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
  • A61K31/74—Synthetic polymeric materials
  • A61K31/795—Polymers containing sulfur
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/12—Antivirals
  • A61P31/14—Antivirals for RNA viruses
  • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
• • 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
  • 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
  • A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
• • 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

• TITLE COMPOSITION FOR THE TREATMENT OF RESPIRATORY SYSTEM INJURIES
• the present invention relates to a pharmaceutical composition for its use in the prophylaxis and / or treatment of lesions of the respiratory system, in particular of pulmonary lesions, caused by a microorganism.
• the present invention also relates to a pharmaceutical composition for its use in the treatment of lesions of the respiratory system, in particular of pulmonary lesions, caused by a microorganism.
• the present invention finds application in particular in the therapeutic, pharmaceutical and veterinary fields.
• references in parentheses refer to the list of references presented at the end of the text.
• Tissue damage in particular of the respiratory system, can occur and / or be caused by many factors, for example air pollution, microorganisms, for example viruses, bacteria, fungi. Pathologies can also be the cause of damage to the respiratory system, for example bronchitis, pneumonia, tuberculosis, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bronchopulmonary cancer.
• COPD chronic obstructive pulmonary disease
• the administration of inhaled corticosteroids can be used to decrease, for example inflammation of the bronchi
• the administration of antibiotics is also used for pathologies linked to bacteria, for example in the case of pneumonia.
• Lung infections also called pneumopathies
• a microorganism in particular a virus.
• Symptoms of pneumonia vary depending on the organism. For example, they can cause a high fever, for example close to 40 degrees, chest pain, cough, fatigue, shortness of breath etc.
• Infections of the lungs and / or the respiratory system are known to be contagious, particularly if they are caused by a microorganism, for example a bacteria or a virus.
• lung infections depends on the infectious microorganism.
• known treatments involve the use of antibiotics.
• viral lung infections for example influenza
• the object of the present invention is precisely to meet these needs by providing a pharmaceutical composition for its use in the treatment of lesions of the respiratory system caused by a microorganism, preferably of pulmonary lesions caused by a microorganism, said composition comprising
• A represents a monomer
• Y represents an O or N-sulfonate group and corresponding to one of the following formulas -R3OSO3R4, -R5NSO3R6, R7SO3R8 in which: Ri, R3, R 5 and Rg independently represent an aliphatic hydrocarbon chain, optionally branched and / or unsaturated and which optionally contains one or more aromatic rings with the exception of benzylamine and benzylamine sulfonate, R 2 , R 4 , R6 and Re independently represent a hydrogen atom or an M + cation,
• R 7 and R 10 independently represent a bond, an aliphatic hydrocarbon chain, optionally branched and / or unsaturated, a represents the number of monomers, x represents the degree of substitution of monomers A by groups X, y represents the degree of substitution of the A monomers by Y groups.
• the present invention also aims to meet these needs by providing a pharmaceutical composition for its use in the prophylaxis of lesions of the respiratory system caused by a microorganism, preferably of pulmonary lesions caused by a microorganism, said composition comprising
• A represents a monomer
• Y represents an O or N-sulfonate group and corresponding to one of the following formulas -R3OSO3R4, -R5NSO3R6, R7SO3R8 in which: Ri, R3, R 5 and Rg independently represent an aliphatic hydrocarbon chain, optionally branched and / or unsaturated and which optionally contains one or more aromatic rings with the exception of benzylamine and benzylamine sulfonate, R 2 , R 4 , R6 and Re independently represent a hydrogen atom or an M + cation,
• R 7 and R 10 independently represent a bond, an aliphatic hydrocarbon chain, optionally branched and / or unsaturated, a represents the number of monomers, x represents the degree of substitution of monomers A by groups X, y represents the degree of substitution of monomers A by Y groups.
• the inventor has surprisingly demonstrated that the use of a biocompatible polymer according to the invention, in particular the composition comprising a biocompatible polymer according to the invention, advantageously makes it possible to treat lesions of the respiratory system caused by a microorganism.
• the composition according to the invention allows advantageously synergistically to repair damage to lung tissue caused by microorganisms, in particular and advantageously by viral infections.
• the inventor has surprisingly and unexpectedly demonstrated that the composition according to the invention advantageously allows repair of lesions of pulmonary tissues in a very short time and also advantageously and unexpectedly allows functional recovery of the tissues and / or organs of the respiratory system injured.
• the inventor has also demonstrated that the composition according to the invention advantageously allows recovery of the function of the capillary alveolar barrier or air-blood barrier.
• the composition according to the invention advantageously makes it possible to neutralize the effects of infections of the respiratory system, in particular of infections of the pulmonary system, in particular of viral infections, through respiratory functional recovery, namely a return to a functioning of the normal pulmonary system, in particular obtained in a short time, for example a few days following the treatment.
• the composition according to the invention advantageously allows repair of pulmonary tissue damage without relapse.
• the composition according to the invention advantageously and unexpectedly allows protection of the capillary alveolar barrier or air-blood barrier.
• the inventors have demonstrated that the composition according to the invention can advantageously be used prophylactically in subjects exposed to at least one microorganism causing lesions of the respiratory system and / or in subjects exhibiting lesions of the respiratory system caused by a microorganism.
• the composition according to the invention advantageously makes it possible to neutralize the effects of infections of the respiratory system caused by a microorganism, in particular of infections of the pulmonary system, in particular of viral infections, and allows thus to use the composition according to the invention prophylactically, for example before any symptom, for example respiratory.
• composition allows rapid recovery of respiratory functions impaired by pulmonary lesions caused by a microorganism and advantageously recovery of pulmonary function, in particular restoration of the function of the capillary alveolar barrier or air-blood barrier. .
• a subject of the present invention is therefore also a pharmaceutical composition for its use in the treatment of impairments in respiratory functions due to lesions of the respiratory system caused by a microorganism, preferably pulmonary lesions caused by a microorganism, said composition comprising
• A represents a monomer
• Y represents an O or N-sulfonate group and corresponding to one of the following formulas -R3OSO3R4, -R5NSO3R6, R7SO3R8 in which:
• Ri, R3, R 5 and Rg independently represent an aliphatic hydrocarbon chain, optionally branched and / or unsaturated and which optionally contains one or more aromatic rings with the exception of benzylamine and benzylamine sulfonate, R 2 , R 4 , R6 and Re independently represent a hydrogen atom or an M + cation,
• R 7 and R 10 independently represent a bond, an aliphatic hydrocarbon chain, optionally branched and / or unsaturated, a represents the number of monomers, x represents the degree of substitution of monomers A by groups X, y represents the degree of substitution of monomers A by Y groups.
