HUE031098T2 - Antibakteriális készítmény felsõ és alsó légúti fertõzések kezelésére - Google Patents
Antibakteriális készítmény felsõ és alsó légúti fertõzések kezelésére Download PDFInfo
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- HUE031098T2 HUE031098T2 HUE09166600A HUE09166600A HUE031098T2 HU E031098 T2 HUE031098 T2 HU E031098T2 HU E09166600 A HUE09166600 A HU E09166600A HU E09166600 A HUE09166600 A HU E09166600A HU E031098 T2 HUE031098 T2 HU E031098T2
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- treatment
- hyaluronic acid
- infections
- lower airways
- salt
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- 238000011282 treatment Methods 0.000 title description 7
- 208000015181 infectious disease Diseases 0.000 title description 6
- 230000000844 anti-bacterial effect Effects 0.000 title description 2
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- 150000002148 esters Chemical class 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims 1
- 241000282553 Macaca Species 0.000 claims 1
- 241000183024 Populus tremula Species 0.000 claims 1
- 230000001631 hypertensive effect Effects 0.000 claims 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 12
- 229920002674 hyaluronan Polymers 0.000 description 12
- 229960003160 hyaluronic acid Drugs 0.000 description 12
- 238000009472 formulation Methods 0.000 description 10
- 201000003883 Cystic fibrosis Diseases 0.000 description 9
- 241000894006 Bacteria Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 4
- 239000000819 hypertonic solution Substances 0.000 description 4
- 229940021223 hypertonic solution Drugs 0.000 description 4
- 208000034309 Bacterial disease carrier Diseases 0.000 description 3
- 241000589516 Pseudomonas Species 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
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- 239000011780 sodium chloride Substances 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 2
- 241000475481 Nebula Species 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
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- 230000003110 anti-inflammatory effect Effects 0.000 description 2
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- 210000000621 bronchi Anatomy 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
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- 230000004054 inflammatory process Effects 0.000 description 2
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- 201000009266 primary ciliary dyskinesia Diseases 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 208000025678 Ciliary Motility disease Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010024769 Local reaction Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 101150034459 Parpbp gene Proteins 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 208000032536 Pseudomonas Infections Diseases 0.000 description 1
- 241000589774 Pseudomonas sp. Species 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 229940008201 allegra Drugs 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 229940014041 hyaluronate Drugs 0.000 description 1
- 239000000076 hypertonic saline solution Substances 0.000 description 1
- 230000037427 ion transport Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 210000003695 paranasal sinus Anatomy 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000000518 rheometry Methods 0.000 description 1
- 102220240796 rs553605556 Human genes 0.000 description 1
- -1 salt salt Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
- 230000032895 transmembrane transport Effects 0.000 description 1
Classifications
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- 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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
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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
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- 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
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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Description
(12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 9108 <2006 01> A61K 31114 <2006 01> 31.08.2016 Bulletin 2016/35 A61K 3117024 <2006 01> A61P 11IOO<2006 01> (21) Application number: 09166600.8 (22) Date of filing: 06.04.2007
Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).
Description the function of trapping germs, pollen, dust and all the other particles in the air we breathe, preventing them [0001] This invention relates to compositions compris- from reaching the internal respiratory organs. ing hyaluronic acid and an hypertonic saline solution as [0011] Extreme dryness of the mucus drastically re- suitable vehicle, which can be administered by inhalation. 5 duces the efficacy of the nasal secretions, which inexo rably become the ideal substrate for bacterial growth.
Prior art [0012] Before becoming chronic, Pseudomonas infec tion is manifested by a first infection, indicated by a first [0002] Pseudomonas aeruginosa infection is one of appearance of bacteria in the sputum; at this stage, a the main unfavourable prognosticfactorsfor patients suf- 10 specifically-targeted antibiotic treatment can eradicate fering from cystic fibrosis (CF). the germ and delay chronic infection, but the infection [0003] This disease is characterised by a gene defect later returns intermittently, until it becomes chronic. At that causes abnormal functioning of CFTR (cystic fibrosis this stage, elimination of the germ from the nasal sinuses transmembrane conductance regulator), a protein in- performs a significant preventive action against bacterial volved in the transmembrane transport of salts. 15 colonisation of the lower airways.
