EP4370144A1 - Glutahtione c4 contre les affections des voies respiratoires - Google Patents

Glutahtione c4 contre les affections des voies respiratoires

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Publication number
EP4370144A1
EP4370144A1 EP22743925.4A EP22743925A EP4370144A1 EP 4370144 A1 EP4370144 A1 EP 4370144A1 EP 22743925 A EP22743925 A EP 22743925A EP 4370144 A1 EP4370144 A1 EP 4370144A1
Authority
EP
European Patent Office
Prior art keywords
composition
gsh
nasal
treatment
use according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP22743925.4A
Other languages
German (de)
English (en)
Inventor
Rocco Crimi
Enrico Garaci
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Redox Co Srl
Original Assignee
Redox Co Srl
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Redox Co Srl filed Critical Redox Co Srl
Publication of EP4370144A1 publication Critical patent/EP4370144A1/fr
Pending legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A61K38/063—Glutathione
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • 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

Definitions

  • the present invention relates to the GSH-C4 compound for use in the treatment of respiratory tract diseases as well as to a composition comprising said compound, optionally in combination with at least one further active substance for said use.
  • the mucous membranes suffer more or less serious damage, starting from irritation to actual lesions such as, for example, in the case of crusty haemorrhagic rhinopathies, chronic cough.
  • the therapies of choice for the treatment of disorders related to the airways include corticosteroid therapies, optionally in combination with antibiotics, emollients, vasoconstrictors or others.
  • corticosteroid drugs have numerous side effects both when inhaled and when taken systemically (in the latter case the damage is greater) including mucosal damage, superimposed fungal infections, bleeding, weight gain, osteoporosis, increased blood sugar, skin alterations etc.
  • GSH- C4 the GSH derivative
  • GSH- C4 can be used effectively, in the treatment or in adjuvating treatment of airway diseases, including post-operative trauma, when administered by inhalation solution to a concentration (w/w) from 0.1 to 1.5%; optionally in combination with 0.05-0.5% (w/w) of hyaluronic acid.
  • the authors of the invention have in fact shown that GSH-C4 is effective in the treatment of upper and lower respiratory tract diseases without causing side relevant effects.
  • GSH-C4 is able to inhibit inflammatory pathways, restore the cellular redox state, and is expelled from the cells once oxidized.
  • GSH-C4 compound for use in the treatment or to assist in the treatment of airway diseases;
  • a composition comprising GSH-C4 at a concentration of 0.1% to 1.5% (w/w) and one or more excipients and/or pharmaceutically acceptable additives for use in the treatment or in the adjuvant treatment of diseases of the airways.
  • a device for delivery by inhalation or by nasal or oronasal spray comprising a composition according to any of the embodiments described/claimed.
  • GSH-C4 alias butanoyl glutathione or n-butanoyl y- glutamylcysteinylglycine indicates the molecule having the formula and can be prepared as described in example 2 of the patent application W02005063795 and/or as described in the examples of the patent application WO2019102397A1
  • hyaluronic acid has the meaning commonly used in the art and defines a natural polysaccharide, formed by a linear chain of glucuronic acid and N- acetylglucosamine particles. It has anti-inflammatory, mucoregulatory, anti-oedema and restructuring functions and also performs a bacteriostatic function through the creation of a protective patina on the mucosa, hinders the penetration of pathogens and reduces the proliferation of already existing ones.
  • Hyaluronic acid has excellent viscoelasticity, high moisture retention capacity, high biocompatibility and hygroscopic properties (Gupta, 2019).
  • hyaluronic acid In aqueous solution, hyaluronic acid is negatively charged and forms salts generally referred to as hyaluronan or hyaluronate (Laurent, 1989), which are highly hydrophilic and, consequently, surrounded by water molecules.
  • hyaluronan or hyaluronate e.g., 1989
  • low molecular weight sodium hyaluronate is able to hydrate itself and can reach a level of water mobilization up to 1000 times its own weight. Its physico-chemical characteristics allow the aggregation of polymer chains with the formation of an extended network (Scott, 1991).
  • hyaluronate occupies a large volume, forming a gel, resisting mechanical pressure.
  • MW molecular weights
