WO2022170405A1 - Composition pharmaceutique aqueuse à base d'hyaluronate de sodium sous forme de pulvérisation nasale - Google Patents
Composition pharmaceutique aqueuse à base d'hyaluronate de sodium sous forme de pulvérisation nasale Download PDFInfo
- Publication number
- WO2022170405A1 WO2022170405A1 PCT/BR2021/050068 BR2021050068W WO2022170405A1 WO 2022170405 A1 WO2022170405 A1 WO 2022170405A1 BR 2021050068 W BR2021050068 W BR 2021050068W WO 2022170405 A1 WO2022170405 A1 WO 2022170405A1
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- WO
- WIPO (PCT)
- Prior art keywords
- sodium hyaluronate
- pharmaceutical composition
- aqueous sodium
- nasal spray
- spray
- Prior art date
Links
- 229920002385 Sodium hyaluronate Polymers 0.000 title claims abstract description 40
- 229940010747 sodium hyaluronate Drugs 0.000 title claims abstract description 40
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 title claims abstract description 40
- 239000007922 nasal spray Substances 0.000 title claims abstract description 26
- 229940097496 nasal spray Drugs 0.000 title claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 25
- 239000007921 spray Substances 0.000 claims abstract description 53
- 239000000203 mixture Substances 0.000 claims abstract description 44
- 238000009826 distribution Methods 0.000 claims abstract description 29
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- 206010028740 Nasal dryness Diseases 0.000 claims abstract description 3
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 claims description 12
- 235000004866 D-panthenol Nutrition 0.000 claims description 8
- 239000011703 D-panthenol Substances 0.000 claims description 8
- 229960003949 dexpanthenol Drugs 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 6
- 230000004913 activation Effects 0.000 claims description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 4
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims description 4
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 4
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 4
- 239000008213 purified water Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 3
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 3
- 229940061607 dibasic sodium phosphate Drugs 0.000 claims description 3
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 2
- 206010028735 Nasal congestion Diseases 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical class [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 2
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 2
- 230000001954 sterilising effect Effects 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 5
- 238000004519 manufacturing process Methods 0.000 claims 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims 1
- 239000001488 sodium phosphate Substances 0.000 claims 1
- 235000011008 sodium phosphates Nutrition 0.000 claims 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims 1
- 238000009472 formulation Methods 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 7
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- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 6
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 6
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 6
- 229920002674 hyaluronan Polymers 0.000 description 6
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- 229940101267 panthenol Drugs 0.000 description 4
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- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 3
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- 230000033001 locomotion Effects 0.000 description 3
- 235000019161 pantothenic acid Nutrition 0.000 description 3
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- 235000019129 pluma Nutrition 0.000 description 3
- 244000276444 pluma Species 0.000 description 3
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- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
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- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 1
- 229940075564 anhydrous dibasic sodium phosphate Drugs 0.000 description 1
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- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
Definitions
- the present invention relates to an innovative pharmaceutical composition, which consists of a Sodium Hyaluronate nasal spray, which relieves dryness and irritation of the nostrils caused by aging, low humidity, colds, congestion or medication side effects.
- nasal epithelial cells Under certain conditions the ability of nasal epithelial cells to secrete mucus, preserve moisture and filter air may be impaired. Conditions such as low humidity, aging, side effects of medications used to treat allergies, common colds or acne result in dryness of the nose and crust buildup causing discomfort, pain, nosebleeds and coughing.
- Nasal inhalation as a route of drug administration is restricted to the treatment of processes that take place locally, in the upper airways, such as, for example, different cases of rhinitis.
- the respiratory tree can be divided into three well-differentiated zones:
- Nasopharyngeal Region It is the upper respiratory tract, which comprises the nose, mouth, pharynx and larynx.
- Tracheobronchial Region Includes the trachea, bronchi, and terminal bronchioles.
- Pulmonary or respiratory region corresponds to the respiratory bronchioles, the alveolar canal, the alveolar sacs and the alveoli. This region is where gas exchange takes place.
- the factors that condition the transit of nasal medications in spray form are the size of particles or droplets, the breathing mode, the anatomical characteristics of the airways and possible pathological factors, among others. Depending on the size of particles or droplets, these are deposited in the different regions seen above. We can thus make the following differentiation, also shown in Figure 2:
- Patent number 20050164979 Pharmaceutical composition for ophthalmological and rhinological application describes a pharmaceutical composition that contains at least panthenol and/or pantothenic acid and hyaluronic acid and/or hyaluronate and, optionally, additional pharmaceutical auxiliary agents.
