IP Library › Granted Patent US 12,440,459
Granted Patent B2
US 12,440,459 · App. 19/054,330 · Granted Oct 14, 2025

Norepinephrine compositions and methods therefor

Inventors: Harshil H. Jain (Monmouth Junction, NJ); Tushar Hingorani (Bridgewater, NJ); Kumaresh Soppimath (Skillman, NJ)
Assignee: NEVAKAR INJECTABLES INC.
A61K31/137A61K9/0019A61K47/12A61K47/183A61P9/02
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Quick Facts
Patent No.
US 12,440,459
App. No.
19/054,330
Granted
Oct 14, 2025
Kind
B2
Abstract

The inventive subject matter is directed to compositions and methods for ready-to-inject norepinephrine compositions with improved stability. Most preferably, compositions presented herein are substantially antioxidant free and exhibit less than 10% isomerization of R-norepinephrine and exhibit less than 5% degradation of total norepinephrine.

Claims (30)

1. A sterile and ready to ready-to-administer norepinephrine composition, comprising:

an aqueous acidic solution having a pH range of between 3.8 and 4.1, wherein the aqueous solution further comprises a chelating agent, and a pharmaceutically acceptable salt or tonicity agent;

wherein the ready-to-administer norepinephrine composition is substantially free of antioxidants;

norepinephrine or salt thereof, dissolved in the composition at a norepinephrine concentration of between about 16 μg/ml (+/−10%) and 128 μg/ml (+/−10%), wherein the norepinephrine is an R-isomer of norepinephrine; and

wherein the ready-to-administer norepinephrine composition is formulated such that after terminal sterilization and storage over at least three months at 25° C. equal or less than 10% of the R-isomer form will isomerize to the S-isomer and such that no more than 0.5% total impurities are formed.

2. The composition of claim 1 wherein the salt of the norepinephrine is norepinephrine bitartrate.

3. The composition of claim 2 wherein the composition contains no buffer.

4. The composition of claim 1 wherein the chelating agent is selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid.

5. The composition of claim 4 wherein the chelating agent is present at a concentration of between 10 μg/ml and 100 μg/ml.

6. The composition of claim 2 wherein the chelating agent is selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid.

7. The composition of claim 6 wherein the chelating agent is present at a concentration of between 10 μg/ml and 100 g/ml.

8. The composition of claim 3 wherein the chelating agent is selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid.

9. The composition of claim 8 wherein the chelating agent is present at a concentration of between 10 μg/ml and 100 μg/ml.

10. The composition of claim 1 wherein the pharmaceutically acceptable salt is sodium chloride.

11. The composition of claim 1 wherein the tonicity agent is glycerol, thioglycerol, mannitol, lactose, or dextrose.

12. The composition of claim 1 wherein the composition is heat sterilized at 121° C. for at least 15 minutes.

13. The composition of claim 1 wherein the norepinephrine is present at a concentration of at least 100 μg/ml.

14. The composition of claim 1 wherein the norepinephrine is present at a concentration of 16 μg/ml (+/−10%), 64 μg/ml (+/−10%), or 128 μg/ml (+/−10%).

15. The composition of claim 1 wherein equal or less than 5% of the R-isomer form will isomerize to the S-isomer.

16. The composition of claim 1 wherein the composition has a dissolved oxygen concentration of equal or less than 1 ppm.

17. A kit, comprising:

a container filled with a sterile, ready-to-administer norepinephrine composition and packaged in a secondary container;

wherein the sterile, ready-to-administer norepinephrine composition comprises in an aqueous acidic solution having a pH range of between 3.8 and 4.1 a chelating agent, a pharmaceutically acceptable salt or tonicity agent, and dissolved norepinephrine or salt thereof at a norepinephrine concentration of between about 16 μg/ml (+/−10%) and 128 μg/ml (+/−10%), wherein the norepinephrine is an R-isomer of norepinephrine;

wherein the ready-to-administer norepinephrine composition is substantially free of antioxidants; and

wherein the ready-to-administer norepinephrine composition is formulated such that after terminal sterilization and storage over at least three months at 25° C. equal or less than 10% of the R-isomer form will isomerize to the S-isomer and such that no more than 0.5% total impurities are formed.

18. The kit of claim 17 , wherein the container is a large volume, polymeric, semi-permeable infusion container, and optionally wherein the secondary container is impervious to light and/or contains an oxygen scavenger.

19. A method of treating hypotension, comprising:

administering a ready-to-inject norepinephrine composition according to claim 1 at an initial dose per minute; and

administering the ready-to-inject norepinephrine composition at a second dose per minute, wherein the initial dose per minute is greater than the second dose per minute.

20. The method of claim 19 , wherein the initial dose per minute is a dose of between 8 and 12 μg/min, and wherein the second dose per minute is a dose of between 2 and 4 μg/min.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2026
From: NEVAKAR INJECTABLES INC.
To: NEVAKAR PHARMACEUTICALS, INC.
Reel/Frame 074672/0415 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 14, 2025
From: JAIN, HARSHIL H.; HINGORANI, TUSHAR; SOPPIMATH, KUMARESH
To: NEVAKAR INJECTABLES INC.
Reel/Frame 070224/0138 →
Continuity (7)
Continuation 19043163 · Jan 31, 2025
Continuation In Part 17861752 · Jul 11, 2022
Division 16839450 · Apr 3, 2020
Division 16239465 · Jan 3, 2019
Division 15883798 · Jan 30, 2018
Provisional Application 62452220 · Jan 30, 2017
Related Publication 20250186370A1 · Jun 12, 2025
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