  • concentration hyaluronic acid networks are strengthened and, as a result, hyaluronic acid solutions show progressively increased viscosity and viscoelasticity (Kobayashi, 1994).
  • Hyaluronic acid solutions are characterized by a non- Newtonian, thinning-cutting (pseudoplastic) and viscoelastic behaviour. This unique rheological behaviour is peculiar and extremely important, as it determines many physiological roles and pharmaceutical, medical, food and cosmetic applications of hyaluronan (Fallacara, 2018).
  • FIG. 1 Images obtained by nasal video-endoscopy from a patient suffering from crusted haemorrhagic rhinopathy after 15 days of treatment with a GSH-4 based spray having a composition as shown in Table 1.
  • Figure 3 Images obtained by nasal video-endoscopy from a patient suffering from perforation of the septum with blood serum diffuse crustiness, before treatment with a GSH-4 based spray.
  • Figure 4 Images obtained by nasal video-endoscopy from a patient suffering from perforation of the septum with diffuse blood serum crustiness, after 15 days of treatment with a GSH-4 based spray having a composition as shown in Table 1.
  • Figure 6 A-B Images obtained by nasal video-endoscopy from a patient suffering from iatrogenic rhinopathy from abuse of nasal sprays with vasoconstrictors, after 15 days of treatment with GSH-4 based spray having a composition as shown in Table 1.
  • FIG. 7 A-C Computed tomography (CT) images of patient 1, A.P. Female, 62 years old, smoker, suffering from acute bronchitis, cough. Period 4-10 November 2019.
  • SEA start 6, end 3.
  • Figure 8 A-C CT images of patient 2, P.F. Male, 80 years old, former smoker, suffering from right fibrothorax, diffuse bronchiectasis, cough. Period 11-17 November 2019.
  • SEA start 8, end 2.
  • FIG. 9 A-C. CT images of patient 3, L.R. male, 66 years old, former smoker, suffering from idiopathic pulmonary fibrosis, cough. Period 11-17 November 2019.
  • SEA start 8, end 6.
  • FIG. 10 A-C. CT images of patient 4, N.E. male, 71 years old, smoker, suffering from pulmonary emphysema, bronchiectasis, cough. Period 14-21 November 2019.
  • SEA start 5, end 3.
  • the present invention relates to the GSH-C4 compound for use in the treatment or in adjuvating the treatment of airway diseases.
  • said affections comprise pathologies affecting the upper and / or lower airways, irritations, lesions, inflammation of the mucous membranes.
  • a non- limiting example of such conditions comprises, but is not limited to, rhinopathy, post operative injury, cough, acute bronchitis, diffuse bronchiectasis, idiopathic pulmonary fibrosis, pulmonary emphysema.
  • the compound is preferably administered by inhalation or intra-nasal route or by nebulization to an individual in need thereof.
  • the compound can be formulated into a pharmaceutical composition.
  • the object of the present invention is therefore a composition comprising GSH-C4 at a concentration from 0.01% to 1.5% (w/w) and one or more excipients and/or pharmaceutically acceptable additives for use in the treatment or in adjuvating the treatment of airway diseases.
  • GSH-C4 can be at any concentration w/w in the range indicated above, such as 0.1; 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1.0; 1.1; 1.2; 1.3; 1.4; 1.5.
  • said GSH-C4 has a concentration from 0.4% to 1.2% w/w, or from 0.6% to 1% w/w, or 0.8% w/w.
  • the composition as described and claimed herein may comprise other pharmacologically active compounds suitable for the treatment of the airways, such as for example antibiotics; antibacterial, antifungal or other agents.
  • GSH-C4 is the only pharmacologically active ingredient present in the composition.
  • composition may then comprise excipients, such as polysaccharides, including hyaluronic acid, which exert a protective action on the oropharyngeal and/or nasopharyngeal mucosa and a mechanical action useful for administering the active ingredient GSH-C4.
  • excipients such as polysaccharides, including hyaluronic acid, which exert a protective action on the oropharyngeal and/or nasopharyngeal mucosa and a mechanical action useful for administering the active ingredient GSH-C4.
  • the composition may comprise, in addition to excipients commonly used by those skilled in the art in the preparation of pharmaceutical compositions, GSH-C4 at a concentration from 0.01% to 1.5% (w/w) and hyaluronic acid or a pharmaceutically acceptable salt thereof at a concentration of 0.05 to 0.5% (w/w).
  • GSH-C4 can be at any concentration w/w in the range indicated above, such as 0.1; 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1.0; 1.1; 1.2; 1.3; 1.4; 1.5. According to some preferred embodiments, said GSH-C4 has a concentration from 0.4% to 1.2% w/w, or from 0.6% to 1% w/w, or 0.8% w/w.