- the invention also relates to the use of the pharmaceutical composition for the treatment of ophthalmological and/or rhinological functional defects, failing to mention droplet size and physicochemical properties of the composition so that it has an exclusive action on the nostrils.
- Patent number W02003049747 - Synergistic pharmaceutical composition for treating ophthalmological and/or rhinological dysfunction, containing panthenol or pantothenic acid and hyaluronic acid or hyaluronate) presents a pharmaceutical composition containing panthenol and/or pantothenic acid, hyaluronic acid and/or hyaluronate and optionally additional pharmaceutical aids in the treatment of ophthalmological and/or rhinological dysfunction, specifically rhinological dysfunction associated with dryness of the nasal mucosa, especially chronic rhinitis and/or rhinitis sicca, presenting the advantage of the combination of panthenol and hyaluranate that produces a synergistic effect in the treatment of both ophthalmological disorders and rhinological disorders, for example, healing of lesions in the nasal mucosa and improvement of moisture retention.
- the inventors have developed an innovative composition, which consists of a nasal spray of Sodium Hyaluronate, which relieves dryness and irritation of the nostrils caused by aging, low humidity, colds, congestion or side effects of medicines.
- the Sodium Hyaluronate Nasal Spray of the present invention was developed to act at the level of the Nasopharyngeal region, with the Sodium Hyaluronate adhering to the nasal mucous membrane and moisturizing it, thus preventing its dryness. Dryness of the nasal mucosa is also produced by environmental factors such as heat, air conditioning, wind and sun. Nasal dryness prevents the mucosa from fulfilling its function of wetting and cleaning the air we breathe, leaving the nostrils exposed to the invasion of pathogens. Intensive hydration with Sodium Hyaluronate maintains a protective layer on the nasal mucosa and strengthens the resistance of the nostrils against exogenous invasions.
- the pharmaceutical composition of aqueous Sodium Hyaluronate in nasal spray form of the present invention was developed as a formulation in true aqueous solution, specifically balanced in viscosity and density, so that, when administered through a specific actuator, it produces a particular and constant spray plume pattern and Gaussian droplet size distribution where 100% of the droplets are greater than 10 microns , thus ensuring greater effectiveness in local nasal topical treatment without going beyond the nasopharyngeal region.
- FIG. 1 Figure 1 - scheme showing the regions of the respiratory system, with emphasis on the nasopharyngeal, tracheobronchial and respiratory regions.
- FIG. 1 Figure 2 - diagram showing the relationship between spray particle diameter and maximum level of penetration in each of the regions of the respiratory system.
- Figure 3 Individual results of the mass test of each actuation, or pumping, or pressing.
- Figure 4 Individual results of the droplet size distribution test by laser diffraction measured at a distance of 3 cm from the nozzle to the measurement plane.
- Figure 5 Individual results of the droplet size distribution test by laser diffraction measured at a distance of 6 cm from the nozzle to the measurement plane.
- a system consisting of an aqueous solution was chosen, for spray application, forming a liquid discharge aerosol, without propellant, with mechanical pressurization (actuator) with droplets of size well above 10 microns, which ensures limited action on the nostrils, protecting and strengthening the nasal mucous membrane.
- actuator mechanical pressurization
- this invention sought the optimal relationship between the particular Spray System chosen and the liquid formulation as a true solution in order to comply with ANVISA Normative Instruction No. 2019 that deals specifically with Nasal Sprays, and arriving at the results presented in the “RESULTS OF STUDY” section to a FEATHER Spray Standard.
- the inventors of the present invention determined that the viscosity of the aqueous solution used has a fundamental role in obtaining the characteristics of the Spray Pattern sought and, mainly, in the droplet size. desired, i.e. 100% droplets larger than 10 microns, to avoid inadequate penetration of the product into the aforementioned tracheobronchial and/or respiratory tracts.
- the viscosity of the solution proposed by this invention is strongly influenced by the concentration of Sodium Hyaluronate, and, additionally, by the concentration of Dexpanthenol.
- the inventors of the present invention have obtained intermediate or high molecular weight Hyaluranates, preferably high molecular weight Hyaluranates at low concentration in the final composition, and even more preferably a combination of intermediate molecular weight Hyaluranates and high so that the final concentration of Hyaluronate in the composition is not less than 0.005% weight/volume of Hyaluronate.
- the composition uses hyaluronic acid or its sodium salt, sodium hyaluronate, as the natural active ingredient capable of producing a pronounced hydration and coating effect on the nasal mucosa.
- Hyaluronic acid or its sodium salt is produced according to the microorganism fermentation method and consists of a linear polysaccharide polymer where the repeating unit is a disaccharide of D-Glucuronic acid and D-Glucosamine.
