Electrolyte composition in powder form for topical applications

Abstract

The invention relates to an electrolyte mineral composition in powder form, intended to be dissolved in a predetermined volume of water, for topical applications for use as a medicinal product and as a medical device, the composition comprising a specific concentration of chloride (Cl), sodium (Na), sulfate (SO4), sulfur (S), magnesium (Mg), calcium (Ca), potassium (K), and bicarbonate (HCO3). This composition, combining pharmaceutical-grade salts, is dosable, reproducible, stable, and well tolerated, and may be used alone or in combination with other ingredients, to inhibit inflammatory factors and / or to promote healing and / or to promote ciliary beating, in particular in the treatment and prevention of diseases associated with inflammatory disorders and / or for healing purposes and / or disorders of mucociliary function.

Description

Description Title of the invention: Electrolytic composition in powder form for topical applications

[0001] The invention relates to an electrolytic mineral composition in powder form, to be dissolved in a predetermined volume of water, for topical applications for use as a medicinal product and medical device, comprising a specific concentration of chloride (Cl), sodium (Na), sulfate (SO4), sulfur (S), magnesium (Mg), calcium (Ca), potassium (K), and bicarbonate (HCO3). This composition, combining pharmaceutical-grade salts, is dosable, reproducible, stable, well-tolerated, and can be used alone or in combination with other ingredients to inhibit inflammatory and / or allergic factors and / or promote wound healing and / or ciliary beat, particularly in the treatment and prevention of diseases associated with inflammatory disorders, allergic reactions, wound healing, and / or mucociliary dysfunction. Previous Art

[0002] In a number of chronic inflammatory pathologies involving the mucous membranes and / or skin, a link is observed between increased oxidative stress (Mishra 2018), impaired barrier function leading to microlesions and dysfunctions of local immune processes.

[0003] In ENT, in polyposis, the severity of oxidative stress is significantly correlated with the severity of nasal obstruction and congestion (Topai 2014).

[0004] Since permeability is a key factor in triggering inflammatory mechanisms, we better understand the importance of limiting oxidative stress and preserving or restoring the protective barrier function of mucous membranes.

[0005] The nasal mucosa plays a particularly important protective role. Mucociliary clearance is a defense mechanism involving the secretory cells of the epithelium that produce respiratory mucus, which traps inhaled airborne contaminants. Through the coordinated beating of the cilia of the epithelial cilia, the mucus and the particles it contains are transported to the nasopharynx and then eliminated from the airways by swallowing, blowing the nose, or coughing.

[0006] It is known that the main components of air pollution can induce oxidative stress and inflammatory responses in nasal epithelial cells (Hong, 2016). Prolonged contact with air pollutants and allergens, or with respiratory pathogens, leads to pulmonary inflammation and damage to the respiratory epithelium.

[0007] It has also been shown that ciliary beat frequency can be impacted by air pollutants (Hong 2016, Calderon 2001), by Certain antibiotics (Hong 2016) or factors produced by bacteria found in the lungs, such as Pseudomonas aeruginosa, Streptococcus pneumoniae, or Haemophilus influenzae (Janson 1999; Read 1992; Steinfort 1989), can alter ciliary beat frequency. This is also seen in respiratory conditions such as allergic rhinitis and asthma (Holmstrom 1992; Maurizi 1984; Mezey 1978; Ohashi 1985).

[0008] Repair of lesions and regeneration of a mature and functional epithelium are crucial to restoring epithelial defense properties, particularly in terms of mucociliary clearance.

[0009] Various saline nasal irrigation solutions are commonly used as adjunctive treatment for both upper airway pathologies and post-surgical treatments (Tomooka 2000). Numerous studies have demonstrated the benefits of these saline solutions in cases of acute rhinitis (Mezey 1978, Ohashi 1985, Tomooka 2000, Salpak 2008 and Tano 2004), allergic rhinitis (Gallant 2018, Hermelingmeier 2012, Roberts 2013, Anigier 2010, Chia-Ling 2019, Head 2018), acute sinusitis (Scadding 2017, Wang 2014, Wang 2009), chronic rhinosinusitis (Rosenfeld 2015, Fokkens 2012, Seppey 1996, Holmstrom 1997, Slapak 2008, Culig 2010, Hahn 2013, Salib 2013) or after endonasal surgery (Rosenfeld 2015). : - the reduction of nasal symptoms including nasal obstruction, rhinorrhea, postnasal drip, itching, sneezing, loss of smell, dry nose (Seppey 1996-Holmstrom 1997, Slapak 2008, Culig 2010, Hahn 2013, Salib 2013, Tugrul 2015, Atar 2022) - improvement in quality of life (Culig 2010, Hahn 2013, Tugrul 2015) - the prevention or reduction of allergic reactions (Chen 2014) - improved healing after endonasal surgery (Salib 2013 Tugrul 2015) - the reduction of drug treatments (Seppey 1996, Slapak 2008) particularly in acute rhinitis.

[0010] In vitro, various studies show the role of certain electrolytes, in particular calcium on ciliary beat or magnesium in the mechanisms of inflammation.

[0011] In vitro, an experiment on the respiratory mucosa (Bonnomet 2016) demonstrated the benefits of seawater on ciliary beat frequency and the rate of wound repair in the nasal epithelium, suggesting a potential therapeutic role for electrolytes in respiratory pathologies and post-surgical treatment. The seawater used was isotonic and obtained by two different manufacturing processes: one by electrodialysis, the other by dilution. A difference favoring the first process was shown in 14 subjects. This same study demonstrated the deleterious impact of solutions of sodium chloride.

[0012] A multicenter randomized post-surgical study demonstrated the clinical superiority of a solution containing sodium chloride, potassium, bicarbonates, calcium, and magnesium (vs. a sodium chloride solution alone). The addition of these minerals led to a postoperative reduction in crusting, faster resolution of secretions, and a decrease in epistaxis, particularly in subjects aged 60 years and older, smokers, and the most severely ill patients (de Gabory 2019).

[0013] However, the mechanisms of action that take place at the level of the mucosa are little known and the conclusions of the consensus are unanimous on the need to determine the composition of the saline solution in qualitative and quantitative terms (which minerals and in what quantity) according to the objective aimed at and in particular in order to restore the barrier function more effectively, by optimizing the action of the solutions at the level of the ciliary beat, in terms of healing, anti-inflammatory, and antioxidant.

[0014] The contact times of these solutions with the mucous membrane, particularly in daily, multiple daily or prolonged use, justify the search for electrolytic matrices adapted to the respiratory system.

[0015] The Applicant has surprisingly identified electrolytic compositions including mineral salts that inhibit 9 markers of inflammation, the interleukins IL8, IL6, IL18, IL5, IL13, IL4, the cytokines TSLP (Thymia Stromal LymphoPoietin), GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor), the chemokine CCL26 (CC Motif Chemokine Ligand 26), also called eotaxin-3.

[0016] These compositions can be used to reduce the inflammatory markers IL-8, IL-6, TSLP, GM-CSF, CCL26, IL-18, and IL-5, or markers most often associated with allergic reactions, asthma, or atopic dermatitis, such as TSLP, CCL26, and IL-5. They are beneficial in the treatment or prevention of all local inflammatory conditions, including rhinitis, pharyngitis, bronchitis, and dermatitis, but particularly nasal polyposis, allergic rhinitis, asthma, and atopic dermatitis. They can be used alone or in combination with other ingredients for the prevention, pretreatment, treatment, or monitoring of anti-inflammatory and allergy medications such as corticosteroids, antihistamines, vasoconstrictors, vasodilators, and even antifibrotics or therapeutic antibodies.

[0017] These (corticosteroids, antihistamines, vasoconstrictors, vasodilators, therapeutic antibodies) are satisfactory but they have problematic side effects and adverse effects, especially in chronic, prolonged use, or in sensitive subjects such as children, pregnant women, breastfeeding women, the elderly or those taking multiple medications.

[0018] Advantageously, the plaintiff also identified compositions that combine both anti-inflammatory properties as described above with healing properties. Description of the invention

[0019] Thus, according to a first aspect, the invention relates to an electrolytic composition of minerals in powder form, to be dissolved in a predetermined volume of water, intended to provide, after reconstitution in one liter of water, a solution having the following characteristics: - a pH of 7.2 to 8.2; - a conductivity of 17 to 19 mS / cm; - an osmolarity of 280 to 360 mOsm / kg, preferably 280 to 330 mOsm / kg, even more preferably 290 to 320 mOsm / kg, and comprising the following content of the main constituents: - 2200 to 3800 mg / L of sodium (Na); - 5200 to 6700 mg / L of chloride (Cl); - 30 to 120 mg / L of bicarbonate (HCO3); - 850 to 1900 mg / L of magnesium (Mg); - 450 to 750 mg / L of calcium (Ca); - 50 to 150 mg / L of potassium (K); - 1250 to 2600 mg / L of sulfate (SO4).

[0020] According to one embodiment, the composition further comprises: - 550 to 3000 mg / L of sulfur (S).

[0021] According to one embodiment, the composition according to the invention further comprises at least one of: zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), iron (Fe).

[0022] Preferably, the pH of the composition is between 7.2 and 8.2.

[0023] According to one embodiment, the pH of the solution is 7.9.

[0024] According to one embodiment, the pH of the solution is 7.4.

[0025] According to one embodiment, the pH of the solution is 7.5.

[0026] Preferably, the composition has an osmolarity of 290 to 315 mOsm / kg.

[0027] According to one embodiment, the composition has an osmolarity of 314 mOsm / kg.

[0028] According to one embodiment, the composition has an osmolarity of 293 mOsm / kg.

[0029] According to one embodiment, the composition has an osmolarity of 306 mOsm / kg.

[0030] According to one embodiment, the composition has an osmolarity of 351 mOsm / kg.

[0031] Preferably, the composition has a conductivity of 18 to 19 mS / cm.

[0032] According to one embodiment, the composition has a conductivity of 18.6 mS / cm

[0033] According to one embodiment, the composition has a conductivity of 18.4 mS / cm

[0034] According to one embodiment, the composition has a conductivity of 18.7 mS / cm

[0035] According to one embodiment, the composition comprises the following content of the main constituents: - 2200 to 3500 mg / L of sodium; - 5200 to 6700 mg / L of chloride (Cl) - 95 to 120 mg / L of bicarbonate; - 1400 to 1900 mg / L of magnesium; - 450 to 750 mg / L of calcium (Ca) - 50 to 60 mg / L of potassium; - 1900 to 2600 mg / L of sulfate.