[0004] As a result of altered ion transport in the cell, [0013] For this reason, specific antibacterial formula- cystic fibrosis is manifested by an alteration of the secre- tions directed towards these pathogens are highly desir- tions of epithelial cells of bronchi, sinuses, pancreas, in- able; such formulations should take account of the phys- testine, bile ducts and sweat glands. iology of the nasal sinuses and of bronchi and perform [0005] Patients suffering from cystic fibrosis conse- 20 an antibacterial and anti-inflammatory action thus pre- quently produce mucus which is very thick and difficult venting chronic infection and colonisation of the lower to expectorate. The most serious problems generally af- airways due to bacterial migration from the upper air-fect the bronchi, where mucus viscosity makes it difficult ways, reduce the bacteria count once the infection can for the bronchial cilia to remove inhaled particles. The no longer be eradicated, and at the same time reduce mucus therefore fails to perform its main task of facilitat- 25 the correlated inflammation. ing the removal of inhaled particles, thus generating con- [0014] However, chronic bacterial colonisation, espe-ditions highly favourable to bacterial colonisation as a dally by Gram-negative germs, and Pseudomonas sp. result of stagnation in the upper and lower airways. In in particular, is a possible and frequent event even in particular, nearly all patients develop Pseudomonas aer- patients not suffering from CF, especially those with PCD uginosa infection, which becomes irreversible, and con- 30 (primary ciliary dyskinesia), severe chronic obstructive sequently chronic. As a result, CF patients are affected pulmonary disease (COPD), or patients with functional by a self-perpetuating trio of events that lead to an inex- alterations of the nasal sinuses who are particularly pre-orable decline in the respiratory function. disposed to bacterial infection and the correlated inflam- [0006] This trio of events is known as obstruction - in- matory symptoms. At bronchial level, patients with alter- fection - inflammation. The mucus also protects bacteria 25 ationsofthe bronchial wall presenting sac-shaped areas against attack by antibiotics, which means that very high (bronchiectasis) are particularly exposed to chronic indoses are needed to perform a bactericidal action. fection.
[0007] In the case of aminoglycosides, the family of [0015] Hyaluronic acid is a natural biopolymer belong- drugs which are most effective against this germ and ing to the glycosaminoglycan (GAG) family, and is one Gram-negative bacteria in general, concentrations 25 40 of the main components of connective tissue matrix. The times higher than the MIC are required to perform a bac- lungs, together with the skin and intestine, contain the tericidal action, because concentrations 10 times greater largest amount of hyaluronic acid. Of the many known than the MIC are considered only just bacteriostatic. properties of hyaluronic acid, perhaps the main one is [0008] In order to administer repeated cycles of anti- that it binds and retains a considerable amount of water, biotic treatment at the high concentrations required by 45 [0016] Hyaluronic acid has also been used for its prop- chronic infection, antibiotic-based inhalation solutions for erties in numerous inflammation conditions. For exam-nebulisation in the lower airways only have been used pie, its action on joint cartilage is known; hyaluronic acid for some time. These formulations enable the antibiotic is used by the intra-articular route to increase the viscous to be conveyed to the site of the infection, allowing the properties of the synovial fluid, and also because it per-useofhighdosesandatthesametimereducingsystemic 50 forms a direct anti-inflammatory action, in both acute inexposure. flammation models and situations of chronic inflamma- [0009] Bacterial colonisation by Pseudomonas aeru- tion. The anti-inflammatory properties of hyaluronic acid ginosa and other pathogens takes place by direct con- are also used in dentistry, plastic surgery and dermatol- tact, especially by inhaling particles of bacteria in sus- ogy. pension in the air. The upper airways play a crucial part 55 [0017] The ability of hyaluronic acid to prevent bron- in this colonisation process, representing a preferential choconstriction in the stress test when administered by access route for many germs. inhalation was also recently described (see e.g. G.