• lesions of the respiratory system caused by a microorganism are understood to mean any lesion of the respiratory system caused by a microorganism known to those skilled in the art. It could be for example damage to the pharynx, damage to the larynx, damage to the trachea, damage to the lungs, damage to the bronchi and / or damage to the bronchioles caused by a microorganism.
• lung damage caused by a microorganism is understood to mean any lung damage caused by a microorganism known to those skilled in the art. These may, for example, be lesions of lesions of the lungs, lesions of the bronchi and / or lesions of the bronchioles caused by a microorganism. This may be, for example, respiratory complications following an infection by a microorganism, for example a virus, a bacterium, a fungus, a parasite.
• treatment refers to prophylaxis and / or therapy, particularly when the objective is to prevent and / or slow (decrease) an injury to the respiratory system caused by a microorganism, preferably a virus, and / or a lung injury caused by a microorganism, for example a microorganism selected from the group consisting of a virus, a bacterium, a parasite and a fungus, preferably a virus.
• Beneficial or desired clinical outcomes include, but are not limited to, alleviation of symptoms, reduction in the extent of the disease, stabilization (i.e. not worsening) of the condition.
• Treatment can also mean prolonging survival and / or improving quality of life relative to expected survival and / or quality of life if the patient does not receive treatment.
• treatment may include any of the following: decreased respiratory syndrome, decreased respiratory distress, decreased lung pain, decreased difficulty and / or pain in breathing, decreased frequency of cough.
• prophylaxis in particular the prevention of alterations and / or lesions of the respiratory system caused by a microorganism, for example a microorganism chosen from the group comprising a virus, a bacterium, a parasite and a fungus, preferably a virus.
• prophylaxis is also meant any degree of delay in the time of onset of clinical signs or symptoms of lesions of the respiratory system as well as any degree of inhibition of the severity of clinical signs or symptoms of lesions of the respiratory system. , including, but not limited to, total prevention of damage to the respiratory system.
• a prophylaxis can comprise an administration of a composition according to the invention to a mammal, preferably a human being capable of being colonized and / or infected by a microorganism capable of causing pulmonary lesions, for example one by way of preventive, that is to say in order to prevent colonization by said microorganism or to avoid the appearance of any clinical sign or symptom of pulmonary lesions.
• the prophylactic administration can be carried out before said mammal, preferably a human being, is exposed to an organism capable of causing lung damage in said mammal (in particular in said human) or at the time of exposure.
• Such prophylactic administration can advantageously prevent, ameliorate, and / or reduce the severity of any subsequent lung injury.
• a cough or repeated sneezing are advantageously controlled by an administration, for example by inhalation, of the composition.
• respiratory functions we mean the ventilation and the exchange of oxygen (O 2 ) and carbon dioxide (CO 2 ) between the air and the blood, in the pulmonary alveoli.
• This may be, for example, the pulmonary function associated with the function of the capillary alveolar barrier or air-blood barrier involved in the exchange of gases, in particular oxygen (O2) and carbon dioxide (CO2) between the air and blood.
• impairment of respiratory functions is understood to mean a decrease and / or impairment of the exchange of oxygen (O2) and carbon dioxide (CO2) between the air and the blood, at the level of the pulmonary alveoli.
• O2 oxygen
• CO2 carbon dioxide
• This could be, for example, a deficiency in respiratory functions which could lead to respiratory acidosis.
• This can be clinically manifested by difficult, panting breathing, shortness of breath and a sometimes painful feeling of suffocation in the chest area, and severe fatigue.
• the skin on the fingers and lips may turn blue.
• microorganism any microorganism known to those skilled in the art capable of causing lesions of the respiratory system and / or pulmonary lesions. It may be, for example, a microorganism chosen from the group comprising viruses, bacteria, fungi and parasites
• virus any virus known to those skilled in the art capable of causing lesions of the respiratory system and / or pulmonary lesions. It may for example be a virus chosen from the group comprising the Picornavirus family, for example rhinoviruses, the Coronaviridae family, for example coronaviruses, the Orthomyxoviridae family, for example influenzaviruses. It may, for example, be a virus chosen from the group comprising coronaviruses, rhinoviruses and influenzaviruses.
• viruses may for example be viruses, in particular viruses of the Coronaviridae family, chosen from the group comprising 229E coronaviruses, NL63 coronavirus (HCoV-NL63) (human coronavirus NL63 or in English “Human coronavirus” NL63) , the human coronavirus OC43 (HCoV-OC43), the human coronavirus HKU1 ((HC0V-HKUI) in English "human coronavirus HKU1”), acronym, the coronavirus SARS (severe acute respiratory syndrome), the coronavirus MERS-CoV (Coronavirus du Middle East Respiratory Syndrome), SARS-CoV-1 coronaviruses (severe acute respiratory syndrome coronavirus or in English "severe acute respiratory syndrome coronavirus "), the SARS-CoV-2 coronaviruses (severe acute respiratory syndrome coronavirus 2 or in English” severe acute respiratory syndrome coronavirus 2 ").
• NL63 coronavirus H
• viruses may for example be viruses, in particular viruses of the Picornavirus family, chosen from the group comprising human rhinoviruses C, human rhinoviruses B and human rhinoviruses A. They may for example be viruses, in particular viruses of the Orthomyxoviridae family, chosen from the group comprising influenza A viruses (“Influenza A virus”), influenza B viruses (“Influenza B virus “), Influenza C viruses (“ Influenza C virus ").
• composition according to the invention can advantageously make it possible to treat lesions of the respiratory system and / or pulmonary lesions of viruses using heparan sulfates as a portal of entry to infest the target cell, for example. as described in the document Cagno et al. “Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias?” Viruses. 2019 Jul; 11 (7): 596.
