# US 8,541,465 B2 · Docetaxel formulations with lipoic acid and/or dihydrolipoic acid > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,541,465 B2 - Document ID: US8541465B2 - Status: Granted - Kind: B2 - Application number: 12/589,145 - Filed: 2009-10-19 - Published: 2011-04-21 - Granted: 2013-09-24 - Earliest claimed: 2009-10-19 - Assignees: Scidose LLC - Applicants: Nageswara R. Palepu - Inventors: Nageswara R. Palepu - Web page: https://patentgrep.com/patent/US8541465B2 ## CPC - A61K 31/337: having four-membered rings, e.g. taxol - 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 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones - 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) ## Abstract Formulations comprising docetaxel or a salt thereof in combination with α-lipoic acid and/or dihydrolipoic acid and/or salts thereof in narrow concentration ranges have improved stability as concentrate liquid formulations and permit longer times between dilution from higher concentrations through completion of infusions prepared therefrom allowing for lesser waste and more efficient use of personnel in infusion preparation. ## Claims ### Claim 1 A solid docetaxel formulation comprising a first component comprising docetaxel or a pharmaceutically acceptable salt thereof and a second component comprising a member selected from the group consisting of α-lipoic acid or a pharmaceutically acceptable salt thereof, dihydrolipoic acid or a pharmaceutically acceptable salt thereof, and mixtures thereof, where the second component is present and in an amount of greater than 0.025 to less than 2.5 parts by weight based on α-lipoic acid or dihydrolipoic acid respectively per 1 part of said first component based on free docetaxel. ### Claim 2 (depends on 1) The formulation of claim 1 wherein said second component is present in an amount of more than 0.025 parts by weight to not more than 0.2 parts by weight based on said α-lipoic acid or dihydrolipoic acid respectively per 1 part by weight of said first component based on free docetaxel. ### Claim 3 (depends on 1) The formulation of claim 1 wherein said second component is present in an amount of more than 0.03125 parts by weight to not more than 0.1875 parts by weight based on said α-lipoic acid or dihydrolipoic acid respectively per 1 part by weight of said first component based on free docetaxel. ### Claim 4 (depends on 1) The formulation of claim 1 wherein said second component is present in an amount of more than 0.0375 parts by weight to not more than 0.1275 parts by weight based on said α-lipoic acid or dihydrolipoic acid respectively per 1 part by weight of said first component based on free docetaxel. ### Claim 5 (depends on 1) The formulation of claim 1 wherein said second component is present in an amount of more than 0.05 parts by weight to not more than 0.09375 parts by weight based on said α-lipoic acid or dihydrolipoic acid respectively per 1 part by weight of said first component based on free docetaxel. ### Claim 6 (depends on 1) The formulation of claim 1 wherein said second component is present in an amount of about 0.0625 parts by weight based on said α-lipoic acid or dihydrolipoic acid respectively per 1 part by weight of said first component based on free docetaxel. ### Claim 7 (depends on 1) The formulation of claim 1 wherein said member is α-lipoic acid or a pharmaceutically acceptable salt thereof. ### Claim 8 (depends on 7) The formulation of claim 7 wherein said member is selected from the group consisting of α-lipoic acid, the sodium salt thereof, and the potassium salt thereof, and mixtures thereof. ### Claim 9 (depends on 1) The formulation of claim 1 wherein said member is dihydrolipoic acid or a pharmaceutically acceptable salt thereof. ### Claim 10 (depends on 1) The formulation of claim 1 wherein said member is selected from the group consisting of dihydrolipoic acid, the sodium salt thereof, and the potassium salt thereof, and mixtures thereof. ### Claim 11 A liquid solution docetaxel formulation comprising a first component comprising docetaxel or a pharmaceutically acceptable salt thereof in an amount less than 15 mg (based on free docetaxel)/ml of said solution; a second component comprising a member selected from the group consisting of α-lipoic acid or a pharmaceutically acceptable salt thereof, dihydrolipoic acid or a pharmaceutically acceptable salt thereof, and mixtures thereof, and in an amount of greater than 0.025 to less than 2.5 parts by weight based on α-lipoic acid or dihydrolipoic acid respectively per part of said first component based on free docetaxel; and a solvent capable of dissolving said docetaxel at a concentration of at least up to 15 mg/ml of solution. ### Claim 12 (depends on 11) The formulation of claim 11 comprising (a) Docetaxel 10-<15 mg or salt thereof (b) Glycofurol 1 ml (c) dihydroLipoic acid >0.025-<2.5 mg (based on or salt thereof dihydrolipoic acid moiety) per mg of docetaxel moiety (d) TPGS 750-2000 mg (e) PEG-400 2.0-3.0 ml (f) NaCl 0-100 mg (g) Water qs to 8 ml. ### Claim 13 A liquid solution docetaxel formulation comprising a first component comprising docetaxel or a pharmaceutically acceptable salt thereof in an amount in excess of 10 mg/ml of said solution; a second component comprising a member selected from the group consisting of α-lipoic acid or a pharmaceutically acceptable salt thereof, dihydrolipoic acid or a pharmaceutically acceptable salt thereof, and mixtures thereof, and in an amount of greater than 0.025 to less than 2.5 parts by weight based on α-lipoic acid or dihydrolipoic acid respectively per part of said first component based on free docetaxel; and a solvent for said docetaxel capable of dissolving said docetaxel in an amount in excess of 10 mg/ml of solution. ### Claim 14 (depends on 11) The formulation of claim 11 comprising (a) Docetaxel 10-<15 mg or salt there of (b) Glycofurol 1 ml (c) α-Lipoic acid >0.025-<2.5 mg (based on lipoic acid moiety) or salt thereof per mg of docetaxel moiety (d) TPGS 750-2000 