Claims for Patent: 10,420,735

Summary for Patent: 10,420,735

Title:	Norepinephrine compositions and methods therefor
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.
Inventor(s):	Hingorani Tushar, Akasapu Prem Sagar, Soppimath Kumaresh
Assignee:	NEVAKAR INC.
Application Number:	US16163480
Patent Claims:	1. A method of treating hypotension , comprising:administering a ready-to-administer norepinephrine composition at an initial dose per minute;administering the norepinephrine composition at a maintenance dose per minute, wherein the initial dose per minute is greater than the maintenance dose per minute;wherein the initial dose per minute is a dose of between 8 and 12 μg/min, and wherein the maintenance dose per minute is a dose of between 2 and 4 μg/min;wherein the norepinephrine composition comprises norepinephrine or a salt thereof at a concentration of between 10 μg/ml and 100 μg/ml in an aqueous acidic solution having a pH range of between 3.7 and 4.3, wherein the aqueous acidic solution further comprises a chelating agent at a concentration of between 1 μg/ml and 100 μg/ml and a tonicity agent;wherein the norepinephrine composition is substantially free of antioxidants; andwherein the norepinephrine or a salt thereof in the norepinephrine composition comprises at least about 90% R-isomer of norepinephrine after storage at 25±2° C. and 60±5% relative humidity, over at least three months as determined by HPLC.2. The method of wherein the aqueous acidic solution has a pH range of between 4.0 and 4.2.3. The method of wherein the aqueous acidic solution has a pH range of between 3.7 and 4.0.4. The method of wherein the norepinephrine is present in the composition at a concentration of about 16 μg/ml claim 1 , about 32 μg/ml claim 1 , or about 64 μg/ml.5. The method of wherein the norepinephrine in the composition is a salt of norepinephrine.6. The method of wherein the salt of norepinephrine in the composition is norepinephrine bitartrate.7. The method of wherein the chelating agent in the composition is selected from the group consisting of a bicarboxylic acid claim 1 , a tricarboxylic acid claim 1 , and an aminopolycarboxylic acid.8. The method of claim 1 , wherein the chelating agent is present in the composition at a concentration of between 10 μg/ml and 100 μg/ml.9. The method of claim 1 , wherein the tonicity agent is present in the composition in an amount of between 0.6 wt % and 1.2 wt %.10. The method of claim 1 , wherein the norepinephrine or a salt thereof in the norepinephrine composition comprises at least about 95% R-isomer of norepinephrine after storage at 25±2° C. and 60±5% relative humidity claim 1 , over at least three months as determined by HPLC.11. The method of claim 1 , wherein the norepinephrine or a salt thereof in the norepinephrine composition comprises equal or less than about 5% S-isomer of norepinephrine or a salt thereof after storage at 25±2° C. and 60±5% relative humidity claim 1 , over at least three months as determined by HPLC.12. The method of claim 1 , wherein the norepinephrine or a salt thereof in the norepinephrine composition comprises equal or less than about 10% S-isomer of norepinephrine or a salt thereof after storage at 25±2° C. and 60±5% relative humidity claim 1 , over at least six months as determined by HPLC.13. The method of claim 1 , wherein the norepinephrine composition comprises equal or less than about 5% of total degradation of norepinephrine or salt thereof excluding S-norepinephrine after storage at 25±2° C. and 60±5% relative humidity claim 1 , over at least three months as determined by HPLC.14. A method of administering a ready-to-administer norepinephrine composition to an individual in need thereof claim 1 , comprising:administering the norepinephrine composition at an initial rate of between 8 and 12 μg/min;adjusting administration of norepinephrine composition to a maintenance rate of between 2 and 4 μg/min;wherein the norepinephrine composition comprises norepinephrine or a salt thereof at a concentration of between 10 μg/ml and 100 μg/ml as a base and further comprises a chelating agent in an amount of between 1 μg/ml and 100 μg/ml;wherein the norepinephrine composition is substantially free of antioxidants; andwherein the norepinephrine composition comprises norepinephrine or a salt thereof in an aqueous acidic solution having a pH range of between 3.7 and 4.3, wherein the aqueous acidic solution further comprises a tonicity agent; andwherein the norepinephrine or a salt thereof in the norepinephrine composition comprises at least about 90% R-isomer of norepinephrine or a salt thereof after storage at 25±2° C. and 60±5% relative humidity, over at least three months as determined by HPLC.15. The method of claim 14 , wherein the norepinephrine is present in the composition at a concentration of about 16 μg/ml claim 14 , about 32 μg/ml claim 14 , or about 64 μg/ml.16. The method of claim 14 , wherein the norepinephrine in the norepinephrine in the composition is a salt of norepinephrine claim 14 , and wherein the salt of norepinephrine is norepinephrine bitartrate.17. The method of wherein the aqueous acidic solution has a pH range of between 4.0 and 4.2.18. The method of wherein the aqueous acidic solution has a pH range of between 3.7 and 4.0.19. The method of claim 14 , wherein the tonicity agent is present in an amount of between 0.6 wt % and 1.2 wt %.20. The method of claim 14 , wherein the norepinephrine or a salt thereof in the norepinephrine composition comprises at least about 95% R-isomer of norepinephrine or a salt thereof after storage at 25±2° C. and 60±5% relative humidity claim 14 , over at least three months as determined by HPLC.21. The method of claim 14 , wherein the norepinephrine or a salt thereof in the ready-to-administer norepinephrine composition comprises equal or less than about 10% S-isomer of norepinephrine or a salt thereof after storage at 25±2° C. and 60±5% relative humidity claim 14 , over at least three months as determined by HPLC.22. The method of claim 14 , wherein the ready-to-administer norepinephrine composition comprises equal or less than about 5% of total degradation of norpepinephrine or salt thereof excluding S-norepinephrine after storage at 25±2° C. and 60±5% relative humidity claim 14 , over at least three months as determined by HPLC.