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WO2021083867A1 - Composition pharmaceutique comprenant une combinaison synergique d'ibuprofène et de n-acétylcystéine - Google Patents

Composition pharmaceutique comprenant une combinaison synergique d'ibuprofène et de n-acétylcystéine Download PDF

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Publication number
WO2021083867A1
WO2021083867A1 PCT/EP2020/080135 EP2020080135W WO2021083867A1 WO 2021083867 A1 WO2021083867 A1 WO 2021083867A1 EP 2020080135 W EP2020080135 W EP 2020080135W WO 2021083867 A1 WO2021083867 A1 WO 2021083867A1
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WIPO (PCT)
Prior art keywords
pharmaceutical composition
ibuprofen
use according
composition
cysteine
Prior art date
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Ceased
Application number
PCT/EP2020/080135
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English (en)
Inventor
Silvia Boschetti
Claudio BENVENUTI
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E-Pharma Trento SpA
E PHARMA TRENTO SpA
Original Assignee
E-Pharma Trento SpA
E PHARMA TRENTO SpA
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Priority to EP20793412.6A priority Critical patent/EP4051256A1/fr
Publication of WO2021083867A1 publication Critical patent/WO2021083867A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61P11/12—Mucolytics
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61P11/14—Antitussive agents

Definitions

  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising a synergistic combination of ibuprofen and N-acetylcysteine with anti inflammatory, mucolytic and fluidifying action for the treatment of upper respiratory tract disorders characterized by the excessive presence of mucus (wet or productive cough) in inflammatory and painful conditions affecting the mucosa of throat (tonsillitis, laryngitis, pharyngitis), nose (sinusitis, rhinitis, nasopharyngitis) and ear (otitis) present in influenza syndromes.
  • the invention relates to a solid pharmaceutical composition, e.g. in the form of granules, tablets or effervescent tablets, or liquid, e.g. in the form of a solution or suspension, comprising ibuprofen and N-acetylcysteine for use with synergistic effect in the treatment of wet or productive cough, even when associated with fever and/or sore throat or, in general, with inflammation and/or infections of the upper respiratory tract.
  • a solid pharmaceutical composition e.g. in the form of granules, tablets or effervescent tablets
  • liquid e.g. in the form of a solution or suspension
  • ibuprofen and N-acetylcysteine for use with synergistic effect in the treatment of wet or productive cough, even when associated with fever and/or sore throat or, in general, with inflammation and/or infections of the upper respiratory tract.
  • STATE OF THE ART Coughing is a sensory-motor reflex aimed at expelling airway obstructive material. As such it has obvious protective characteristics and it is known that its absence, as for example in coma patients, is the cause of serious lung diseases that can compromise the life of the patient. Nevertheless, there are many respiratory diseases, and not only, in which the cough acquires negative connotations, representing in fact a disturbance for the patient. Examples include acute coughing in viral tracheobronchitis, chronic coughing in hypereosinophilia associated with aspecific broncoreactivity and coughing that typically accompanies gastroesophageal reflux. Undoubtedly, the most frequent cause of coughing, especially in the pediatric population is that which originates from upper respiratory tract infections, better known as URTI.
  • cough medicines so-called antitussive, act on the respiratory system with different mechanisms of action.
  • Some drugs act with a central or peripheral sedative effect.
  • Central sedatives act by inhibiting the center of the cough by eliminating the stimulus.
  • Peripheral sedatives act by inhibiting the afferent or efferent pathways of the tussive stimulus. Examples of central sedatives are codeine, dihydrocodeine, dextromethorphan, butamirate, zipeprol and domiodol.
  • Examples of peripheral sedatives are dopropizine, levodropizine, benzonatate and oxolamine. They are indicated only in cases of dry or testy coughs or in any case without mucus production.
  • Mucolytic drugs act mainly by breaking the proteins in the mucus, making it more fluid and facilitating the work of expulsion by the bronchi and trachea.
  • the active ingredients "expectorants” are products based on plant extracts able to increase the production of mucus. These drugs do not immediately calm the cough, as happens with sedatives, but facilitate the expulsion of mucus.
  • NSAIDs or inhibitors of cyclooxygenase 2 potentially useful in reducing cough stimulation are, for example, aspirin, benzidamine, ibuprofen, diclofenac, naproxen, flurbiprofen, phenoprofen, ketoprofen, ketorolac, indoprofen, pyroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, suprofen, aminoprofen, thiaprofenic acid, fluprofen, benzadac, ibufenac, tolmetin, zomepirac, tiopinac, zidometacine, acemetacine, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid, tolfen
  • COX-2 cyclooxygenas