mg (e) PEG-400 2.0-3.0 ml (f) NaCl 0-100 mg (g) Water qs to 8 ml. ### Claim 15 An infusion solution comprising a first component comprising docetaxel or a pharmaceutically acceptable salt thereof in an infusion suitable concentration; a second component comprising a member selected from the group consisting of α-lipoic acid or a pharmaceutically acceptable salt thereof, dihydrolipoic acid or a pharmaceutically acceptable salt thereof, and mixtures thereof, a solvent for said first component; said solvent capable of dissolving said first component; and an infusion liquid diluent in an amount such that said first component is present in an infusion acceptable concentration and said second component is present in an amount of from more than 0.025 parts to less than 2.5 parts by weight of α-lipoic acid (or a pharmaceutically acceptable salt thereof based upon free α-lipoic acid) or dihydrolipoic acid (or a pharmaceutically acceptable salt thereof based upon free dihydrolipoic acid) per part by weight of said first component based on free docetaxel. ### Claim 16 A method of preparing an infusion solution containing docetaxel or a pharmaceutically acceptable salt thereof, said infusion solution comprising (a) docetaxel or a pharmaceutically acceptable salt thereof, (b) a member selected from the group consisting of α-lipoic acid or a pharmaceutically acceptable salt thereof, dihydrolipoic acid or a pharmaceutically acceptable salt thereof, and mixtures thereof; and (c) an infusion suitable infusion fluid; comprising firstly combining said member with at least one of (a) a solid formulation of docetaxel or pharmaceutically acceptable salt thereof; (b) a liquid solution of docetaxel or a pharmaceutically acceptable salt thereof; to result in a combination product and further secondly combining said combination product with said infusion fluid; said firstly combining being in an amount for said first member to be present in at least said infusion solution in an amount of from more than 0.025 parts to less than 2.5 parts by weight based on free α-lipoic acid or free dihydrolipoic acid respectively per 1 part by weight of said docetaxel or pharmaceutically acceptable salt thereof based on free docetaxel. ### Claim 17 A method of preparing a concentrate solution containing docetaxel or a pharmaceutically acceptable salt thereof, said concentrate solution comprising (a) docetaxel or a pharmaceutically acceptable salt thereof, (b) a member selected from the group consisting of α-lipoic acid or a pharmaceutically acceptable salt thereof, dihydrolipoic acid or a pharmaceutically acceptable salt thereof, and mixtures thereof, and (c) a solvent for said docetaxel or pharmaceutically acceptable salt thereof comprising combining said member with at least one of (a) a solid formulation of docetaxel or pharmaceutically acceptable salt thereof; and (b) a liquid solution of docetaxel or a pharmaceutically acceptable salt thereof; in an amount for said member to be present in at least said concentrate solution in an amount of from more than 0.025 parts to less than 2.5 parts by weight based on free α-lipoic acid or free dihydrolipoic acid respectively per 1 part by weight of said docetaxel or pharmaceutically acceptable salt thereof based on free docetaxel. ### Claim 18 A method of treating a docetaxel responsive condition in a patient in need thereof via an infusion comprising administering to said patient a pharmaceutically effective amount for said docetaxel responsive condition of an infusion containing docetaxel or a pharmaceutically acceptable salt thereof and a member selected from the group consisting of α-lipoic acid or a pharmaceutically acceptable salt thereof, dihydrolipoic acid or a pharmaceutically acceptable salt thereof, and mixtures thereof, in an amount of from more than 0.025 parts to less than 2.5 parts by weight based on free α-lipoic acid or free dihydrolipoic acid respectively per 1 part by weight of said docetaxel or pharmaceutically acceptable salt thereof based on free docetaxel. ### Claim 19 A method of extending the stability of a liquid concentrate formulation containing docetaxel or a pharmaceutically acceptable salt thereof comprising incorporating into said concentrate formulation a member selected from the group consisting of α-lipoic acid or a pharmaceutically acceptable salt thereof, dihydrolipoic acid or a pharmaceutically acceptable salt thereof, and mixtures thereof, in an amount of from more than 0.025 parts to less than 2.5 parts by weight based on free α-lipoic acid or free dihydrolipoic acid respectively per 1 part by weight of said docetaxel or pharmaceutically acceptable salt thereof based on free docetaxel. ### Claim 20 A method of extending the time period in which a docetaxel liquid formulation is to be used, measured between (a) dilution of a more highly concentrated formulation to concentrations of less than 15 mg docetaxel/ml of solution until (b) completion of administration of an infusion made therefrom; said extending being measured between (a) a period of not more than 4 hours to (b) a period greater than 4 hours; comprising including a member selected from the group consisting of α-lipoic acid or a pharmaceutically acceptable salt thereof, dihydrolipoic acid or a pharmaceutically acceptable salt thereof, and mixtures thereof, in an amount of from more than 0.025 parts to less than 2.5 parts by weight based on free α-lipoic acid or free dihydrolipoic acid respectively per 1 part by weight of said docetaxel or pharmaceutically acceptable salt thereof based on free docetaxel into said formulation and inclusion of said member is at least one of (a) a point in time when said more highly concentrated formulation is diluted to concentrations of less than about 15 mg/ml of docetaxel or pharmaceutically acceptable salt thereof based on free docetaxel, or (b) inclusion in said more highly concentrated formulation prior to said dilution, or (c) inclusion as a blend with said solid docetaxel or pharmaceutically acceptable salt thereof.