WO2014023720A1

WO2014023720A1 - Composition for washing or treating the nasal-sinus cavities

Info

Publication number: WO2014023720A1
Application number: PCT/EP2013/066450
Authority: WO
Inventors: Anne Beaulieu; François Andro; Clémence LECARLIER
Original assignee: Laboratoire De La Mer
Priority date: 2012-08-10
Filing date: 2013-08-06
Publication date: 2014-02-13
Also published as: FR2994389B1; FR2994389A1

Abstract

The present invention concerns a composition for washing or treating the nasal-sinus cavities. The invention also concerns the use of such a composition in a device for irrigating the nasal-sinus cavities. To this end, the invention concerns a composition characterised in that it comprises, or consists of, a mixture of the following mineral salts: - sodium chloride, - potassium chloride, - calcium chloride, - magnesium chloride and, - one or a plurality of buffer salts.

Description

Composition for washing or treating nasosinus cavities

The present invention relates to a composition for washing or treating nasosinus cavities. The invention also relates to the use of such a composition in a device for irrigating naso-sinus cavities.

The naso-sinus cavities are a gateway for various microorganisms such as bacteria or viruses that can then colonize the ENT sphere and even extend their progression into the bronchi with consequent development of various pathologies. The mucous membranes of the nasal passages act as filters to prevent these aggressions but can be weakened for example by cold or pollution. A solution known to be effective is to clean the naso-sinus cavities, especially the nasal cavities, to rid them of impurities and to support mucosal cleansing activity. The irrigation, or washing, can be carried out using solutions provided for this purpose, such as saline solutions, for example isoosmotic or hyperosmotic seawater solutions or physiological saline or the water rendered isotonic or hypertonic.

In a pathological situation, for example during rhinosinusitis, we observe: • Surface lesions of the naso-sinus mucosa,

• Congested cells,

• Overproduction and thickening of mucus secretions.

The eyelashes allowing the natural evacuation of the secretions are stuck and can no longer play their role of protective barrier of the respiratory epithelium.

Nasal congestion is the most troublesome symptomatic manifestation. It can be accompanied by rhinorrhea, sneezing, itching, rhino-pharyngeal discharge. In case of congestion of the meatus, sinuses are no longer ventilated. Sinus manifestations are felt such as frontal pain, sinus headache, frontal pressure ...

The washing and irrigation treatment of the nasosinus cavities are recognized as beneficial by otolaryngologists.

Generally irrigation is carried out using a device provided for this purpose, such as a neti pot. This device consists of a container provided with a conduit projecting from the container and terminated by a nozzle intended to be engaged in a nostril. The container is filled with the solution provided for irrigation. Irrigation into the nostril is done by tilting the container and passing the solution through the naso-sinus cavities.

Irrigation of the naso-sinus cavities helps to thin the mucus, allows to evacuate or take off all forms of secretions (fluids, purulent, crusts), to decongest the naso-sinus cavities, to drain the sinus meatus, to help ventilate the sinus cavities. This results in an improvement of the ciliary beat, the clearance, or a better functioning of the defense system of the respiratory system. There is a rapid decrease and a favorable evolution of the naso-sinus symptoms, patients relieved in the long term, a rapid improvement of the quality of life and a quality of life found.

Irrigation with seawater has long been known to be effective. However, the choice and control of osmolarity are not easily achievable. In addition, the amount required to perform a nasal irrigation, that is to say between 120 and 240 mL per application, does not allow the use of sprays too low capacity, or pockets that are not practical for the patients. In addition, pH control, which is recognized today as an important element in an irrigation process, is not easily achievable. The use of saline solution does not solve all these difficulties. In in addition, it is advantageous to have a solution that can easily and safely be used either in hypertonic conditions or in isotonic conditions.

In addition, the so-called "house" solutions prepared with table salt are not suitable for washing and treating nasosinus cavities because of the chemical refining of table salt and the added food additives such as anti-caking agents or acidic salts.

