottis, consequent to a viral or bacterial infection, which determines a swelling of the organ with possible obstruction of the respiratory tracts. It is mainly caused by H. influenzae of type b, but even by streptococci, staphylococci or by a thermal trauma. It appears with pain in the ears (in adults), dysphonia, whereas fever is absent up to 50% of cases and it can develop in a late stage. The treatment is antibiotic when the bacteria are the cause of disease, whereas intubation can be requested in case of a severe obstruction of the respiratory tracts. Laryngitis

Inflammation of larynx which appears with aphonia and hoarseness, mainly caused by viruses, but up to 10% of cases even by bacteria (including streptococci and C. dyphtheriae) . Not infective causes can be tumours, thermal or caustic trauma, GERD. Laryngitis has symptoms lasting 3-4 days and, unless bacteria are present, antibiotics are not used .

Diseases of the Lower Respiratory Tracts

Bronchiolitis

Bronchiolitis, frequently paediatric disease, is characterized by an extended inflammation of the respiratory tracts accompanied by an intense production of mucus and by necrosis of epithelial cells. Primarily it is caused by a viral infection, in particular by RSV (respiratory syncytial virus), but even adenovirus, influenza and parainfluenza virus, human metapneumovirus and rhinovirus, whereas the most frequently involved bacteria are of Clamidia genus. In paediatric age the main clinical manifestations are tachypnea, breathlessness or crackles to auscultation, which generally follow an infection of the upper respiratory tracts. The treatment can provide hospitalization in case saturation of oxygen is comprised between 92 and 94%, together with other clinical manifestations like poor nutrition, dehydration and dyspnea anamnesis .

Cystic fibrosis

This disease is caused by a mutation of the gene codifying for protein CFTR, an anionic channel expressed in the epithelial cells in the whole body. Although it acts above all as channel of the chloride ion, it is capable of regulating even the function of other membrane proteins, like the sodium epithelial channel (ENaC) , the activity thereof is inhibited. Among the other several functions, CFTR adjusts even the intracellular secretion of bicarbonate, which is reduced and determines a lowering in epithelial pH with a consequent reduced protection from the microbes and an increase in the viscoelasticity of mucus. The dysfunction of CFTR channel in the lung thus determines an excessive sodium absorption and a reduced active secretion of chlorine with a consequent reduction in the liquid layer of the mucosa surface. This involves an anomalous mucociliary clearance, with retention of viscous mucus which favours the infections and inflammation and then the pulmonary damage. Several studies support the hypothesis that the pulmonary damage is caused even by the vulnerability of the dehydrated mucosa, based thereupon, it was assumed that the hypertonic saline solutions could constitute a new option to increase mucosa hydration and to improve mucociliary clearance.

Bronchiectasis It is a disease characterized by an irreversible dilation of a portion of the bronchial tree in the lungs. The bronchial dilation can be the result of a structural defect of the wall, of the exposure to an abnormal pressure, or of a damage of cartilage or of the elastic tissue after inflammation. It involves bronchi and bronchioles wherein a vicious circle of infection and inflammation can be established, even with release of mediators. Common symptoms are cough producing mucus and chest pain. Mucus has an increased quantity of elastase, and of TNF a, IL-8 and prostanoids. It can appear like a local obstructive process or widespread in a portion of both lobes, even accompanied by sinusitis or asthma. The causes are various, for example, above all in paediatric age, even mycotic infections which leave a permanent damage. Or primary ciliary dyskinesia, wherein there is a marked retention of secretions followed by infections. The cystic fibrosis, as immunodeficiency conditions can be predisposing factors. It was further observed that in patients with ulcerative colitis there are infections of the respiratory tract and bronchiectasis .

The treatment provides the use of antimicrobial agents to fight against the infections sustained both by bacteria and fungi. Moreover, it results to be particularly useful to perform washing of respiratory tracts to increase the removal of secretions, by using saline solutions and to keep the patient, generally, well hydrated.

EXAMPLES

As previously mentioned, in the present invention the synergic action takes place between Propolis, extract of Matricaria recutita and b- glucans . There is synergy when Propolis is present in an amount between 1 mg and 1000 mg, the extract of Matricaria recutita is present in an amount between 0.1 mg and 150 mg and b-glucans are present in an amount between 0.1 mg and 2000 mg.

Hereinafter some not limitative examples of daily dosages of the combination of active ingredients used in the compositions of the present invention are shown. EXAMPLE 1

Pharmaceutical form: Bottle, with dosing pump and dispenser .

EXAMPLE 2

Pharmaceutical form: Capsule.

EXAMPLE 3

Pharmaceutical form: Tablets.

EXAMPLE 4

Pharmaceutical form: Bottle, with dosing pump and dispenser .

Claims

1. A composition comprising Propolis, extract of Matricaria recutita and b-glucans.

2. The composition according to claim 1 for oral, nasal or inhalation administration.

3. The composition according to claim 1 or 2 comprising per dosage unit:

- propolis in an amount between 1 mg and 1000 mg; and/or

- extract of Matricaria recutita in an amount between 0.1 mg and 150 mg; and/or

- b-glucans in an amount between 0.1 mg and 2000 mg .

4. The composition for oral administration according to any one of claims 1 to 3 in a form selected from capsule, soft capsule, tablet, pill, gelatine, powder, granule, emulsion, solution, suspension, syrup.

5. The composition for oral, nasal or inhalation administration according to any one of claims 1 to 3 in a form selected from liquid, solution, suspension, ointment, cream, powder, nebulization solution, aerosol.

6. The composition according to any one of claims 1 to 5 further comprising one or more carriers and/or excipients.

7. The composition according to any one of claims 1 to 6 wherein said composition is a medical device, food supplement, a nutraceutical , dietetic and nutritional composition, food product, a beverage, a nutraceutical product, a medicament, medicated food or food for special medical purposes.

8. The composition according to any one of claims 1 to 7 for use in the prevention and/or treatment of respiratory and/or oropharyngeal disease .

9. The composition according to any one of claims 1 a 7 for use in the prevention and/or treatment of respiratory and/or oropharyngeal disease, wherein said disease is selected from rhinitis, sinusitis, pharyngitis, epiglottitis, laryngitis, bronchiolitis, cystic fibrosis, bronchiectasis .

10. An oral or nasal spray comprising a dispensing composition according to any one of claims 1 to 9.