  • EP2905020 describes an effervescent formulation comprising ibuprofen or its pharmaceutical acceptable salt and N-acetylcysteine or its pharmaceutical acceptable salt and one or more pharmaceutical acceptable excipients. EP2905020 does not describe any synergistic effect of the ibuprofen/N- acetylcysteine combination, whose therapeutic action is described separately for each active substance.
  • US2002037855 describes a stabilized drug including active ingredients containing cysteine groups and NSAID compounds, in which the stabilization of the combination, in particular the active ingredients containing the cysteine group, is made with a mixture of at least three antioxidant components.
  • the therapeutic and prophylactic use of the stabilized drug is in the field of prevention and therapy of inflammatory diseases.
  • US2002037855 does not describe the use of the combination in cough treatment.
  • EP2106258 and US2010022608 describe the use of an NSAID for the treatment of non-productive cough caused by viruses or bacteria, possibly in combination with an antitussive with sedative action such as codeine, dihydrocodeine, dextromethorphan, hydrocodone, clobutinol, pentoxyproxyverine and mixtures and combinations thereof.
  • EP2106258 and US2010022608 define as counterproductive the combination of a product able to sedate non-productive cough with a mucolytic, as it would make impossible the expulsion of mucus.
  • the Applicant has therefore faced the problem of obtaining a pharmaceutical composition that, starting from the teachings of the known art, would allow to improve the treatment therapy of productive cough even when associated with fever and/or sore throat and/or, in general, upper respiratory tract infections.
  • the Applicant hypothesized that the combination with an expectorant or mucolytic drug could have a synergistic action against wet cough.
  • the Applicant has therefore promoted a research activity aimed at finding the most effective combination in the treatment of the wet or productive cough resulting from upper respiratory tract infections.
  • the Applicant also surprisingly found that this effect had synergistic characteristics as it was superior to the antitussive effect obtainable with the single administration of the two active ingredients.
  • the optimal amounts of the combination included 400 mg ibuprofen and 200 mg N-acetylcysteine.
  • the Applicant surprisingly observed that the administration of the combination of ibuprofen and N-acetylcysteine was also able to significantly reduce at least one or more of the typical symptoms of URTI diseases, such as, for example, fever, sore throat, shortness of breath and limitation of daily activities, especially when taken 2-3 times a day, depending on the characteristics of the patient, for 3-5 days, depending on the characteristics of the symptoms.
  • URTI diseases such as, for example, fever, sore throat, shortness of breath and limitation of daily activities, especially when taken 2-3 times a day, depending on the characteristics of the patient, for 3-5 days, depending on the characteristics of the symptoms.
  • the present invention therefore relates to a synergistic combination of (i) ibuprofen or a pharmaceutical acceptable salt thereof and (ii) N-acetylcysteine or a pharmaceutical acceptable salt thereof, for use in the treatment of wet or productive cough, in particular in the treatment of wet or productive cough resulting from upper respiratory tract infections.
  • a second aspect of the present invention also relates to a pharmaceutical composition
  • a pharmaceutical composition comprising (a) a synergistic combination of (i) ibuprofen or a pharmaceutical acceptable salt thereof, and (ii) N-acetylcysteine or a pharmaceutical acceptable salt thereof, and (b) at least one pharmaceutical acceptable excipient, for use in the treatment of wet or productive cough, particularly in the treatment of wet or productive cough resulting from upper respiratory tract infections.
  • Ibuprofen is an active ingredient belonging to the family of non-steroidal anti-inflammatory drugs (NSAIDs).
  • NSAIDs non-steroidal anti-inflammatory drugs
  • the drug has analgesic, anti-inflammatory and antipyretic properties. This class of drugs is the most widely used in the treatment of rheumatic diseases.
  • the lUPAC name for ibuprofen is (RS)-2[4-(2- methylpropyl)phenyl]propanoic acid, with the following structural formula:
  • Ibuprofen can be formulated as such or as salt with a pharmaceutically acceptable base.
  • Pharmaceutically acceptable bases include, for example, organic bases, such as tromethamine, lysine, arginine, glycine, alanine, and ethanolamine, or inorganic bases, such as hydroxide or carbonate of alkali or alkaline earth metals, such as sodium, potassium, and calcium.
  • the combination of the present invention comprises, per dosage unit, an amount of ibuprofen, expressed as free non-salified form, ranging from approximately 200 mg to approximately 600 mg, preferably from approximately 300 mg to approximately 500 mg.
  • the combination of the present invention comprises, per dosage unit, approximately 400 mg of ibuprofen, expressed as free non-salified form.
  • N-acetylcysteine also simply called acetylcysteine, is an N-acetylated derivative of the sulfide-containing amino acid cysteine.