Finally, the salt solutions known to OTO-Rhino-Laryngologists based on coarse salt, and possibly sodium bicarbonate such as that described by Talbot, have a cloudy appearance and are filled with impurities. Surprisingly, these solutions do not restore the mineral wealth of seawater, especially magnesium.

The object of the present invention is to provide a composition for washing and treating nasosinus cavities which does not have the aforementioned drawbacks.

In particular, the object of the present invention is to provide such a composition which allows washing and treatment of nasosinus cavities effective and safe, especially in case of strong nasal congestion, for example in case of rhinitis, sinusitis, rhinosinusitis chronic or in postoperative care. The composition must also be used in preventive care or daily out of pathology period.

Another object of the present invention is to provide such a composition which is quick and easy to use, whose osmolarity can be controlled and safe, in particular which can be used as an isoosmotic or hyperoosmotic solution, and whose pH is known in a certain way and located in a range of effective value.

For this purpose, the invention relates to a composition for washing or treating nasosinus cavities which comprises a mixture of the following mineral salts:

sodium chloride,

- potassium chloride,

- calcium chloride,

magnesium chloride and,

one or more buffer salts.

Treatment of naso-sinus cavities is understood to mean the relief of naso-sinus symptoms such as nasal congestion, rhinorrhea, stagnation, itching, nasopharyngeal discharge, frontal pain, sinus headache and / or frontal pressure.

Preferably, the composition according to the invention consists solely of said mineral salts mentioned above. In particular, the composition is devoid of preservatives or stabilizing agents which may cause undesirable side effects.

According to a first embodiment, the composition comprises:

between 25 and 29%, preferably between 26 and 28%, of sodium chloride,

between 0.5 and 5%, preferably between 0.5 and 2% of potassium chloride, between 5 and 10%, preferentially between 6 and 8% of calcium chloride,

between 61 and 65%, preferably between 62 and 64% of chloride of

magnesium and,

between 1 and 2.5%, preferably between 1 and 1.5% of buffer salt,

According to a second embodiment, the composition comprises:

between 15 and 25%, preferably between 19 and 22%, of sodium chloride,

between 0.5 and 5%, preferably between 0.5 and 2% of potassium chloride,

between 5 and 10%, preferably between 6 and 8% of calcium chloride,

between 32 and 36%, preferably between 33 and 35% of

magnesium and,

between 35 and 39%, preferably between 36 and 38% of buffer salts.

Preferentially, the buffer salt is an acetate, more preferably a bicarbonate, for example sodium.

The composition according to the invention, thanks to the combined action of the five mineral salts, is perfectly adapted to the washing and treatment of the nasosinus cavities by irrigation.

Sodium chloride produces a lytic action to facilitate the evacuation of nasal secretions and plays a role in the prevention of diseases. In particular, the sodium chloride concentration of the composition according to the invention makes it possible to prevent the slowing of the mucociliary beat and the increase in the secretion of the goblet cells. Sodium chloride also has a positive effect on mediators of inflammation (Interleukin-8 and Interleukin-6).

Potassium chloride has a positive effect on the function of the cells of the respiratory epithelium and participates in the cellular regeneration ¹ ' ^{1 ~ 3} \ Calcium chloride has a positive effect on the frequency of beats and mucociliary clearance

Magnesium chloride contributes to the decrease of the local and systemic inflammatory process of allergy. It promotes the decrease of inflammatory cytokine concentrations and the dilation of the airway ^ ^{5 ~ s}

The buffering salt, such as sodium bicarbonate, is to a good tolerability of the composition and ensures an effective dispersion of mucus to facilitate its evacuation ¹ ^.

According to one embodiment of the invention, the composition has a pH of between 7 and 9, preferably 7.2 and 8.8.

The pH range of the composition according to the invention is selected to observe a frequency optimal ciliary beat ^ ¹ For comparison, commonly used saline in irrigation processes naso-sinus cavities has a pH of between 4 , 5 and 7. At such pH, we observe the stop or the massive decrease of the frequency of the ciliary beat.

