# US 10,117,951 B2 · Sulfoalkyl ether cyclodextrin compositions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,117,951 B2 - Document ID: US10117951B2 - Status: Granted - Kind: B2 - Application number: 14/954,772 - Filed: 2015-11-30 - Published: 2016-06-09 - Granted: 2018-11-06 - Earliest claimed: 2008-04-28 - Assignees: CyDex Pharmaceuticals, Inc. - Applicants: CyDex Pharmaceuticals, Inc. - Inventors: Vincent D. Antle - Web page: https://patentgrep.com/patent/US10117951B2 ## CPC - A61K 47/40: Cyclodextrins; Derivatives thereof - A61K 9/08: Solutions {(composition of solutions A61K47/00)} - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) - A61K 31/724: Cyclodextrins - A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof - A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)} - C08B 31/00: Preparation of derivatives of starch (derivatives of amylose C08B33/00; derivatives of amylopectin C08B35/00) - C08B 37/0012: {Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof} - C08L 5/16: Cyclodextrin; Derivatives thereof - A61K 9/205: {Polysaccharides, e.g. alginate, gums; Cyclodextrin} - 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) - C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21) - C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06) ## Abstract SAE-CD compositions are provided, along with methods of making and using the same. The SAE-CD compositions comprise a sulfoalkyl ether cyclodextrin having an absorption of less than 0.5 A.U. due to a drug-degrading agent, as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ## Claims ### Claim 1 A sulfoalkyl ether cyclodextrin (SAE-CD) composition comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5, wherein the SAE-CD composition does not contain phosphate in an amount of 200 ppm or more and does not contain underivatized cyclodextrin in an amount of 0.5% wt. or more, and wherein the SAE-CD composition has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length, wherein the amounts of the phosphate and the underivatized cyclodextrin are with respect to the SAE-CD composition. ### Claim 2 (depends on 1) The SAE-CD composition of claim 1, wherein the SAE-CD composition does not comprise 0.2% wt. or more of an underivatized cyclodextrin. ### Claim 3 (depends on 2) The SAE-CD composition of claim 2, wherein the SAE-CD composition does not comprise 0.1% wt. or more of an underivatized cyclodextrin. ### Claim 4 (depends on 1) The SAE-CD composition of claim 1, wherein the SAE-CD is sulfobutyl ether β-cyclodextrin (SBE-β-CD) having an average degree of substitution of 6 to 7.1. ### Claim 5 (depends on 1) The SAE-CD composition of claim 1, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL, of solution in a cell having a 1 cm path length. ### Claim 6 (depends on 4) The SAE-CD composition of claim 4, wherein the SAE-CD has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 7 (depends on 6) The SAE-CD composition of claim 6, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 8 A sulfoalkyl ether cyclodextrin (SAE-CD) composition comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5, wherein the SAE-CD composition does not contain phosphate in an amount of 200 ppm or more and does not contain sulfoalkylating agent in an amount of 20 ppm or more, and wherein the SAE-CD composition has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length, wherein the amounts of the phosphate and the sulfoalkylating agent are with respect to the SAE-CD composition. ### Claim 9 (depends on 8) The SAE-CD composition of claim 8, wherein the SAE-CD composition does not comprise 10 ppm or more of a sulfoalkylating agent. ### Claim 10 (depends on 8) The SAE-CD composition of claim 8, wherein the SAE-CD composition does not comprise 2 ppm or more of a sulfoallcylating agent. ### Claim 11 (depends on 8) The SAE-CD composition of claim 8, wherein the SAE-CD composition does not comprise 250 ppb or more of a sulfoalkylating agent. ### Claim 12 (depends on 8) The SAE-CD composition of claim 8, wherein the sulfoalkylating agent is 1,4-butane sultone. ### Claim 