Claims for Patent: 11,679,125

Summary for Patent: 11,679,125

Title:	Stable, highly pure L-cysteine compositions for injection and methods of use
Abstract:	The subject matter described herein is directed to stable L-cysteine compositions for injection, comprising: L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof in an amount from about 10 mg/mL to about 100 mg/mL; Aluminum in an amount from about 1.0 parts per billion (ppb) to about 250 ppb; cystine in an amount from about 0.01 wt % to about 2 wt % relative to L-cysteine; pyruvic acid in an amount from about 0.01 wt % to about 2 wt % relative to L-cysteine; a pharmaceutically acceptable carrier, comprising water; headspace O2 that is less than 1.0%; dissolved oxygen present in the carrier in an amount from about 0.01 parts per million (ppm) to about 1 ppm, wherein the composition is enclosed in a single-use container having a volume of from 10 mL to 100 mL. Also described are compositions for a total parenteral nutrition regimen and methods for their use.
Inventor(s):	John Maloney, Aruna Koganti, Phanesh Koneru
Assignee:	Exela Pharma Sciences LLC
Application Number:	US18/067,605
Patent Claims:	1. A solution of L-cysteine for use in total parenteral nutrition (TPN) comprising, about 10 mg/mL to about 100 mg/mL of L-cysteine or a pharmaceutically acceptable salt or hydrate thereof, in a pharmaceutically acceptable carrier; wherein the solution is stored in a sealed vial; and wherein for at least 6 months from the time of manufacture of the solution, the solution will: remain substantially free of visually detectable particulate matter; remain at a pH from 1.0 to 2.5; and contribute no more than about 0.8 micrograms (mcg)/kg/day of aluminum as dosed to an individual as part of a TPN regimen containing a therapeutically effective dose of L-cysteine. 2. The solution of claim 1, wherein the L-cysteine dose is 15 mg L-cysteine per gram of amino acids. 3. The solution of claim 1, wherein for at least 6 months from the time of manufacture of the solution, aluminum exposure to a patient from the solution, as administered to a patient receiving a dose of 15 mg L-cysteine per gram of amino acids and no more than 4 grams of amino acids/kg/day, is no more than about 0.4 mcg/kg/day of aluminum. 4. The solution of claim 1, wherein for at least 6 months from the time of manufacture of the solution, aluminum exposure to a patient from the solution, as administered to a patient receiving a dose of 15 mg L-cysteine per gram of amino acids and no more than 4 grams of amino acids/kg/day, is no more than 0.27 mcg/kg/day of aluminum. 5. The solution of claim 1, wherein for at least 6 months from the time of manufacture of the solution, aluminum exposure to a patient from the solution, as administered to a patient receiving a dose of 15 mg L-cysteine per gram of amino acids and no more than 4 grams of amino acids/kg/day, is no more than 0.21 mcg/kg/day of aluminum. 6. A method of preparing the solution of claim 1 comprising, applying an inert gas to the carrier to reduce the dissolved oxygen content in the carrier to no more than 2 ppm; under an inert gas, mixing the carrier with L-cysteine or a pharmaceutically acceptable salt or hydrate thereof, optionally adjusting the pH of the mixture to from 1.0 to 2.5; transferring an amount of the mixture into a vial; overlaying the mixture with an inert gas; and sealing the vial, wherein the headspace oxygen within the sealed vial is no more than 5%. 7. The solution of claim 1, wherein after 6 months of storage in a sealed vial at room temperature, the total amount of oxygen within the sealed vial is no more than about 5%. 8. A method of preparing the solution of claim 2 comprising, applying an inert gas to the carrier to reduce the dissolved oxygen content in the carrier to no more than 2 ppm; under an inert gas, mixing the carrier with L-cysteine or a pharmaceutically acceptable salt or hydrate thereof, optionally adjusting the pH of the mixture to from 1.0 to 2.5; transferring an amount of the mixture into a vial; overlaying the mixture with an inert gas; and sealing the vial, wherein the headspace oxygen within the sealed vial is no more than 5%. 