  • N-acetylcysteine 2R-acetamide-3-sulfanylpropanoic acid, with the following structural formula: N-acetylcysteine can be formulated as such or as a salt with a pharmaceutically acceptable base or acid.
  • Pharmaceutically acceptable bases include, for example, organic bases, such as tromethamine, lysine, arginine, glycine, alanine, and ethanolamine, or inorganic bases, such as hydroxide or carbonate of alkali or alkali earth metal, such as sodium, potassium, and calcium.
  • Examples of pharmaceutically acceptable acids are organic acids, such as oxalic, maleic, metansulfonic, paratoluensulfonic, succinic, citric, malic, and tartaric acids, or inorganic acids, such as hydrochloric, bromidic, phosphoric, and sulfuric acids.
  • the combination of the present invention comprises, per dosage unit, an amount of N-acetylcysteine, expressed as free non-salified form, ranging from approximately 50 mg to approximately 400 mg, preferably from approximately 100 mg to approximately 300 mg.
  • the combination of the present invention comprises, per dosage unit, approximately 200 mg of N- acetylcysteine, expressed as free non-salified form.
  • the combination of the present invention comprises a synergistic combination of ibuprofen and N-acetylcysteine with an ibuprofen : N- acetylcysteine weight ratio ranging from 2.5:1 to 1 .5:1 , preferably from 2.2:1 to 1 .8:1 , more preferably from 2.1 :1 to 1 .9:1 , and advantageously of about 2:1 .
  • the combination of the present invention is useful in the treatment of wet or productive cough, particularly in the treatment of wet or productive cough caused by upper respiratory tract infections, and in the treatment of other symptoms of upper respiratory tract infections.
  • Upper respiratory tract infections are relatively mild diseases caused by an infection involving parts of the upper respiratory tract of the body, the latter including nose, paranasal sinuses, pharynx and larynx. These diseases include, for example, tonsillitis, laryngitis, pharyngitis, sinusitis, otitis, rhinitis and rhinopharyngitis (the common cold).
  • upper respiratory tract infections In addition to coughing, symptoms of upper respiratory tract infections are mainly sore throat, nasal congestion, runny nose, sneezing, facial pressure, and fever.
  • the etiology of upper respiratory tract infections is predominantly viral, and in some cases bacterial.
  • the virus primarily responsible is the rhinovirus, but other viruses, such as coronavirus, parainfluenza virus, adenovirus, enterovirus, and syncytial respiratory virus, can cause upper respiratory tract infections.
  • Symptoms usually begin one to three days after a person has been exposed to the infection. The disease usually lasts 7-10 days. The cough occurs in the form of a dry or non-productive cough, or a wet or productive cough.
  • the dry cough is defined "non-productive” because it is not accompanied by expectorate. It is generally irritating and tickling and is one of the symptoms of the onset of upper respiratory tract infections or inflammations. Conversely, the wet cough is defined “productive” because of the presence of phlegm or mucus, a normal secretion of mucous membranes of the respiratory tract that becomes abundant in case of infection or inflammation.
  • Infections or inflammation of the upper respiratory tract are clinically distinct from infections or inflammations of the lower respiratory tract affecting bronchi and lungs, such as pneumonia and bronchitis, and other more serious lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and cystic fibrosis.
  • COPD chronic obstructive pulmonary disease
  • COPD chronic obstructive pulmonary disease
  • the pharmaceutical composition of the present invention may be formulated in solid or liquid form, preferably by oral administration.
  • the solid pharmaceutical composition of the present invention may be formulated as a granulate, tablet, orodispersible tablet, effervescent tablet, or water-soluble or water-dispersible powder to be taken as such orally or after dissolution in the appropriate volume of water.
  • the liquid pharmaceutical composition of the present invention may be in the form of a solution, suspension or syrup.
  • the pharmaceutical composition of the present invention may comprise ingredients typically used in the preparation of oral formulations, such as solvents, pH regulators, buffering agents, fillers, binders, disintegrating agents, acidifiers, foaming agents, lubricants, dyes, stabilizers, antioxidants, surfactants, sweeteners, flavorings, and the like.
  • ingredients typically used in the preparation of oral formulations such as solvents, pH regulators, buffering agents, fillers, binders, disintegrating agents, acidifiers, foaming agents, lubricants, dyes, stabilizers, antioxidants, surfactants, sweeteners, flavorings, and the like.
  • Suitable solvents are water, ethanol, propylene glycol, glycerin, mixtures thereof, and the like.
  • suitable pH regulators are sodium bicarbonate, calcium carbonate, magnesium carbonate, sodium phosphate, sodium citrate, and the like.
  • buffering agents are sodium dihydrogen phosphate, sodium hydrogen phosphate, citrate buffer (sodium citrate / citric acid), and the like.
  • fillers include lactose, starch, corn starch, microcrystalline cellulose, sorbitol, xylitol, mannitol, light anhydrous silicic acid, magnesium carbonate, calcium carbonate, sucrose, inulin, glucose, maltodextrin and the like.
