# US 10,869,928 B2 · Lyophilized preparation of cytotoxic dipeptides > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,869,928 B2 - Document ID: US10869928B2 - Status: Granted - Kind: B2 - Application number: 16/721,639 - Filed: 2019-12-19 - Published: 2020-04-23 - Granted: 2020-12-22 - Earliest claimed: 2011-04-28 - Assignees: Oncopeptides AB - Applicants: Oncopeptides AB - Inventors: Jack Spira; Fredrik Lehmann - Web page: https://patentgrep.com/patent/US10869928B2 ## CPC - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61K 31/195: having an amino group - A61K 31/222: with compounds having aromatic groups, e.g. dipivefrine, ibopamine - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 38/05: Dipeptides - A61K 38/105: {Bombesin; Related peptides} - A61K 47/02: Inorganic compounds - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61K 47/40: Cyclodextrins; Derivatives thereof - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - F26B 5/06: the process involving freezing - 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 - F26B: DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM (drying devices for combines A01D41/133; racks for drying fruit or vegetables A01F25/12; drying foodstuffs A23; drying hair A45D20/00; body-drying implements A47K10/00; drying household articles A47L; drying gases or vapours B01D; chemical or physical processes for dewatering or like separating liquids from solids B01D43/00; centrifugal apparatus B04; drying ceramics C04B33/30; drying yarns or fabrics in association with some other form of treatment D06C; drying frames for laundry without heating or positive air circulation, domestic laundry-or spin-driers, wringing or hot pressing laundry D06F; furnaces, kilns, ovens F27) ## Abstract The present invention is directed to novel lyophilized pharmaceutical preparations comprising a cytotoxic dipeptides such as melphalan flufenamide and one or more excipient(s) selected from the group comprising a polysorbate; a polyethylene glycol; β-cyclodextrin; ocyclodextrin; hydroxypropyl-β-cyclodextrin; sulfobutylether-β-cyclodextrin; lactose; benzyl alcohol; disodium succinate; propylene glycol; Cremophor EL; Dimethyl sulfoxide; D-mannitol; Trehalose; Sucrose and an amino acid. This preparation may be further formulated and is useful in cancer therapy. ## Claims ### Claim 1 A lyophilized pharmaceutical preparation which is directly soluble in a physiologically acceptable aqueous solution, comprising melphalan flufenamide, or a pharmaceutically acceptable salt thereof, and sucrose. ### Claim 2 (depends on 1) The lyophilized pharmaceutical preparation according to claim 1, wherein the amount of sucrose is 10-100% by weight of the melphalan flufenamide or pharmaceutically acceptable salt thereof. ### Claim 3 (depends on 1) The lyophilized pharmaceutical preparation according to claim 1, which is free, or substantially free from organic solvents. ### Claim 4 (depends on 2) The lyophilized pharmaceutical preparation according to claim 2, which is free, or substantially free from organic solvents. ### Claim 5 (depends on 1) A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 1 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution. ### Claim 6 (depends on 2) A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 2 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution. ### Claim 7 (depends on 3) A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 3 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution. ### Claim 8 (depends on 4) A pharmaceutical composition consisting of the lyophilized pharmaceutical preparation of claim 4 and a physiologically acceptable solution, wherein said physiologically acceptable solution is a glucose solution. ### Claim 9 (depends on 1) The lyophilized pharmaceutical preparation according to claim 1, in which sucrose is the sole excipient. ### Claim 10 (depends on 9) The lyophilized pharmaceutical preparation according to claim 9, which contains trace amounts of an organic solvent. ### Claim 11 (depends on 1) The lyophilized pharmaceutical preparation according to claim 1, which consists essentially of melphalan flufenamide, or a pharmaceutically acceptable salt thereof, and sucrose. ### Claim 12 (depends on 11) The lyophilized pharmaceutical preparation according to claim 11, which contains trace amounts of an organic solvent. ### Claim 13 (depends on 9) The lyophilized pharmaceutical preparation according to claim 9, which consists essentially of melphalan flufenamide, or a pharmaceutically acceptable salt thereof, and sucrose. ### Claim 14 (depends on 13) The lyophilized pharmaceutical preparation according to claim 13, which contains trace amounts of an organic solvent. ### Claim 15 (depends on 1, 2, 3, 4) The lyophilized pharmaceutical preparation according to any one of claims 1 to 4, which is obtained by lyophilizing a solution comprising melphalan flufenamide, or a pharmaceutically acceptable salt thereof, sucrose, an organic solvent and water. ### Claim 16 (depends on 9, 10, 11, 12, 13, 14) The lyophilized pharmaceutical preparation according to any one of claims 9 to 14, which is obtained by lyophilizing a solution of melphalan flufenamide, or a pharmaceutically acceptable salt thereof, sucrose, an organic solvent and water.