[0036] According to one embodiment, the composition comprises 800 to 3000 mg / L of sulfur.

[0037] According to one embodiment, the composition comprises a chloride (Cl) content selected from: 5200 mg / L or 5210 mg / L or 5220 mg / L or 5230 mg / L or 5240 mg / L or 5250 mg / L or 5260 mg / L or 5270 mg / L or 5280 mg / L or 5290 mg / L or 5300 mg / L or 5310 mg / L or 5320 mg / L or 5330 mg / L or 5340 mg / L or 5350 mg / L or 5360 mg / L or 5370 mg / L or 5380 mg / L or 5390 mg / L or 5400 mg / L or 5410 mg / L or 5420 mg / L or 5430 mg / L or 5440 mg / L or 5450 mg / L or 5460 mg / L or 5470 mg / L or 5480 mg / L or 5490 mg / L or 5500 mg / L or 5510 mg / L or 5520 mg / L or 5530 mg / L or 5540 mg / L or 5550 mg / L or 5560 mg / L or 5570 mg / L or 5580 mg / L or 5590 mg / L or 5600 mg / L or 5610 mg / L or 5620 mg / L or 5630 mg / L or 5640 mg / L or 5650 mg / L or 5660 mg / L or 5670 mg / L or 5680 mg / L or 5690 mg / L or 5700 mg / L or 5710 mg / L or 5720 mg / L or 5730 mg / L or 5740 mg / L or 5750 mg / L or 5760 mg / L or 5770 mg / L or 5780 mg / L or 5790 mg / L or 5800 mg / L or 5810 mg / L or 5820 mg / L or 5830 mg / L or 5840 mg / L or 5850 mg / L or 5860 mg / L or 5870 mg / L or 5880 mg / L or 5890mg / L or 5900 mg / L or 5910 mg / L or 5920 mg / L or 5930 mg / L or 5940 mg / L or 5950 mg / L or 5960 mg / L or 5970 mg / L or 5980 mg / L or 5990 mg / L or 6000 mg / L or 6010 mg / L or 6020 mg / L or 6030 mg / L or 6040 mg / L or 6050 mg / L or 6060 mg / L or 6070 mg / L or 6080 mg / L or 6090 mg / L or 6100 mg / L or 6110 mg / L or 6120 mg / L or 6130 mg / L or 6140 mg / L or 6150 mg / L or 6160 mg / L or 6170 mg / L or 6180 mg / L or 6190 mg / L or 6200 mg / L or 6210 mg / L or 6220 mg / L or 6230 mg / L or 6240 mg / L or 6250 mg / L or 6260 mg / L or 6270 mg / L or 6280 mg / L or 6290 mg / L or 6300 mg / L or 6310 mg / L or 6320 mg / L or 6330 mg / L or 6340 mg / L or 6350 mg / L or 6360 mg / L or 6370 mg / L or 6380 mg / L or 6390 mg / L or 6400 mg / L or 6410 mg / L or 6420 mg / L or 6430 mg / L or 6440 mg / L or 6450 mg / L or 6460 mg / L or 6470 mg / L or 6480 mg / L or 6490 mg / L or 6500 mg / L or 6510 mg / L or 6520 mg / L or 6530 mg / L or 6540 mg / L or 6550 mg / L or 6560 mg / L or 6570 mg / L or 6580 mg / L or 6590 mg / L or 6600 mg / L or 6610 mg / L or 6620 mg / L or 6630 mg / L or 6640 mg / L or 6650 mg / L or 6660 mg / L or 6670 mg / L or 6680 mg / L or 6690 mg / L or 6700 mg / L.

[0038] Preferably, the composition includes 5400 to 6600 mg / L of chloride (Cl).

[0039] According to one embodiment, the composition comprises 6200 to 6600 mg / L of chloride (Cl), preferably 6478 mg / L.

[0040] According to one embodiment, the composition comprises 5300 to 5800 mg / L of chloride (Cl), preferably 5485 mg / L or 5672 mg / L.

[0041] According to one embodiment, the composition comprises 6471 mg / L of chloride (Cl).

[0042] According to one embodiment, the composition comprises a sodium (Na) content selected from: 2200 mg / L or 2210 mg / L or 2220 mg / L or 2230 mg / L or 2240 mg / L or 2250 mg / L or 2260 mg / L or 2270 mg / L or 2280 mg / L or 2290 mg / L or 2300 mg / L or 2310 mg / L or 2320 mg / L or 2330 mg / L or 2340 mg / L or 2350 mg / L or 2360 mg / L or 2370 mg / L or 2380 mg / L or 2390 mg / L or 2400 mg / L or 2410 mg / L or 2420 mg / L or 2430 mg / L or 2440 mg / L or 2450 mg / L or 2460 mg / L or 2470 mg / L or 2480 mg / L or 2490 mg / L or 2500 mg / L or 2510 mg / L or 2520 mg / L or 2530 mg / L or 2540 mg / L or 2550 mg / L or 2560 mg / L or 2570 mg / L or 2580 mg / L or 2590 mg / L or 2600 mg / L or 2610 mg / L or 2620 mg / L or 2630 mg / L or 2640 mg / L or 2650 mg / L or 2660 mg / L or 2670 mg / L or 2680 mg / L or 2690 mg / L or 2700 mg / L or 2710 mg / L or 2720 ​​mg / L or 2730 mg / L or 2740 mg / L or 2750 mg / L or 2760 mg / L or 2770 mg / L or 2780 mg / L or 2790 mg / L or 2800 mg / L or 2810 mg / L or 2820 mg / L or 2830 mg / L or 2840 mg / L or 2850 mg / L or 2860 mg / L or 2870 mg / L or 2880 mg / L or 2890mg / L or 2900 mg / L or 2910 mg / L or 2920 mg / L or 2930 mg / L or 2940 mg / L or 2950 mg / L or 2960 mg / L or 2970 mg / L or 2980 mg / L or 2990 mg / L or 3000 mg / L or 3010 mg / L or 3020 mg / L or 3030 mg / L or 3040 mg / L or 3050 mg / L or 3060 mg / L or 3070 mg / L or 3080 mg / L or 3090 mg / L or 3100 mg / L or 3110 mg / L or 3120 mg / L or 3130 mg / L or 3140 mg / L or 3150 mg / L or 3160 mg / L or 3170 mg / L or 3180 mg / L or 3190 mg / L or 3200 mg / L or 3210 mg / L or 3220 mg / L or 3230 mg / L or 3240 mg / L or 3250 mg / L or 3260 mg / L or 3270 mg / L or 3280 mg / L or 3290 mg / L or 3300 mg / L or 3310 mg / L or 3320 mg / L or 3330 mg / L or 3340 mg / L or 3350 mg / L or 3360 mg / L or 3370 mg / L or 3380 mg / L or 3390 mg / L or 3400 mg / L or 3410 mg / L or 3420 mg / L or 3430 mg / L or 3440 mg / L or 3450 mg / L or 3460 mg / L or 3470 mg / L or 3480 mg / L or 3490 mg / L or 3500 mg / L or 3510 mg / L or 3520 mg / L or 3530 mg / L or 3540 mg / L or 3550 mg / L or 3560 mg / L or 3570 mg / L or 3580 mg / L or 3590 mg / L or 3600 mg / L or 3610 mg / L or 3620 mg / L or 3630 mg / L or 3640 mg / L or 3650 mg / L or 3660 mg / L or 3670 mg / L or 3680 mg / L or 3690 mg / L or 3700 mg / L or 3710 mg / L or 3720 mg / L or 3730 mg / L or 3740 mg / L or 3750 mg / L or 3760 mg / L or 3770 mg / L or 3780 mg / L or 3790 mg / L or 3800 mg / L.

[0043] Preferably, the composition includes 2300 to 3400 mg / L of sodium (Na).

[0044] According to one embodiment, the composition comprises 2200 to 2500 mg / L of sodium (Na), preferably 2369 mg / L or 2463 mg / L.

[0045] According to one embodiment, the composition comprises 3100 to 3300 mg / L of sodium (Na), preferably 3211 mg / L.

[0046] According to one embodiment, the composition comprises 3669 mg / L of sodium (Na).

[0047] According to one embodiment, the composition comprises a bicarbonate (HCO3-) content selected from: 30 mg / L or 31 mg / L or 32 mg / L or 33 mg / L or 34 mg / L or 35 mg / L or 36 mg / L or 37 mg / L or 38 mg / L or 39 mg / L or 40 mg / L or 41 mg / L or 42 mg / L or 43 mg / L or 44 mg / L or 45 mg / L or 46 mg / L or 47 mg / L or 48 mg / L or 49 mg / L or 50 mg / L or 51 mg / L or 52 mg / L or 53 mg / L or 54 mg / L or 55 mg / L or 56 mg / L or 57 mg / L or 58 mg / L or 59 mg / L or 60 mg / L or 61 mg / L or 62 mg / L or 63 mg / L or 64 mg / L or 65 mg / L or 66 mg / L or 67 mg / L or 68 mg / L or 69 mg / L or 70 mg / L or 71 mg / L or 72 mg / L or 73 mg / L or 74 mg / L or 75 mg / L or 76 mg / L or 77 mg / L or 78 mg / L or 79 mg / L or 80 mg / L or 81 mg / L or 82 mg / L or 83 mg / L or 84 mg / L or 85 mg / L or 86 mg / L or 87 mg / L or 88 mg / L or 89 mg / L or 90 mg / L or 91 mg / L or 92 mg / L or 93 mg / L or 94 mg / L or 95 mg / L or 96 mg / L or 97 mg / L or 98 mg / L or 99 mg / L or 100 mg / L or 101 mg / L or 102 mg / L or 103 mg / L or 104 mg / L or 105 mg / L or 106 mg / L or 107 mg / L or 108 mg / L or 109 mg / L or 110mg / L or 111 mg / L or 112 mg / L or 113 mg / L or 114 mg / L or 115 mg / L or 116 mg / L or 117 mg / L or 118 mg / L or 119 mg / L or 120 mg / L.

[0048] Preferably, the composition comprises 95 to 120 mg / L of bicarbonate (HCO3), preferably between 95 and 100 mg / L, even more preferably 97 mg / L.

[0049] Preferably, the composition comprises 95 to 120 mg / L of bicarbonate (HCO3), preferably between 110 and 120 mg / L, even more preferably 113 mg / L or 117 mg / L.

[0050] According to one embodiment, the composition comprises 39 mg / L of bicarbonate (HCO3).

