# US 10,307,418 B2 · Azole pharmaceutical formulations for parenteral administration and methods for preparing and using the same as treatment of diseases sensitive to azole compounds > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,307,418 B2 - Document ID: US10307418B2 - Status: Granted - Kind: B2 - Application number: 13/994,152 - Filed: 2011-12-16 - Published: 2014-01-30 - Granted: 2019-06-04 - Earliest claimed: 2010-12-16 - Assignees: Platform Brightworks Two, Ltd. - Applicants: Borje S. Andersson; Jeffrey Tarrand; Benigno C. Valdez - Inventors: Borje S. Andersson; Jeffrey Tarrand; Benigno C. Valdez - Web page: https://patentgrep.com/patent/US10307418B2 ## CPC - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61P 31/04: Antibacterial agents - A61P 31/10: Antimycotics - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A parenteral azole composition comprises a first solvent, made of benzyl alcohol and/or an acidified alcohol such as ethanol, and a lipophilic component such as PEG400, and the azole, or triazole, such as itraconazole or posaconazole dissolved in this first composite solvent vehicle that is essentially free of surfactants, particularly non-ionic surfactants, and has low levels of water, preferably less than 5% water. The composition may be further diluted with an infusion fluid, such as normal saline or 5% or 10% dextrose in water, before infusion into an immunocompromized mammal, preferably a human. The composition is useful for the treatment and suppression of infections caused by microbes such as yeast and molds that are sensitive to azoles, but it may be extended to dissolve other pharmaceutically active agents that can be used to treat other types of infectious diseases or other ailments, such as malignant and autoimmune diseases. ## Claims ### Claim 1 A clinically acceptable infusion fluid comprising a composition diluted with an infusion fluid selected from the group consisting of normal saline, dextrose in water, and a lipid-based infusion emulsion fluid, wherein the composition is a pharmaceutical composition suitable for parenteral administration comprising an azole antifungal pharmaceutical agent and a first solvent, said first solvent comprising a) an alcohol component selected from benzyl alcohol and/or acidified ethanol, and b) a polyethylene glycol solvent (PEG), wherein the azole agent is dissolved in said first solvent, wherein the composition is essentially free of non-ionic surfactants and particulates and comprises less than 5% water (v/v). ### Claim 2 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein said infusion fluid is dextrose in water. ### Claim 3 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein said fluid comprises between 1 mg/ml and 5 mg/ml of the azole agent after dilution in said infusion fluid. ### Claim 4 (depends on 1) The clinically acceptable infusion fluid of claim 1 wherein said azole pharmaceutical agent is stable for at least 12 hours at room temperature. ### Claim 5 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein the composition is further defined as comprising less than 3% water (v/v). ### Claim 6 (depends on 5) The clinically acceptable infusion fluid of claim 5, wherein the composition is further defined as comprising less than 1% water (v/v). ### Claim 7 (depends on 6) The clinically acceptable infusion fluid of claim 6, wherein the composition is further defined as essentially free of water. ### Claim 8 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein said first solvent of the composition comprises both acidified ethanol and benzyl alcohol. ### Claim 9 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein the first solvent of the composition comprises acidified ethanol. ### Claim 10 (depends on 9) The clinically acceptable infusion fluid of claim 9, wherein the acidified ethanol of the composition is further defined as a combination of ethanol and an acid, and the first solvent has a pH of from about 1 to about 5. ### Claim 11 (depends on 10) The clinically acceptable infusion fluid of claim 10, wherein the first solvent of the composition has a pH of from about 3 to about 4. ### Claim 12 (depends on 10) The clinically acceptable infusion fluid of claim 10, wherein the acid of the composition is HCl, citric acid, acetic acid or glutamic acid. ### Claim 13 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein the ratio of PEG to alcohol in the composition is from 27 to 2 (v/v). ### Claim 14 (depends on 13) The clinically acceptable infusion fluid of claim 13, wherein the ratio of PEG to alcohol in the composition is from 12 to 8 (v/v). ### Claim 15 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein said PEG of the composition is selected from the group consisting of PEG-100, PEG-200, PEG-300, PEG-400 and PEG-800. ### Claim 16 (depends on 15) The clinically acceptable infusion fluid of claim 15, wherein the polyethylene glycol of the composition is PEG-400. ### Claim 17 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein the first solvent of the composition comprises from 10% to 90% (v/v) PEG. ### Claim 18 (depends on 17) The clinically acceptable infusion fluid of claim 17, wherein the first solvent of the composition comprises from 30% to 90% (v/v) PEG. ### Claim 19 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein the first solvent of the composition comprises from 40% to 80% (v/v) PEG. ### Claim 20 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein the alcohol component of the composition is from 1% to 99% of the first solvent (v/v). ### Claim 21 (depends on 20) The clinically acceptable infusion fluid of claim 20, wherein the alcohol component of the composition is from 5% to 60% of the first solvent (v/v). ### Claim 22 (depends on 21) The clinically acceptable infusion fluid of claim 21, wherein the alcohol component of the composition is from 10% to 40% of the first solvent (v/v). ### Claim 23 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein the azole pharmaceutical agent of the composition is an imidazole, triazole or thiazole. ### Claim 24 (depends on 23) The clinically acceptable infusion fluid of claim 23, wherein the azole pharmaceutical agent of the composition is miconazole, ketoconazole, clotrimazole, econazole, omoconazole, bifonazole, butoconazole, fenticonazole, isoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, fluconazole, itraconazole, isavuconazole, ravuconazole, posaconazole, voriconazole, terconazole or abafungin. ### Claim 25 (depends on 24) The clinically acceptable infusion fluid of claim 24, wherein the azole agent of the composition is itraconazole. ### Claim 26 (depends on 24) The clinically acceptable infusion fluid of claim 24, wherein the azole agent of the composition is posconazole. ### Claim 27 (depends on 1) The clinically acceptable infusion fluid of claim 1, wherein said composition comprises between 3 mg/ml to 25 mg/ml of the azole pharmaceutical agent.