9. The solution of claim 2, wherein after 6 months of storage in a sealed vial at room temperature, the total amount of oxygen within the sealed vial is no more than about 5%. 10. A method of preparing the solution of claim 3 comprising, applying an inert gas to the carrier to reduce the dissolved oxygen content in the carrier to no more than 2 ppm; under an inert gas, mixing the carrier with L-cysteine or a pharmaceutically acceptable salt or hydrate thereof, optionally adjusting the pH of the mixture to from 1.0 to 2.5; transferring an amount of the mixture into a vial; overlaying the mixture with an inert gas; and sealing the vial, wherein the headspace oxygen within the sealed vial is no more than 5%. 11. The solution of claim 3, wherein after 6 months of storage in a sealed vial at room temperature, the total amount of oxygen within the sealed vial is no more than about 5%. 12. A method of preparing the solution of claim 4 comprising, applying an inert gas to the carrier to reduce the dissolved oxygen content in the carrier to no more than 2 ppm; under an inert gas, mixing the carrier with L-cysteine or a pharmaceutically acceptable salt or hydrate thereof, optionally adjusting the pH of the mixture to from 1.0 to 2.5; transferring an amount of the mixture into a vial; overlaying the mixture with an inert gas; and sealing the vial, wherein the headspace oxygen within the sealed vial is no more than 5%. 13. The solution of claim 4, wherein after 6 months of storage in a sealed vial at room temperature, the total amount of oxygen within the sealed vial is no more than about 5%. 14. The solution of claim 1, wherein the concentration of L-cysteine is about 34.5 mg/mL to about 50 mg/mL. 15. The solution of claim 2, wherein the concentration of L-cysteine is about 34.5 mg/mL to about 50 mg/mL. 16. The solution of claim 3, wherein the concentration of L-cysteine is about 34.5 mg/mL to about 50 mg/mL. 17. The solution of claim 4, wherein the concentration of L-cysteine is about 34.5 mg/mL to about 50 mg/mL. 18. A solution of L-cysteine for use in total parenteral nutrition (TPN) comprising, about 10 mg/mL to about 100 mg/mL of L-cysteine or a pharmaceutically acceptable salt or hydrate thereof, in a pharmaceutically acceptable carrier; wherein: after 6 months of storage in a sealed vial at room temperature: the total amount of oxygen within the sealed vial is no more than about 5%; and the solution: contains no more than 250 ppb aluminum, is substantially free of visually detectable particulate matter, and has a pH from 1.0 to 2.5. 19. The solution of claim 1, wherein after 6 months of storage at room temperature, the total amount of oxygen within the sealed vial is no more than 4%. 20. The solution of claim 1, wherein after 6 months of storage at room temperature, the solution contains no more than 150 ppb aluminum. 21. The solution of claim 1, wherein the vial is configured to substantially prevent atmospheric oxygen ingress and leaching of aluminum into the solution during storage of the solution in the vial. 22. A method of preparing the solution of claim 1 comprising, applying an inert gas to the carrier to reduce the dissolved oxygen content in the carrier to no more than 2 ppm; under an inert gas, mixing the carrier with L-cysteine hydrochloride monohydrate or a pharmaceutically acceptable L-cysteine or a salt or hydrate thereof, optionally adjusting the pH of the mixture to from 1.0 to 2.5; transferring an amount of the mixture into a vial; overlaying the mixture with an inert gas; and sealing the vial, wherein the headspace oxygen within the sealed vial is no more than 5%. 23. The method of claim 22, wherein the dissolved oxygen content in the carrier is reduced to no more than 1 ppm. 24. The method of claim 22, wherein the headspace oxygen within the sealed vial is no more than 4%. 25. The method of claim 22, wherein the dissolved oxygen content of the solution within the sealed vial is no more than 5 ppm. 26. The method of claim 22, wherein in transferring an amount of the mixture into a vial, an inert gas is utilized to minimize exposure of the solution to oxygen. 27. The solution of claim 18, wherein the concentration of L-cysteine is about 34.5 mg/mL to about 50 mg/mL.