[0051] According to one embodiment, the composition comprises a magnesium (Mg) content selected from: 850 mg / L or 860 mg / L or 870 mg / L or 880 mg / L or 890 mg / L or 900 mg / L or 910 mg / L or 920 mg / L or 930 mg / L or 940 mg / L or 950 mg / L or 960 mg / L or 970 mg / L or 980 mg / L or 990 mg / L or 1000 mg / L or 1010 mg / L or 1020 mg / L or 1030 mg / L or 1040 mg / L or 1050 mg / L or 1060 mg / L or 1070 mg / L or 1080 mg / L or 1090 mg / L or 1100 mg / L or 1110 mg / L or 1120 mg / L or 1130 mg / L or 1140 mg / L or 1150 mg / L or 1160 mg / L or 1170 mg / L or 1180 mg / L or 1190 mg / L or 1200 mg / L or 1210 mg / L or 1220 mg / L or 1230 mg / L or 1240 mg / L or 1250 mg / L or 1260 mg / L or 1270 mg / L or 1280 mg / L or 1290 mg / L or 1300 mg / L or 1310 mg / L or 1320 mg / L or 1330 mg / L or 1340 mg / L or 1350 mg / L or 1360 mg / L or 1370 mg / L or 1380 mg / L or 1390 mg / L or 1400 mg / L or 1410 mg / L or 1420 mg / L or 1430 mg / L or 1440 mg / L or 1450 mg / L or 1460 mg / L or 1470 mg / L or 1480 mg / L or 1490 mg / L or 1500 mg / L or 1510 mg / L or 1520 mg / L or 1530 mg / L or 1540 mg / L or 1550mg / L or 1560 mg / L or 1570 mg / L or 1580 mg / L or 1590 mg / L or 1600 mg / L or 1610 mg / L or 1620 mg / L or 1630 mg / L or 1640 mg / L or 1650 mg / L or 1660 mg / L or 1670 mg / L or 1680 mg / L or 1690 mg / L or 1700 mg / L or 1710 mg / L or 1720 mg / L or 1730 mg / L or 1740 mg / L or 1750 mg / L or 1760 mg / L or 1770 mg / L or 1780 mg / L or 1790 mg / L or 1800 mg / L or 1810 mg / L or 1820 mg / L or 1830 mg / L or 1840 mg / L or 1850 mg / L or 1860 mg / L or 1870 mg / L or 1880 mg / L or 1890 mg / L or 1900 mg / L.

[0052] Preferably, the composition includes 1400 to 1900 mg / L of magnesium (Mg).

[0053] According to one embodiment, the composition comprises 1400 to 1500 mg / L of magnesium (Mg), even more preferably 1483 mg / L.

[0054] According to one embodiment, the composition comprises 1700 to 1850 mg / L of magnesium (Mg), even more preferably 1770 or 1799 mg / L.

[0055] According to one embodiment, the composition comprises 923 mg / l of magnesium (Mg).

[0056] According to one embodiment, the composition comprises a calcium (Ca) content selected from: 450 mg / L or 460 mg / L or 470 mg / L or 480 mg / L or 490 mg / L or 500 mg / L or 510 mg / L or 520 mg / L or 530 mg / L or 540 mg / L or 550 mg / L or 560 mg / L or 570 mg / L or 580 mg / L or 590 mg / L or 600 mg / L or 610 mg / L or 620 mg / L or 630 mg / L or 640 mg / L or 650 mg / L or 660 mg / L or 670 mg / L or 680 mg / L or 690 mg / L or 700 mg / L or 710 mg / L or 720 mg / L or 730 mg / L or 740 mg / L or 750 mg / L.

[0057] Preferably, the composition includes 450 to 650 mg / L of calcium (Ca).

[0058] According to one embodiment, the composition comprises 450 to 500 mg / L of calcium (Ca), preferably 473 mg / L.

[0059] According to one embodiment, the composition comprises 575 to 615 mg / L of calcium (Ca), preferably 595 or 604 mg / L.

[0060] According to one embodiment, the composition comprises 290 mg / L of calcium (Ca).

[0061] According to one embodiment, the composition comprises a potassium (K) content selected from: 50 mg / L or 51 mg / L or 52 mg / L or 53 mg / L or 54 mg / L or 55 mg / L or 56 mg / L or 57 mg / L or 58 mg / L or 59 mg / L or 60 mg / L or 61 mg / L or 62 mg / L or 63 mg / L or 64 mg / L or 65 mg / L or 66 mg / L or 67 mg / L or 68 mg / L or 69 mg / L or 70 mg / L or 71 mg / L or 72 mg / L or 73 mg / L or 74 mg / L or 75 mg / L or 76 mg / L or 77 mg / L or 78 mg / L or 79 mg / L or 80 mg / L or 81 mg / L or 82 mg / L or 83 mg / L or 84 mg / L or 85 mg / L or 86 mg / L or 87 mg / L or 88 mg / L or 89 mg / L or 90 mg / L or 91 mg / L or 92 mg / L or 93 mg / L or 94 mg / L or 95 mg / L or 96 mg / L or 97 mg / L or 98 mg / L or 99 mg / L or 100 mg / L or 101 mg / L or 102 mg / L or 103 mg / L or 104 mg / L or 105 mg / L or 106 mg / L or 107 mg / L or 108 mg / L or 109 mg / L or 110 mg / L or 111 mg / L or 112 mg / L or 113 mg / L or 114 mg / L or 115 mg / L or 116 mg / L or 117 mg / L or 118 mg / L or 119 mg / L or 120 mg / L or 121 mg / L or 122 mg / L or 123 mg / L or 124 mg / L or 125 mg / L or 126 mg / L or 127 mg / L or 128 mg / L or 129mg / L or 130 mg / L or 131 mg / L or 132 mg / L or 133 mg / L or 134 mg / L or 135 mg / L or 136 mg / L or 137 mg / L or 138 mg / L or 139 mg / L or 140 mg / L or 141 mg / L or 142 mg / L or 143 mg / L or 144 mg / L or 145 mg / L or 146 mg / L or 147 mg / L or 148 mg / L or 149 mg / L or 150 mg / L.

[0062] Preferably, the composition includes 51 to 58 mg / L of potassium (K).

[0063] According to one embodiment, the composition comprises 57, 51 or 55 mg / L of potassium (K).

[0064] According to one embodiment, the composition comprises 135 mg / L of potassium (K).

[0065] According to one embodiment, the composition comprises a sulfate (SO4) content selected from: 1250 mg / L or 1260 mg / L or 1270 mg / L or 1280 mg / L or 1290 mg / L or 1300 mg / L or 1310 mg / L or 1320 mg / L or 1330 mg / L or 1340 mg / L or 1350 mg / L or 1360 mg / L or 1370 mg / L or 1380 mg / L or 1390 mg / L or 1400 mg / L or 1410 mg / L or 1420 mg / L or 1430 mg / L or 1440 mg / L or 1450 mg / L or 1460 mg / L or 1470 mg / L or 1480 mg / L or 1490 mg / L or 1500 mg / L or 1510 mg / L or 1520 mg / L or 1530 mg / L or 1540 mg / L or 1550 mg / L or 1560 mg / L or 1570 mg / L or 1580 mg / L or 1590 mg / L or 1600 mg / L or 1610 mg / L or 1620 mg / L or 1630 mg / L or 1640 mg / L or 1650 mg / L or 1660 mg / L or 1670 mg / L or 1680 mg / L or 1690 mg / L or 1700 mg / L or 1710 mg / L or 1720 mg / L or 1730 mg / L or 1740 mg / L or 1750 mg / L or 1760 mg / L or 1770 mg / L or 1780 mg / L or 1790 mg / L or 1800 mg / L or 1810 mg / L or 1820 mg / L or 1830 mg / L or 1840 mg / L or 1850 mg / L or 1860 mg / L or 1870 mg / L or 1880 mg / L or 1890 mg / L or 1900 mg / L or 1910 mg / L or 1920 mg / L or 1930 mg / L or 1940 mg / L or 1950 mg / L or 1960 mg / L or 1970 mg / L or 1980 mg / L or 1990 mg / L or 2000 mg / L or 2010 mg / L or 2020 mg / L or 2030 mg / L or 2040 mg / L or 2050 mg / L or 2060 mg / L or 2070 mg / L or 2080 mg / L or 2090 mg / L or 2100 mg / L or 2110 mg / L or 2120 mg / L or 2130 mg / L or 2140 mg / L or 2150 mg / L or 2160 mg / L or 2170 mg / L or 2180 mg / L or 2190 mg / L or 2200 mg / L or 2210 mg / L or 2220 mg / L or 2230 mg / L or 2240 mg / L or 2250 mg / L or 2260 mg / L or 2270 mg / L or 2280 mg / L or 2290 mg / L or 2300 mg / L or 2310 mg / L or 2320 mg / L or 2330 mg / L or 2340 mg / L or 2350 mg / L or 2360 mg / L or 2370 mg / L or 2380 mg / L or 2390 mg / L or 2400 mg / L or 2410 mg / L or 2420 mg / L or 2430 mg / L or 2440 mg / L or 2450 mg / L or 2460 mg / L or 2470 mg / L or 2480 mg / L or 2490 mg / L or 2500 mg / L or2510 mg / L or 2520 mg / L or 2530 mg / L or 2540 mg / L or 2550 mg / L or 2560 mg / L or 2570 mg / L or 2580 mg / L or 2590 mg / L or 2600 mg / L.

[0066] Preferably, the composition includes 1950 to 2500 mg / L of sulfate (SO4).

[0067] According to one embodiment, the composition comprises 1900 to 2100 mg / L of sulfate (SO4), preferably 2000 to 2050 mg / L of sulfate (SO4), even more preferably 2004 mg / L of sulfate (SO4).

[0068] According to one embodiment, the composition comprises 2350 to 2500 mg / L of sulfate (SO4), preferably 2400 to 2450 mg / L of sulfate (SO4), even more preferably 2417 or 2439 mg / L of sulfate (SO4).

[0069] According to one embodiment, the composition comprises 1357 mg / L of sulfate (SO4).

[0070] According to one embodiment, the composition further comprises: - 800 to 900 mg / L of sulfur (S), preferably 839 mg / L.

[0071] According to one embodiment, the composition further comprises: - 2500 to 3000 mg / L of sulfur (S), preferably 2600 to 2700 mg / L, even more preferably 2621 mg / L.