• the present may be for example a virus chosen from the group comprising the Dengue virus (DENV), the Echovirus 5, for example the meta-pneumovirus, the rhinoviruses, the enteroviruses, the virus of the human immunodeficiency (HIV), Zika viruses, Chykungunya. It can be any virus known to those skilled in the art capable of using heparan sulphates as co-receptors for entry into cells
• bacteria means any bacterium known to a person skilled in the art capable of causing lesions of the respiratory system and / or pulmonary lesions. It may, for example, be a bacterium chosen from the group comprising Streptococcus pneumoniae, Hemophilus influenza type B or a mycoplasma, for example Mycoplasma pneumoniae
• fungus any fungus known to those skilled in the art capable of causing lesions of the respiratory system and / or pulmonary lesions. It may, for example, be a fungus chosen from the group comprising Pneumocystis jirovici, Cryptococcus neoformens, Aspergillus sp and nemathelminths.
• the term parasite is understood to mean any parasite known to those skilled in the art capable of causing lesions of the respiratory system and / or pulmonary lesions. It may for example be a parasite involved in respiratory pathologies, for example Chargass disease, pulmonary amebiosis. It may for example be a parasite chosen from the group comprising trypanosoma cruzi or amoeba, for example Entamoeba histolytica.
• monomer for example a monomer chosen from the group comprising sugars, esters, alcohols, amino acids or nucleotides or derivatives thereof.
• the monomers A constituting the building blocks of the polymers of formula I may be the same or different.
• the identical or different monomers A can be independently chosen from sugars or derivatives thereof.
• the monomers A can be independently of the monomers of the following formula: in which Rn and R12 independently represent an oxygen atom, an aliphatic, optionally branched and / or unsaturated hydrocarbon chain, a heteroaryl group independently comprising one or more oxygen and / or nitrogen atoms, an aldehyde function, a group carboxylic acid, a diol, a substituted diol, a group of formula -R13- (X) n-Ri 4 in which R13 represents a C 1 to C 4 aliphatic carbon chain, optionally branched and / or unsaturated, X represents a heteroatom chosen from oxygen and nitrogen, is an integer ranging from 1 to 4 and R14 is a hydrogen atom, an aliphatic hydrocarbon chain, optionally branched and / or unsaturated, a heteroaryl group comprising independently one or more oxygen and / or
• the combination of monomers can make it possible to form a polymeric backbone, for example a polymeric backbone of polyester, polyalcohol, polysaccharide, of the nucleic acid or protein type.
• polyesters it may be, for example, copolymers of biosynthesis or chemical synthesis, for example aliphatic polyesters or of natural origin, for example polyhydroxyalkonotes.
• the polysaccharides and their derivatives can be of bacterial, animal, fungal and / or plant origin. They may for example be single chain polysaccharides, for example polyglucoses, for example dextran, cellulose, beta glucan, or other monomers comprising more complex units, for example xanthans, for example glucose , mannose and glucuronic acid or also glucuronans and glucoglucuronan.
• polyglucoses for example dextran, cellulose, beta glucan
• monomers comprising more complex units
• xanthans for example glucose , mannose and glucuronic acid or also glucuronans and glucoglucuronan.
• the polysaccharides of plant origin can be single chain, for example cellulose (glucose), pectins (galacturonic acid), fucans, starch or more complex such as alginates (galuronic and mannuronic acid) .
• the polysaccharides of fungal origin can be, for example, steroglucan.
• the polysaccharides of animal origin can be, for example, chitins or chitosan (glucosamine).
• the A monomers constituting the basic elements of the polymers of formula I can advantageously be identical.
• the A monomers constituting the basic elements of the polymers of formula I can advantageously be glucose.
• the number of monomers A defined in formula (I) by “a” can be such that the mass of said polymers of formula (I) is greater than or equal to 2000 Daltons.
• the number of monomers A defined in formula (I) by “a” can be such that the mass of said polymers of formula (I) is approximately between 2,000 and 6,000 Daltons, for example which corresponds to at least 10 monomers of glucose.
• the mass of said polymers of formula (I) can be approximately between 3000 Daltons and 6000 Daltons, for example which corresponds to 12 to 20 glucose monomers.
• the number of monomers A defined in formula (I) by “a” can also be such that the mass of said polymers of formula (I) is less than approximately 2,500,000 Daltons (which corresponds to 7,000 glucose monomers).
• the number of monomers A defined in formula (I) by “a” can also be such that the mass of said polymers of formula (II) can be approximately between 2,000 and 500,000 Daltons, for example between 3,000 and 500,000 Daltons, for example example equal to 3000 Daltons, 5000 Daltons, 6000 Daltons, 10,000 Daltons, 20,000 Daltons, 40,000 Daltons, 80,000 Daltons, 220,000 Daltons, 500,000 Daltons.
• the mass of said polymers of formula (I) can be from 3000 to 250,000 Daltons, for example from 3000 to 6000 Daltons, or for example from 20,000 to 250,000 Daltons, or for example from 75,000 to 150,000 Daltons.
• the mass of said polymers of formula (I) may be from 3000 to 500000 Daltons, for example from 3000 to 250,000 Daltons, for example from 3000 to 6000 Daltons, or for example from 20,000 to 250,000 Daltons, or for example from 75,000 to 150,000 Daltons.
• R 1 can be a C 1 to C 6 alkyl, for example a methyl, an ethyl, a butyl, a propyl, a pentyl, preferably a methyl group
• R2 can be a bond, a C 1 to C 6 alkyl, for example a methyl, an ethyl, a butyl, a propyl, a pentyl, a group R21R22 in which R21 is an anion and R22 a cation selected from the group of alkali metals.
• the group X is the group of formula - R1COOR2 in which R1 is a methyl group -CH2- and R2 is a group R21R22 in which R21 is an anion and R22 is a cation chosen from the group of alkali metals, preferably the group X is a group of formula -CH2-COO or carboxymethyl.
• the degree of substitution of all the monomers A by the groups X defined in general formula (I) by “x” can be from 10 to 150%, from 40 to 80%, and preferably of the order of 50% or 60%.
• R3 may be a bond, a C1 to C6 alkyl, for example a methyl, an ethyl , a butyl, a propyl, a pentyl, preferably a methyl group
• R5 can be a bond, a C1 to C6 alkyl, for example a methyl, an ethyl, a butyl, a propyl, a pentyl, preferably a group methyl
• R7 can be a bond, C1-C6 alkyl, for example methyl, ethyl, butyl, propyl, pentyl, preferably a methyl group
• R 4 , R6 and Re can independently be a d atom hydrogen or an M + cation, for example M + can be an alkal
• the Y group is the group of formula - R 7 SO3R8 in which R 7 is a bond and Rs is an alkali metal chosen from the group comprising lithium, sodium, potassium, rubidium and cesium.
