Methods of administering high concentrations of nitric oxide

Inventors

Goldstein, Brahm • Greene, Douglas Stuart

Assignees

Mallinckrodt Pharma IP Trading DAC • Mallinckrodt Pharmaceuticals Ireland Ltd • Therakos Inc • Mallinckrodt Critical Care Finance Inc

Abstract

Described are methods of administering therapeutic gases comprising high concentrations of nitric oxide, particularly concentrations above 2,000 ppm. The therapeutic gas may be administered at a certain dosing rate, such as less than 166 micrograms of nitric oxide per second. Also described are methods of administering a therapeutic gas comprising nitric oxide to a patient, wherein a dose of nitric oxide is administered from a portable device that includes a delivery system and a mini-cylinder. Methods of intermittent administration of nitric oxide pulses are also described.

Core Innovation

The invention provides methods for treating pulmonary hypertension by administering nitric oxide (NO) to a patient in need thereof. The administered dose includes a delivery concentration greater than 2,000 ppm NO and is administered at a dosing rate less than or equal to 166 μg NO per second.

The invention also provides methods for reducing nasal irritation during nitric oxide administration. A therapeutic gas comprising nitric oxide (NO) is administered to a patient at a delivery concentration greater than 2,000 ppm NO and at a dosing rate less than or equal to 166 μg NO per second.

The document further describes delivery at high NO delivery concentrations using undiluted delivery where the delivery concentration matches cylinder or storage concentration, enabling use of portable delivery devices and mini-cylinders with small cylinder volumes. The administration timing includes inspiration-timed administration, with continuous versus pulsed or bolus delivery, including intermittent dosing schedules such as every n-th breath.

For pulmonary hypertension treatment, the described dosing relates to amounts such as 0.001–4.5 mg/kg/hr, and the use encompasses pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with chronic obstructive pulmonary disease (COPD).

Claims Coverage

The partial content includes two independent claims covering pulmonary hypertension treatment with NO at delivery concentration greater than 2,000 ppm and a dosing rate less than or equal to 166 μg NO per second, and reducing nasal irritation during NO administration using the same delivery concentration and dosing-rate constraints. Across the partial content, dependent claims further narrow quantitative ranges and administration scheduling.

Overall, the claim coverage is centered on delivering nitric oxide at delivery concentrations greater than 2,000 ppm while constraining the dosing rate to no more than 166 μg NO per second, with the clinical purposes split between pulmonary hypertension treatment and reducing nasal irritation during NO administration. Dependent claims in the partial content further narrow delivery concentration subranges and dosing-related metrics, and some narrow administration timing such as every breath or intermittently.

Stated Advantages

Documented Applications