[0072] According to one embodiment, the composition further comprises: - 2500 to 3000 mg / L of sulfur (S), preferably 2800 to 2900 mg / L, even more preferably 2833 mg / L.

[0073] According to one embodiment, the composition further comprises 600 mg / L of sulfur (S).

[0074] According to one embodiment, the composition according to the invention is devoid of of any preservative agent.

[0075] According to one embodiment, the composition according to the invention comprises: - 3211 mg / L of sodium (Na); - 6478 mg / L of chloride (Cl); - 117 mg / L of bicarbonate (HCO3); - 1483 mg / L of magnesium (Mg); - 473 mg / L of calcium (Ca); - 55 mg / L of potassium (K); - 2004 mg / L of sulfate (S 04); - 839 mg / L of sulfur (S).

[0076] According to one embodiment, the composition according to the invention comprises: - 2369 mg / L of sodium (Na); - 5485 mg / L of chloride (Cl); - 97 mg / L of bicarbonate (HCO3); - 1799 mg / L of magnesium (Mg); - 595 mg / L of calcium (Ca); - 51 mg / L of potassium (K); - 2439 mg / L of sulfate (S 04); - 2833 mg / L of sulfur (S).

[0077] According to another embodiment, the composition according to the invention comprises: - 2463 mg / L of sodium (Na); - 5672 mg / L of chloride (Cl); - 113 mg / L of bicarbonate (HCO3); - 1770 mg / L of magnesium (Mg); - 604 mg / L of calcium (Ca); - 57 mg / L of potassium (K); - 2417 mg / L of sulfate (S O4); - 2621 mg / L of sulfur (S).

[0078] According to another embodiment, the composition according to the invention comprises: - 3669 mg / L of sodium (Na); - 6471 mg / L of chloride (Cl); - 39 mg / L of bicarbonate (HCO3); - 923 mg / L of magnesium (Mg); - 290 mg / L of calcium (Ca); - 135 mg / L of potassium (K); - 1357 mg / L of sulfate (SO4); - 600 mg / L of sulfur (S).

[0079] According to another aspect, the invention relates to a composition as defined above, for use as a medicinal product.

[0080] According to one embodiment, said composition for use is administered topically, on the skin or mucous membranes.

[0081] Preferably, said topical application is carried out by local application, by installation, continuous spray, metered spray, spraying, misting, irrigation, nebulization, gargling, washing, inhalation, suspension, gel, emulsion, cream, emulsion, ointment.

[0082] According to one embodiment, said compositions according to the invention are intended for topical administration, chosen from intranasal, buccopharyngeal, pulmonary nebulization, administration on any other mucous tissue, or cutaneous administration.

[0083] According to one embodiment, the composition may be formulated as a spray, preferably in the form of droplets greater than or equal to 10 µm, preferably for intranasal, buccal or pharyngeal use.

[0084] According to one embodiment, the composition can be formulated by nebulization, preferably in the form of droplets smaller than 1 Opm, allowing penetration into the pulmonary tree.

[0085] According to one embodiment, the composition can be formulated as a suspension, gel, cream, emulsion and / or ointment, preferably with a viscosity of 100 to 1,000,000 mPa.s at 25 °C.

[0086] The composition may include other ingredients of interest including active ingredients, pharmaceutical actives, solvents, fatty substances, protectants, sensory agents, penetration release agents, and / or inert propellant gases (air, nitrogen), and / or liquefied gases.

[0087] According to one embodiment, the composition for use according to the invention is used in the treatment or prevention of respiratory conditions aiming at an anti-inflammatory, or scarring action or on mucociliary clearance.

[0088] According to one embodiment, the composition for use according to the invention is used in the treatment or prevention of nasal polyposis, allergic rhinitis, asthma.

[0089] According to one embodiment, the composition for use according to the invention is used in the treatment or prevention of dermatological conditions aiming for an anti-inflammatory or scarring action.

[0090] According to one embodiment, the composition for use according to the invention is used in the treatment or prevention of skin reactions of allergic origin, and / or atopic dermatitis.

[0091] According to one embodiment, the composition for use according to the invention is used in the treatment or prevention of oropharyngeal conditions aiming for an anti-inflammatory or scarring action.

[0092] According to one embodiment, the composition for use according to the invention is administered concomitantly with other treatments for nasal polyposis, allergic rhinitis, asthma, atopic dermatitis.

[0093] According to one embodiment, the composition is used in the treatment or prevention of respiratory conditions in cases of inflammatory, allergic conditions or in wound healing.

[0094] According to one embodiment, the composition is used in the treatment or prevention of nasal polyposis, allergic rhinitis, or asthma.

[0095] According to one embodiment, use as a medicinal product is achieved by administration through a medical device suitable for administration to a patient.

[0096] According to one embodiment, the composition is used in the treatment or prevention of dermatological pathologies requiring an anti-inflammatory and / or healing effect.

[0097] According to one embodiment, the composition is used in the treatment or prevention of skin reactions of allergic origin, and / or atopic dermatitis.

[0098] According to one embodiment, the composition is used in the treatment or prevention of oropharyngeal conditions with an anti-inflammatory or scarring action.

[0099] According to one embodiment, the composition for use according to the invention is administered alone, or in combination with other physiologically acceptable ingredients, or in combination concomitantly, in prevention, pre-treatment, treatment or follow-up of inflammation and allergy drugs such as corticosteroids, antihistamines, vasoconstrictors, vasodilators, antifibrotics and / or therapeutic antibodies.

[0100] According to one embodiment, the composition for use according to the invention is associated in the same composition with local drugs such as corticosteroids, antihistamines, vasoconstrictors, vasodilators.

[0101] Preferably, the water is purified water or low mineral content water (having between 50mg / L and 300mg / L of dry residue at most).

[0102] According to another aspect, the invention relates to a medical device intended for the administration of a composition according to the invention.

[0103] According to another aspect, the invention relates to a sachet-dose to be dissolved in a predetermined volume of water, comprising the composition according to the invention in powder form.

[0104] In order to obtain the indicated parameters (pH, osmolarity, minerals), the said powder should preferably be dissolved in 1 liter of purified water.

[0105] According to one embodiment, the reconstitution water is purified water conforming to the European Pharmacopoeia (Ph. EUE), and reconstitution is carried out at 20-25 °C under moderate stirring until complete dissolution of the powder.

[0106] According to another aspect, the invention relates to a kit comprising (i) the composition in sachet-doses, (ii) Optionally, an irrigation device.

[0107] According to another aspect, the invention relates to bottles comprising the composition in powder form according to the invention, dissolved in water and ready for use, for example for nasal washing.

[0108] According to another aspect, the invention relates to a composition for use according to the invention, wherein said reconstituted composition is then diluted in water, preferably purified, at a ratio of 3% to 50%, preferably 5% to 40% (w / w).

[0109] According to one embodiment, the composition for use according to the invention is diluted in water, preferably purified, at a ratio (w / w) selected from 3%, or 4%, or 5%, or 6%, or 7%, or 8%, or 9%, or 10%, or 11%, or 12%, or 13%, or 14%, or 15%, or 16%, or 17%, or 18%, or 19%, or 20%, or 21%, or 22%, or 23%, or 24%, or 25%, or 26%, or 27%, or 28%, or 29%, or 30%, or 31%, or 32%, or 33%, or 34%, or 35%, or 36%, or 37 %, or 38%, or 39%, or 40%, or 41%, or 42%, or 43%, or 44%, or 45%, or 46%, or 47%, or 48%, or 49%, or 50% (m / m).

[0110] According to one embodiment, said composition is for use to promote the healing of epithelial tissues, preferably of the nasal or pharyngeal or pulmonary mucosa.

[0111] The reconstituted solution can be used alone or in sequential / concomitant combination with other topical active ingredients of interest or pharmaceutical active ingredients (including corticosteroids, antihistamines, vasoconstrictors, vasodilators).

[0001] According to another aspect, the invention relates to the non-therapeutic cosmetic use of said reconstituted electrolytic mineral composition in a healthy subject.

[0002] According to one embodiment, said cosmetic use is a non-therapeutic use.

[0003] According to one embodiment, said cosmetic use is carried out by topical administration, on the skin or mucous membranes.

[0004] According to one embodiment, said cosmetic use is carried out by topical administration, local application, preferably by installation, continuous spray, metered spray, spraying, misting, nebulizing, gargling, washing, inhalation, suspension, gel, cream, emulsion, and / or ointment.

[0005] According to one embodiment, cosmetic use in healthy subjects aims to rinse, cleanse and / or sanitize the skin and / or mucous membranes, to promote the repair of the skin or mucous membranes, to promote the barrier function of the skin or mucous membranes, to promote the reduction of oxidative stress of the skin and / or mucous membranes, to relieve redness, swelling, irritation, itching, oozing, scratching, reduce signs of aging or burning sensations.

[0006] According to one embodiment, cosmetic use in healthy subjects is carried out in place of water, preferably purified, present in the cosmetic composition.

[0007] According to another aspect, the invention relates to a non-therapeutic cosmetic composition for healthy subjects, comprising the reconstituted electrolytic mineral composition according to the invention as a replacement for the water, preferably purified, present in said composition.

[0008] According to another aspect, the invention relates to the use of the reconstituted electrolytic mineral composition according to the invention to replace water, preferably purified, present in a non-therapeutic cosmetic composition for healthy subjects.

[0009] Preferably, all of the water, preferably purified, is replaced by the reconstituted electrolytic mineral composition according to the invention.

[0010] Preferably, at least 1% or 2% or 3% or 4% or 5% or 6% or 7% or 8% or 9% or 10% or 11% or 12% or 13% or 14% or 15% or 16% or 17% or 18% or 19% or 20% or 21% or 22% or 23% or 24% or 25% or 26% or 27% or 28% or 29% or 30% or 31% or 32% or 33% or 34% or 35% or 36% or 37% or 38% or 39% or 40% or 41% or 42% or 43% or 44% or 45% or 46% or 47% or 48% or 49% or 50% or 51% or 52% or 53% or 54% or 55% or 56% or 57% or 58% or 59% or 60% or 61% or 62% or 63% or 64% or 65% or 66% or 67% or 68% or 69% or 70% or 71% or 72% or 73% or 74% or 75% or 76% or 77% or 78% or 79% or 80% or 81% or 82% or 83% or 84% or 85% or 86% or 87% or 88% or 89% or 90% or 91% or 92% or 93% or 94% or 95% or 96% or 97% or 98% or 99% of the water, preferably purified, is replaced by the reconstituted electrolytic mineral composition according to the invention.