  • binders are hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinyl alcohol, methyl cellulose, arabic gum and the like.
  • disintegrating agents are: sodium croscarmellose, hydroxypropylcellulose with low level of substituents, carmellose, methylcellulose, sodium carboxymethylenediamide, crospovidone, partially pregelatinized starch, corn starch, potato starch, calcium carmellose, sodium carmellose, and the like.
  • acidifying agents are citric acid, tartaric acid, malic acid and the like.
  • foaming agents are sodium bicarbonate and the like.
  • lubricants examples include magnesium stearate, calcium stearate, sucrose ester of fatty acids, polyethylene glycol, talc, stearic acid and the like.
  • colorants are: yellow ferric oxide, red ferric oxide, food yellow No. 4, food yellow No. 5, food red No. 3, food red No. 102, food blue No. 3 and the like.
  • antioxidants examples include ascorbic acid, dibutyl hydroxytoluene, propyl gallate, and the like.
  • surfactants are polysorbate 80, sodium lauryl sulfate, polyoxyethylene hydrogenated castor oil and the like.
  • sweetening agents examples include aspartame, saccharin, sucralose, neohesperidine, acesulfame, glycyrrhizinate, stevia, somatin and so on.
  • suitable flavoring agents comprises grapefruit flavor, raspberry flavor, lemon flavor, orange flavor, caramel flavor, vanilla flavor, cream flavor, mint flavor, licorice flavor, aniseed flavor, strawberry flavor, banana flavor and the like.
  • the pharmaceutical composition of the present invention can also be formulated in effervescent compositions.
  • effervescent agents are added to the composition.
  • Effervescent agents typically comprise an acid-base pair capable of developing a gas when dissolved in water.
  • Useful examples of effervescent agents are acid-base pairs comprising an organic acid, such as citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, and mixtures thereof, and an alkaline or alkaline earthy metal carbonate or bicarbonate, such as calcium carbonate, sodium bicarbonate, sodium sesquicarbonate, and mixtures thereof.
  • the pharmaceutical composition of the present invention is useful in the treatment of wet cough resulting from upper respiratory tract infections.
  • Table 1 represents the qualitative-quantitative composition of a 6-gram sachet of water-soluble granulate according to one aspect of the present invention.
  • the granulate in Table 1 has been prepared with conventional techniques by wet granulation of the mixture of ibuprofen sodium dihydrate and sucrose, followed by mixing with the other ingredients (N-Acetylcysteine, Sodium bicarbonate, Orange flavor, Maltodextrin, Sucralose), and finally by packaging in a controlled environment at a temperature of 22°C ⁇ 3°C and relative humidity equal to or lower than 20%.
  • Table 2 represents the qualitative-quantitative composition of a 1.64-gram sachet of orodispersible granulate according to one aspect of the present invention.
  • the granulate in Table 2 has been prepared using conventional techniques by mixing and dry granulating all the ingredients until a homogeneous powder was obtained, which is then packaged in a controlled environment at a temperature of 22°C ⁇ 3°C and relative humidity equal to or lower than 20%.
  • Example 3
  • a total of 360 patients of both sexes (equally divided into 3 different treatment groups) aged between 18 and 65 years, suffering from wet coughing caused by symptomatic upper respiratory tract infections (URTI) without complications were enrolled to reach a sample size of 270 evaluable patients (90 in each treatment group).
  • URTI symptomatic upper respiratory tract infections
  • the primary objective of the study was to demonstrate the superior and possibly synergistic efficacy of the combination of the present invention over monotherapy with only ibuprofen or only N-acetylcysteine in reducing the resolution time of productive day and night coughing and other symptoms (fever, sore throat, shortness of breath, and limitation of daily activities) in enlisted subjects.
  • Group A was treated with the combination of the present invention comprising 400 mg ibuprofen and 200 mg N-acetylcysteine as granules per oral solution, as described in Example 1 , three times daily.
  • Group B was treated with 400 mg ibuprofen as granules per oral solution three times daily
  • Group C was treated with 200 mg N-acetylcysteine as granules per oral solution three times daily.
  • the duration of treatment was 7 days, while the study continued for a further 7 days.
  • the continuous variables were summarized by descriptive statistics (number of cases, average and standard deviation, median, minimum and maximum).
  • the categorical variables were summarized using the number of patients and percentages.
  • the results achieved showed a significant reduction in symptoms (one or more of the following: daytime cough, nighttime cough, fever, sore throat, shortness of breath and limitation of daily activities) in subjects in group A compared to subjects in group B or C, with a surprisingly greater reduction in daytime and nighttime cough symptoms, confirming the synergistic effect of the combination of the present invention in the treatment of coughing from upper respiratory tract infections.

