Reperfusion with omega-3 glycerides promotes donor organ protection for transplantation

Patent metadata

Field	Value
Publication number	US-11076593-B2
Application number	US-201816113407-A
Country	US
Kind code	B2
Filing date	Aug 27, 2018
Priority date	Mar 28, 2013
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

It has been discovered that isolated organs and tissues perfused/reperfused in perfusion buffer to which omega-3 glyceride oil had been added retain higher levels of function than if perfused/reperfused without the omega-3 glycerides. Isolated hearts reperfused ex vivo after induced ischemia in n-3 triglyceride perfusion emulsion maintained a normal heart rate and normal LVDP and showed a dramatically reduced frequency of arrhythmias compared to control hearts. Further, test hearts reperfused with n-3 oil triglyceride emulsion showed a decrease in creatine kinase and upregulation of certain beneficial proteins including the anti-apoptotic gene marker Bcl-2.

First claim

What is claimed is:

1. An omega-3 oil in water emulsion application for perfusion of an organ or tissue ex vivo, wherein the emulsion comprises
(a) a perfusion buffer suitable for organ or tissue preservation and transplantation,
(b) from 0.05% to 0.5% of an omega-3 oil by weight in grams per 100 ml of perfusion buffer, wherein the omega-3 oil
(i) comprises from about 10% to about 99% omega-3 diglyceride, omega-3 triglyceride or combinations thereof by weight per total weight of the omega-3 oil, and at least about 20% to about 99% of the total acyl groups of the diglycerides and triglycerides comprise EPA or DHA or combinations thereof, and
(ii) comprises less than 10% omega-6 fatty acids by weight per total weight of the omega-3 oil,
(c) less than 10% omega-6 oil by weight in grams per 100 ml of perfusion buffer, and
(d) the mean diameter of lipid droplets in the emulsion is from about 100 nm to less than about 5 microns.

2. The omega-3 oil in water emulsion of claim 1 , wherein the emulsion comprises from about 0.05% to about 0.3% in grams per 100 ml of perfusion buffer.

3. The omega-3 oil in water emulsion of claim 1 , wherein from about 20% to about 40% of the total acyl groups of the omega-3 diglycerides and triglycerides comprise EPA, DHA or a combination thereof.

4. The omega-3 oil in water emulsion of claim 1 , wherein from about 40% to about 60% of the total acyl groups of the omega-3 diglycerides and triglycerides comprise EPA, DHA or a combination thereof.

5. The omega-3 oil in water emulsion of claim 1 , from about 60% to about 80% of the total acyl groups of the omega-3 diglycerides and triglycerides comprise EPA, DHA or a combination thereof.

6. The omega-3 oil in water emulsion of claim 1 , from about 80% to about 99% of the total acyl groups at the omega-3 diglycerides and triglycerides comprise EPA, DHA or a combination thereof.

7. The omega-3 oil in water emulsion of claim 1 , wherein the lipid droplets are less than about 1 micron in diameter.

8. The omega-3 oil in water emulsion of claim 1 , wherein the lipid droplets are from about 100 nm to about 500 nm in diameter.

9. The omega-3 oil in water emulsion of claim 1 , wherein the perfusion buffer comprises an aqueous solution at a physiologic pH.

10. An omega-3 oil in water emulsion for cold storage of an organ or tissue ex vivo, wherein the emulsion comprises
(a) storage solution suitable for organ or tissue preservation and transplantation,
(b) from about 0.05% less than 0.5% of an omega-3 oil by weight in grams per 100 ml of the storage solution suitable for organ or tissue preservation and transplantation, wherein the omega-3 oil
(i) comprises from about 10% to about 99% omega-3 diglyceride, omega-3 triglyceride or combinations thereof by weight per total weight of the omega-3 oil, and at least about 20% to about 99% of the total acyl groups of the diglycerides and triglycerides comprise EPA or DHA, and
(ii) comprises less than 10% omega-6 fatty acids by weight per total weight of the omega-3 oil,
(c) less than 10% omega-6 oil by weight in grams per 100 ml of perfusion buffer, and
(d) the mean diameter of lipid droplets in the emulsion is from about 100 nm to less than about 5 microns.

Assignees

• Univ Columbia

Inventors

• Deckelbaum Richard J
• Ramasamy Ravichandran

Classifications

• A01N1/126 Primary

  Physiologically active agents, e.g. antioxidants or nutrients · CPC title

• A61K31/202

  having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557) · CPC title

• A01N1/0226 Primary

  Human Necessities · mapped topic