13 (depends on 8) The SAE-CD composition of claim 8, wherein the SAE-CD is sulfobutyl ether β-cyclodextrin (SBE-β-CD) having an average degree of substitution of 6 to 7.1. ### Claim 14 (depends on 8) The SAE-CD composition of claim 8, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 15 (depends on 13) The SAE-CD composition of claim 13, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 16 (depends on 15) The SAE-CD composition of claim 15, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 17 A sulfoalkyl ether cyclodextrin (SAE-CD) composition comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5, wherein the SAE-CD composition does not contain sulfoalkylating agent in an amount of 0.25% wt. or more, and does not contain phosphate in an amount of 200 ppm or more, and wherein the SAE-CD composition has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length, wherein the amount of the hydrolyzed sulfoalkylating agent with respect to the SAE-CD composition. ### Claim 18 (depends on 17) The SAE-CD composition of claim 17, wherein the SAE-CD composition does not comprise 0.1% wt. or more of a hydrolyzed sulfoalkylating agent. ### Claim 19 (depends on 17) The SAE-CD composition of claim 17, wherein the SAE-CD composition does not comprise 0.08% wt. or more of a hydrolyzed sulfoalkylating agent. ### Claim 20 (depends on 17) The SAE-CD composition of claim 17, wherein the hydrolyzed sulfoalkylating agent is 4-hydroxybutane-1-sulfonic acid or disodium bis(4-sulfobutyl)ether. ### Claim 21 (depends on 17) The SAE-CD composition of claim 17, wherein the SAE-CD is sulfobutyl ether β-cyclodextrin (SBE-β-CD) having an average degree of substitution of 6 to 7.1. ### Claim 22 (depends on 17) The SAE-CD composition of claim 17, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 23 (depends on 21) The SAE-CD composition of claim 21, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 24 (depends on 23) The SAE-CD composition of claim 23, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 25 A sulfoalkyl ether cyclodextrin (SAE-CD) composition comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5, wherein the SAE-CD composition does not contain 200 ppm or more of a phosphate, and does not contain an alkali metal halide salt in an amount of 1% wt. or more, and wherein the SAE-CD composition has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length, wherein the amounts of the phosphate and the alkali metal halide salt are with respect to the SAE-CD composition. ### Claim 26 (depends on 25) The SAE-CD composition of claim 25, wherein the SAE-CD composition does not comprise 0.5% wt. or more of an alkali metal halide salt. ### Claim 27 (depends on 25) The SAE-CD composition of claim 25, wherein the SAE-CD composition does not comprise 0.2% wt. or more of an alkali metal halide salt. ### Claim 28 (depends on 25) The SAE-CD composition of claim 25, wherein the SAE-CD composition does not comprise 0.05% wt. or more of an alkali metal halide salt. ### Claim 29 (depends on 25) The SAE-CD composition of claim 25, wherein the alkali metal halide salt is sodium chloride. ### Claim 30 (depends on 25) The SAE-CD composition of claim 25, wherein the SAE-CD is sulfobutyl ether β-cyclodextrin (SBE-β-CD) having an average degree of substitution of 6 to 7.1. ### Claim 31 (depends on 25) The SAE-CD composition of claim 25, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 32 (depends on 30) The SAE-CD composition of claim 30, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 33 (depends on 32) The SAE-CD composition of claim 32, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 34 A sulfoalkyl ether cyclodextrin (SAE-CD) composition comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5 wherein the SAE-CD composition does not contain: 20 ppm or more of a sulfoalkylating agent; 0.5% wt. or more of an underivatized cyclodextrin; 1% wt. or more of an alkali metal halide salt; 200 ppm or more of a phosphate; or 0.25% wt. or more of a hydrolyzed alkylating agent; wherein the SAE-CD composition has an absorption of less than 