[0010] The nose normally produces mucus, which has Petrigni and L. Allegra, Pulm Pharmacol Ther. 2006,19, 166-171). boy®, Nebula®, etc. and suitable nebulisers, or a vibra- [0018] The administration of antibiotics by inhalation tion system such as Eflow rapid®, ultrasound nebulisa- is normally characterised by good systemic tolerability tion systems, or systems such as l-neb AAD. due to low systemic absorption, but is often accompanied [0027] Hyaluronic acid, its salts (such as sodium salt) by side effects such as bronchospasm due to local reac- 5 or esters have a molecular weight preferably between tivity (see e.g. A.L. Smith, Journal of Cystic Fibrosis 1 50,000 and 200,000 Da, and are present in a concentra- 2002 S189-S193; P.J. Cole, Journal of Chemotherapy tion of between 0.01 and 5%. The mean aerodynamic 2001, 13, 354-362; W.H. Nikolaizik et al., Eur J Pediatr diameterofthe particles in the nebulised solutions is pref- 1996, 155, 608-611). erably between 2 and 5 microns.
This event is observed in some 10-15% of patients, who to [0028] The solutions to be nebulised, described above, are consequently obliged to stop taking antibiotics, es- can also be used for nebulisation in the upper airways, pecially tobramycin. through a suitable system such as SinuNeb®.
[0019] In aerosol treatment of CF patients, treatment [0029] The solution contains hyaluronic acid, its salts with a hypertonic solution (6-7% NaCI) has recently been or esters, in the quantity of between 0.01% and 5% by suggested in addition to antibiotic treatment, with a view 15 weight, preferably between 0.05% and 1%, and more to hydrating the viscous secretions, thus improving their preferably between 0.05% and 0.5%. rheology and facilitating their elimination. This treatment [0030] The solution can be distributed between 5 ml has been found to improve the respiratory function (see monodose bottles containing the same composition as e.g. M.R. Elkis et al., N Engl J Med 2006, 354, 229-240). the multidose formulation.
[0020] However, the administration of a hypertonic so- 20 [0031] The invention is illustrated in greater detail in lution presents considerable problems, especially in the examples below. terms of tolerability, as its inhalation causes inflammation ofthe respiratory mucosa, pharyngitis, laryngitis with red- Example 1 dening and local oedema, requiring discontinuance of the treatment, in a large number of patients (see e.g. 25 4 ml Disposable ampoule M.R. Elkis et al., N Engl J Med 2006, 354, 229-240).
[0032]
DESCRIPTION OF THE INVENTION
Sterile solution [0021] It has now been found that the administration 30 NaCI 7% of a hypertonic solution, associated with hyaluronic acid Sodium hyaluronate 0.05% or its salts, leads to better local tolerability, with a reduction in the inflammatory component affecting the mucosa ofthe airways, a lower risk of discontinuance ofthe treat- Example 2 ment, and better compliance by patients affected by cyst- 35 ic fibrosis. 4ml Disposable ampoule [0022] The hyaluronic acid usable according to the invention will preferably have a low or intermediate molec- [0033] ular weight.
[0023] The invention supplies formulations in sterile 40 Sterile solution monodose ampoules of 5-7% hypertonic solution con- NaCI 7% taining hyaluronic acid or a salt or ester thereof with a Sodium hyaluronate 0.02% low molecularweightoran intermediate molecularweight at a concentration of between 0.01% and 1%, and preferably between 0.01% and 0.1%. 45 Claims [0024] These formulations are rendered suitable for administration as aerosols in the lower airways by neb- 1. Inhalation formulations in sterile monodose am-ulisation through "Venturi effect" compressors such as poules of 5-7% hypertonic solution containing hy-
Pari boy®, Pari Turbo boy®, Nebula®, etc. and suitable aluronic acid or a salt or ester thereof with a low nebulisers, or through a vibration system such as Eflow so molecular weight or an intermediate molecular rapid® or ultrasound nebulisation systems such as l-neb weight at a concentration of between 0.01% and 1%. AAD.