• R 7 is a bond
• Rs is an alkali metal chosen from the group comprising lithium, sodium, potassium, rubidium and cesium.
• the Y group is an -SO3, -SO3 Na + group
• the degree of substitution of all of the A monomers by the Y groups defined in general formula (I) by “y” can be from 10 to 170%, from 30 to 150%, from 55 to 160%, from 55 at 85%, from 120 to 160%, and preferably of the order of 70, 140 or 150%.
• substitution rates means by a substitution rate "x" of 100%, the fact that each monomer A of the polymer of the invention statistically contains an X group.
• a degree of substitution “y” of 100% is meant the fact that each monomer of the polymer of the invention contains statistically a Y group.
• the substitution rates greater than 100% reflect the fact that each monomer statistically carries more than one group of the type considered; conversely, the substitution rates of less than 100% reflect the fact that each monomer statistically bears less than one group of the type considered.
• the polymers can also comprise functional chemical groups, designated Z, other than X and Y.
• the Z groups may be the same or different, and may independently be selected from the group consisting of amino acids, fatty acids, fatty alcohols, ceramides, or derivatives thereof, or nucleotide sequences of 'addressing, antibodies, antibody fragments.
• the Z groups can also represent identical or different active agents. They may be, for example, therapeutic agents, diagnostic agents, an anti-inflammatory, an antimicrobial, an antibiotic, an antiviral agent, a growth factor, a cellular communication cytokine, eg an interferon, an enzyme, an antioxidant compound, polyphenols, tannins, anthocyanins, lycopenes, terpenoids and resveratrol.
• the Z group can advantageously be a saturated or unsaturated fatty acid. It may for example be a fatty acid chosen from the group comprising acetic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, acid.
• stearic acid arachidic acid, behenic acid, lignoceric acid, cerotic acid, myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, acid trans-vaccenic acid, linoleic acid, linolelaidic acid, ⁇ -linolenic acid, g-linolenic acid, dihomo-y-linolenic acid, arachidonic acid, eicosapentaenoic acid, clupanodonic or docosahexaenoic acid.
• the fatty acid is acetic acid.
• the Z group can advantageously be an amino acid of the L or D series chosen from the group comprising alanine, asparagine, an aromatic chain, for example tyrosine, phenylalanine, tryptophan, thyroxine or histidine.
• the amino acid is phenylalanine.
• the Z group can be an antioxidant, for example vitamin A, C, E, B9, B6, glutathione, selenium, polyphenols, for example catechins, for example green tea, flavonoids, tannins, anthocyanins, for example red fruits, lycopenes, terpenoids and resveratrol.
• an antioxidant for example vitamin A, C, E, B9, B6, glutathione, selenium, polyphenols, for example catechins, for example green tea, flavonoids, tannins, anthocyanins, for example red fruits, lycopenes, terpenoids and resveratrol.
• the Z group can be anti-aging compounds, for example retinoids, allantoins.
• the Z group can be antibodies, antibody fragments, for example Fab fragments. They may be, for example, antibodies and / or fragments of targeting antibodies, for example antibodies and / or fragments of antibodies capable of targeting the blood brain barrier.
• the Z group can be antiviral agents. It may be any suitable antiviral agent, for example an antiviral agent blocking access to the entry of the virus into the cell or acting as decoys of the receptor and / or mimetics of the receptor and / or of the co-receptor. or anti-idiotype antibodies mimicking the natural virus as ligand with respect to its receptor.
• Coronavirus inhibitors of the enzyme of the conversion of Angiotensin 2 (ACE) or an inhibitor of the serine protease, for example TMPRSS2 involved as co-receptors to the entry of this virus into cells as described by Aleksandra Milewska et al, “Human Coronavirus NL63 Uses Heparan Sulfate Proteoglycans for Attachment to Target Cells” November 2014 Volume 88 Number 22 Journal of Virology p.
• ACE Angiotensin 2
• TMPRSS2 serine protease
• the Z groups can give the polymers additional biological or physicochemical properties.
• Z groups can increase solubility or lipophilicity of said polymer allowing for example better diffusion or tissue penetration.
• the Z groups can give the polymers additional biological or physicochemical properties.
• the polymers of the invention for example when the Z group is chosen from an antioxidant compound, an anti-aging compound, the polymers of the invention can advantageously convey these compounds and thus provide an additional and / or complementary biological effect.
• Polymers in which Z is present can correspond to the following formula II: Aa Xx Yy Zz (II) in which, A, X, Y, a, x, y are as defined above and z represents the degree of substitution by Z groups.
• the A monomers constituting the basic elements of the polymers of formula (II) can advantageously be identical.
• the A monomers constituting the basic elements of the polymers of formula (II) can advantageously be glucose.
• the number of monomers A defined in formula (II) by “a” can be such that the mass of said polymers of formula (II) is greater than or equal to 2000 Daltons.
• the number of monomers A defined in formula (II) by “a” can be such that the mass of said polymers of formula (II) is approximately between 2,000 and 6,000 Daltons, for example which corresponds to at least 10 monomers of glucose.
• the mass of said polymers of formula (II) can be approximately between 3000 Daltons and 6000 Daltons, for example, which corresponds to 12 to 20 glucose monomers.
• the number of monomers A defined in formula (II) by “a” can also be such that the mass of said polymers of formula (II) is less than approximately 2,500,000 Daltons (which corresponds to 7,000 glucose monomers).
• the number of monomers A defined in formula (II) by “a” can also be such that the mass of said polymers of formula (II) can be approximately between 2,000 and 500,000 Daltons, for example between 3,000 and 500,000 Daltons, for example example equal to 3000 Daltons, 5000 Daltons, 6000 Daltons, 10,000 Daltons, 20,000 Daltons, 40,000 Daltons, 80,000 Daltons, 220,000 Daltons, 500,000 Daltons.