According to one embodiment, the composition is in the form of a powder. The powder is preferentially dissolved in tap water previously boiled and lukewarm or simply spring water. The hydrophilic formulation of the composition allows instant dissolution of the composition in water.

Advantageously, the composition is in the form of a pre-dosed and bagged powder. The use of pre-dosed sachets facilitates the preparation of hypertonic or isotonic solutions.

For the purposes of the invention, the term "isotonic" is intended to mean a composition whose salt concentration is similar to that of the human body and, by hypertonic means a composition whose concentration in salts is greater than that of the human body.

The invention relates to a composition as described above, that is to say a composition comprising or consisting of a mixture of sodium chloride, potassium chloride, calcium chloride, magnesium chloride and a or several buffer salts, for its use in washing and / or treatment, or irrigation, nasosinus cavities or the relief of naso-sinus symptoms.

The invention also relates to a method or a method for irrigating, washing and / or treating nasosinus cavities or for relieving naso-sinus symptoms, using a composition according to the invention and as described above.

The invention further relates to a composition according to the invention and as previously described as a medicament.

The invention also relates to a composition according to the invention and as described above for its use in the prevention and / or treatment of sinusitis, rhinitis, rhino sinusitis such as chronic rhinosinusitis, post-operative care and / or or nasal congestion of different origin than those mentioned above.

The invention finally relates to the use of such a composition in a device for irrigating naso-sinus cavities.

The characteristics of the invention mentioned above, as well as others, will appear more clearly on reading the following description of exemplary embodiments.

Example:

A composition according to the invention is prepared by mixing the components listed in Table 1.

Table 1 (according to a first embodiment)

Components Quantity (%)

Sodium chloride 26-28%

Calcium chloride 6-8%

Magnesium chloride 62-64%

0.5-2% potassium chloride

Sodium bicarbonate 1-1.5%

TOTAL 100%

pH 7.2-8.8 The various components are reduced to powder and the powders weighed and mixed according to the final amount of desired composition. The composition is buffered to obtain a pH close to 8.

The composition is prepared in the form of a bagged powder of 3.5 to 4.5 g and preferably 4 g.

The dissolution of a sachet in a volume of water of 240 mL allows the preparation of an isotonic solution. This is suitable for nasal-sinus cavity irrigation, for example one to three times a day, or four to six times, in case of rhinitis, sinusitis, chronic rhinosinusitis and postoperative care.

The dissolution of two sachets in a volume of water of 240 mL allows the preparation of a hypertonic solution. This is suitable for irrigation of nasosinus cavities, for example once a day, or two to three times, in case of strong nasal congestion. Table 2 below lists the main electrolytes of a composition according to the invention in comparison with a physiological saline composition and a composition called "home" prepared using fleur de sel.

Table 2

Composition Serum Recipe ORL recipe according to the physiological invention Talbot

(according to one of NaCl 1 liter of water (of 1 liter of water (of first mode of source) in bottle bottle) in bottle realization) + 2 to 3 spoons to + 2 tablespoons coffee convex of coarse salt + 1 coarse salt + 1 tablespoon spoon of slightly baking soda bicarbonate of baking soda

welded

Buffer salts <2% 0% <2% <2%

It is found that the composition according to the invention contains elements such as magnesium, potassium and magnesium that do not comprise the other compositions generally used. These elements are the main electrolytes involved in the regeneration of the respiratory epithelium.

It is further observed that the composition according to the invention, in a method of irrigating the nasosinus cavities, acts favorably on the ciliary beat and its restoration, in particular because of the combined action of pH, calcium and potassium, thereby accelerating mucociliary clearance. The absence of preservatives which have deleterious effects on the nasal mucosa also has an additional advantage.