- the purity of sodium hyaluronate is a minimum of 92% W/W, with a maximum moisture content of 10% W/W; it is a hygroscopic substance.
- the molecular weight range of sodium hyaluronate used in the present Nasal Spray composition is from 850,000 Daltons to 1,600,000 Daltons, combination of intermediate and high molecular weights.
- the concentration of hyaluronic acid or its sodium salt used in the Nasal Spray is in the range of 0.020% W/V to 0.050% W/V, even more preferably between 0.040% W/V and 0.045% W/V and preferably 0.040% W/V. v.
- Higher concentrations of Sodium Hyaluronate could increase the viscosity of the system whose main result would be the total deformation of the Spray Pattern sought with Dmax/Dmin values » 1 ,12. It should be noted that the Spray-PLUMA Standard is very important for all Sprays as it shows the efficiency of product entry into the nasal cavities, without the need to introduce the applicator pump tip into them.
- Dexpanthenol at 1.0% P/V helps to obtain the correct Viscosity needed to obtain both the Spray Pattern and the desired droplet size distribution.
- a concentration of dexpanthenol greater or less than the concentration of 1.0% W/V would result in the same effect mentioned above for Sodium Hyaluronate.
- concentrations greater than 1% P/V can also cause an increase in the final density of the Spray, and the latter, as we will see below, also strongly influences the Spray Pattern and Droplet Size Distribution of the product.
- the inventors of the present invention determined that the density (in g/ml at 25°C) of the aqueous solution strongly influences the characteristics of the Spray Pattern sought and, mainly , the desired droplet size, i.e. 100% droplets larger than 10 microns, to avoid inadequate penetration of the product into the aforementioned tracheobronchial and/or respiratory tract.
- the density of the product of the present invention is mainly influenced by the concentrations of Dexpanthenol and the pH Regulating System Dibasic Sodium Phosphate Anhydrous and Monobasic Sodium Phosphate Anhydrous.
- concentrations chosen for each of these components of the formulation were balanced in order to stay within the allowable range of densities of the final product compatible with the PLUMA Spray Standard and the Gaussian-type droplet size distribution with 100% of the droplets containing a size greater than 10 microns.
- Sodium Hyaluronate is the active hydration agent of the nasal mucosa and an agent for obtaining an optimal viscosity
- Dexpanthenol assists in said hydration, in the relief of any epithelial wound, also acting in the control of the viscosity and density of the formulation in order to obtain an optimal spray effect with the chosen Spray Pump applicator.
- the Viscosity and Density required to obtain a constant and Elliptical Plume Spray Pattern with Dmax/Dmin from 1.00 to 1.12 to 3 and 6 cm of distance, with 100% of the Droplets larger than 10 microns and in Spray distribution must meet the following specifications:
- the pH (7.0 - 7.5) and physiological isotonicity are provided by the pH Regulator Monobasic Sodium Phosphate/Dibasic Sodium Phosphate. This system also strongly controls the density of the final product. To preserve the sterility of the product throughout its use, the classic Benzalkonium Chloride/EDTA antimicrobial system is used in nasal preparations. This formulation allows for continuous wetting of the nostrils, relief from nasal congestion, and lacks irritating effects.
- the content should range from 0.038% to 0.042% W/V of Sodium Hyaluronate.
- the density should range from 1.015 to 1.025 g/ml at 25°C by the pycnometry method. Brookfield viscosity at 25°C, Spindle 1 , 100 rpm should range from 4.0 to 5.0 cps.
- the liquid content should vary between 32 to 34 ml/vial.
- the pH should be between 7.0 and 7.5.
- the flow for each actuation must vary between 0.054 to 0.058 ml/pump.
- the product must pass the sterility test.
- Droplet size distribution assay by laser diffraction measured at a distance of 3 cm from the nozzle to the measurement plane
- REPLACEMENT SHEETS (RULE 26) [047] This test was performed on 10 vials of the composition manufactured according to example 1; each one of them was initially activated 1 time and the measurement called START was performed on the spray launched; then the bottle was activated without interruption until reaching the final content, where the final pump was carried out, whose spray released was measured again, called FIM.
- the laser beam diffractor performed the reading of the droplet size distribution results at a distance of 3 cm, which have a direct relationship with the formulation of example 1 and the peculiar spray system used. The result is expressed as a percentage of droplets that have a certain size expressed in microns. So, for example, choose:
- DV (10) indicates that 10% by volume of the droplets has a size equal to or smaller than that reported in the result, in microns.