• the mass of said polymers of formula (II) may be from 3000 to 500000 Daltons, for example from 3000 to 250,000 Daltons, for example from 3000 to 6000 Daltons, or for example from 20,000 to 250,000 Daltons, or for example from 75,000 to 150,000 Daltons.
• the degree of substitution of all the monomers A by the groups X defined in general formula (II) by “x” can be from 10 to 150%, from 40 to 80%, and preferably of the order of 50% or 60%.
• the degree of substitution of all of the A monomers by the Y groups defined in general formula (II) by “y” can be from 10 to 170%, from 30 to 150%, from 55 to 160%, from 55 at 85%, from 120 to 160%, and preferably of the order of 70, 140 or 150%.
• the degree of substitution by Z groups represented by “z” can be between 1 and 50%, from 10 to 25%, preferably equal to 15, 20 or 25%.
• the X, Y and Z groups can be independently attached to the monomer A and / or independently attached to each other. When at least one of the X, Y and Z groups is independently attached to an X, Y and Z group other than the first, one of said X, Y or Z groups is attached to the A monomer.
• the Z groups can be covalently attached directly to the A monomers or covalently attached to the X and / or Y groups.
• the Z groups can also be conjugated to the polymers of formula AaXxYy by bonds other than covalent, for example by ionic bonds, for example via ionic interactions, hydrophilic bonds or hydrophobic bonds.
• bonds other than covalent for example by ionic bonds, for example via ionic interactions, hydrophilic bonds or hydrophobic bonds.
• the polymers of the invention can then constitute a Z vectorization system.
• the polymer may for example be a polymer chosen from the group comprising the compounds OTR4120, OTR41201, OTR41202, OTR41203, OTR41205, OTR41210 OTR41301, OTR41302, OTR41303, OTR41305, OTR 41310, OTR3131.
• the polymer can be, for example, a polymer chosen from the group comprising the compounds OTR41201, OTR41202, OTR41203, OTR41205, OTR41210, OTR4120, OTR4122, OTR4125,
• OTR41301, OTR41302, OTR41303, OTR41305, OTR41310, OTR3131, OTR4132, OTR4135, OTR415 with the characteristics mentioned in table 1 below
• Table 1 Polymers of the families Aa Xx Yy (I) and Aa Xx Yy Zz (I) in which A is glucose (MW 180Da), X is CarboxyMethyl (MW 58 Da) Y: SO3 ' (MW 80Da) and Z is Acetate (PM 43Da) or phenylalanine (PM 165Da).
• the composition may comprise a concentration of 0.1 to 100 ⁇ g / nnL by weight of biocompatible polymer based on the volume of the composition.
• the composition can comprise a concentration of 1 to 100 pg / ml, of 10 to 100 pg / nnl by weight of biocompatible polymer relative to the total volume of the composition.
• the composition can be formulated and / or adapted according to its administration.
• the composition can be administered in order to deliver a dose of biocompatible polymer of 0.01 to 5 mg per kilogram of body weight, preferably 0.1 to 1.5 mg per kilogram of body weight. body weight at frequency of administration, administration every two or three days, for example 2 to 3 times per week.
• the composition can be administered in order to deliver a dose of biocompatible polymer of 0.1 to 5 mg per kilogram of body weight, preferably 0.01 to 1.5 mg / kg to the frequency of daily or bi-weekly administration.
• the intake can be daily or twice weekly and between 0.5 pg / kg and 100 pg / kg.
• the biocompatible polymer may be at a concentration of from 0.1 to 100 pg / ml by weight of biocompatible polymer relative to the total volume of the composition, preferably from 1 to 20 ml.
• the biocompatible polymer may be at a concentration of 0.1 to 100 pg / mL by weight of biocompatible polymer relative to the total volume of the composition, preferably 1 to 20 mL, preferably equal to 5 ml_.
• the biocompatible polymer can be at a concentration of 0.1 to 100 pg / mL by weight of biocompatible polymer. relative to the total volume of the composition, preferably from 1 to 20 ml_, preferably equal to 5 ml_. It may for example be a composition, preferably from 1 to 20 ml_, of an aqueous solution of OTR4120 at 100 pg / ml_ or OTR4131 at 10 pg / ml_ placed in a nebulizer making it possible to deliver from 1 to 3 ml_ per minutes with an administration time included, for example 5 to 10 minutes.
• It may be for example a composition, preferably from 1 to 20 ml_, of an aqueous solution of OTR4120 of 10 to 100 pg / ml_, for example to 10 pg / nnL of OTR4120, or of OTR4131 of 10 pg / ml_ to 100 pg / ml placed in a nebulizer making it possible to deliver from 0.5 to 3 ml_ per minute with a duration of administration included, for example from 5 to 10 minutes.
• It may for example be a composition of an aqueous solution of OTR4120 of 10 to 100 pg / nnL, for example 10 pg / nnL of OTR4120 placed in a nebulizer. allowing the delivery of 0.5 ml_ per minute with an administration time of 5 minutes.
• the composition may further comprise hyaluronic acid.
• hyaluronic acid any hyaluronic acid known to those skilled in the art, for example a non-sulfated linear glycosaminoglycan composed of repeating units of D-glucuronic acid and of N-acetyl-D. -glucosamine.
• hyaluronic acid in its acid form or in the form of salt (hyaluronate), of crosslinked hyaluronic acid HA is a non-sulfated linear glycosaminoglycan composed of repeating units of D-glucuronic acid and N-acetyl-D-glucosamine (Tammi R., Agren UM., Tuhkanen AL., Tammi M. Hyaluronan metabolism in skin. Progress in Histochemistry & Cytochemistry. 29 (2): 1-81, 1994 [26]) . It may be, for example, hyaluronic acid having average molecular weight fractions of 5,000 to 3,000,000 Dalton, preferably between 50,000 and 2,000,000 Dalton.
• hyaluronic acid can be obtained by any method known to those skilled in the art. These may, for example, be methods described in the journal Hyaluronan fragments: an information-rich System (R. Stern et al., European Journal of Cell Biology 58 (2006) 699-715 [27]). It may also be natural or modified hyaluronic acid, available commercially, regardless of their designations and / or molecular weight, for example commercial hyaluronic acid chosen from Hyactive CPN; Cristalhyal; Nutra HA; Oligo HA; D Factor; Hyaluderm; juvelift; Restylane; Revitacare without this list being exhaustive. It may also be hyaluronic acid marketed by the company Contipro (https://www.contipro.com/portfolio/manufacturer-of-anti-aging-cosmetic-raw-materials / HyActive ").
