Details for Patent: 9,533,000

Title:	Inhalable aztreonam for treatment and prevention of pulmonary bacterial infections
Abstract:	A method and a composition for treatment of pulmonary bacterial infections caused by gram-negative bacteria suitable for treatment of infection caused by Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Haemophilus influenzae, Proteus mirabilis, Enterobacter species, Serratia marcescens as well as those caused by Burkholderia cepacia, Stenotrophomonas maltophilia, Alcaligenes xylosoxidans, and multidrug resistant Pseudomonas aeruginosa, using a concentrated formulation of aztreonam, or a pharmaceutically acceptable salt thereof, delivered as an aerosol or dry powder formulation.
Inventor(s):	Montgomery; Alan Bruce (Medina, WA)
Assignee:	GILEAD SCIENCES, INC. (Foster City, CA)
Filing Date:	Oct 04, 2013
Application Number:	14/046,539
Claims:	1. A method of treating pulmonary infections in a human in need thereof comprising administering to the human a tobramycin aerosol in a treatment cycle of 28 days on the tobramycin aerosol and 28 days off the tobramcycin aerosol; the method comprising administering by inhalation to the human, during the 28 days the human is off the tobramcycin aerosol, an inhalable aerosol comprising from about 1 to about 250 mg of purified aztreonam or a pharmaceutically acceptable salt thereof in a dry powder form dissolved in a saline solution per one dose, said aerosol being suitable for treatment of pulmonary bacterial infections caused by gram-negative bacteria Burkholderia cepacia, Stenotrophomonas maltophilia, Alcaligenes xylosoxidans, and multidrug resistant Pseudomonas aeruginosa; provided that the pharmaceutically acceptable salt of aztreonam is not arginine. 2. The method of claim 1 wherein the pharmaceutically acceptable salt is selected from the group consisting of acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, nicotinate, 2-napthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, p-toluenesulfonate and undecanoate, or the pharmaceutically acceptable salt is made using lysine. 3. The method of claim 2 wherein aztreonam or the salt thereof is dissolved in from about 1 to about 5 ml of the aerosolable solution comprising at least 0.09% of chloride or equivalent amount of bromine or iodine or bicarbonate. 4. The method of claim 2 wherein aztreonam is dissolved in a saline diluted to from about 0.1 to about 0.45% of sodium chloride to form an aerosolable solution. 5. The method of claim 4 wherein the aerosolable solution has a pH from about 5.5 to about 7. 6. The method of claim 1 wherein the inhalable aerosol comprising from about 1 to about 250 mg of purified aztreonam or a pharmaceutically acceptable salt thereof in a dry powder form dissolved in a saline solution per one dose is administered one to twelve times per day, provided that a total daily dose of aztreonam is not higher than 750 mg. 7. The method of claim 1 wherein one administration is at least 25 mg of aztreonam or a salt thereof. 8. A method of treating pulmonary infections in a human in need thereof comprising administering to the human a tobramycin aerosol in a treatment cycle of 28 days on the tobramycin aerosol and 28 days off the tobramcycin aerosol; the method comprising, during the 28 days the human is off the tobramcycin aerosol: a) preparing an inhalable aztreonam aerosol consisting of from about 1 to about 200 mg of purified aztreonam base, or a pharmaceutically acceptable salt selected from the group consisting of acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, nicotinate, 2-napthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, p-toluenesulfonate and undecanoate, or the pharmaceutically acceptable salt of azetreonam is made using lysine; said aztreonam or salt thereof being dissolved in from about 1 to about 5 ml of an aqueous solution having pH from 5.5 to 7.0; and b) delivering said inhalable aztreonam aerosol to the lung endobronchial space of airways of the human in need thereof by a jet nebulizer in an aerosol having particle sizes between 1 and 5 microns. 9. The method of claim 8 wherein said aztreonam salt is made using lysine and the aqueous solution is a normal or diluted saline comprising from 0.225% to 0.9% of sodium chloride. 10. The method of claim 9 wherein the inhalable aztreonam aerosol is delivered one to twelve times a day, provided that if said aerosol is delivered more than twice a day, a total dose of aztreonam is not higher than 500 mg a day. 11. The method of claim 10 wherein said aztreonam aerosol comprises from about 1 to about 100 mg of the aztreonam per one dosage. 12. The method of claim 11 wherein said aztreonam aerosol comprises from about 10 to about 50 mg of the aztreonam per dose. 13. The method of claim 12 wherein said aztreonam is delivered once, twice, three, or four times per day. 14. The method of claim 8 wherein a delivered dose of aztreonam or a pharmaceutically salt thereof into the lung endobronchial space of airways during one administration is at least 25 mg of aztreonam or the salt thereof.