Lipid Emulsions in the Treatment of Systemic Poisoning

• US 20080021411A1
• Filed: 07/25/2007
• Published: 01/24/2008
• Est. Priority Date: 02/24/1998
• Status: Active Grant

• Current Assignee: ResQ Pharma, Inc.
• Original Assignee: Guy Weinberg, Paul Hertz
• Inventors: Weinberg, Guy, Hertz, Paul
• Granted Patent: US 8,834,919 B2
• Time in Patent Office: Days
• US Class Current: 604/218
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61P 39/02 Antidotes

Abstract

The present invention provides lipid emulsions and methods of intravenously administering lipid emulsions to treat systemic toxicity caused by foreign lipophilic and amphiphilic substances. In particular, methods are provided to treat cardiovascular impairment, such as cardiotoxicity, asystole and ischemia of the brain and heart, and neurological impairments, such as seizures and comas, caused by foreign lipophilic and amphiphilic substances, including cardiovascular impairment caused by local anesthetics, tricyclic antidepressants, sodium channel blockers, and calcium channel blockers.

Claims

1. A method of treating severe systemic toxicity in a patient caused by one or more foreign substances, said method comprising:

intravenously administering a lipid emulsion composition to the patient, wherein said lipid emulsion comprises between about 10 and about 40 percent oil by weight, about 1 to about 5 percent emulsifier by weight, about 1 to about 5 percent tonicity modifier by weight, and about 58 to about 88 percent water by weight,

wherein said one or more foreign substances are lipophilic or amphiphilic substances able to be absorbed by the lipid emulsion composition in the patient'"'"'s bloodstream.

2. The method of claim 1 wherein said one or more foreign substances are selected from the group consisting of bupivacaine, lidocaine, mepivacaine, etidocaine, amethocaine, tetracaine, procaine, 2-chloroprocaine, cocaine, prilocalne, procainamide, levobupivacaine, ropivacaine, dibucaine, bupropion, imipramine, desipramine, trimipramine, clomipramine, lofepramine, amitriptyline, nortriptyline, protriptyline, dothiepin hydrochloride, doxepin, nifedipine, verapamil, diltiazem, propranolol, metoprolol, carvedilol, bisoprolol and combinations thereof.

3. The method of claim 1 wherein said one or more foreign substances are selected from the group consisting of lipophilic and amphiphilic local anesthetics.

4. The method of claim 1 wherein said one or more foreign substances include cocaine.

5. The method of claim 1 wherein said one or more foreign substances are selected from the group consisting of lipophilic and amphiphilic tricyclic antidepressants.

6. The method of claim 1 wherein said one or more foreign substances are selected from the group consisting of lipophilic and amphiphilic sodium channel blockers.

7. The method of claim 1 wherein the oil is a naturally occurring vegetable or animal oil.

8. The method of claim 1 wherein the oil is selected from the group consisting of soybean oil, cottonseed oil, safflower oil, corn oil, coconut oil, sesame oil, peanut oil, olive oil, cod liver oil and mixtures thereof.

9. The method of claim 1 wherein the oil is soybean oil.

10. The method of claim 1 wherein the lipid emulsion composition comprises between about 10 and about 30 percent oil by weight, about 1 to about 5 percent emulsifier by weight, about 1 to about 5 percent tonicity modifier by weight, and about 68 to about 88 percent water by weight.

11. The method of claim 1 wherein said lipid emulsion composition is administered at a steady rate of about 0.25 ml to about 0.5 ml per kilogram of the patient'"'"'s weight per minute for a time period of about 30 minutes to about 60 minutes.

12. The method of claim 1 wherein an initial bolus of the lipid emulsion composition between about 1.0 ml to about 3.0 ml per kilogram of the patient'"'"'s weight is administered to the patient for a period of about 30 seconds to about 60 seconds.

13. The method of claim 1 wherein the patient receiving the lipid emulsion composition is in asystole.

14. A kit for use in the method of claim 1 comprising:

a) a lightweight container;

b) a sterile syringe suitable for intravenously injecting the contents of the syringe into the patient;

c) a lipid emulsion composition contained within the syringe, wherein the lipid emulsion comprises between about 10 and about 40 percent oil by weight, about 1 to about 5 percent emulsifier by weight, about 1 to about 5 percent tonicity modifier by weight, and about 58 to about 88 percent water by weight; and

d) printed instructions for administration of said lipid emulsion composition for the treatment of severe systemic shock.

15. The kit of claim 14 further comprising a nomogram showing the preferred dose of the lipid emulsion composition to be administered to the patient according to weight of the patient.

16. The kit of claim 14 wherein the lipid emulsion comprises between about 10 and about 30 percent oil by weight, about 1 to about 5 percent emulsifier by weight, about 1 to about 5 percent tonicity modifier by weight, and about 68 to about 88 percent water by weight.

17. The kit of claim 14 wherein the lipid emulsion comprises about 20 percent vegetable oil by weight, about 2 percent glycerin by weight, about 1 percent egg yolk phospholipid by weight, and about 77 percent water by weight.

18. A kit for use in the method of claim 1 comprising:

a) a lightweight container;

b) a sterile medical bag;

c) intravenous tubing having one end fluidly connected to the medical bag and a second end fluidly connected to a needle or cannulae suitable for insertion into a vein;

c) a lipid emulsion composition contained within the medical bag, wherein the lipid emulsion comprises between about 10 and about 40 percent oil by weight, about 1 to about 5 percent emulsifier by weight, about 1 to about 5 percent tonicity modifier by weight, and about 58 to about 88 percent water by weight; and

d) printed instructions for administration of said lipid emulsion composition for the treatment of severe systemic shock.

19. The kit of claim 18 further comprising a nomogram showing the preferred dose of the lipid emulsion composition to be administered to the patient according to weight of the patient.

20. The kit of claim 18 wherein the lipid emulsion comprises between about 10 and about 30 percent oil by weight, about 1 to about 5 percent emulsifier by weight, about 1 to about 5 percent tonicity modifier by weight, and about 68 to about 88 percent water by weight.