[0011] According to another aspect, the invention relates to the non-therapeutic cosmetic use can be used in a healthy subject of the composition according to the invention, where said reconstituted composition is diluted in water, preferably purified, at a ratio between 3% and 50%, preferably 5% to 40 (w / w).

[0012] According to one embodiment, said non-therapeutic cosmetic composition is diluted in water, preferably purified (European Pharmacopoeia standard), at a ratio (w / w) selected from: 3.0%, or 3.5%, or 4.0%, or 4.5%, or 5.0%, or 5.5%, or 6.0%, or 6.5%, or 7.0%, or 7.5%, or 8.0%, or 8.5%, or 9.0%, or 9.5%, or 10.0%, or 10.5%, or 11.0%, or 11.5%, or 12.0%, or 12.5%, or 13.0%, or 13.5%, or 14.0%, or 14.5%, or 15.0%, or 15.5%, or 16.0%, or 16.5%, or 17.0%, or 17.5%, or 18.0%, or 18.5%, or 19.0%, or 19.5%, or 20.0%, or 20.5%, or 21.0%, or 21.5%, or 22.0%, or 22.5%, or 23.0%, or 23.5%, or 24.0%, or 24.5%, or 25.0%, or 25.5%, or 26.0%, or 26.5%, or 27.0%, or 27.5%, or 28.0%, or 28.5%, or 29.0%, or 29.5%, or 30.0%, or 30.5%, or 31.0%, or 31.5%, or 32.0%, or 32.5%, or 33.0%, or 33.5%, or 34.0%, or 34.5%, or 35.0%, or 35.5%, or 36.0%, or 36.5%, or 37.0%, or 37.5%, or 38.0%, or 38.5%, or 39.0%, or 39.5%, or 40.0%, or 40.5%, or 41.0%, or 41.5%, or 42.0%, or 42.5%, or 43.0%, or 43.5%, or 44.0%, or 44.5%, or 45.0%, or 45.5%, or 46.0%, or 46.5%, or 47.0%, or 47.5%, or 48.0%, or 48.5%, or 49.0%, or 49.5%, or 50.0%.

[0013] According to another aspect, the invention relates to the use of the composition according to the invention for the manufacture of a medical device intended for the administration of said composition to patients.

[0014] According to one embodiment, said medical device is used in the treatment or prevention of respiratory conditions in the event of an inflammatory, allergic state or in wound healing.

[0015] Preferably, said medical device is used in the treatment or prevention of nasal polyposis, allergic rhinitis, asthma.

[0016] Preferably, said medical device is used in the treatment or prevention of dermatological pathologies requiring an anti-inflammatory and / or healing effect, for example atopic dermatitis.

[0017] According to one embodiment, said medical device is used in the treatment or prevention of all oropharyngeal conditions requiring an anti-inflammatory and / or healing effect.

[0018] The compositions according to the invention are preferably free of, or contain only very small amounts of, any preservative. This latter advantage is of great importance. Indeed, the preservatives present in most synthetic electrolyte compositions cause undesirable effects in the short or long term. However, according to the invention, the electrolyte composition is administered over periods ranging from one week to several months, or even for years.

[0019] The composition according to the invention has an anti-inflammatory and healing effect, as characterized in the example section.

[0020] The composition according to the invention has a favorable effect on ciliary beat, as characterized in the example section

[0021] This composition also has a much faster effect than usual treatments such as topical corticosteroids.

[0022] The results presented as examples demonstrate a surprising activity identified with electrolyte compositions comprising mineral salts that inhibit nine markers of inflammation: the interleukins IL-8, IL-6, IL-18, IL-5, IL-13, and IL-4; the cytokines TSLP (Thymia Stromal Lymphopoietin), GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor), and the chemokine CCL26 (CC Motif Chemokine Ligand 26), also known as eotaxin-3, compared to a control of dexamethasone (a potent corticosteroid commonly used for its anti-inflammatory and immunosuppressive properties). The distinctive features of these results are the massive, even near-total, reduction in interleukin secretion obtained with these electrolyte solutions compared to a reference drug, the overall non-specific nature of the observed anti-inflammatory effects, and their rapidity (less than 24 hours).

[0023] According to another aspect, the invention relates to a treatment method using a composition according to the invention as defined above, administered as a drug.

[0024] According to one embodiment, the method comprises administering said composition for the treatment or prevention of respiratory conditions, preferably to exert an anti-inflammatory, scarring, or mucociliary clearance-enhancing action.

[0025] According to one embodiment, the method includes administering said composition for the treatment or prevention of nasal polyposis, allergic rhinitis, or asthma.

[0026] According to one embodiment, the method comprises the administration of said composition for the treatment or prevention of dermatological conditions, aiming at an anti-inflammatory or scarring action.

[0027] According to one embodiment, the method includes administering said composition for the treatment or prevention of skin reactions of allergic origin, and / or atopic dermatitis.

[0028] According to one embodiment, the method includes the administration of said composition for the treatment or prevention of oropharyngeal conditions, aiming at an anti-inflammatory or scarring action.

[0029] According to one embodiment, the method comprises the administration of said composition for the treatment or prevention of ophthalmic and peri-ophthalmic conditions aimed at an anti-inflammatory or scarring action.

[0030] According to one embodiment, the method comprises administering said composition for the treatment or prevention of intravaginal conditions and vulvar products aimed at an anti-inflammatory or scar-reducing action.

[0031] According to one embodiment, the method includes administering said composition in conjunction with other treatments for nasal polyposis, allergic rhinitis, asthma or atopic dermatitis.

[0032] According to one embodiment, the method includes administering said composition alone or in combination with other physiologically acceptable ingredients, or in therapeutic association with drugs used in the prevention, pre-treatment, treatment or follow-up of inflammation and allergy, such as corticosteroids, antihistamines, vasoconstrictors, vasodilators, antifibrotics and / or therapeutic antibodies.

[0033] According to one embodiment, the method comprises administering said composition in combination in the same formulation with local drugs such as corticosteroids, antihistamines, vasoconstrictors, or vasodilators.

[0034] According to another aspect, the invention relates to a method for preparing an electrolytic composition of minerals, in powder form, to be dissolved in a predetermined volume of water, comprising: (a) the selection of a combination of pharmaceutical salts, and prior drying if necessary; (b) Optionally, grinding and then sieving, to obtain a target particle size; (c) Premixing the minor salts in the formulation with one of the major salts in an inverting mixer (e.g. bin-blender type); (d) The final mixing of all the salts, preferably in an inverting mixer; (e) Packaging in multi-layer vapor / water barrier sachets (preferably Alu / PE or alternative barrier material without aluminium), under a dry atmosphere (preferably RH < 30%, 20-25 °C).

[0035] According to one embodiment, the target particle size of the powder obtained according to the invention is controlled to optimize its dissolution in purified water. In one embodiment, the median particle size (D50) is adjusted, with the D50 range being between 20 and 300 µm. In another embodiment, the maximum size of 90% of the particles (D90) can be between 250 µm and 1000 µm. This control of the particle size ensures rapid and homogeneous dissolution, while limiting the transient turbidity of the solution.

[0036] According to one embodiment, said electrolytic mineral composition obtained in the context of this preparation process is hermetically sealed in a bag.

[0037] According to one embodiment, in step (d) for validation batches, a uniformity check of minerals on N > 10 samples is carried out.

[0038] According to one embodiment, the process also includes a release control step (f) on the appearance of the powder, the appearance of the solution, the pH (20°C), and the osmolarity

[0039] According to one embodiment, the powder has a particle size distribution such that the median diameter D50 is between 150 and 400 pm and that D90 is less than or equal to 800 pm.

[0040] According to one embodiment, the powder further has a D10 greater than or equal to 50 pm, so as to limit the very fine fraction and improve the flow.

[0041] According to one embodiment, the powder is sieved through a nominal mesh size of between 500 and 850 pm.

[0042] According to one embodiment, the gravimetric mixing is carried out in a closed mixer chosen from a V mixer, a double-cone mixer, a ribbon mixer or a plow mixer.

[0043] According to one embodiment, the powder has a Carr index less than or equal to 15%, guaranteeing good flowability.

[0044] According to one embodiment, the composition includes a pharmaceutical anti-caking agent, preferably selected from colloidal silica, tricalcium phosphate, magnesium stearate or calcium stearate.

[0045] According to one embodiment, the anti-caking agent is present at a rate of 0.10 to 0.80% by mass, preferably 0.20 to 0.50% by mass, and is added after obtaining the target particle size and before packaging.

[0046] According to one embodiment, the conditioning is carried out under a dry atmosphere having a relative humidity less than or equal to 15%, preferably less than or equal to 10%, at a temperature between 20 and 25 °C.

[0047] According to one embodiment, the sachet-dose is made of a multi-layer material comprising at least one metallic barrier layer, for example a PET / A1 / PE or PA / A1 / PE structure.

[0048] According to one embodiment, each sachet-dose contains an amount of powder such that after dissolution in 1 L of water, preferably purified, the solution has a pH between 7.2 and 8.2, a conductivity between 17 and 19 mS / cm and an osmolarity between 280 and 360 mOsm / kg.

[0049] According to one embodiment, each sachet-dose contains a quantity of powder such that after dissolution in 1 L of water, preferably purified, the solution comprises a content of the main constituents as defined in the compositions according to the invention.

[0050] According to one embodiment, each sachet contains a quantity of powder such that, after dissolution in 1 L of water, preferably purified, the solution comprises a content of the main constituents: - 2200 to 3800mg / L of sodium (Na); - 5200 to 6700 mg / L of chloride (Cl); - 30 to 120 mg / L of bicarbonate (HCO3); - 850 to 1900 mg / L of magnesium (Mg); - 450 to 750 mg / L of calcium (Ca); - 50 to 150 mg / L of potassium (K); - 1250 to 2600 mg / L of sulfate (SO4).

[0051] According to one embodiment, the conditioning is carried out under an inert atmosphere, for example under nitrogen.

[0052] According to one embodiment, the powder has a water activity (aw) less than or equal to 0.30 at 25 °C. Figures

[0053] [Fig 1] Graph showing the quantities of inflammatory markers secreted per seawater-based solution in pg / mL after stimulation, for IL8, IL6, TSLP, IL4, IL5, IL13, GM-CSF, IL18, and CCL26. Graph 1A shows IL8 secretion per solution. Graph IB shows IL6 secretion per solution (pg / mL). Graph IC shows TSLP secretion per solution. Graph 1D shows IL5 secretion per solution. Graph 1E shows CCL26 secretion per solution (pg / mL). Graph 1F shows GM-CSF secretion per solution (pg / mL). Graph IG shows IL18 secretion per solution (pg / mL).

