IP Library Granted Patent US 11,266,611
Granted Patent B2
US 11,266,611 · App. 15/991,501 · Granted Mar 8, 2022

More potent and less toxic formulations of epinephrine and methods of medical use

Inventor: Darren Rubin (Largo, FL)
Assignee: ETON PHARMACEUTICALS, INC.
A61K31/137A61K47/26A61P7/04A61P9/02A61P41/00A61K9/0019A61K9/0085A61K45/06A61K47/02A61K2300/00
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Quick Facts
Patent No.
US 11,266,611
App. No.
15/991,501
Granted
Mar 8, 2022
Kind
B2
Abstract

The present invention provides pharmaceutical formulations of levorotatory-epinephrine, 1-epinephrine, more potent and less toxic than existing pharmaceutical formulations of epinephrine, along with methods of producing and using these pharmaceutical formulations of 1-epinephrine, including preventing and or treating hypotension and hemostasis under surgical anesthesia.

Claims (20)

1. A method of treating a cardiac arrhythmia in a patient having or recovering from invasive orthopedic or gynecological procedures, surgery, or a combination thereof, the method comprising:

injecting said patient with an at least 1 microgram per mL solution of l-epinephrine in saline into a subarachnoid space, epidural space, or a combination thereof to prolong anesthesia; and

then administering a continuous intravenous infusion of l-epinephrine via an at least one intravenous fluid bag with either or both of an at least one intravenous line and an at least one intravenous catheter,

wherein at least one syringe of a 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine is injected into each said at least one intravenous fluid bag or medication port thereof, thereby diluting the formulation of 1-epinephrine to a concentration of about 1 microgram per mL during said continuous intravenous infusion of 1-epinephrine, said at least one syringe of a 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine including a tonicity agent and having no more than 12.5% total impurities or no more than 12% d-epinephrine, and

wherein said at least one intravenous fluid bag comprises, prior to injection of the at least one syringe of a 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine, up to about 1,000 mL of a dextrose-containing solution, a saline-containing solution, or a combination thereof.

2. A method of treating hypotension in a patient having or recovering from invasive orthopedic or gynecological procedures, surgery, or a combination thereof, the method comprising:

injecting an at least one syringe of a 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine into an at least one intravenous fluid bag or medication port thereof, said at least one syringe of a 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine including a tonicity agent and having no more than 12.5% total impurities or no more than 12% d-epinephrine;

injecting said patient with an at least 1 microgram per mL of 1-epinephrine in anesthetic solution into a subarachnoid space to treat or prevent pain; and

administering a continuous intravenous infusion of l-epinephrine via the at least one injected intravenous fluid bag with an at least one intravenous line, an at least one intravenous catheter, or a combination thereof,

wherein said at least one intravenous fluid bag comprises, prior to injection of the at least one syringe of a 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine, up to about 1,000 mL of a dextrose-containing solution, a saline-containing solution, or a combination thereof, and

wherein said 1-epinephrine is diluted to a concentration of about 1 microgram per mL in each said at least one said intravenous fluid bag during said continuous intravenous infusion of 1-epinephrine.

3. A method of treating a cardiac arrhythmia or hypotension in a patient having or recovering from invasive orthopedic or gynecological procedures, surgery, or a combination thereof, said method comprising:

replacing general anesthesia with regional anesthesia;

injecting said patient with an at least 1 microgram per mL of 1-epinephrine in anesthetic solution into a subarachnoid space, epidural space, or a combination thereof to treat pain, wherein said at least 1 microgram per mL of 1-epinephrine in anesthetic solution is prepared, just prior to said injecting into said subarachnoid space, epidural space, or a combination thereof, by mixing at least some of a 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine including a tonicity agent and having no more than 12.5% total impurities or no more than 12% d-epinephrine with at least some of an anesthetic solution;

injecting an at least one syringe of a 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine into an at least one intravenous fluid bag or medication port thereof, said at least one syringe of a 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine including a tonicity agent and having no more than 12.5% total impurities or no more than 12% d-epinephrine, and said at least one intravenous fluid bag comprising, prior to injecting the at least one syringe of the 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine, up to about 1,000 mL of a dextrose-containing solution, a saline-containing solution, or a combination thereof;

providing said patient with a continuous intravenous infusion of said at least one intravenous fluid bag into which said 1 mg injectable liquid pharmaceutical formulation of 1-epinephrine has been injected, wherein said 1-epinephrine is diluted to a concentration of about 1 microgram per mL in each said at least one said intravenous fluid bag during said continuous intravenous infusion.

4. The method of claim 1 , comprising protecting said at least one intravenous fluid bag from light or UV-radiation after injecting said syringe into said at least one intravenous fluid bag or medication port thereof to reduce 1-epinephrine degradation and impurities from forming.

5. The method of claim 2 , comprising protecting said at least one intravenous fluid bag from light or UV-radiation after injecting said syringe into said at least one intravenous fluid bag or medication port thereof to reduce 1-epinephrine degradation and impurities from forming.

6. The method of claim 3 , comprising protecting said at least one said intravenous fluid bag from light or UV-radiation after injecting said syringe into said at least one intravenous fluid bag or medication port thereof to reduce 1-epinephrine degradation and impurities from forming.

7. The method of claim 3 , wherein said continuous intravenous infusion of 1-epinephrine has a ratio of 1-epinephrine:d-epinephrine greater than 4:1.

Assignments (7)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 9, 2025
From: ETON PHARMACEUTICALS, INC.
To: RUBIN, DARREN
Reel/Frame 071358/0612 →
SECURITY INTEREST Recorded Feb 20, 2025
From: BELCHER PHARMACEUTICALS, LLC
To: TRUIST BANK, AS ADMINISTRATIVE AGENT
Reel/Frame 070279/0798 →
RELEASE OF SECURITY INTEREST IN INTELLECTUAL PROPERTY COLLATERAL Recorded Sep 16, 2021
From: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
To: BELCHER PHARMACEUTICALS, LLC
Reel/Frame 057525/0648 →
NOTICE OF GRANT OF SECURITY INTEREST IN PATENTS Recorded Sep 14, 2021
From: BELCHER PHARMACEUTICALS, LLC
To: TRUIST BANK
Reel/Frame 057499/0790 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 13, 2021
From: RUBIN, DARREN
To: ETON PHARMACEUTICALS, INC.
Reel/Frame 057167/0949 →
SECURITY INTEREST Recorded Sep 10, 2020
From: BELCHER PHARMACEUTICALS, LLC
To: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 053731/0843 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 28, 2019
From: TANEJA, JUGAL K.
To: BELCHER PHARMACEUTICALS, LLC
Reel/Frame 049619/0328 →
Continuity (3)
Continuation In Part 15616157 · Jun 7, 2017
Continuation In Part 15596440 · May 16, 2017
Related Publication 20180333374A1 · Nov 22, 2018
Cited By (1)
US 12,539,283