[0025] The monodose formulations according to the 2. Formulations according to claim 1 wherein the con- invention will preferably be in the form of sterile aqueous centration of hyaluronic acid, salt or ester thereof solutions. 55 ranges from 0.01% to 0.1 %.
[0026] For the administration of aerosols in the lower airways, the solutions can be nebulised through a "Ven- 3. Formulations as claimed in claim 1 or 2, administra-turi effect" compressor such as Pari boy®, Pari Turbo ble by the nasal route.
Patentansprüche 1. Inhalationsformulierungen in sterilen Einzeldosi-sampullen von 5-7% hypertonischerLösung, enthal-tend Hyaluronsáure Oder ein Salz Oder einen Ester davon mit niedrigem Molekulargewicht oder mittle-rem Molekulargewicht bei einer Konzentration von zwischen 0,01% und 1%. 2. Formulierungen gerr^ Anspruch 1, wobei die Konzentration dér Hyaluronsáure, des Salzes Oder Esters davon von 0,01% bis 0,1% reicht. 3. Formulierungen gerr^ Anspruch 1 oder 2, verab-reichbar auf nasalem Weg.
Revendications 1. Formulations pour inhalation en ampoules unidoses stériles de solution hypertonique á 5 á 7 % contenant de l’acide hyaluroniqueou unselou un ester de célúiéi ayant un faible poids moléculaire ou un poids mo-léculaire intermédiaire á une concentration comprise entre 0,01 % et 1 %. 2. Formulations selon la revendication 1, dans lesquel-les la concentration de l’acide hyaluronique, du sel ou de l’ester de celui-ci est comprise entre 0,01 % et 0,1 %. 3. Formulations selon la revendication 1 ou 2, adminis-trable par la voie nasale.
REFERENCES CITED IN THE DESCRIPTION
This list of references cited by the applicant is for the reader’s convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.
Non-patent literature cited in the description • G.PETRIGNI ;L.ALLEGRA. Pulm Pharmacol Then, · W.H. NIKOLAIZIKetal. EurJPed/'afr, 1996, vol. 155, 2006, vol. 19, 166-171 [0017] 608-611 [0018] • A.L. SMITH. Journal of Cystic Fibrosis, 2002, vol. 1, · M.R. ELKIS et al. N Engl J Med, 2006, vol. 354, 189-S193 [0018] 229-240 [0019] [0020] • P.J. COLE. Journal of Chemotherapy, 2001, vol. 13, 354-362 [0018]
Claims (2)
- :5¾¾Mdakni tgcnyponnd1..- Inhtdakldy kdsr.U-nényok 5-7 %-«« hipertóniás Oltlntot kgiakgagd sterii mrooaidnisns ampullákként amely didst kis msdéktda tömegű vágy köyppps nnööktda tönmgö hlakennsavat vagy söját vagy észterét maakoa/ra 0,(M kkűy 1% kdaíM; kön cap tráglöfeap.
- 2, As. 1... igénypont sseHnti kns.donémek. fáin] a hiakanonsvy sója vagy esaíare kununnráa ima 0,(M % - i) J 74. ö> Λ/ 1, vágy j;. Igénygönt vc-lnn késkittt jny; apinly tiaaálbstion adagolható.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT000742A ITMI20060742A1 (it) | 2006-04-13 | 2006-04-13 | Composizioni antibatteriche per il trattamento di infezioni delle alte e basse via aeree |
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| HUE031098T2 true HUE031098T2 (hu) | 2017-07-28 |
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| HUE09166600A HUE031098T2 (hu) | 2006-04-13 | 2007-04-06 | Antibakteriális készítmény felsõ és alsó légúti fertõzések kezelésére |
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| DK (1) | DK1847256T3 (hu) |
| ES (2) | ES2482815T3 (hu) |
| HU (1) | HUE031098T2 (hu) |
| IT (1) | ITMI20060742A1 (hu) |
| LT (1) | LT2111855T (hu) |
| PL (2) | PL2111855T3 (hu) |
| PT (1) | PT1847256E (hu) |