[0054] [Fig 2] Graph showing the rate of repair of the nasal epithelium by solution vs. control and NaCl (pm 2 / hour). Figure 2A compares the repair rates observed for the solutions obtained from the dissolution of powders S4, S6, S7, S8, and S9, with respect to the SI control and the NaCl solution S3. Figure 2B shows the repair rate measured with S10, compared to the SI control and the NaCl solution S3.

[0055] [Fig 3] Graph showing the ciliary beat frequency velocity by solution vs. control and NaCl (Hz). Definitions

[0056] By "electrolytic composition" is meant a composition comprising ions, cations and / or anions, and which therefore includes in particular Sodium, Magnesium, Calcium, Potassium, Chloride, Sulfate, Bicarbonate, Sulfur.

[0057] The "dry matter content" of an electrolytic composition refers to the amount of non-volatile substances that remain after the evaporation of water in a solution containing ions. It is therefore the residual mass of solids, mainly composed of salts and minerals, that persists when All the water has been removed. In the case of an electrolytic solution, such as seawater for example, the dry matter would be composed of dissolved ions (such as sodium, chloride, sulfate, etc.) which, after the evaporation of the water, are found in the form of solid salts.

[0058] The osmolarity of an electrolytic composition is a measure of the total concentration of osmotically active particles (mainly ions) in a solution. It indicates how many moles of ions or molecules are dissolved in one liter of solution and reflects the solution's ability to generate osmotic pressure, that is, to attract water across a semi-permeable membrane.

[0059] By "isoosmotic" is meant an electrolytic composition having the same osmolarity as body fluids.

[0060] By “hyperosmotic” is meant an electrolytic composition having a higher osmolarity than that of body fluids.

[0061] Nasal spraying involves administering a medication or solution into the nasal passages using a spray. This method allows for rapid local application.

[0062] By "dissolving powder" is meant the action of passing a solid (the powder according to the invention) into a solution in a liquid.

[0063] By "dilute" or "dilution" is meant the action of reducing the concentration of the solution obtained by dissolving the composition in powder form according to the invention, by adding more solvent (for example water).

[0064] Nasal irrigation or misting is the distribution of saline solution into the nasal and sinus passages using a device. It promotes uniform distribution, often to treat or prevent rhinosinusitis symptoms, particularly nasal congestion or irritation.

[0065] By "treatment" or "treat" is meant the alleviation of symptoms associated with a specific disorder or condition and / or the elimination of said symptoms.

[0066] “Prevention” means the use of a composition or a medicinal product to prevent the onset or progression of diseases.

[0067] Nasal polyposis is a condition in which noncancerous polyps form in the nasal cavities or sinuses, causing congestion, runny nose, and difficulty breathing. These polyps are swollen growths of the nasal mucosa, often associated with allergies or chronic infections.

[0068] Allergic rhinitis is an inflammation of the nasal mucous membranes caused by an allergic reaction to allergens such as pollen, dust mites, or animal dander. It manifests itself through symptoms such as congestion, runny nose, sneezing, and itching.

[0069] Atopic dermatitis is a chronic skin disease characterized by dry, red, itchy rashes. It is often linked to allergies and genetic factors, and can affect any part of the body.

[0070] Asthma is a chronic respiratory disease characterized by inflammation and constriction of the airways, causing symptoms such as coughing, wheezing, shortness of breath and chest tightness.

[0071] Ciliary beating is the rhythmic movement of cilia lining the nasal mucosa that plays a crucial role in the nose's defense system. Their main function is to move mucus, which contains particles such as dust, allergens, microbes, and other impurities, to the back of the throat, where it can be swallowed or expelled. This constant movement helps keep the airways clear and prevent infections.

[0072] The term "powder" refers to a dry, homogeneous, and stable composition designed to be reconstituted with a liquid, generally water, to form, at the time of use, a solution or suspension conforming to the desired functional or therapeutic characteristics. This dosage form ensures the preservation of the composition's properties prior to reconstitution, while guaranteeing, after dilution in a predetermined volume, the specified concentration and performance (for example, in terms of osmolarity).

[0073] IL8, IL6, IL18, IL5, IL13, IL4 are the acronyms for interleukin 8, 6, 18, 5, 13 and 4.

[0074] TSLP stands for Thymic Stromal Lymphopoietin. It is a cytokine that plays a key role in the activation of immune cells, particularly in allergic-type inflammatory responses. TSLP is notably implicated in diseases such as asthma and atopic dermatitis.

[0075] The acronym GM-CSF stands for Granulocyte-Macrophage Colony-Stimulating Factor. It is a cytokine, that is, a protein involved in the developmental mechanisms of immune system cells. It plays a key role in the immune response and inflammation.

[0076] CCL26 stands for CC Motif Chemokine Ligand 26, also known as eotaxin-3. It is a chemokine, a small protein involved in guiding immune cells to areas of inflammation or infection. It plays an important role in diseases such as asthma or allergies.

[0077] By "healthy subject" is meant a human individual not exhibiting dermatological diseases that would be treated by the administration of the composition according to the invention, which only allows the improvement of the superficial visual appearance of the skin and mucous membranes.

[0078] For the purposes of this invention, "topical application" means application to the skin (including the scalp) and mucous membranes.

[0079] For the purposes of this invention, "cosmetically acceptable" means something that is useful in the preparation of a cosmetic composition, that is generally safe, non-toxic and neither biologically nor otherwise undesirable, and that is acceptable for cosmetic use, in particular by topical application to the skin or mucous membranes.

[0080] For the purposes of this invention, "non-therapeutic" means a cosmetic application not intended to treat a patient. In fact, the cosmetic composition according to the invention does not act as a drug for the treatment of pathologies, but rather improves the superficial visual appearance of the skin and mucous membranes.

[0081] For the purposes of this invention, "replacing water" means the action of substituting, totally or partially, water, preferably purified, usually used as the aqueous phase in a non-therapeutic cosmetic composition.

[0082] By "physiologically acceptable medium" is meant a vehicle or set of pharmaceutically acceptable excipients, compatible with topical, nasal and / or cutaneous administration, not presenting any toxic, irritating or sensitizing risk to the user, and not altering the physico-chemical properties or the efficacy of the composition.

[0083] By "purified water" or "purified water according to the European Pharmacopoeia standard", we mean water that meets the requirements of the Ph. Eur. monograph "Purified Water".

[0084] By "electrodialysis" or "electrodialyzed", we mean a membrane process using an electric field and ion exchange membranes to modulate the ionic profile of seawater.

[0085] The term "sachet-dose" means a unit-dose presentation of the composition in the form of a dry powder, packaged so that a sachet reconstituted in a predetermined volume of water provides, after complete dissolution, a solution whose pH and osmolarity are within the ranges specified in this application. The predetermined volume is typically 1 L (+ / - 2%), unless otherwise specified.

[0086] By "ciliary beat frequency" is meant the frequency (Hz) of the coordinated movement of the cilia measured by videomicros copying at a defined rate (e.g. 50 frames / s), as used in the examples.

[0087] Water activity, denoted aw, represents the amount of free water in a product. It differs from the total water content, which also includes water bound to the product's components. Technically, it is defined as the ratio between the partial pressure of water vapor in the product and that of pure water at the same temperature. It varies between 0 (no water available) and 1 (pure water).

[0088] Unless otherwise indicated, one sachet-dose is dissolved in 1 L of purified water Ph. Eur. (20-25 °C) under moderate stirring, to provide a solution exhibiting the parameters according to the invention, of pH and osmolarity.

[0089] In the description and the following examples, unless otherwise indicated, percentages are percentages by weight, and value ranges expressed as "between ... and ..." include the specified lower and upper bounds. The following examples are provided by way of illustration and are not intended to limit the scope of the invention. Examples

[0090] Example 1: In vitro comparison of the healing and anti-inflammatory capacities of several electrolytic solutions containing mineral salts, on the nasal mucosa.

[0091] MATERIALS AND METHODS

[0092] Experimental solutions:

[0093] Seven experimental solutions were defined with: - an isotonic osmolarity oscillating between 270 and 310 mOsm / L, + / - 10%; - modulations of composition at the qualitative and quantitative level.

[0094] Isotonic solutions were deliberately chosen for their tolerance and efficacy profile in the literature, and to avoid any osmotic movement that could cause bias.

[0095] Hypotonic solutions are not marketed for nasal irrigation, and are prohibited in practice as they may promote aqueous flows inside cells and create swelling and risk of edema.

[0096] The literature is conflicting on the benefits of hypertonic vs. isotonic solutions. While they show better results specifically for nasal congestion, particularly in allergies, overall assessments do not show a significant difference.

[0097] Three control solutions: - SI: cell culture medium (BEGM) *BEGM™ Bronchial Epithelial Cell Growth Medium BulletKit™: Culture system containing BEBMTM Bronchial Epithelial Cell Growth Basal Medium (CC-3171) and BEGMTM Bronchial Epithelial Cell Growth Medium SingleQuotsTM Supplements and Growth Factors (CC-4175) https: / / bioscience.lonza.com - S2: Cell culture medium and corticosteroid, dexamethasone. Dexamethasone is a potent corticosteroid, commonly used for its anti-inflammatory and immunosuppressive properties. It is used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis, ulcerative colitis, and Crohn's disease. In the lungs, dexamethasone is used for severe allergies, severe asthma attacks, and the treatment of chronic obstructive pulmonary disease. (COPD), and in the treatment of COVID-19 to reduce excessive inflammation due to the body's immune response to the virus. - S3: a 0.9% sodium chloride solution (physiological saline). This is a widely used comparator for daily nasal hygiene in infants, available with or without a tampon for nasal irrigation under brands such as Neilmed, Simply Saline, Fess, Arm & Hammer, and Simply Saline.