0.5 AU as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length; wherein the amounts of the sulfoalkylating agent, the underivatized cyclodextrin, the alkali metal halide salt, the phosphate, and the hydrolyzed alkylating agent are with respect to the SAE-CD composition. ### Claim 35 (depends on 34) The SAE-CD composition of claim 34, wherein the SAE-CD composition does not contain: 10 ppm or more of a sulfoalkylating agent; 0.2% wt. or more of an underivatized cyclodextrin; less than 0.5% wt. or more of an alkali metal halide salt; and 0.1% wt. or more of a hydrolyzed alkylating agent. ### Claim 36 (depends on 34) The SAE-CD composition of claim 34, wherein the SAE-CD composition does not contain: 2 ppm or more of a sulfoalkylating agent; 0.1% wt. or more of an underivatized cyclodextrin; less than 0.2% wt. or more of an alkali metal halide salt; and 0.08% wt. or more of a hydrolyzed alkylating agent. ### Claim 37 (depends on 34) The SAE-CD composition of claim 34, wherein the SAE-CD composition does not contain: 250 ppb or more of a sulfoalkylating agent; 0.1% wt. or more of an underivatized cyclodextrin; 0.05% wt. or more of an alkali metal halide salt; and 0.08% wt. or more of a hydrolyzed alkylating agent. ### Claim 38 (depends on 34) The SAE-CD composition of claim 34, wherein the sulfoalkylating agent is 1,4-butane sultone. ### Claim 39 (depends on 34) The SAE-CD composition of claim 34, wherein the underivatized cyclodextrin is β-cyclodextrin. ### Claim 40 (depends on 34) The SAE-CD composition of claim 34, wherein the alkali metal halide salt is sodium chloride. ### Claim 41 (depends on 34) The SAE-CD composition of claim 34, wherein the hydrolyzed alkylating agent is 4-hydroxybutane-1-sulfonic acid or disodium bis(4-sulfobutyl)ether. ### Claim 42 (depends on 34) The SAE-CD composition of claim 34, wherein the sulfoalykylating agent is 1,4-butane sultone; the underivatized cyclodextrin is β-cyclodextrin; the alkali metal halide salt is sodium chloride; and the hydrolyzed alkylating agent is 4-hydroxybutane-1-sulfonic acid or disodium bis(4-sulfobutyl)ether. ### Claim 43 (depends on 42) The SAE-CD composition of claim 42, wherein the SAE-CD is sulfobutyl ether β-cyclodextrin (SBE-β-CD) having an average degree of substitution of 6 to 7.1. ### Claim 44 (depends on 42) The SAE-CD composition of claim 42, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 45 (depends on 43) The SAE-CD composition of claim 43, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 46 (depends on 45) The SAE-CD composition of claim 45, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 47 (depends on 45) The SAE-CD composition of claim 45, wherein the SAE-CD comprises less than 200 ppm of a phosphate. ### Claim 48 A sulfoalkyl ether cyclodextrin (SAE-CD) composition comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 6 to 7.1 wherein the SAE-CD composition is sulfobutyl ether β-cyclodextrin (SBE-β-CD) that does not contain: 200 ppm or more of a phosphate; 20 ppm or more of 1,4-butane sultone; 0.5% wt. or more of β-cyclodextrin; 1% wt. or more of sodium chloride; 0.25% wt. or more of 4-hydroxybutane-1-sulfonic acid; or 0.25% wt. or more of disodium bis(4-sulfobutyl)ether; wherein the SAE-CD composition has an absorption of less than 0.5 AU as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length; wherein the amounts of the phosphate, the 1,4-butans sultone, the β-cyclodextrin, the sodium chloride, the phosphate, and the hydrolyzed alkylating agent are with respect to the SAE-CD composition. ### Claim 49 (depends on 48) The SAE-CD composition of claim 48, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 50 (depends on 48) The SAE-CD composition of claim 48, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 51 (depends on 50) The SAE-CD composition of claim 50, wherein the SAE-CD composition has an absorption of less than 0.2 A.U. as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length. ### Claim 52 (depends on 48) The SAE-CD composition of claim 48, wherein the SAE-CD does not comprise 10.0% wt. or more of water.