• the composition can comprise a concentration of 0.1 to 5% by weight of hyaluronic acid relative to the total weight of the composition.
• the composition can comprise a concentration of 0.2% to 2.5% by weight of hyaluronic acid relative to the total weight of the composition.
• the composition can comprise a concentration of 1 to 10 mg / ml by weight of hyaluronic acid relative to the total volume of the composition.
• the inventor has demonstrated that the composition comprising a biopolymer and hyaluronic acid makes it possible to treat lesions of the respiratory system caused by a microorganism, in particular a virus.
• the composition comprising a biopolymer and hyaluronic acid advantageously makes it possible to provide a synergistic effect of repairing lesions of the respiratory system, advantageously pulmonary lesions.
• the pharmaceutical composition can be for example an injectable solution. It may, for example, be an injectable solution, for example for local or systemic injection, for example in physiological serum, in injectable glucose solution, in the presence of excipients, for example dextrans, for example at known concentrations of l a person skilled in the art, for example from micrograms to a few milligrams per ml_.
• the pharmaceutical composition can be, for example, a medicament intended for oral administration chosen from the group comprising a liquid formulation, an effervescent oral dosage form, an oral powder, a multiparticulate system, an orodispersible dosage form.
• the pharmaceutical composition when it is for oral administration, it can be in the form of a liquid formulation chosen from the group comprising a solution, a syrup, a suspension or an emulsion.
• the pharmaceutical composition when it is in the form of an effervescent oral dosage form, it may be in a form selected from the group comprising tablets, granules, powders.
• the pharmaceutical composition when the pharmaceutical composition is in the form of an oral powder or a multiparticulate system, it may be in a form selected from the group consisting of beads, granules, mini-tablets and microgranules.
• the pharmaceutical composition when in the form of an orodispersible dosage form, it may be in a selected form from the group consisting of orodispersible tablets, lyophilized wafers, thin films, a chewable tablet, a tablet, a capsule or a medical chewing gum.
• the pharmaceutical composition can be a pharmaceutical composition for oral administration, for example buccal and / or sublingual, for example chosen from the group comprising buccal or sublingual tablets, lozenges, drops, a solution for sprays.
• the pharmaceutical composition can be a pharmaceutical composition for topical or transdermal administration, for example chosen from the group comprising ointments, creams, gels, lotions, patches and foams.
• the pharmaceutical composition may be a pharmaceutical composition for administration by the respiratory or nasal route, for example in the form of an aerosol, for example administered with a nebulizer and / or inhaler.
• the composition may be a composition for nasal or respiratory nasal or respiratory administration, for example chosen from the group comprising nasal drops, nasal spray, nasal powder, aerosols, for example aerosols and / or spray nasal compressed gas, or nebulizers
• the pharmaceutical composition can be a pharmaceutical composition suitable for intra-pulmonary administration, for example by intra-pulmonary injection.
• the pharmaceutical composition when suitable for nasal or respiratory administration, it can advantageously be for bronchopulmonary purposes.
• the pharmaceutical composition may be a pharmaceutical composition for administration by the nasal or respiratory route, nasal or respiratory.
• the pharmaceutical composition may be a pharmaceutical composition for parenteral administration, for example example subcutaneous, intramuscular, intravenous, intraarterial, intracranial, intrathecal.
• composition of the present invention can also comprise at least one other active ingredient, particularly another therapeutically active ingredient, for example for simultaneous, separate or staggered use depending on the galenic formulation used.
• This other ingredient can be for example an active ingredient used for example in the treatment of opportune diseases which can develop in a patient having infection of the respiratory system caused by a microorganism, for example by a virus or a bacterium.
• It can also be pharmaceutical products known to those skilled in the art, for example antibiotics, anti-inflammatories, antivirals
• composition of the present invention can also comprise at least one other active ingredient, particularly another therapeutically active ingredient, for example for simultaneous, separate or staggered use depending on the galenic formulation used.
• This other ingredient can be for example an active ingredient used for example in the treatment of opportune diseases or a vitamin, for example vitamin C used in high dose, for example 50 to 100 mg / kg / day or an analgesic or an antibiotic or a bronchodilator, for example salbutamol, or a corticosteroid, for example methylprednisolone or an antiviral, for example interferon alfa-2b or lopinavir antiviral therapy, etc.
• the administration of the biocompatible polymer and the hyaluronic acid can be simultaneous, sequential or concomitant.
• At least one of the administrations can be carried out by topical, oral, respiratory route or by injection, preferably by respiratory route.
• the two administrations can be carried out in the same way or in different ways.
• administration of the biocompatible polymer and hyaluronic acid can be by respiratory route.
• the administration can also depend on the area and / or the biological tissue to be treated.
• the composition can be, for example, administered only once.
• the composition can be further, for example, administered daily, twice daily and weekly or less. It may for example be an administration once a day, twice a day or less, for example once every two days, or per week.
• the composition may be, for example, for a saline composition administered daily, twice daily and weekly or less. For example, this could be once a day, twice a day or less.
• the composition can be, for example, administered over a period of 1 day to 3 months, for example for 2 months, for example for 1 month, for example for a week.
• the composition can be administered over a period of 1 to 3 weeks, for example with a frequency of administration every day or every other day.
• the composition when the composition is in a form suitable for administration by the respiratory route, the composition may be administered preferably with a frequency of administration every two or three days.
• the composition can be, for example, administered daily, twice daily and weekly. For example, this may be once a day, twice a day or more.
• the composition can be, for example, administered over a period of 1 day to 3 months, for example for 2 months.
• the composition can be administered over a period of 3 months with frequency of administration every day.
• the inventor has surprisingly demonstrated that the combination of a biocompatible polymer of formula AaXxYy or AaXxYyZz and natural or modified hyaluronic acid advantageously and surprisingly makes it possible to obtain a synergistic effect in the treatment.
• the inventor has demonstrated that the effect obtained was both a synergy going beyond the individual effects of each of the compounds and also advantageously an increase in the duration of these effects.
• Other advantages may also appear to a person skilled in the art on reading the examples below, illustrated by the appended figures, given by way of illustration.