[0098] Solutions studied

[0099] Five powders containing pharmaceutical-grade salts, namely sodium chloride and various electrolytes at different concentrations allowing for the reconstitution of electrolyte solutions: - S4: Powder of 6 minerals: chlorides, sodium, magnesium, calcium, bicarbonates, and potassium. This is the comparator marketed under the brand name "Respimer®". All the salts used in this composition are chlorides. - S6: Powder of 8 minerals: Chlorides, sodium, sulfates, magnesium, sulfur, calcium, bicarbonates, and potassium. Two major components of seawater have been added: sulfur and sulfates, in the form of magnesium sulfate. Magnesium sulfate exhibits bronchodilator activity. It is used as an adjunct to local treatment (nebulization) of COPD exacerbations (Ni H, et al. 2022) and asthma (Rovsing AH et al. 2023). - S7: Boosted 8-mineral powder. Qualitative composition S6 with different dosages: chlorides, sulfur, sulfates, sodium, magnesium, calcium, bicarbonates, and potassium. Electrolyte modulation was achieved in particular with magnesium sulfate and sodium thiosulfate (Tang SM et al. 2024). - S8: Qualitative composition S7. Boosted 8 mineral powder + trace elements: zinc, copper and selenium provided by sodium selenite, copper sulfate and zinc sulfate. - S9: Hypotonic NaCl powder of 8 minerals. Qualitative composition S6 with varying dosages: sodium chloride, sulfates, magnesium, sodium, sulfur, calcium, bicarbonates, and potassium. Electrolyte modulation was achieved, in particular, with magnesium lactate and potassium bicarbonate.

[0100] These compositions are restored by dissolving purified water in IL, in order to obtain the mineral concentrations shown in Table 1 below.

[0101] Furthermore, a diluted seawater solution enriched in sulfate, magnesium, sulfur, and calcium was also studied (S 10) and could advantageously be offered in powder form, consisting of 8 minerals with the dosages indicated in Table 1. This solution was obtained by diluting seawater Seawater (Chemineau process) and a cascade of filtrations. The seawater used is collected in Brittany, France. The raw material is filtered and treated under UV light. It undergoes a series of five successive filtrations: two clarifying filtrations, two microfiltrations at 0.2 microns, and one microfiltration at 0.1 microns. It is diluted as follows: 30% natural seawater and 70% purified water meeting European Pharmacopoeia standards, then enriched with magnesium sulfate, magnesium lactate, and calcium sulfate. Finally, the seawater is radio-decontaminated.

[0102] Composition of solutions [Table 1]

[0103] Design

[0104] Ex vivo, blinded study vs control and reference specialty as comparator.

[0105] Parameters studied

[0106] The experimental solutions produced were studied on various validated functional parameters of the human nasal epithelium. - the rate of repair of epithelial lesions (pm 2 / h) - the frequency of ciliary beats (Hz) - the secretion of pro-inflammatory cytokines (pg / mL).

[0107] Protocol

[0108] The experiments were performed with cells from nasal polyps of subjects over 50 years of age with stage III or IV polyposis (chronic rhinosinusitis with polyps) resistant to well-conducted medical treatment and with an indication for surgery (EPOS 2020). Tissues and cells from 39 different patients were used. The nasal polyps were provided by the ENT surgery department of the Bordeaux University Hospital (Dr. Ludovic de Gabory). The samples were processed and transported to the Inserm UMR-S 1250 laboratory in accordance with current regulations.

[0109] 1) Study of the ciliary beat frequency

[0110] Upon receipt, the polyps are examined by inverted microscopy to determine the presence of ciliated epithelium. The ciliated borders are then cut with a scalpel and fractionated into expiants of approximately 1 mm². The expiants are seeded into 12-well culture plates pre-coated with collagen IV (Sigma Aldrich) in BEGM medium (Lonza). Several expiants are deposited per well. After several days of culture, cell growth develops around the expiants, containing ciliated cells.

[0111] Each well is then rinsed with one of the solutions to be tested and incubated for 30 minutes with the same solution. Each well is then analyzed by videomicroscopy. For each condition, at least 10 areas containing hair cells are filmed for 10 seconds each at an acquisition rate of 50 frames / second at 32x magnification. An ImageJ plug-in developed in the laboratory will determine the ciliary beat frequency, which will be expressed in Hertz. The expiants from 20 different patients are thus analyzed.

[0112] 2) Study of the rate of repair of the nasal epithelium

[0113] Epithelial cells are isolated from tissues by enzymatic treatment with pronase E (Sigma Aldrich). The cells are seeded in 24-well plates (BD Falcon) previously coated with type IV collagen (Sigma Aldrich) in CnT17 culture medium (CELLnTEC). At 90% confluence, the cells are transferred to BEGM medium (Lonza).

[0114] At total confluence, the cells are rinsed with PBS (Gibco) and then pre-incubated with each of the 12 solutions to be tested for 4 hours at 37°C. A linear wound is then made in each well using a 100pL pipette tip. Each well is rinsed with PBS and then re-incubated with the corresponding pre-incubation solution. A technical duplicate is prepared for each solution (2 wells per solution).

[0115] Each wound is then examined using videomicroscopy (at least 3 different positions along the wound) at xlO magnification, with one image every 10 minutes for 24 hours. An ImageJ plug-in developed in the laboratory allows the lesion repair rate to be determined in pm2 / hour.

[0116] At the end of the experiment, the wells are rinsed with PBS and the plates are kept at -80°C for a potential future study of gene expression in cells.

[0117] Cell cultures from 39 different patients were thus analyzed.

[0118] 3) Study of the secretion of pro-inflammatory cytokines

[0119] Epithelial cells isolated from tissues are seeded in 48-well plates (BD Falcon) previously coated with type IV collagen (Sigma Aldrich) in CnT17 culture medium (CELLnTEC). At 90% confluence, the cells are transferred to BEGM medium (Lonza).

[0120] At total confluence, the cells are rinsed with PBS (Gibco) and then pre-incubated for 4 hours with BEGM culture medium or with a mixture of pro-inflammatory cytokines (IL-β, TNFα, IFNγ) known to inflame respiratory epithelial cells (22). The cells are then incubated for 4 hours with each of the 12 solutions to be tested. A technical duplicate is prepared for each condition (2 wells for each incubation combination). One of the solutions (S2) contains a known anti-inflammatory (dexamethasone) used as a positive control.

[0121] Following the various incubations, the culture medium from each well is collected. A multiplex analysis of its cytokine content is performed.

[0122] The remaining culture medium is frozen for potential future use. Plates still containing cells are also stored at -80°C for potential future study of gene or protein expression in the cells.

[0123] The following cytokines are analyzed: IL-4, IL-5, IL-6, IL-8, IL-13, IL-25, IL-33, TSLP, GM-CSF, TNFa, eotaxin-3 (CCL26).

[0124] Cell cultures from 39 different patients were thus analyzed.

[0125] Results

[0126] At the inflammatory level and in terms of the secretion of interleukins and other inflammatory substances:

[0127] Figure 1 shows the quantities of inflammation markers secreted per solution in pg / mL after stimulation, for IL8, IL6, TSLP, IL5, CCL26, GM-CSF and IL 18 TSLP, IL5 and CC26, often associated with allergic reactions or asthma or atopic dermatitis, have been grouped together. Interleukins IL 25, 33, 13 and 4 were not represented due to the absence or very low quantities secreted.

[0128] [Table 2] Variation in interleukin secretion vs. control (SI) per solution after stimulation, expressed as a median %:

[0129] We chose to study a wide range of interleukins (IL) and molecules involved as mediators of the inflammatory and immune response, and in particular TSLP, CCL26, IL-4, IL-5, IL-13 which are specifically involved in the Th2 type immune response, and the allergic and asthmatic response.

[0130] We also studied less specific interleukins of inflammation and immunity such as IL8.

[0131] The Bronchial Epithelial Cell Growth Medium (BEGM) does not show anti-inflammatory activity, which is not surprising.

[0132] Unexpectedly, the control (S2) containing the potent corticosteroid dexamethasone showed no reduction in interleukin production; our hypothesis is that the initial effects of nasal corticosteroid therapy are often modest. The full and optimal effect may take 1 to 2 weeks of regular use. To be effective, nasal corticosteroid therapy requires good adherence and consistent use.

[0133] All experimental solutions tested show a dramatic decrease in interleukin secretions vs control (SI) and (S2) containing dexamethasone.

[0134] One distinctive feature of these results is that they are observed rapidly, as early as 4 a.m. The benefit of a composition containing corticosteroids within one of the experimental solutions rich in electrolytes is evident in order to obtain an immediate effect before the corticosteroids take effect and to improve the adherence to these treatments and their effectiveness.

[0135] The almost imperceptible results in physiological saline (S3) and (S9) may reflect apoptosis of epithelial cells: without minerals or in contact In the presence of a hypotonic NaCl solution, respiratory epithelial cells undergo paralysis or cell death. Both of these solutions should be avoided for respiratory use.

[0136] We note the favorable results obtained by solution (S10) on the IL 18 and CCL26 markers.

[0137] Minerals and trace elements play a crucial role in the body's antioxidant system, helping to neutralize free radicals and prevent cellular damage, particularly magnesium and sulfur.

[0138] A distinctive feature of these results is their overall non-specific anti-inflammatory nature. An effect was observed on 7 of the 11 inflammation markers tested: IL8, IL6, TSLP, GM-CSF, eotaxin-3, IL18, and IL5.

[0139] All interleukins showed dramatic decreases or even suppressions compared to the control (medium), regardless of the solution, and particularly interestingly, TSLP, CCL26, and IL-5. These interleukins are often associated with allergic reactions and asthma. IL-5, -4, and -13 are not produced by epithelial cells but primarily by immune cells, which may explain their low or absent expression.

[0140] IL-8 is the most abundantly secreted interleukin by nasal cells in pg / mL; dramatic reductions are observed compared to SI and S2 dexamethasone. IL-8 plays an important role in acute immune responses to bacterial and viral infections. Excessive IL-8 production may contribute to chronic inflammation and tissue damage in diseases such as rheumatoid arthritis, Crohn's disease, and chronic obstructive pulmonary disease (COPD).

[0141] The solutions show dramatic reductions in IL6, TSLP, GM-CSF, eotaxin-3, IL18, IL5 (figure 1)

[0142] IL-6 is involved in the regulation of inflammation, immunity, and metabolism. It is found in many chronic inflammatory and autoimmune diseases, as well as some cancers. Therapies targeting IL-6 or its receptor (IL-6R) have been developed; for example, tocilizumab, a monoclonal antibody that inhibits IL-6R, is used to treat rheumatoid arthritis and other inflammatory diseases.