- Dv (10) and Dv (90) together delimit the lower and upper limits of droplet size comprising 80% of the distribution centered on the mean Dv (50) with 40% for each side; the remaining 20% of the distribution is, 10% below the Dv value (10), and 10% above the value Dv (90).
- 10% that are below Dv (10) as mentioned before, looking at the individual distribution of each vial, it is easy to understand that, in all cases, there is no droplet size equal to or less than 10 microns.
- Droplet size distribution assay by laser diffraction measured at a distance of 6 cm from the nozzle to the measurement plane
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Abstract
L'invention concerne une composition pharmaceutique aqueuse à base d'hyaluronate de sodium sous forme de pulvérisation nasale soulageant et aidant en cas de sécheresse et d'irritation des narines causées par le vieillissement, hydratant et humidifiant toute la narine, ainsi que par la faible humidité, les refroidissements, la congestion ou les effets secondaires de médicaments. Cette composition se présente sous la forme d'une formulation en solution aqueuse véritable, spécifiquement équilibrée en viscosité et densité, de sorte que, lors de son administration au moyen d'un actionneur spécifique, un panache de pulvérisation standard particulier et constant est obtenu, de même qu'une distribution de taille des gouttelettes gaussienne, 100% des gouttelettes étant supérieures à 10 micromètres, d'où une plus grande efficacité dans le traitement topique local nasal sans dépasser la région naso-pharyngée.
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PCT/BR2021/050068 WO2022170405A1 (fr) | 2021-02-12 | 2021-02-12 | Composition pharmaceutique aqueuse à base d'hyaluronate de sodium sous forme de pulvérisation nasale |
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PCT/BR2021/050068 WO2022170405A1 (fr) | 2021-02-12 | 2021-02-12 | Composition pharmaceutique aqueuse à base d'hyaluronate de sodium sous forme de pulvérisation nasale |
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Citations (6)
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CN102579478A (zh) * | 2012-03-30 | 2012-07-18 | 济南康众医药科技开发有限公司 | 玻璃酸钠在制备药物中的应用 |
WO2013009519A2 (fr) * | 2011-07-12 | 2013-01-17 | Aihol Corporation | Matériaux pour traiter et prévenir une maladie liée aux muqueuses |
CN108066401A (zh) * | 2018-01-04 | 2018-05-25 | 蓝栋林 | 一种用于治疗鼻炎的药物 |
WO2019025040A1 (fr) * | 2017-07-31 | 2019-02-07 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Composition pour application nasale |
WO2019125330A2 (fr) * | 2017-08-10 | 2019-06-27 | Eli̇xi̇r İlaç Araştirma Ve Geli̇şti̇rme A.Ş. | Compositions de décongestionnant nasal comprenant du dexpanthénol et du hyaluronate de sodium |
WO2020053783A1 (fr) * | 2018-09-12 | 2020-03-19 | Neilos S.r.l. | Composition destinée à être utilisée dans la prévention et/ou le traitement de l'épistaxis |
-
2021
- 2021-02-12 WO PCT/BR2021/050068 patent/WO2022170405A1/fr active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2013009519A2 (fr) * | 2011-07-12 | 2013-01-17 | Aihol Corporation | Matériaux pour traiter et prévenir une maladie liée aux muqueuses |
CN102579478A (zh) * | 2012-03-30 | 2012-07-18 | 济南康众医药科技开发有限公司 | 玻璃酸钠在制备药物中的应用 |
WO2019025040A1 (fr) * | 2017-07-31 | 2019-02-07 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Composition pour application nasale |
WO2019125330A2 (fr) * | 2017-08-10 | 2019-06-27 | Eli̇xi̇r İlaç Araştirma Ve Geli̇şti̇rme A.Ş. | Compositions de décongestionnant nasal comprenant du dexpanthénol et du hyaluronate de sodium |
CN108066401A (zh) * | 2018-01-04 | 2018-05-25 | 蓝栋林 | 一种用于治疗鼻炎的药物 |
WO2020053783A1 (fr) * | 2018-09-12 | 2020-03-19 | Neilos S.r.l. | Composition destinée à être utilisée dans la prévention et/ou le traitement de l'épistaxis |
Non-Patent Citations (1)
Title |
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GOUTEVA INA, SHAH-HOSSEINI KIJA, MEISER PETER: "Clinical Efficacy of a Spray Containing Hyaluronic Acid and Dexpanthenol after Surgery in the Nasal Cavity (Septoplasty, Simple Ethmoid Sinus Surgery, and Turbinate Surgery)", JOURNAL OF ALLERGY, vol. 2014, 1 July 2014 (2014-07-01), pages 1 - 10, XP055880503, ISSN: 1687-9783, DOI: 10.1155/2014/635490 * |
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