Claims for Patent: 10,653,719

Summary for Patent: 10,653,719

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 O.sub.2 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):	Maloney; John (Salisbury, NC), Koganti; Aruna (Lenoir, NC), Koneru; Phanesh (Waxhaw, NC)
Assignee:	EXELA PHARMA SCIENCES, LLC (Lenoir, NC)
Application Number:	16/773,563
Patent Claims:	1. A solution of L-cysteine comprising, a pharmaceutically acceptable carrier, about 50 mg/mL of L-cysteine hydrochloride monohydrate, or equivalent amount of a pharmaceutically acceptable L-cysteine or a salt or hydrate thereof, less than about 150 ppb of aluminum, a pH from about 1.0 to about 2.5, and wherein the solution is substantially free of visually detectable particulate matter and suitable for use as an additive in a parenteral nutrition composition for administration to an individual. 2. The solution of claim 1, which comprises less than about 100 ppb of aluminum. 3. The solution of claim 1, which comprises less than about 50 ppb of aluminum. 4. The solution of claim 1, which comprises less than about 20 ppb of aluminum. 5. The solution of claim 1, which comprises less than about 10 ppb of aluminum. 6. The solution of claim 1, which comprises from about 1 ppb to about 150 ppb of aluminum. 7. The solution of claim 1, which has a dissolved oxygen content of less than 2 ppm. 8. The solution of claim 1, wherein the pH is about 1.8 and in which the solution is substantially free of cystine precipitates. 9. The solution of claim 1, wherein the solution is substantially free of visually detectable particulate matter when stored for 18 months at about 25.degree. C. and about 60% relative humidity. 10. The solution of claim 9, wherein the pharmaceutically acceptable carrier is aqueous. 11. The solution of claim 1, wherein the solution is essentially free of cystine precipitates. 12. A solution of L-cysteine comprising, a pharmaceutically acceptable carrier, about 50 mg/mL of L-cysteine hydrochloride monohydrate, or equivalent amount of a pharmaceutically acceptable L-cysteine or a salt or hydrate thereof, less than about 150 ppb of aluminum, and a pH from about 1.0 to about 2.5, wherein the solution is substantially free of visually detectable particulate matter for at least 6 months from the time of manufacture of the solution and is suitable for use as an additive in a parenteral nutrition composition for administration to a neonate or infant. 13. The solution of claim 12, wherein the solution is substantially free of visually detectable particulate matter for at least 9 months from the time of manufacture of the solution. 14. The solution of claim 12, wherein the solution is substantially free of visually detectable particulate matter for at least 12 months from the time of manufacture of the solution. 15. The solution of claim 12, wherein the solution is substantially free of visually detectable particulate matter for at least 24 months from the time of manufacture of the solution. 16. The solution of claim 12, wherein the solution is essentially free of cystine precipitates. 17. A solution of L-cysteine comprising, a pharmaceutically acceptable carrier, about 50 mg/mL of L-cysteine hydrochloride monohydrate, or equivalent amount of a pharmaceutically acceptable L-cysteine or a salt or hydrate thereof, in a low oxygen environment, less than about 150 ppb of aluminum, and a pH from about 1.0 to about 2.5, wherein the solution is substantially free of visually detectable particulate matter and is suitable for use as an additive in a parenteral nutrition composition for administration to a neonate or infant. 18. The solution of claim 17, wherein the solution is substantially free of visually detectable particulate matter for at least 6 months after the time of manufacture of the solution. 19. The solution of claim 17, wherein the solution is substantially free of visually detectable particulate matter for at least 9 months after the time of manufacture of the solution. 20. The solution of claim 17, wherein the solution is substantially free of visually detectable particulate matter for at least 12 months after the time of manufacture of the solution. 21. The solution of claim 17, wherein the solution is substantially free of visually detectable particulate matter for at least 24 months after the time of manufacture of the solution. 22. The solution of claim 17, wherein the solution has a dissolved oxygen content of less than about 5 ppm. 23. The solution of claim 17, wherein the solution has a dissolved oxygen content of less than about 2 ppm. 24. The solution of claim 17, wherein the solution has a dissolved oxygen content of less than about 1 ppm. 25. The solution of claim 17, wherein the solution has a dissolved oxygen content of about 0.4 ppm to about 3.8 ppm. 26. The solution of claim 17, wherein the solution is essentially free of cystine precipitates. 27. The solution of claim 18, wherein the solution is essentially free of cystine precipitates.