# US 11,076,593 B2 · Reperfusion with omega-3 glycerides promotes donor organ protection for transplantation

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- Number: US 11,076,593 B2
- Document ID: US11076593B2
- Status: Granted
- Kind: B2
- Application number: 16/113,407
- Filed: 2018-08-27
- Published: 2019-01-03
- Granted: 2021-08-03
- Earliest claimed: 2013-03-28
- Assignees: The Trustees of Columbia University in the City of New York
- Applicants: The Trustees of Columbia University in the City of New York
- Inventors: Richard J. Deckelbaum; Ravichandran Ramasamy
- Web page: https://patentgrep.com/patent/US11076593B2

## CPC

- A01N 1/126: Physiologically active agents, e.g. antioxidants or nutrients
- A61K 31/202: having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 1)

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.

### Claim 9 (depends on 1)

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

### Claim 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.
