Methods and compositions for treatment of pulmonary hypertension and other lung disorders
Inventors
Weers, Jeffry • ROMERO, ALAIN • SMYTH, HUGH • Curtis, Robert • FROST, Adaani • Xu, Zhen • Shreeniwas, Revati • Donovan, Martin
Assignees
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Publication Number
US-11491161-B2
Publication Date
2022-11-08
Expiration Date
Abstract
Provided herein are methods for treating pulmonary hypertension. The methods include administering to a subject in need thereof an effective amount of a vasodilator, wherein the vasodilator is administered to the subject via inhalation pro re nata using a portable inhaler. In some embodiments, the vasodilator is a PDE5 inhibitor. Pharmaceutical compositions for pro re nata administration of vasodilators are also described.
Core Innovation
The invention relates to treating pulmonary arterial hypertension in a subject in need thereof by administering a therapeutically effective amount of micronized vardenafil hydrochloride trihydrate in dry powder form by oral inhalation. The administration is pro re nata and is delivered by a portable inhaler. The approach is described for pulmonary hypertension contexts including PAH and other PH/Group 3-5 lung conditions.
The core concept includes using oral inhalation of micronized vardenafil hydrochloride trihydrate in dry powder form to target rapid onset and acute improvement associated with exertion-related symptoms. The described rationale emphasizes reduced systemic and gastrointestinal exposure while providing a suitable add-on background therapy approach. The patent further associates the treatment with pulmonary vascular outcomes such as mean pulmonary artery pressure and pulmonary vascular resistance, together with functional measures such as a 6-minute walk test and Borg Dyspnea Index.
The invention additionally covers composition and device characteristics supporting delivery of the micronized drug as a dry powder via a portable inhaler. The patent describes carrier-based inhalable formulations and aerosol targeting metrics using a Next Generation Impactor, including fine particle fraction deposited on a specified NGI stage and associated aerodynamic performance metrics. Portable inhaler hardware features such as an oscillating actuator and/or oscillating bead powder dispersion mechanism are also described as part of the delivery system.
In addition to vardenafil, the disclosed framework includes alternative vasodilator classes for oral inhalation in pulmonary hypertension contexts, including soluble guanylate cyclase stimulators and prostacyclin/prostacyclin-analog and prostacyclin receptor agonist classes. The patent also describes potential co-administration with a bronchodilator and, in some cases, with a second vasodilator as part of the disclosed treatment framework.
Claims Coverage
The document provides one independent claim directed to PRN treatment of pulmonary arterial hypertension using micronized vardenafil hydrochloride trihydrate as a dry powder by oral inhalation delivered with a portable inhaler. Dependent claims refine this independent claim by adding quantitative drug-product parameters and narrowing delivery/device characteristics, including particle size, nominal dose range, pharmacokinetic timing, and aerosol/deposition performance metrics tied to NGI stage 4-F.
PRN oral inhalation of micronized vardenafil hydrochloride trihydrate via a portable inhaler
A method of treating pulmonary arterial hypertension comprising administering to the subject a therapeutically effective amount of micronized vardenafil hydrochloride trihydrate in dry powder form by oral inhalation, pro re nata, delivered by a portable inhaler.
Micronized powder particle size defined by Dv50 range
The method is characterized by using micronized vardenafil hydrochloride trihydrate having a volume weighted median diameter in the range of about 0.1 µm to about 2.5 µm.
Nominal administered dose range
The method includes administering vardenafil hydrochloride trihydrate in a nominal dose ranging from about 0.1 mg to about 2.0 mg of vardenafil.
Rapid pharmacokinetic timing using T_max constraint
The method is further limited such that vardenafil hydrochloride trihydrate has a T_max of 2 minutes or less following administration.
Portable inhaler dispersion chamber with an axially oscillating sphere
The method further specifies that the portable dry powder inhaler includes an axially oscillating sphere located inside a dispersion chamber.
NGI stage 4-F deposition performance metric constrained by d_a^2Q
The method is further defined such that the portable inhaler combination achieves a d_a^2Q value less than 467 µm2/L/minute when vardenafil hydrochloride trihydrate in dry powder form is deposited on stage 4-F of a Next Generation Impactor.
Overall claim coverage centers on PRN treatment of pulmonary arterial hypertension using dry powder oral inhalation of micronized vardenafil hydrochloride trihydrate via a portable inhaler, with dependent claims further constraining particle size, nominal dose, pharmacokinetic timing, inhaler internal dispersion features, and aerosol deposition performance.
Stated Advantages
Rapid onset and acute improvement associated with exertion-related symptoms.
Reduced systemic and gastrointestinal exposure.
Suitable add-on background therapy approach.
Documented Applications
Treating pulmonary arterial hypertension in a subject in need thereof.
Pulmonary hypertension contexts including PAH and other PH/Group 3-5 lung conditions.
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