The composition according to the invention is also effective in detaching and evacuating secretions and crusts in the naso-sinus cavities. It makes it possible to thin the mucus thanks to the presence of sodium bicarbonate, relieves the sinus pressure by decongesting the naso-sinus cavities, effectively drains the maxillary sinuses, regenerates the epithelium by cell multiplication and differentiation, to which is added a reinforcement of cell membranes and helps to ventilate sinus cavities and stimulates the respiratory system of the respiratory system.

Users themselves see a significant decrease in annoying symptoms of the nose and sinuses. More precisely, it is observed that the decongestion takes place by osmotic effect, in which participates the combination of the five inorganic salts of the composition.

Bibliography:

I. Bardou O, Trinh NT, E. Brochiero Molecular diversity and function of K + channels in airway and alveolar epithelial cells. Am Physiol Lung Cell Mol Physiol. 2009; 296 (2): L145-L155.

2. Trinh NT, Prive A, Kheir L, Stuff JC, Hijazi T, Amraei MG, Christmas J,

Brochiero E. Involvement of KATP and KvLQTl K channels in EGF-stimulated alveolar epithelial cell repair processes. Am Physiol Lung Cell Mol Physiol. 2007; 293 (4): L870-882.

3. Trinh NT, Prive A, Mesh E, Noel J, Brochiero E. EGF and K + normal channel activity control and cystic fibrosis bronchial epithelia repair. Am J Physiol

Lung Cell Mol Physiol. 2008; 295 (5): L866-80.

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5. Cordray S, Harjo JB, Miner L. Comparison of intranasal hypertonic dead sea salt spray and intranasal aqueous triamcinolone spray in seasonal allergy rhinitis. Ear Nose Throat J. 2005; 84 (7): 426-430.

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9. A new role for bicarbonate in mucus formation 299: L542-L549, 2010. First published 6 August 2010; Am J Physiol Lung Cell Mol Physiol Eric Y. Chen T., Ning Yang, Paul Quinton M. and Wei-Chun Chin ial explants; 1983; Clinical Science, 64, pp 449-451 doi: 10.1152 / ajplung.00180.2010

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Claims

1) Composition for washing and / or treating nasosinus cavities, characterized in that it consists solely of a mixture of the following mineral salts:

sodium chloride,

- potassium chloride,

- calcium chloride,

magnesium chloride and,

one or more buffer salts chosen from acetates and / or bicarbonates.

2) Composition according to claim 1, characterized in that it consists of:

between 25 and 29%, preferably between 26 and 28%, of sodium chloride, between 0.5 and 5%, preferentially between 0.5 and 2% of potassium chloride,

between 5 and 10%, preferably between 6 and 8% of calcium chloride,

between 61 and 65%, preferably between 62 and 64% of magnesium chloride and,

between 1 and 2.5%, preferably between 1 and 1.5% of one or more buffer salts chosen from acetates and / or bicarbonates.

3) Composition according to claim 1, characterized in that it consists of:

between 15 and 25%, preferably between 19 and 22%, of sodium chloride, between 0.5 and 5%, preferentially between 0.5 and 2% of potassium chloride,

between 5 and 10%, preferably between 6 and 8% of calcium chloride,

between 32 and 36%, preferably between 33 and 35% magnesium chloride and,

between 35 and 39%, preferably between 36 and 38% of one or more buffer salts chosen from acetates and / or bicarbonates.

4) Composition according to one of claims 1 to 3, characterized in that it is in the form of a powder. 5) Composition according to one of claims 1 to 4, characterized in that it is in the form of a pre-dosed and bagged powder.

6) A medicament or pharmaceutical composition comprising a composition as described in one of claims 1 to 5.

7) Composition as defined in one of claims 1 to 5, for its use in the washing and / or treatment of naso-sinus cavities, or the relief of naso-sinus symptoms or the irrigation of nasal cavities. sinus.

8) Composition as defined in one of claims 1 to 5, for its use in the prevention and / or treatment of sinusitis, rhinitis, rhinosinusitis such as chronic rhinosinusitis, in post-operative care and / or nasal congestion of different origin than those mentioned above.