  • Hyaluronic acid or its pharmaceutically acceptable salt may be at any w/w concentration within the above range. In one embodiment, hyaluronic acid or its pharmaceutically acceptable salt may be at a concentration between 0.8 and 0.3% w/w.
  • the composition will therefore consist of GSH-C4 at a concentration from 0.1% to 1.5% (w/w) and hyaluronic acid or a pharmaceutically acceptable salt thereof at a concentration of 0.05. 0.5% (w/w) and suitable excipients.
  • the excipients may vary according to the type of formulation chosen according to what is commonly used by those skilled in the art.
  • Hyaluronic acid or its salt suitable to be used for the preparation of the composition of the invention may be hyaluronic acid or its high, medium or low molecular weight salt; whose molecular weights are respectively included within the following ranges: 1 ,800- 2,200 KDa, 1000-1800 kDa, 100-500 KDa.
  • hyaluronic acid and/or any salt of hyaluronic acid suitable for use by inhalation such as for example the sodium salt of hyaluronic acid (sodium hyaluronate).
  • the present invention refers to a composition formulated in liquid form according to the qualitative-quantitative composition reported in Table 1.
  • Table 1 :
  • the present invention refers to a composition formulated in liquid form according to the qualitative-quantitative composition shown in Table 2.
  • the liquid composition indicated in table 2 can be administered to an individual in need thereof in a dose equal to 3 ml_, every twelve hours, morning and evening, for a total duration of 7 days.
  • the present invention refers to a composition formulated in liquid form according to the qualitative-quantitative composition reported in Table 3.
  • the present invention refers to a composition formulated in liquid form according to the qualitative-quantitative composition reported in Table 4.
  • the liquid composition indicated in table 4 can be administered to an individual in need thereof in a dose equal to 3 ml_, every twelve hours, morning and evening, for a total duration of 7 days.
  • the composition as described and claimed can be used for the treatment and/or to adjuvate the treatment of diseases affecting the upper and/or lower airways, irritation, injury, inflammation of the mucous membranes.
  • diseases affecting the upper and/or lower airways irritation, injury, inflammation of the mucous membranes.
  • a non-limiting example is given by rhinopathies, post-operative injuries, cough, acute bronchitis, diffuse bronchiectasis, idiopathic pulmonary fibrosis, pulmonary emphysema.
  • composition of the invention can be used for the treatment of those pathologies in which the nasal mucosa is affected by infectious- inflammatory, dysreactive, granulomatous and neoplastic pathologies.
  • a nasal spray containing a composition based on GSH-C4 based and hyaluronic acid as reported in Table 1 is effective in the treatment of nasopharyngeal diseases in which there is a need for a tissue repair, either as a result of a mechanical-traumatic injury (nasal surgery) or due to an infection, viral or bacterial.
  • the authors also demonstrated that the composition of the invention as shown in table 2 is effective in the treatment of cough, in particular chronic cough.
  • cough is a reflex selected by evolution in order to protect the airways, primarily from the inhalation of foreign bodies.
  • a protective reflex it has intrinsic analogies with pain: both have conservative purposes in acute, have a more or less predominant psychological component and become pathological when they occur in chronic.
  • Mild complications are more frequent and of low risk to the patient's health. Nevertheless, the definition "mild” does not correspond to a low impact on the quality of life, which is however more compromised in patients who manifest these complications. The most frequent are: muscle aches, depression, fatigue, insomnia, headache, gastroesophageal reflux and vomiting. Serious complications are those events that can cause immediate permanent damage or pose a life risk to the patient. They are not common events and are never perceived as normal by people with chronic cough, including rib fractures, pneumothorax and pneumomediastinum, syncope, arrhythmias, urinary incontinence.
  • the GSH-C4 compound can be used with benefit for the treatment of chronic cough and for the protection of the respiratory tract.
  • the examples section shows experiments carried out with a liquid composition as reported in Table 2 according to the invention, with the dosage of a 3 ml vial, every 12 hours for 7 consecutive days, on patients suffering from cough and various pulmonary diseases, which demonstrated the effectiveness of the composition of the invention.
