# US 2014/0155486 A1 · Administration of Iloprost as Aerosol Bolus > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0155486 A1 - Document ID: US20140155486A1 - Status: Published application - Kind: A1 - Application number: 14/061,525 - Filed: 2012-04-26 - Published: 2014-06-05 - Earliest claimed: 2011-04-26 - Inventors: Tobias Gessler; Thomas Schmehl; Werner Seeger; Robert Voswinckel - Web page: https://patentgrep.com/patent/US20140155486A1 ## CPC - A61K 31/5578: having a pentalene ring system, e.g. carbacyclin, iloprost - A61K 9/0078: {for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions} - A61K 31/191: having two or more hydroxy groups, e.g. gluconic acid - A61M 11/005: {using ultrasonics (spraying or atomising liquids using ultrasonic vibrations in general B05B17/06)} - A61M 15/0021: {Mouthpieces therefor} - A61P 9/12: Antihypertensives - A61P 11/00: Drugs for disorders of the respiratory system - A61K 9/08: Solutions {(composition of solutions A61K47/00)} - A61M 11/06: of the injector type - A61M 15/0085: {using ultrasonics (spraying or atomising liquids using ultrasonic vibrations in general B05B17/06)} - A61M 15/009: {using medicine packages with incorporated spraying means, e.g. aerosol cans (pocket atomiser of the injector type A61M11/08)} - A61M 2016/0024: {with an on-off output signal, e.g. from a switch} - A61M 2205/50: with microprocessors or computers - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to novel methods, compositions and kits useful for the treatment of pulmonary diseases such as pulmonary arterial hypertension. In particular, aerosolisable compositions of iloprost are provided which are for use in inhalation therapy. Their administration is by bolus inhalation, which is patient-friendly, effective, and well tolerated. Bolus inhalation may, for example, be achieved using an efficient nebuliser based on the vibrating mesh technology. ## Claims ### Claim at position 1 1-15. (canceled) ### Claim 16 A pharmaceutical composition comprising an active ingredient selected from iloprost and salts thereof for use as an aerosol for pulmonary administration to a patient in need thereof, wherein an amount of the composition comprises an effective single dose of the active ingredient and is provided in aerosolised form for bolus inhalation within a period of 2 minutes or less. ### Claim 17 (depends on 16) The composition of claim 16, wherein the effective single dose is from about 1.5 μg to about 5.0 μg. ### Claim 18 (depends on 16) The composition of claim 16, wherein the amount of the composition has a strength of 10 μg/mL or more. ### Claim 19 (depends on 16) The composition of claim 16, wherein the effective single dose is 2.5 μg and the amount of the composition has a strength of 10 μg/mL. ### Claim 20 (depends on 16) The composition of claim 16, wherein the effective single dose is 5 μg and the amount of the composition has a strength of 20 μg/mL. ### Claim 21 (depends on 16) The composition of claim 16, wherein the composition is formulated as an aqueous solution further comprising one or more of: (a) a cosolvent; (b) an isotonising agent; (c) a pH-adjusting agent; and (d) a stabilising agent. ### Claim 22 A method of treating a patient suffering from pulmonary arterial hypertension, comprising: (a) providing a pharmaceutical composition comprising an active ingredient selected from iloprost and salts thereof; (b) providing an inhaler adapted for delivering an amount of the composition comprising an effective single dose of the active ingredient in aerosolised form for bolus inhalation within a period of 2 minutes or less; and (c) administering the composition as an aerosol bolus to the patient by using the inhaler. ### Claim 23 (depends on 22) The method of claim 22, wherein administering the composition requires 12 or less breathing manoeuvres. ### Claim 24 (depends on 22) The method of claim 22, wherein administering the composition requires 8 or less breathing manoeuvres. ### Claim 25 (depends on 22) The method of claim 22, wherein the inhaler is adapted to emit the composition in aerosolised form at an output rate of 0.5 mL/min or more. ### Claim 26 (depends on 22) The method of claim 22, wherein the inhaler is adapted to emit the composition in aerosolised form at a rate of 5 μg of iloprost per minute or more. ### Claim 27 (depends on 22) The method of claim 22, wherein the inhaler is adapted to emit, per inhalation phase, a predetermined volume of aerosol-free air immediately following a predetermined volume of the aerosol. ### Claim 28 (depends on 27) The method of claim 27, wherein the predetermined volume of aerosol-free air is emitted by the inhaler over a period of 0.2 to 2 seconds at the end of each inhalation phase. ### Claim 29 (depends on 27) The method of claim 27, wherein the predetermined volume of the aerosol is emitted by the inhaler over a period of 3 to 6 seconds per inhalation phase. ### Claim 30 (depends on 22) The method of claim 22, wherein the inhaler is selected from metered-dose inhalers, soft mist inhalers, and vibrating mesh nebulisers. ### Claim 31 (depends on 22) The method of claim 22, wherein administering the composition requires not more than four breathing manoeuvres. ### Claim 32 (depends on 22) The method of claim 22, wherein the composition is aerosolised by a soft mist inhaler or a vibrating mesh nebuliser and the composition is formulated as an aqueous solution further comprising one or more of: (a) a cosolvent; (b) an isotonising agent; (c) a pH-adjusting agent; and (d) a stabilising agent. ### Claim 33 (depends on 22) The method of claim 22, wherein per inhalation phase, a predetermined volume of aerosol-free air is emitted immediately following the aerosol, and wherein a ratio of the aerosol volume to the volume of aerosol-free air is not higher than about 75:25. ### Claim 34 (depends on 22) The method of claim 22, wherein per inhalation phase, a predetermined volume of aerosol-free air is emitted immediately following the aerosol, and wherein a ratio of the aerosol volume to the volume of aerosol-free air is not higher than about 85:15. ### Claim 35 A pharmaceutical kit comprising: (a) a composition comprising an active ingredient selected from iloprost and salts thereof; and (b) an inhaler adapted for providing an amount of the composition comprising an effective single dose of the active ingredient in aerosolised form for bolus inhalation within a period of 2 minutes or less. ### Claim 36 (depends on 35) The pharmaceutical kit of claim 35, wherein the inhaler is adapted to emit the composition at an output rate of 0.5 mL/min or more. ### Claim 37 (depends on 35) The pharmaceutical kit of claim 35, wherein the inhaler is adapted to emit the composition at a rate of 5 μg of iloprost per minute or more. ### Claim 38 (depends on 35) The pharmaceutical kit of claim 35, wherein the inhaler is adapted to emit, per inhalation phase, a predetermined volume of aerosol-free air immediately following a predetermined volume of the aerosol. ### Claim 39 (depends on 35) The pharmaceutical kit of claim 35, wherein the inhaler is selected from metered-dose inhalers, soft mist inhalers, and vibrating mesh nebulisers. ### Claim 40 (depends on 35) The pharmaceutical kit of claim 35, wherein the composition is formulated as an aqueous solution further comprising one or more of: (a) a cosolvent; (b) an isotonising agent; (c) a pH-adjusting agent; and (d) a stabilising agent. ### Claim 41 (depends on 35) The pharmaceutical kit of claim 35 further comprising (d) an electronic data storage means capable of controlling the operation of the inhaler so as to provide the amount of the composition comprising the effective single dose of the active ingredient in aerosolised form for bolus inhalation within the period of 2 minutes or less. ### Claim 42 A nebulised aerosol comprising at least about 0.5 μg of iloprost or an equivalent amount of a salt thereof per litre of aerosol volume. ### Claim 43 (depends on 42) The nebulised aerosol of claim 42, being emitted from a nebuliser (a) at an inspiratory flow rate from about 10 L/min to about 20 L/min; and/or (b) at an output rate of at least 0.5 to 1.5 mL/min during active nebulisation; and/or (c) such as to deliver a dose of 2.5 μg or more during four or less breathing manoeuvres.