• Example 1 Use of a biocompatible polymer in the treatment of subjects infected with influenza virus (influenza virus)
• RGTA®-based matrix therapy A new branch of regenerative medicine in locomotion.
• Barritault D Desgranges P, Meddahi-Pellé A, Denoix JM, Saffar JL. Joint Bone Spine. 2017 May; 84 (3): 283-292.
• the compound OTR4131 is a compound comprising a radical Z which is a fatty acid, namely acetic acid as described in Frescaline G.
• RGTA OTR4120 an evaluation of the effects of the biocompatible polymer according to the invention, RGTA OTR4120 on improving respiration in an asthmatic subject affected by influenza was carried out.
• the subject was a 35-year-old woman with influenza infection with a history of hospitalizations (length of hospital stay 10 days in intensive care) for complications of the viral infection related in particular to chronic asthma.
• the subject was treated with a biocompatible polymer, namely the compound OTR4120, taken every other day over a week (7 days) of 5 mL of a saline solution (CACIPLIQ ®, OTR3 Paris France) at 100 pg / nnL of OTR4120 by inhalation.
• the solution was administered orally by inhalation with an electric nebulizer.
• the inhalation time was 10 minutes using an electric inhaler type Omron or similar.
• the clinical signs of distress and / or deterioration of the respiratory system were greatly reduced.
• the frequency of the coughing fits namely several per minute, rapidly decreased and with it the pain associated with the breathing, which was very panting, as well as the chills that ran through the patient.
• Body temperature also decreased from 40 ° C to a normal temperature of 37 ° C in a week, fatigue also shifting from exhaustion to gradual recovery.
• results were subsequently confirmed in subsequent viral infections with an influenza virus of the above subject, a female subject with an identical clinical profile and in infants infected with an influenza virus.
• composition according to the invention comprising a polymer of formula AaXxYy or AaXxYyZz advantageously makes it possible to treat and / or improve treatment of lesions of the respiratory system caused by a microorganism, namely a virus, preferably of lung damage caused by a microorganism, in particular a virus.
• a virus preferably of lung damage caused by a microorganism, in particular a virus.
• examples of the composition according to the invention in particular for administration by the pulmonary route, makes it possible to treat pulmonary lesions caused by a virus, in particular the influenza virus.
• compositions according to the invention make it possible to treat pulmonary lesions caused by a virus, in particular the influenza virus in a very short time, which can advantageously make it possible to reduce the risk of morbidity. linked to lesions of the respiratory and / or pulmonary system caused in particular by a virus.
• This example also clearly demonstrates, through functional recovery, recovery of pulmonary function linked in particular to a restoration of the function of the capillary alveolar barrier or air-blood barrier.
• an example of a composition according to the invention makes it possible both to treat pulmonary lesions due to a microorganism, in particular a virus, and also to restore pulmonary function via a restoration of the function of the alveolar barrier.
• capillary or air-blood barrier also, as demonstrated in this example, the present invention goes beyond the simple treatment of pulmonary lesions and advantageously makes it possible, during an impairment of pulmonary function, for example respiratory distress, to synergistically restore pulmonary function.
• Example 2 Use of a biocompatible polymer in the treatment of subjects infected with the MERS-CoV virus and presenting a respiratory syndrome
• composition used was identical to that of Example 1 above, namely the polymer OTR4120 (product CACIPLIQ®, OTR3 Paris France (OTR4120)).
• the subjects were treated with a biocompatible polymer, namely the compound OTR4120, taken every other day over a week (7 days) of 5 mL of a saline solution (CACIPLIQ®, OTR3 Paris France (OTR4120)) at 100pg / nnL of OTR4120 by inhalation.
• the solution was administered orally by inhalation.
• the inhalation time was 10 minutes.
• composition according to the invention comprising a polymer of formula AaXxYy or AaXxYyZz advantageously makes it possible to treat and / or improve treatment of lesions of the respiratory system caused by a microorganism, namely a virus, preferably of lung damage caused by a microorganism, in particular a virus.
• examples of the composition according to the invention in particular for administration by the pulmonary route, makes it possible to treat pulmonary lesions caused by viruses of the coronaviridae family, in particular the MERS-CoV virus.
• composition according to the invention make it possible to treat pulmonary lesions caused by a virus, in particular a coronavirus, in a very short time which can advantageously make it possible to reduce the risk of morbidity linked to lesions of the respiratory system and / or pulmonary caused in particular by viruses of the Coronaviridae family.
• This example also clearly demonstrates, through the functional recovery, a recovery of pulmonary function linked in particular to a restoration of the function of the capillary alveolar barrier or air-blood barrier.
• an example of a composition according to the invention makes it possible both to treat pulmonary lesions due to a microorganism, in particular a virus, and also to restore pulmonary function via a restoration of the function of the alveolar barrier. capillary or air-blood barrier.
• the present invention goes beyond the simple treatment of pulmonary lesions and advantageously makes it possible, during a deficiency in pulmonary function, for example a distress and / or deterioration of the respiratory system, to restore synergistically the lung function.
• Example 3 Use of a biocompatible polymer in the treatment of subjects infected with seasonal influenza virus
• the composition used was different from that of example 1 above, namely the polymer OTR4131 was in saline solution at a concentration of 10 pg / ml_ with 0.2% of high molecular weight hyaluronic acid (HTL laboratories ).
• the subject was a 74-year-old man with clinical signs of influenza, namely a high fever, approximately 39 degrees, breathing difficulty and pain, and coughing fits with suffocation. As the subject was elderly, hospitalization was scheduled within 48 hours depending on the evolution of the clinical condition.
• the subject was treated with a biocompatible polymer, namely the compound OTR4131, taken every other day of 5 mL of a 100 ⁇ g / nnL saline solution of OTR4131 also comprising 0.2% hyaluronic acid.
• a biocompatible polymer namely the compound OTR4131
• IOTR4131 was used at 10 m / mL in a 5 mg / mL solution of commercial HA (injectable quality).
• the solution was administered orally by inhalation.
• the inhalation time was 10 minutes.
• a second setting, approximately 48 hours after the first setting, of the aforementioned composition was carried out. Confirming, the observations made at 24 hours, surprisingly, 48 hours after the first dose, the treated subject presented a significant reduction in coughing and also in respiratory difficulties and pain.
