# US 2022/0031618 A1 · Irinotecan liposome preparation, and preparation and application thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2022/0031618 A1 - Document ID: US20220031618A1 - Status: Published application - Kind: A1 - Application number: 17/290,263 - Filed: 2019-10-11 - Published: 2022-02-03 - Earliest claimed: 2018-11-05 - Assignees: Highfield Biopharmaceutical Corporation - Applicants: HighField BioPharmaceutical Corporation - Inventors: Xiaohui WEI; Bingqi JIANG - Web page: https://patentgrep.com/patent/US20220031618A1 ## CPC - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61P 35/00: Antineoplastic agents - A61K 9/1277: Preparation processes; Proliposomes - A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) - A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids - 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 An irinotecan liposome preparation, a preparation method, and use thereof. The irinotecan liposome includes: irinotecan, a liposome carrier, an internal aqueous phase located inside a liposome membrane and an external aqueous phase located outside the liposome membrane, the irinotecan being encapsulated in the internal aqueous phase; a sulfonate gradient exists between the internal aqueous phases inside the liposome membrane and the external aqueous phase outside the liposome membrane. The liposome takes monovalent sulfonate and disulfonate as the internal aqueous phases, encapsulates the irinotecan in the internal aqueous phases of the liposome in the form of insoluble sulfonate or disulfonate, and has a good sustained-release effect. ## Claims ### Claim 1 An irinotecan liposome preparation, comprising an irinotecan liposome, wherein the irinotecan liposome comprises: irinotecan, a liposome carrier, an internal aqueous phase located inside a liposome membrane, and an external aqueous phase located outside the liposome membrane, the irinotecan being encapsulated in the internal aqueous phases; a sulfonate gradient exists between the internal aqueous phases inside the liposome membrane and the external aqueous phase outside the liposome membrane. ### Claim 2 (depends on 1) The irinotecan liposome preparation according to claim 1, wherein the internal aqueous phase comprises an aqueous sulfonate solution; and the external aqueous phase is a physiological isotonic solution. ### Claim 3 (depends on 2) The irinotecan liposome preparation according to claim 2, wherein an irinotecan cation and a sulfonate anion in the internal aqueous phase form an insoluble salt. ### Claim 4 (depends on 2) The irinotecan liposome preparation according to claim 2, wherein the sulfonate comprises monovalent sulfonate and/or disulfonate. ### Claim 5 (depends on 4) The irinotecan liposome preparation according to claim 4, characterized by comprising one or more of the followings: a. the monovalent sulfonate is one or more selected from the group consisting of ammonium methanesulfonate, ammonium 4-hydroxybenzenesulfonate, triethylamine methanesulfonate and triethylamine 4-hydroxybenzenesulfonate; b. the disulfonate is one or more selected from the group consisting of ammonium ethanedisulfonate, ammonium propanedisulfonate, triethylamine ethanedisulfonate, and triethylamine propanedisulfonate. ### Claim 6 (depends on 1) The irinotecan liposome preparation according to claim 1, characterized by comprising one or more of the followings: a. the internal aqueous phase of the liposome has a pH value of 4.0-9.0; b. in the irinotecan liposome preparation, the irinotecan has a concentration of greater than or equal to 0.1 mg/ml; c. in the irinotecan liposome preparation, the irinotecan has an encapsulation efficiency of greater than or equal to 85%. ### Claim 7 (depends on 1) A method for preparing the irinotecan liposome preparation according to claim 1, wherein the method is an active loading method comprising the following steps: (1) preparing a blank liposome, of which both an internal aqueous phase and an external aqueous phase comprise an aqueous sulfonate solution; (2) preparing a blank liposome, of which the internal aqueous phase comprises an aqueous sulfonate solution and the external aqueous phase comprises a physiological isotonic solution, to form a sulfonate concentration gradient between the internal and the external aqueous phases of the blank liposome; and (3) mixing the blank liposome obtained in Step (2) with an aqueous solution of an irinotecan soluble salt, incubating the mixture, and removing the free soluble irinotecan salt to obtain the irinotecan liposome. ### Claim 8 (depends on 7) The method for preparing the irinotecan liposome preparation according to claim 7, further comprising one or more of the followings: a. in Step (1) and Step (2), the aqueous sulfonate solution has a sulfonate concentration of 100 mM to 800 mM; b. in Step (1) and Step (2), the aqueous sulfonate solution has a pH value of 4.0-9.0; c. in Step (1) and Step (2), the aqueous sulfonate solution has a sulfonate ion concentration of 50 mM to 800 mM; d. in Step (1) and Step (2), the aqueous sulfonate solution has a cation concentration of 50 mM to 800 mM; e. in Step (2), the physiological isotonic solution is 5% (w/v) aqueous glucose solution, 10% (w/v) aqueous sucrose solution or 0.9% (w/v) aqueous sodium chloride solution; f. in Step (2), the external aqueous phase has a pH value of 4.0-9.0; g. in Step (3), a drug-liposome molar ratio is greater than or equal to 0.1; h. in Step (3), the irinotecan soluble