Aerosol pirfenidone and pyridone analog compound and uses thereof
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Publication Number
US-11071741-B2
Publication Date
2021-07-27
Expiration Date
Abstract
Disclosed herein are formulations of pirfenidone or pyridone analog compounds for aerosolization and use of such formulations for aerosol administration of pirfenidone or pyridone analog compounds for the prevention or treatment of various fibrotic and inflammatory diseases, including disease associated with the lung, heart, kidney, liver, eye and central nervous system. In some embodiments, pirfenidone or pyridone analog compound formulations and delivery options described herein allow for efficacious local delivery of pirfenidone or pyridone analog compound. Compositions include all formulations, kits, and device combinations described herein. Methods include inhalation procedures, indications and manufacturing processes for production and use of the compositions described.
Core Innovation
The invention provides a method of modulating NLRP3 inflammasome activation or NF-KappaB activation in a viral pneumonia patient by administering by inhalation an aqueous solution of pirfenidone. The aqueous solution includes pirfenidone, sodium citrate, citric acid, sodium chloride, and sodium saccharin, with pirfenidone at a concentration from about 0.1 mg/mL to about 20 mg/mL. The sodium saccharin to pirfenidone molar ratio is between 1 to 53.9 and 1 to 215.9.
The aqueous solution has an osmolality from about 200 mOsmol/kg to about 500 mOsmol/kg and a pH of about 5 to about 6. The administration reduces local inflammation in the lung and reduces pro-fibrotic cellular responses resulting from viral pneumonia. The disclosed approach is an inhaled delivery of a specifically defined pirfenidone formulation for viral pneumonia modulation of inflammation-related activation pathways.
The disclosure further describes inhalation delivery device options and aerosolization formats, including liquid nebulizer use, jet nebulizers, ultrasonic nebulizers, vibrating-mesh or nebulizer plate devices, high efficiency liquid nebulizers, in-line nebulizer use, mechanically ventilated patient administration, liquid nebulized aerosol, dry powder aerosol, metered-dose inhaler, dry powder inhaler, and kits. Separated-compartment nebulizer approaches are also described, and device-performance characteristics are stated in terms of lung deposition and aerosol metrics.
Claims Coverage
The consolidated claim coverage includes one independent method centered on inhalation administration of a specifically formulated aqueous pirfenidone solution to modulate NLRP3 inflammasome activation or NF-KappaB activation in viral pneumonia, with reduction of local lung inflammation and pro-fibrotic cellular responses. Dependent features further refine the formulation and delivery configuration. In total, four inventive features are directly reflected across the independent-claim content.
Inhalation modulation of NLRP3 or NF-kappaB in viral pneumonia
A method of modulating NLRP3 inflammasome activation or NF-KappaB activation in a viral pneumonia patient by administering pirfenidone by inhalation.
Aqueous pirfenidone formulation with citrate, salt, and sodium saccharin
Administering by inhalation an aqueous solution of pirfenidone with sodium citrate, citric acid, sodium chloride, and sodium saccharin, wherein the molar ratio of sodium saccharin to pirfenidone is between 1 to 53.9 and 1 to 215.9.
Defined concentration, osmolality, and pH
Administering an aqueous solution of pirfenidone having a concentration from about 0.1 mg/mL to about 20 mg/mL, an osmolality from about 200 mOsmol/kg to about 500 mOsmol/kg, and a pH of about 5 to about 6.
Therapeutic reduction of lung inflammation and pro-fibrotic responses
Wherein the administration reduces local inflammation in the lung and reduces pro-fibrotic cellular responses resulting from viral pneumonia.
The claim coverage centers on inhaled aqueous pirfenidone with specified excipients and physicochemical parameters for modulating NLRP3 inflammasome activation or NF-KappaB activation in viral pneumonia and reducing local lung inflammation and pro-fibrotic cellular responses. Additional disclosed claim features relate to nebulizer and mechanically ventilated in-line administration contexts.
Stated Advantages
Reduces local inflammation in the lung.
Reduces pro-fibrotic cellular responses resulting from viral pneumonia.
Documented Applications
Treatment of a viral pneumonia patient by inhalation administration of an aqueous pirfenidone formulation to modulate NLRP3 inflammasome activation or NF-KappaB activation.
Modulating NLRP3 inflammasome activation or NF-KappaB activation in a mechanically ventilated viral pneumonia patient using an aqueous solution administered by inhalation.
Inhalation delivery of pirfenidone-containing aqueous solutions using a nebulizer system, including nebulizer types and separated-compartment nebulizer approaches.
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