  • the composition for use according to the present invention is a composition suitable for administration by inhalation or intra-nasal route or by nebulization.
  • said composition is in a form selected from aerosol, nasal spray, solution, suspension, nasal drops, powder for inhalation.
  • composition object of the invention offers the advantage of being able to be administered by inhalation, by aerosol, nebulization, or spray, therefore in a simple and easy way, even at home, directly into the respiratory tract of patients in need thereof. Thanks to the presence of the highly vascularized nasal mucosa, the inhaled administration of the composition object of the invention allows the action of GSH-C4 at the mucosa level.
  • the composition may comprise excipients, carriers, solvents, dispersion media, diluents, viscosifying agents, salts, adjuvants, or surfactants, provided they are physiologically compatible.
  • composition object of the invention includes, for example, water, saline, phosphate buffered saline, glycerol, mixture of water and ethanol and the like, as well as combinations thereof.
  • isotonic agents for example sugars or poly alcohols, such as mannitol or sorbitol.
  • Agents capable of increasing the shelf life of the composition can also be used in the composition object of the invention and include wetting agents, emulsifiers, preservatives or buffers.
  • composition object of the invention in any of the embodiments described here may also contain stabilizing agents of the microbial load, such as benzalkonium chloride or the like.
  • compositions according to any of the embodiments described herein are sterile and stable under the storage conditions.
  • the pharmaceutical composition according to any of the previously described embodiments can be administered by inhalation and / or intra-nasal and / or oronasal.
  • the dispersion of a pharmaceutical composition according to the invention in very fine drops facilitates its transport through the respiratory tract, increasing the bioavailability of the active ingredients at the level of the mucosal membranes.
  • the composition object of the invention can be made in any form as long as it is suitable for administration of the inhalation and/or intra-nasal and/or oronasal type, and in particular in a form selected from aerosol and/or nasal or oronasal spray, nebulized formulation, solution, emulsion, suspension, nasal drops, powder.
  • the composition object of the invention can also be packaged both in multi-dose containers and in single-dose containers, for example in vials in the case of liquid compositions.
  • Non-limiting examples of generating devices that can be used for aerosol administration of a pharmaceutical composition according to the invention include a nebulizer (or small volume nebulizer, SVN), a metered-dose inhaler (or pressurized metered-dose inhaler, pMDI), or a dry powder inhaler (DPI).
  • a nebulizer or small volume nebulizer, SVN
  • a metered-dose inhaler or pressurized metered-dose inhaler, pMDI
  • DPI dry powder inhaler
  • the GSH-C4 can be administered to an individual in need thereof, in the form of a liquid or powder composition for aerosol, from a nebulizer activated by inspiring from the appropriate dispenser or through the classic ultrasonic electric devices or with a piston.
  • a nebulizer activated by inspiring from the appropriate dispenser or through the classic ultrasonic electric devices or with a piston.
  • the selection of the most appropriate dispensing device for administering a composition object of the invention can be made in relation to the type of patient, the greater ease of use, or the frequency of administration. Therefore, an inhaled delivery device or a delivery device by means of a nasal or oronasal spray comprising a pharmaceutical composition according to any of the previously described embodiments is also object of the invention.
  • said nasal or oronasal spray delivery device can comprise a bottle and/or vial containing the pharmaceutical composition to be administered and a spray atomizer system connected to a terminal syringe, for example in the form of a spout, to allow the delivery of an optimal volume of the composition per dose directly into the nasal or oronasal cavity.
  • said delivery device by means of a nasal or oronasal spray enables the delivery of an appropriate dose of the composition object of the invention quickly and effectively within the nasal or oronasal cavity.
  • the device can alternatively be equipped with an oronasal mask in order to allow delivery throughout the oropharyngeal cavity.
  • a further example of an inhaled delivery device according to the present invention is a metered dose inhaler device (MDI) comprising the pharmaceutical composition to be administered in a suitable dose.
