Claims for Patent: 10,117,951

Summary for Patent: 10,117,951

Title:	Sulfoalkyl ether cyclodextrin compositions
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.
Inventor(s):	Antle; Vincent D. (Olathe, KS)
Assignee:	CyDex Pharmaceuticals, Inc. (San Diego, CA)
Application Number:	14/954,772
Patent Claims:	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. 2. The SAE-CD composition of claim 1, wherein the SAE-CD composition does not comprise 0.2% wt. or more of an underivatized cyclodextrin. 3. The SAE-CD composition of claim 2, wherein the SAE-CD composition does not comprise 0.1% wt. or more of an underivatized cyclodextrin. 4. The SAE-CD composition of claim 1, wherein the SAE-CD is sulfobutyl ether .beta.-cyclodextrin (SBE-.beta.-CD) having an average degree of substitution of 6 to 7.1. 5. 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. 6. 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. 7. 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. 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. 9. The SAE-CD composition of claim 8, wherein the SAE-CD composition does not comprise 10 ppm or more of a sulfoalkylating agent. 10. The SAE-CD composition of claim 8, wherein the SAE-CD composition does not comprise 2 ppm or more of a sulfoallcylating agent. 11. The SAE-CD composition of claim 8, wherein the SAE-CD composition does not comprise 250 ppb or more of a sulfoalkylating agent. 12. The SAE-CD composition of claim 8, wherein the sulfoalkylating agent is 1,4-butane sultone. 13. The SAE-CD composition of claim 8, wherein the SAE-CD is sulfobutyl ether .beta.-cyclodextrin (SBE-.beta.-CD) having an average degree of substitution of 6 to 7.1. 14. 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. 15. 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. 16. 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. 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. 18. 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. 19. 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. 20. The SAE-CD composition of claim 17, wherein the hydrolyzed sulfoalkylating agent is 4-hydroxybutane-1-sulfonic acid or disodium bis(4-sulfobutyl)ether. 21. The SAE-CD composition of claim 17, wherein the SAE-CD is sulfobutyl ether .beta.-cyclodextrin (SBE-.beta.-CD) having an average degree of substitution of 6 to 7.1. 22. 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. 23. 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. 24. 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. 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. 26. 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. 27. 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. 28. 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. 29. The SAE-CD composition of claim 25, wherein the alkali metal halide salt is sodium chloride. 30. The SAE-CD composition of claim 25, wherein the SAE-CD is sulfobutyl ether .beta.-cyclodextrin (SBE-.beta.-CD) having an average degree of substitution of 6 to 7.1. 31. 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. 32. 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. 33. 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. 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. 35. 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. 36. 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. 37. 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. 38. The SAE-CD composition of claim 34, wherein the sulfoalkylating agent is 1,4-butane sultone. 39. The SAE-CD composition of claim 34, wherein the underivatized cyclodextrin is .beta.-cyclodextrin. 40. The SAE-CD composition of claim 34, wherein the alkali metal halide salt is sodium chloride. 41. The SAE-CD composition of claim 34, wherein the hydrolyzed alkylating agent is 4-hydroxybutane-1-sulfonic acid or disodium bis(4-sulfobutyl)ether. 42. The SAE-CD composition of claim 34, wherein the sulfoalykylating agent is 1,4-butane sultone; the underivatized cyclodextrin is .beta.-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. 43. The SAE-CD composition of claim 42, wherein the SAE-CD is sulfobutyl ether .beta.-cyclodextrin (SBE-.beta.-CD) having an average degree of substitution of 6 to 7.1. 44. 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. 45. 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. 46. 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. 47. The SAE-CD composition of claim 45, wherein the SAE-CD comprises less than 200 ppm of a phosphate. 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 .beta.-cyclodextrin (SBE-.beta.-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 .beta.-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 .beta.-cyclodextrin, the sodium chloride, the phosphate, and the hydrolyzed alkylating agent are with respect to the SAE-CD composition. 49. 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. 50. 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. 51. 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. 52. The SAE-CD composition of claim 48, wherein the SAE-CD does not comprise 10.0% wt. or more of water.