salt is irinotecan hydrochloride. ### Claim 9 (depends on 7) An irinotecan liposome preparation prepared by the method according to claim 7. ### Claim 10 (depends on 1) The use of the irinotecan liposome preparation according to claim 1 in preparation of a drug for treating colorectal cancer, lung cancer, breast cancer, or pancreatic cancer. ### Claim 11 (depends on 2) A method for preparing the irinotecan liposome preparation according to claim 2, wherein the method is an active loading method comprising the following steps: (1) preparing a blank liposome, of which both an internal aqueous phase and an external aqueous phase comprise an aqueous sulfonate solution; (2) preparing a blank liposome, of which the internal aqueous phase comprises an aqueous sulfonate solution and the external aqueous phase comprises a physiological isotonic solution, to form a sulfonate concentration gradient between the internal and the external aqueous phases of the blank liposome; and (3) mixing the blank liposome obtained in Step (2) with an aqueous solution of an irinotecan soluble salt, incubating the mixture, and removing the free soluble irinotecan salt to obtain the irinotecan liposome. ### Claim 12 (depends on 3) A method for preparing the irinotecan liposome preparation according to claim 3, wherein the method is an active loading method comprising the following steps: (1) preparing a blank liposome, of which both an internal aqueous phase and an external aqueous phase comprise an aqueous sulfonate solution; (2) preparing a blank liposome, of which the internal aqueous phase comprises an aqueous sulfonate solution and the external aqueous phase comprises a physiological isotonic solution, to form a sulfonate concentration gradient between the internal and the external aqueous phases of the blank liposome; and (3) mixing the blank liposome obtained in Step (2) with an aqueous solution of an irinotecan soluble salt, incubating the mixture, and removing the free soluble irinotecan salt to obtain the irinotecan liposome. ### Claim 13 (depends on 4) A method for preparing the irinotecan liposome preparation according to claim 4, wherein the method is an active loading method comprising the following steps: (1) preparing a blank liposome, of which both an internal aqueous phase and an external aqueous phase comprise an aqueous sulfonate solution; (2) preparing a blank liposome, of which the internal aqueous phase comprises an aqueous sulfonate solution and the external aqueous phase comprises a physiological isotonic solution, to form a sulfonate concentration gradient between the internal and the external aqueous phases of the blank liposome; and (3) mixing the blank liposome obtained in Step (2) with an aqueous solution of an irinotecan soluble salt, incubating the mixture, and removing the free soluble irinotecan salt to obtain the irinotecan liposome. ### Claim 14 (depends on 5) A method for preparing the irinotecan liposome preparation according to claim 5, wherein the method is an active loading method comprising the following steps: (1) preparing a blank liposome, of which both an internal aqueous phase and an external aqueous phase comprise an aqueous sulfonate solution; (2) preparing a blank liposome, of which the internal aqueous phase comprises an aqueous sulfonate solution and the external aqueous phase comprises a physiological isotonic solution, to form a sulfonate concentration gradient between the internal and the external aqueous phases of the blank liposome; and (3) mixing the blank liposome obtained in Step (2) with an aqueous solution of an irinotecan soluble salt, incubating the mixture, and removing the free soluble irinotecan salt to obtain the irinotecan liposome. ### Claim 15 (depends on 6) A method for preparing the irinotecan liposome preparation according to claim 6, wherein the method is an active loading method comprising the following steps: (1) preparing a blank liposome, of which both an internal aqueous phase and an external aqueous phase comprise an aqueous sulfonate solution; (2) preparing a blank liposome, of which the internal aqueous phase comprises an aqueous sulfonate solution and the external aqueous phase comprises a physiological isotonic solution, to form a sulfonate concentration gradient between the internal and the external aqueous phases of the blank liposome; and (3) mixing the blank liposome obtained in Step (2) with an aqueous solution of an irinotecan soluble salt, incubating the mixture, and removing the free soluble irinotecan salt to obtain the irinotecan liposome. ### Claim 16 (depends on 8) An irinotecan liposome preparation prepared by the method according to claim 8. ### Claim 17 (depends on 2) The use of the irinotecan liposome preparation according to claim 2 in preparation of a drug for treating colorectal cancer, lung cancer, breast cancer, or pancreatic cancer. ### Claim 18 (depends on 3) The use of the irinotecan liposome preparation according to claim 3 in preparation of a drug for treating colorectal cancer, lung cancer, breast cancer, or pancreatic cancer. ### Claim 19 (depends on 4) The use of the irinotecan liposome preparation according to claim 4 in preparation of a drug for treating colorectal cancer, lung cancer, breast cancer, or pancreatic cancer. ### Claim 20 (depends on 5) The use of the irinotecan liposome preparation according to claim 5 in preparation of a drug for treating colorectal cancer, lung cancer, breast cancer, or pancreatic cancer.