[0143] TSLP is highly expressed in the upper respiratory tract (allergic rhinitis, where it contributes to nasal inflammation) and in the lower respiratory tract of asthmatic patients. It plays a key role in initiating and maintaining allergic inflammation in asthma. It is also implicated in atopic dermatitis, where it is overexpressed in the skin, contributing to chronic inflammation and increased sensitivity to allergens. Its expression can be increased in response to viral infections or environmental irritants, thus amplifying inflammation. It is a target for the development of new treatments for allergic diseases. and inflammatory. For example, monoclonal antibodies targeting TSLP, such as tezepelumab, to treat conditions like severe asthma or mepolizumab (Astra Zeneca) in polyposis.

[0144] GM-CSF is implicated in the pathology of rheumatoid arthritis (RA), where it contributes to inflammation and joint destruction, and in certain inflammatory lung diseases, such as interstitial pneumonia and pulmonary alveolar proteinosis, where it is essential for maintaining alveolar macrophages, which clear the lungs of cellular debris. While beneficial for fighting infections and supporting the immune system, it may also contribute to chronic inflammatory and autoimmune conditions.

[0145] CCL26 (eotaxin-3) is a chemokine primarily involved in recruiting eosinophils to sites of inflammation, particularly in allergic and inflammatory diseases such as asthma, allergic rhinitis, and atopic dermatitis.

[0146] IL-5 is a cytokine involved in the regulation of eosinophils and in immune responses against parasites and in allergic diseases, such as asthma and allergic rhinitis. Several treatments targeting IL-5 have been developed. For example, mepolizumab and reslizumab are monoclonal antibodies that neutralize IL-5, thereby reducing the number of eosinophils and alleviating symptoms in patients with severe eosinophilic asthma.

[0147] The results presented allow us to consider using these solutions alone or with other medications for any condition involving a form of inflammation or allergy, separately or in the same composition for synergistic purposes.

[0148] Rate of nasal epithelial repair (scarring):

[0149] Figure 2A shows the rate of nasal epithelial repair in solutions obtained by dissolving powder (S4), (S6), (S7), (S8), (S9) vs. control (S1) and NaCl (S3) (pm 2 / hour).

[0150] Figure 2B shows the rate of nasal epithelium repair in S10 vs control (S1) and NaCl (S3) (pm 2 / hour).

[0151] Solution (S3), which is 0.9% NaCl physiological saline, shows results significantly lower than all other solutions. The phenomenon of apoptosis is confirmed by videomicroscopy.

[0152] The results of solution (S9) compared to (S3) demonstrate a less marked difference, showing the limitations of hypotonic NaCl solutions.

[0153] Unexpected differences are visible in this figure regarding the healing process.

[0154] The BEGM (SI) culture medium gives superior results to all other solutions.

[0155] Solutions (S7), (S6) and (S8) then demonstrate superior efficiency vs the comparator product on the market (S4).

[0156] No difference is observed between (S7), (S6) and (S8).

[0157] Solution (S4) demonstrates lower efficiency than solutions (S7), (S6), and (S8). The particularly significant difference between (S4) and (S6) is noteworthy.

[0158] In general, (S6) is superior to the comparator. Magnesium sulfate improves wound healing performance when added to the 6 basic minerals (chlorides, sodium, magnesium, calcium, bicarbonates, and potassium).

[0159] The most favorable results were observed with S10 regarding the speed of healing, giving this composition a notable interest, both from a qualitative and quantitative point of view. Ciliary beat frequency

[0160] Figure 3 shows the ciliary beat frequency velocity per solution vs. control (SI) and NaCl (S3) (Hz).

[0161] Solution (S3), which is 0.9% NaCl physiological saline, has results that are significantly lower than all the other solutions.

[0162] The BEGM (SI) culture medium gives superior results to all other solutions.

[0163] Solutions (S6), (S8) and (S4) in trend order have similar results showing good tolerance.

[0164] (S6) shows significantly greater activity on the ciliary beat than (S7) and (S9).

[0165] Summary and Discussion

[0166] The various experiments carried out above have made it possible to identify the effectiveness of the compositions studied in anti-inflammatory indications, in healing and the frequency of ciliary beat. [Table 3] Performance of solutions according to observed parameters

[0167] The effect on IL8, IL6, TSLP, IL5, GM-CSF, IL18, eotaxin-3, is comparable between (S6), (S7), (S8), (S10) and (S4); no significant difference is seen.

[0168] The favorable effect on the ciliary beat frequency is comparable between (S6), (S8) and (S4).

[0169] The favorable effect on the speed of healing is comparable between (S6), (S7) and (S8).

[0170] Compositions (S6) and (S8) demonstrate efficacy in anti-inflammatory indications and in wound healing.

[0171] Composition (S6) shows statistically much superior results in healing speed vs. (S4).

[0172] This study reveals a dual activity: scar-reducing and anti-inflammatory, beyond the traditional markers IL 8 and IL6, for composition (S 6).

[0173] This composition has an anti-inflammatory action on 7 of the tested markers of inflammation: IL8, IL6, TSLP, IL5, GM-CSF, IL18, eotaxin-3.

[0174] This anti-inflammatory activity is observed on markers involved in allergy and chronic respiratory diseases such as polyposis or asthma: TSLP, IL 5

[0175] These effects are significant compared to the corticosteroid dexamethasone, and even more so compared to corticosteroids sharing the same mechanism of action.

[0176] These effects are rapid and were observed within 4 hours.

[0177] We are seeing dramatic decreases in inflammation markers

[0178] The properties of irrigation in preventing colds open the way to prophylactic applications on all respiratory pathologies, particularly in the context of allergies, asthma, air pollution and the chronicity of diseases.

[0179] Use in combination or as an adjunct is possible, with corticosteroids or monoclonal antibodies, particularly those used in polyposis which act on the reduction of IL 5

[0180] Furthermore, these results suggest potential use in immune diseases impacting lung health, such as rheumatoid arthritis, in combination with or as an adjunct to antifibrotic agents in pulmonary fibrosis, in therapies or prevention of lower respiratory tract diseases such as acute bronchitis, acute pneumonia, asthma, chronic lung disease, COPD, superinfections of chronic obstructive bronchitis, occupational lung diseases, or GERD.

[0181] These results also suggest applications in nebulization for COPD, bronchitis, and asthma.

[0182] The results presented demonstrate that in the solution in powder form (S6), les électrolytes influents sont le chlorure, sodium, potassium, bicarbonates, calcium, magnésium, sulfates, et / ou soufre sous forme de chlorures ou sulfates, en particulier de sulfate de magnésium. Références

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[0185] Hong Z, Guo Z, Zhang R, Xu J, Dong W, Zhuang G, Deng C. Airborne Fine Particulate Matter Induces Oxidative Stress and Inflammation in Human Nasal Epithelial Cells. Tohoku J Exp Med. 2016 Jun;239(2): 117-25.

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[0213] Seppey 1996

[0214] Holmstrom 1997

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[0216] Culig 2010

[0217] Hahn 2013

[0218] Salib 2013

[0219] Tugrul 2015

[0220] Atar 2022

[0221] Chen 2014

Claims

Demands

1. Electrolytic composition of minerals, in powder form, to be dissolved in a predetermined volume of water, intended to provide, after reconstitution in one liter of water, a solution having the following characteristics: - a pH of 7.2 to 8.2; - a conductivity of 17 to 19 mS / cm; - an osmolarity of 280 to 360 mOsm / kg, preferably 290 to 320 mOsm / kg, and comprising the following content of the main constituents: - 2200 to 3800 mg / L of sodium (Na); - 5200 to 6700 mg / L of chloride (Cl); - 30 to 120 mg / L of bicarbonate (HCO3); - 850 to 1900 mg / L of magnesium (Mg); - 450 to 750 mg / L of calcium (Ca); - 50 to 150 mg / L of potassium (K); - 1250 to 2600 mg / L of sulfate (SO4).

2. Composition according to the preceding claim, further comprising: - 550 to 3000 mg / L of sulfur (S).

3. Composition according to any one of the preceding claims, further comprising at least one of: zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), iron (Fe).

4. Composition according to any one of the preceding claims, comprising: - 2369 mg / L of sodium (Na); - 5485 mg / L of chloride (Cl); - 97 mg / L of bicarbonate (HCO3); - 1799 mg / L of magnesium (Mg); - 595 mg / L of calcium (Ca); - 51 mg / L of potassium (K); - 2439 mg / L of sulfate (SO4); - 2833 mg / L of sulfur (S).

5. Composition according to any one of claims 1 to 3, comprising: - 3211 mg / L of sodium (Na); - 6478 mg / L of chloride (Cl); - 117 mg / L of bicarbonate (HCO3); - 1483 mg / L of magnesium (Mg); - 473 mg / L of calcium (Ca); - 55 mg / L of potassium (K); - 2004 mg / L of sulfate (SO4); - 839 mg / L of sulfur (S).

6. Composition according to any one of claims 1 to 3, comprising: - 3669 mg / L of sodium (Na); - 6471 mg / L of chloride (Cl); - 39 mg / L of bicarbonate (HCO3); - 923 mg / L of magnesium (Mg); - 290 mg / L of calcium (Ca); - 135 mg / L of potassium (K); - 1357 mg / L of sulfate (SO4); - 600 mg / L of sulfur (S).

7. Composition according to any one of claims 1 to 6, for use as a medicinal product.

8. Composition according to the preceding claim, for use in the treatment or prevention of respiratory conditions in cases of inflammatory, allergic state or in wound healing.

9. Composition according to the preceding claim, for use in the treatment or prevention of nasal polyposis, allergic rhinitis, or asthma.

10. Composition according to any one of claims 7 to 9, wherein the use as a medicinal product is effected by administration thanks to a medical device adapted for administration to a patient.

11. Composition according to claim 7, for use in the treatment or prevention of dermatological pathologies requiring an anti-inflammatory and / or healing effect.

12. Composition according to claim 7, for use in the treatment or prevention of skin reactions of allergic origin, and / or atopic dermatitis.

13. Composition according to claim 7, for use in the treatment or prevention of oropharyngeal conditions aimed at an anti-inflammatory or scarring action.

14. Composition according to any one of claims 1 to 6, for use, wherein said reconstituted composition is further diluted in purified water at a ratio of 3% to 50%, preferably 5% to 40% (w / w).

15. Composition according to any one of claims 1 to 6, intended for topical administration, selected from intranasal, oropharyngeal, pulmonary nebulization, administration on any other mucous tissue, or cutaneous administration.

16. Dissolving sachet comprising a composition according to any one of claims 1 to 6, in powder form.

17. Use of the reconstituted mineral electrolytic composition according to any one of claims 1 to 6 to replace water, preferably purified, present in a non-therapeutic cosmetic composition for healthy subjects.

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