Claims for Patent: 10,226,436

Summary for Patent: 10,226,436

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):	Puri Navneet, Soppimath Kumaresh, Akasapu Prem Sagar, Yadav Vivek, Ilitchev Iouri V., Garapati Sriramya, Hingorani Tushar
Assignee:	Nevakar Inc.
Application Number:	US15883798
Patent Claims:	1. A ready-to-administer norepinephrine composition , comprising: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 and a pharmaceutically acceptable salt;wherein the chelating agent is present in an amount of between 1 μg/ml and 100 μg/ml, and wherein the pharmaceutically acceptable salt is present in an amount of between 0.6 wt % and 1.2 wt %;norepinephrine dissolved at a concentration suitable for administration to a patient in need thereof, wherein the norepinephrine is an R-isomer;wherein the ready-to-administer norepinephrine composition is substantially free of antioxidants; andwherein the ready-to-administer norepinephrine composition is formulated such that after storage over at least three months equal or less than 10% of the R-isomer form will isomerize to the S-isomer and such that equal or less than 5% of the total norepinephrine will degrade to degradation products.2. The composition of wherein the aqueous acidic solution has a pH between 3.7 and 4.0.3. The composition of wherein the chelating agent is selected from the group consisting of a bicarboxylic acid claim 1 , a tricarboxylic acid claim 1 , and an aminopolycarboxylic acid.4. The composition of wherein the chelating agent is present at a concentration of between 10 μg/ml and 100 μg/ml.5. The composition of wherein the pharmaceutically acceptable salt is sodium chloride.6. The composition of wherein the composition is heat sterilized.7. The composition of wherein the norepinephrine is present at a concentration of between 10 μg/ml and 100 μg/ml.8. The composition of wherein the norepinephrine is present at a concentration of 16 μg/ml (+/−10%) claim 1 , 32 μg/ml (+/−10%) claim 1 , or 64 μg/ml (+/−10%).9. The composition of wherein the storage over at least three months is at 40° C. and 75% (+/−5) relative humidity.10. The composition of wherein equal or less than 6% of the R-isomer form will isomerize to the S-isomer.11. The composition of wherein equal or less than 3.5% of the total norepinephrine will degrade to degradation products.12. The composition of wherein the composition has a dissolved oxygen concentration of equal or less than 1 ppm.13. A method of preparing a ready-to-administer norepinephrine composition according to claim 1 , comprising: (a) the formulation exhibits less than 10% of isomerization of the R-isomer to an S-isomer after three months of storage of the liquid composition, and', '(b) the formulation exhibits equal or less than 5% degradation of total norepinephrine after three months of storage of the liquid composition;, 'formulating a liquid parenteral composition that contains in an aqueous acidic solution norepinephrine as an R-isomer such thatwherein the aqueous acidic solution has a pH range of between 3.7 and 4.3, and wherein the aqueous acidic solution further comprises a chelating agent and a pharmaceutically acceptable salt;wherein the total norepinephrine is present in the liquid parenteral composition at a concentration of between 10 μg/ml and 100 μg/ml; andwherein the ready-to-administer norepinephrine composition is substantially free of antioxidants,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'thereby obtaining a ready-to-administer norepinephrine composition according to .'}14. The method of wherein the aqueous acidic solution has a pH between 3.7 and 4.0.15. The method of wherein the norepinephrine is present at a concentration of 16 μg/ml (+/−10%) claim 13 , 32 μg/ml (+/−10%) claim 13 , or 64 μg/ml (+/−10%).16. The method of wherein the step of formulating the liquid parenteral composition uses deoxygenated water having dissolved oxygen at a concentration of equal or less than 1 ppm.17. The method of further comprising a step of heat sterilizing the liquid parenteral composition.18. The method of further comprising a step of packaging the liquid parenteral composition in a container claim 17 , and placing the container in a second container that includes a metal-free oxygen scavenger claim 17 , and optionally wherein the container and/or the second container is configured to reduce light-mediated oxidation of the norepinephrine.19. A method of treating hypotension claim 17 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering the ready-to-administer norepinephrine composition according to at an initial dose per minute; and'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering the ready-to-administer norepinephrine composition according to 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 claim 19 , and wherein the second dose per minute is a dose of between 2 and 4 μg/min.