# US 10,864,183 B2 · Injectable nitrogen mustard compositions comprising a cyclodextrin derivative and methods of making and using the same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,864,183 B2 - Document ID: US10864183B2 - Status: Granted - Kind: B2 - Application number: 16/728,840 - Filed: 2019-12-27 - Published: 2020-08-27 - Granted: 2020-12-15 - Earliest claimed: 2009-05-29 - Assignees: CyDex Pharmaceuticals, Inc. - Applicants: Cydex Pharmaceuticals, Inc. - Inventors: James D. Pipkin; Stephen G. Machatha - Web page: https://patentgrep.com/patent/US10864183B2 ## CPC - A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) - 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 9/19: 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 47/40: Cyclodextrins; Derivatives thereof - 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 The present disclosure is directed to pharmaceutical compositions comprising a nitrogen mustard and a cyclodextrin derivative, and methods of making and using the same. ## Claims ### Claim 1 An injectable aqueous pharmaceutical formulation comprising 8.5 mL of an aqueous solution at a pH of 5, said solution consisting of 9 g/L sodium chloride, a sulfobutyl ether-β-cyclodextrin, and 5 mg/mL melphalan, wherein said sulfobutyl ether-β-cyclodextrin and said melphalan are present in a weight ratio of 54:1; and wherein said aqueous pharmaceutical formulation is stable at room temperature for at least one hour, as compared to a cyclodextrin-free reference melphalan standard. ### Claim 2 (depends on 1) The aqueous formulation of claim 1, wherein less than 2% by weight of said melphalan is degraded after 5 hours at room temperature as compared to the amount of melphalan present before holding said formulation at room temperature for 5 hours. ### Claim 3 (depends on 1) The aqueous formulation of claim 1, wherein less than 4% by weight of said melphalan is degraded when said formulation is held at room temperature for 10 hours as compared to the amount of melphalan present before holding said formulation at room temperature for 10 hours. ### Claim 4 An injectable aqueous pharmaceutical formulation comprising 10 mL of an aqueous solution with a pH of 5, said formulation consisting of a sulfobutyl ether-β-cyclodextrin and 0.45 mg/mL melphalan; wherein said sulfobutyl ether-β-cyclodextrin and said melphalan are present in a weight ratio of at least 54:1; and wherein said aqueous pharmaceutical formulation is stable at room temperature for at least 4 hours, as compared to a cyclodextrin-free reference melphalan standard. ### Claim 5 (depends on 4) The aqueous formulation of claim 4, wherein less than 2% by weight of said melphalan is degraded when said formulation is held at room temperature for 5 hours as compared to the amount of melphalan present before holding said formulation at room temperature for 5 hours. ### Claim 6 (depends on 4) The aqueous formulation of claim 4, wherein less than 4% by weight of said melphalan is degraded when said formulation is held at room temperature for 10 hours as compared to the amount of melphalan present before holding said formulation at room temperature for 10 hours. ### Claim 7 An injectable aqueous pharmaceutical formulation comprising 8.5 mL of an aqueous solution at a pH of 5, said solution consisting of at least one of an antioxidant, preservative, or buffer, 9 g/L sodium chloride, a sulfobutyl ether-β-cyclodextrin, and 5 mg/mL melphalan, wherein said sulfobutyl ether-β-cyclodextrin and said melphalan are present in a weight ratio of 54:1; wherein said aqueous pharmaceutical formulation is stable at room temperature for at least one hour, as compared to a cyclodextrin-free reference melphalan standard. ### Claim 8 (depends on 1, 4, 7) The aqueous formulation of claim 1 or 4 or 7, wherein administration of the formulation provides up to a 30% increase in the area under the melphalan plasma concentration curve as compared to administration of a cyclodextrin-free melphalan formulation. ### Claim 9 An injectable aqueous pharmaceutical formulation consisting of 5 mg/mL melphalan, sulfobutyl ether-β-cyclodextrin and 9 g/L sodium chloride; wherein said sulfobutyl ether-β-cyclodextrin and said melphalan are present in a weight ratio of 54:1; wherein the aqueous pharmaceutical formulation has a pH of 5; wherein said aqueous pharmaceutical formulation is stable at room temperature for at least one hour, as compared to a cyclodextrin-free reference melphalan standard; and further wherein administering the formulation provides a melphalan AUC0-t in a subject that is at least 20% greater than a melphalan AUC0-t provided by a melphalan formulation containing an equivalent dose of melphalan and lacking the cyclodextrin derivative. ### Claim 10 An injectable aqueous pharmaceutical formulation consisting of 0.45 mg/mL melphalan, sulfobutyl ether-β-cyclodextrin and 9 g/L sodium chloride; wherein said sulfobutyl ether-β-cyclodextrin and said melphalan are present in a weight ratio of at least 54:1; wherein the aqueous pharmaceutical formulation has a pH of 5; wherein said aqueous pharmaceutical formulation is stable at room temperature for at least 4 hours, as compared to a cyclodextrin-free reference melphalan standard; and further wherein administering the formulation provides a melphalan AUC0-t in a subject that is at least 20% greater than a melphalan AUC0-t provided by a melphalan formulation containing an equivalent dose of melphalan and lacking the cyclodextrin derivative.