IP Library › Granted Patent US 12,569,513
Granted Patent B1
US 12,569,513 · App. 19/001,318 · Granted Mar 10, 2026

Stable, highly pure L-cysteine compositions for injection and methods of use

Inventors: John Maloney (Salisbury, NC); Aruna Koganti (Lenoir, NC); Phanesh Koneru (Waxhaw, NC)
Assignee: EXELA PHARMA SCIENCES, LLC
A61K33/06A23L33/16A23L33/175A61K9/0029A61K31/095A61K31/191A61K31/198A61K31/401A61K31/405A61K31/4172A61K33/00A61K33/241A61K33/28A61K33/36A61K47/02A23V2002/00A61J1/1412
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Quick Facts
Patent No.
US 12,569,513
App. No.
19/001,318
Granted
Mar 10, 2026
Kind
B1
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 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.

Claims (68)

1 . A method of preparing a L-cysteine solution, the method comprising:

applying an inert gas to a pharmaceutically acceptable 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 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%; wherein,

for at least 6 months from the time of manufacture the L-cysteine solution will:

remain substantially free of visually detectable particulate matter;

remain at a pH from 1.0 to 2.5; and,

contribute to a parenteral nutrition composition for injection, 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, wherein the parenteral nutrition composition further comprises one or more amino acids selected from the group consisting of: leucine, isoleucine, lysine, valine, phenylalanine, histidine, threonine, methionine, tryptophan, alanine, arginine, glycine, proline, serine, and tyrosine; and wherein the one or more amino acids contribute no more than about 1 mcg/kg/day of Al, and all components of the parenteral nutrition composition combined contribute no more than about 4 mcg/kg/day of Al as dosed as part of a parenteral nutrition regimen.

2 . The method of claim 1 , wherein the dissolved oxygen content in the carrier is reduced to no more than 1 ppm.

3 . The method of claim 1 , wherein the headspace oxygen within the sealed vial is no more than 4%.

4 . The method of claim 1 , wherein the dissolved oxygen content of the solution within the sealed vial is no more than 5 ppm.

5 . The method of claim 1 , wherein in transferring an amount of the mixture into a vial, an inert gas is utilized to minimize exposure of the solution to oxygen.

6 . The method 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.

7 . The method of claim 1 , wherein all components of the parenteral nutrition composition combined contribute no more than about 3 mcg/kg/day of Al as dosed as part of a parenteral nutrition regimen.

8 . A method of preparing a L-cysteine solution, the method comprising:

applying an inert gas to a pharmaceutically acceptable 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 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%; wherein,

for at least 9 months from the time of manufacture the L-cysteine solution will:

remain substantially free of visually detectable particulate matter;

remain at a pH from 1.0 to 2.5; and,

contribute to a parenteral nutrition composition for injection, 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, wherein the parenteral nutrition composition further comprises one or more amino acids selected from the group consisting of: leucine, isoleucine, lysine, valine, phenylalanine, histidine, threonine, methionine, tryptophan, alanine, arginine, glycine, proline, serine, and tyrosine; and wherein the one or more amino acids contribute no more than about 1 mcg/kg/day of Al, and all components of the parenteral nutrition composition combined contribute no more than about 4 mcg/kg/day of Al as dosed as part of a parenteral nutrition regimen.

9 . The method of claim 8 , wherein the dissolved oxygen content in the carrier is reduced to no more than 1 ppm.

10 . The method of claim 8 , wherein the headspace oxygen within the sealed vial is no more than 4%.

11 . The method of claim 8 , wherein the dissolved oxygen content of the solution within the sealed vial is no more than 5 ppm.

12 . The method of claim 8 , wherein in transferring an amount of the mixture into a vial, an inert gas is utilized to minimize exposure of the solution to oxygen.

13 . The method of claim 8 , 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.

14 . The method of claim 8 , wherein all components of the parenteral nutrition composition combined contribute no more than about 3 mcg/kg/day of Al as dosed as part of a parenteral nutrition regimen.

15 . A method of preparing a L-cysteine solution, the method comprising:

applying an inert gas to a pharmaceutically acceptable 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 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%; wherein,

for at least 12 months from the time of manufacture the L-cysteine solution will:

remain substantially free of visually detectable particulate matter;

remain at a pH from 1.0 to 2.5; and,

contribute to a parenteral nutrition composition for injection, 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, wherein the parenteral nutrition composition further comprises one or more amino acids selected from the group consisting of: leucine, isoleucine, lysine, valine, phenylalanine, histidine, threonine, methionine, tryptophan, alanine, arginine, glycine, proline, serine, and tyrosine; and wherein the one or more amino acids contribute no more than about 1 mcg/kg/day of Al, and all components of the parenteral nutrition composition combined contribute no more than about 4 mcg/kg/day of Al as dosed as part of a parenteral nutrition regimen.

16 . The method of claim 15 , wherein the dissolved oxygen content in the carrier is reduced to no more than 1 ppm.

17 . The method of claim 15 , wherein the headspace oxygen within the sealed vial is no more than 4%.

18 . The method of claim 15 , wherein the dissolved oxygen content of the solution within the sealed vial is no more than 5 ppm.

19 . The method of claim 15 , wherein in transferring an amount of the mixture into a vial, an inert gas is utilized to minimize exposure of the solution to oxygen.

20 . The method of claim 15 , 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.

21 . The method of claim 15 , wherein all components of the parenteral nutrition composition combined contribute no more than about 3 mcg/kg/day of Al as dosed as part of a parenteral nutrition regimen.

22 . A method of preparing a L-cysteine solution, the method comprising:

applying an inert gas to a pharmaceutically acceptable 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 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%; wherein,

for at least 18 months from the time of manufacture the L-cysteine solution will:

remain substantially free of visually detectable particulate matter;

remain at a pH from 1.0 to 2.5; and,

contribute to a parenteral nutrition composition for injection, 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, wherein the parenteral nutrition composition further comprises one or more amino acids selected from the group consisting of: leucine, isoleucine, lysine, valine, phenylalanine, histidine, threonine, methionine, tryptophan, alanine, arginine, glycine, proline, serine, and tyrosine; and wherein the one or more amino acids contribute no more than about 1 mcg/kg/day of Al, and all components of the parenteral nutrition composition combined contribute no more than about 4 mcg/kg/day of Al as dosed as part of a parenteral nutrition regimen.

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 method of claim 22 , 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.

28 . The method of claim 22 , wherein all components of the parenteral nutrition composition combined contribute no more than about 3 mcg/kg/day of Al as dosed as part of a parenteral nutrition regimen.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 24, 2024
From: MALONEY, JOHN; KOGANTI, ARUNA; KONERU, PHANESH
To: EXELA PHARMA SCIENCES, LLC
Reel/Frame 069676/0760 →
Continuity (9)
Continuation 18651026 · Apr 30, 2024
Continuation 18520172 · Nov 27, 2023
Continuation 18332677 · Jun 9, 2023
Continuation 18067605 · Dec 16, 2022
Continuation 17950964 · Sep 22, 2022
Continuation 17188922 · Mar 1, 2021
Continuation 16746028 · Jan 17, 2020
Continuation 16665702 · Oct 28, 2019
Continuation 16248460 · Jan 15, 2019
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