  • MDI metered dose inhaler device
  • GSH-C4 or a composition comprising the same according to any of the embodiments described herein may be administered to an individual in need thereof every 12 hours, morning and evening, or every 24 hours, preferably for an overall duration of 7 days, or even more preferably for an overall duration of 15 days.
  • n.1 suffering from specific vasomotor rhinopathy, n.2 from nonspecific vasomotor rhinopathy, n.2 from iatrogenic rhinopathy (abuse of vasoconstrictors) n.2 from crusted haemorrhagic bacterial infectious rhinitis (one with perforation of the nasal septum) and n.2 patients that underwent nasal surgery.
  • a nasal video-endoscopy was performed in each patient before and after the treatment and an anamnesis focused on the nasal symptoms before and after the treatment as well as the degree of satisfaction with the therapy received was collected.
  • a liquid composition as defined in the example of Table 2 was administered by aerosol to all enrolled patients, as sole local therapy, with a dosage of a 3 ml vial, every 12 hours for 7 consecutive days.
  • composition Table 2 The effect of inhalation of the compound based on GSH-C4 at a concentration of 0.8% (composition Table 2) on the cough symptom was evaluated in 5 patients who presented the clinical symptom and who were suffering from various lung diseases (see detail of patients with relative chest CT images, Figs. 7-11).
  • the instrument used for the quantification of the cough symptom was the visual analogic scale (VAS) (from 1 to 10), as per the recommendations of the recent guideline of the European Society of Respiratory Medicine [14]
  • VAS visual analogic scale
  • the duration of treatment was empirically defined as approximately one week with aerosol administration of a dose of 3 ml every 12 hours.
  • Table 5 The data show that in all patients there was a reduction in the intensity of the cough symptom, subjectively assessed using the VAS scale. In 3 out of 5 cases this reduction was equal to or greater than 50%, compared to the starting value. No patient reported side effects following the inhalation of GSH-C4.
  • a nasal spray containing a composition exclusively based on GSH-C4 as reported in the aforementioned Table 3 is effective in the treatment of nasopharyngeal diseases in which there is a need for tissue repair, both as a consequence of a mechanical-traumatic insult (nasal surgery) or as a consequence of a viral or bacterial infection.
  • composition of the invention as shown in Table 4 is effective in the treatment of cough, in particular of chronic cough. It is known that cough is a reflex selected by evolution in order to protect the airways, primarily from the inhalation of foreign bodies.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Immunology (AREA)
  • Otolaryngology (AREA)
  • Pulmonology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne le composé glutathion C4 (GSH-C4) s'utilisant dans le traitement de pathologies des voies respiratoires, ainsi qu'une composition comprenant ledit composé, éventuellement associé à au moins une substance active supplémentaire pour ladite utilisation.
EP22743925.4A 2021-07-14 2022-07-13 Glutahtione c4 contre les affections des voies respiratoires Pending EP4370144A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT202100018605 2021-07-14
PCT/IB2022/056453 WO2023285984A1 (fr) 2021-07-14 2022-07-13 Glutahtione c4 contre les affections des voies respiratoires

Publications (1)

Publication Number Publication Date
EP4370144A1 true EP4370144A1 (fr) 2024-05-22

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Country Status (3)

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EP (1) EP4370144A1 (fr)
CN (1) CN117693352A (fr)
WO (1) WO2023285984A1 (fr)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITTO20031048A1 (it) * 2003-12-30 2005-06-30 Umberto Benatti Derivati del glutatione e loro utilizzi per il trattamento di malattie virali.
IT1396468B1 (it) * 2008-11-11 2012-12-14 Farma Derma Srl Uso topico di acido ialuronico ad azione filmogena in preparati per il trattamento e profilassi di patologie delle vie respiratorie.
AU2017298202A1 (en) * 2016-07-16 2019-02-07 Lauranell Harrison Burch Methods for treating cystic fibrosis and other diseases affecting mucosal surfaces
EP3773614A1 (fr) * 2018-04-12 2021-02-17 Matrx Therapeutics Corporation Compositions et procédés de traitement de rupture de fibre élastique
BR112021007692A2 (pt) * 2018-10-23 2021-08-10 George Edward Hoag composição e método para tratar os pulmões

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WO2023285984A1 (fr) 2023-01-19

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