• a clinical evaluation of the subject was carried out at 72 hours, the latter no longer showing signs of respiratory distress, an absence of pain and breathing difficulties, and an almost total disappearance of the cough. All of the improvements, in particular 24 hours after the first intake, were linked in particular to treatment of lesions of the respiratory system caused by the virus, advantageously allowing an improvement and recovery of the functions of the respiratory system.
• composition according to the invention comprising a polymer of formula AaXxYy or AaXxYyZz and hyaluronic acid advantageously makes it possible to treat and / or improve treatment of lesions of the respiratory system caused by a microorganism, namely a virus, preferably lung damage caused by a microorganism, in particular a virus.
• a virus preferably lung damage caused by a microorganism, in particular a virus.
• examples of the composition according to the invention in particular for administration by the pulmonary route, makes it possible to treat pulmonary lesions caused by viruses of the Orthomyxoviridae family, in particular the influenza virus.
• composition according to the invention make it possible to treat lung lesions caused by a virus in a very short time.
• composition according to the invention comprising a polymer of formula AaXxYy or AaXxYyZz and hyaluronic acid makes it possible, for example in less than 72 hours to treat and / or significantly reduce the lesions. of the respiratory and / or pulmonary system caused in particular by a virus and can advantageously make it possible to reduce the associated risk of morbidity.
• This example also clearly demonstrates, through the functional recovery, a recovery of pulmonary function linked in particular to a restoration of the function of the capillary alveolar barrier or air-blood barrier.
• an example of a composition according to the invention makes it possible both to treat pulmonary lesions due to a microorganism, in particular a virus, and also to restore pulmonary function via a restoration of the function of the alveolar barrier. capillary or air-blood barrier.
• the present invention goes beyond the simple treatment of pulmonary lesions and advantageously allows, during impairment of lung function, eg respiratory distress, synergistically restore lung function.
• Example 4 Use of a biocompatible polymer in the treatment of a subject one month after severe / severe infection with SARS-CoV-2
• the subject was a 69-year-old radiologist infected with a patient with COVID-19 during a consultation for analysis of images from a chest CT scan.
• the day of contamination was therefore clearly identified as the day of the consultation. 4 days later, the radiologist felt the first symptoms of chills, temperature, joint pain, without loss of smell or taste. 10 days after contamination and 6 days after the first symptoms, a PCR test for a diagnosis of SARS-CoV-2 infection was carried out, the result obtained was negative.
• a PCR test for a diagnosis of SARS-CoV-2 infection was performed 7 days after the first symptoms and this time showed a positive result with a value of 28 CT,
• a chest scan performed 7 days after the first symptoms revealed a “frosted glass” lung surface area of around 20% associated with a lymph node nodule and vascular calcifications.
• 15 days after the first symptoms the radiologist lost consciousness, the oxygen pressure fell to 96% and the fever remained constant at 38-39 ° C with repeated loss of consciousness and systolic blood pressure falling between 9 and 9.4 mmHg.
• Usual blood tests namely hematological, biochemical, hemostasis, were performed 10 days, 13 days, 15 days, 17 days, 19 days, 23 days, 27 days, 32 days and 39 days post infection.
• a CT scan was performed in 32 th day after infection before initiation of treatment and showed a very aggravated situation about 50% of lung disease. This state was reflected in particular for the patient by deep fatigue and shortness of breath after a few meters of walking. The patient, accustomed to walking for an hour a day, was unable to walk more than a few meters without shortness of breath and hardly moved from home.
• composition of the invention was initiated.
• the treatment consisted of nebulizing using an ultrasonic or air jet nebulizer (common type found in pharmacies such as Omron, Newgen Medicale or equivalent whose prices vary between 40 and 200 euros).
• the composition used comprised IOTR4120 at 100 ⁇ g / mL diluted in physiological saline (dilution 10 times in water) and poured into the diffusion chamber of the apparatus set at a flow rate of 0.5 mL / min.
• the patient received a total of 11 treatments / administrations / doses of 5 minutes at a rate of one morning and evening per day.
• the radiologist felt some tingling and a slight improvement in his breathing, especially sensitive during the night. When he woke up he felt less tired than on the previous days.
• the second dose / administration by nebulization confirmed this improvement in breathing and the next day (i.e. after 3 doses / administrations) the improvement was very clear both in terms of breathing and in terms of performance and / or movement capacity and tiredness.
• the improvement was confirmed and the radiologist no longer felt shortness of breath or fatigue and started walking again.
• the radiologist stopped the nebulizations, he perfectly recovered his walking performance and no longer felt abnormal fatigue. No clinical signs related to SARS-CoV-2 were observable.
• a chest x-ray taken 17 days after the start of treatment revealed an 80% improvement in the lesion surface at the lung level, only 10% of the injured area was visible from a chest CT scan but was considered non-intrusive.
• surprisingly functional recovery of respiratory function has been obtained in a few days unlike untreated patients for whom months are required in order to recover only part of their previous breathing capacity. disease, see that part of their capacity causing lifelong sequelae.
• composition according to the invention makes it possible to treat pulmonary lesions caused by a virus, in particular a coronavirus, in particular SARS-CoV-2, in a very short time which can advantageously make it possible to reduce the risk of morbidity linked to lesions of the respiratory and / or pulmonary system caused in particular by viruses of the Coronaviridae family.
• a virus in particular a coronavirus, in particular SARS-CoV-2
• Example 5 Use of a biocompatible polymer in a prophylactic treatment of SARS-CoV-2
• an example of a composition according to the invention is used in an application for preventing COVID-19.
• two doctors assigned to Covid emergencies in two large Mexican hospitals used under cover of confidentiality (to be verified / confirmed) IOTR4120 in 100 pg / mL solution marketed for the treatment of chronic wounds under the brand name CACIPLIQ (registered trademark).
• the 5 mL solution was poured into a nosed pear making it possible to give a spray or nasal spray of approximately 100 ⁇ L with each pressure on the pear.
• These doctors took one spray per nostril per day for two months. While all the medical staff in each of these hospitals (i.e. around 100 people per hospital) were contaminated with COVID-19 and did indeed fall ill (with sometimes severe forms and a few deaths), these two doctors were the only healthcare workers in each hospital who were not affected by COVID-19.

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