| SI (1) | SI2111855T1 (hu) |
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| DE102006049580A1 (de) * | 2006-10-20 | 2008-04-24 | Rochel, Michael, Dr. med. | Topische Zusammensetzung zur Behandlung von Ekzemen |
| DE102008007198A1 (de) | 2008-02-01 | 2009-08-13 | Infectopharm Arzneimittel Und Consilium Gmbh | Oral oder nasal applizierbare Epinephrin- haltige Zubereitungen mit verbesserten Eigenschaften |
| IT1401494B1 (it) * | 2010-07-30 | 2013-07-26 | Eupharma Srl | Formulazioni inalatorie in forma di soluzioni o polveri secche, per la rimozione delle secrezioni mucose dall'apparato respiratorio |
| ES2437690B1 (es) * | 2012-07-10 | 2014-10-24 | Chiesi Farmaceutici S.P.A. | Formulaciones inhalatorias en forma de soluciones o de polvos secos, para la eliminación de las secreciones mucosas del aparato respiratorio |
| EP2985019B1 (en) | 2014-08-16 | 2021-10-20 | Church & Dwight Co., Inc. | Nasal composition having anti-viral properties |
| EP2985027B1 (en) * | 2014-08-16 | 2021-03-31 | Church & Dwight Co., Inc. | Nasal composition comprising mixture of hyaluronic acids and saline solution |
| GB201611639D0 (en) | 2016-07-04 | 2016-08-17 | Ockham Biotech Ltd | Delivery device and formulation |
| IT202000016984A1 (it) | 2020-07-13 | 2022-01-13 | Bmg Pharma S P A | Composizioni igienizzanti e antiinfettive per le mucose orali |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5633003A (en) * | 1994-03-31 | 1997-05-27 | Cantor; Jerome O. | Use of intratracheally administered hyaluronic acid to ameliorate emphysema |
| CA2477979A1 (en) * | 2002-03-05 | 2003-09-18 | Transave, Inc. | An inhalation system for treatment of intracellular infections |
| FR2847818B1 (fr) | 2002-11-28 | 2008-04-04 | Agro Ind Rech S Et Dev Ard | Composition pharmaceutique a base d'acide hyaluronique |
| US7452524B2 (en) * | 2004-01-27 | 2008-11-18 | Gilead Sciences, Inc. | Method for improvement of tolerance for therapeutically effective agents delivered by inhalation |
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2006
- 2006-04-13 IT IT000742A patent/ITMI20060742A1/it unknown
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2007
- 2007-04-06 PL PL09166600T patent/PL2111855T3/pl unknown
- 2007-04-06 EP EP07007272.3A patent/EP1847256B1/en not_active Not-in-force
- 2007-04-06 ES ES07007272.3T patent/ES2482815T3/es active Active
- 2007-04-06 PT PT70072723T patent/PT1847256E/pt unknown
- 2007-04-06 PL PL07007272T patent/PL1847256T3/pl unknown
- 2007-04-06 HU HUE09166600A patent/HUE031098T2/hu unknown
- 2007-04-06 SI SI200731867A patent/SI2111855T1/sl unknown
- 2007-04-06 LT LTEP09166600.8T patent/LT2111855T/lt unknown
- 2007-04-06 EP EP09166600.8A patent/EP2111855B1/en active Active
- 2007-04-06 DK DK07007272.3T patent/DK1847256T3/da active
- 2007-04-06 ES ES09166600.8T patent/ES2604212T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| DK1847256T3 (da) | 2014-06-30 |
| LT2111855T (lt) | 2016-12-12 |
| EP1847256A1 (en) | 2007-10-24 |
| PL1847256T3 (pl) | 2014-09-30 |
| ES2604212T3 (es) | 2017-03-03 |
| EP2111855A1 (en) | 2009-10-28 |
| ES2482815T3 (es) | 2014-08-04 |
| PL2111855T3 (pl) | 2017-02-28 |
| EP1847256B1 (en) | 2014-04-23 |
| SI2111855T1 (sl) | 2016-12-30 |
| EP2111855B1 (en) | 2016-08-31 |
| ITMI20060742A1 (it) | 2007-10-14 |
| PT1847256E (pt) | 2014-07-15 |
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