Aerosol pirfenidone and pyridone analog compounds and uses thereof
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Publication Number
US-11559520-B2
Publication Date
2023-01-24
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 unit dose of an aqueous solution comprising water and pirfenidone for delivery by a liquid nebulizer for the daily treatment of interstitial lung disease in an adult human. The solution is defined by a pirfenidone concentration from about 5.0 mg/mL to about 20 mg/mL and an osmolality from about 50 mOsmol/kg to about 2000 mOsmol/kg. One or more respirable delivered doses per day include at least 0.8 mg of pirfenidone, with a total daily respirable delivered dose that does not exceed 360 mg/day.
The invention is directed to treating interstitial lung disease by reducing a decline in forced vital capacity (FVC) in the lung of the adult human. The described rationale emphasizes inhaled delivery of pirfenidone to achieve rapid, localized, and sustained delivery to lung and downstream tissues while reducing oral-route gastrointestinal and systemic toxicities. The delivery framework is described as supporting therapeutically effective lung exposure dependent on lung tissue half-life and maintaining efficacious lung levels to protect against irreversible fibrosis.
The disclosed approach extends the inhaled pirfenidone formulation concept to multiple fibrotic and inflammatory diseases and provides formulation and delivery considerations for controlling solute, osmolality, and pH, optionally using homogeneous aqueous solutions. The partial content also describes aerosol delivery schemes and parameters, including respirable delivered dose and aerosol types such as nebulizer and dry powder, and links route- and dose-dependent exposure measures to in vivo anti-fibrotic efficacy.
Claims Coverage
The consolidated document identifies one independent claim covering a liquid-nebulized aqueous pirfenidone unit dose for interstitial lung disease. Across the claims, the inventive features center on formulation concentration and osmolality, a minimum respirable delivered dose, a cap on total daily respirable delivered dose, and therapeutic effectiveness defined by reduction of decline in forced vital capacity (FVC).
Unit dose aqueous pirfenidone solution for liquid nebulizer daily treatment
A unit dose of an aqueous solution comprising water and pirfenidone for delivery by a liquid nebulizer for the daily treatment of interstitial lung disease in an adult human, wherein the aqueous solution has a pirfenidone concentration from about 5.0 mg/mL to about 20 mg/mL, an osmolality of from about 50 mOsmol/kg to about 2000 mOsmol/kg, and one or more respirable delivered doses per day of at least 0.8 mg of pirfenidone.
Capped total daily respirable delivered dose with FVC decline reduction
The total daily respirable delivered dose of pirfenidone deliverable by the liquid nebulizer does not exceed 360 mg/day, wherein the respirable delivered dose is therapeutically effective to treat interstitial lung disease by reducing a decline in forced vital capacity (FVC) in the lung of the adult human.
The claims are directed to a liquid-nebulized aqueous pirfenidone unit dose with specified concentration and osmolality, a minimum daily respirable pirfenidone dose, a maximum total daily respirable delivered dose of 360 mg/day, and therapeutic effectiveness through reduction of decline in forced vital capacity (FVC).
Stated Advantages
Therapeutically effective to treat interstitial lung disease by reducing a decline in forced vital capacity (FVC) in the lung.
Provides rapid, localized, and sustained delivery to lung and downstream tissues while reducing oral-route gastrointestinal and systemic toxicities.
Supports efficacious lung levels dependent on lung tissue half-life and protects against irreversible fibrosis.
Documented Applications
Daily treatment of interstitial lung disease in an adult human using liquid nebulizer delivery of an aqueous pirfenidone unit dose.
Treatment of interstitial lung disease by reducing decline in forced vital capacity (FVC) in the lung.
Treatment contexts discussed in the partial content include idiopathic pulmonary fibrosis (IPF), interstitial pneumonia (IIP), usual interstitial pneumonia (UIP), COPD, asthma, pulmonary fibrosis, lung inflammation, kidney fibrosis, liver fibrosis, cardiac fibrosis, chemotherapy-induced cardiotoxicity and renal toxicity, multiple sclerosis, glaucoma post-op fibrosis, and pulmonary hypertension.
Co-administration with anti-inflammatory, anti-fibrotic, anti-cancer, and pulmonary hypertension agents is described as a potential cocktail approach.
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