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Abstract

La présente invention concerne une composition pharmaceutique comprenant une combinaison synergique d'ibuprofène et de N-acétylcystéine ou d'un sel pharmaceutiquement acceptable de celle-ci, destinée à être utilisée dans le traitement de la toux humide ou productive et d'autres symptômes associés aux infections des voies respiratoires supérieures telles que la fièvre et le mal de gorge.
PCT/EP2020/080135 2019-10-28 2020-10-27 Composition pharmaceutique comprenant une combinaison synergique d'ibuprofène et de n-acétylcystéine Ceased WO2021083867A1 (fr)

Priority Applications (1)

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EP20793412.6A EP4051256A1 (fr) 2019-10-28 2020-10-27 Composition pharmaceutique comprenant une combinaison synergique d'ibuprofène et de n-acétylcystéine

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IT102019000019858 2019-10-28
IT102019000019858A IT201900019858A1 (it) 2019-10-28 2019-10-28 Composizione farmaceutica comprendente una combinazione sinergica di ibuprofene e N-acetilcisteina

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020037855A1 (en) 2000-05-05 2002-03-28 Fritz Stanislaus Stabilized medicament containing cysteinyl derivatives
EP2106258A2 (fr) 2006-10-20 2009-10-07 Bayer Consumer Care AG Agent antiphlogistique non stéroïdien contre la toux
EP2905020A1 (fr) 2014-02-05 2015-08-12 Sanovel Ilac Sanayi ve Ticaret A.S. Formulations effervescentes comprenant de l'ibuprofène et de la N-acétylecystéine
WO2016120787A1 (fr) * 2015-01-26 2016-08-04 Novartis Consumer Health S.A. N-acétylcystéine destinée à être administrée par voie orale dans le traitement d'infections des voies respiratoires supérieures et de symptômes associés

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020037855A1 (en) 2000-05-05 2002-03-28 Fritz Stanislaus Stabilized medicament containing cysteinyl derivatives
EP2106258A2 (fr) 2006-10-20 2009-10-07 Bayer Consumer Care AG Agent antiphlogistique non stéroïdien contre la toux
US20100022608A1 (en) 2006-10-20 2010-01-28 Marianne Petersen-Braun Non-steroidal anti-inflammatory drugs for cough
EP2905020A1 (fr) 2014-02-05 2015-08-12 Sanovel Ilac Sanayi ve Ticaret A.S. Formulations effervescentes comprenant de l'ibuprofène et de la N-acétylecystéine
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