# US 11,077,083 B2 · Oils with anti-inflammatory activity containing natural Specialized Proresolving Mediators and their precursors

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- Number: US 11,077,083 B2
- Document ID: US11077083B2
- Status: Granted
- Kind: B2
- Application number: 16/297,240
- Filed: 2019-03-08
- Published: 2019-07-04
- Granted: 2021-08-03
- Earliest claimed: 2012-05-10
- Assignees: Solutex NA LLC
- Applicants: Solutex NA LLC
- Inventors: Gerhardus Lucas Bannenberg; Charles Nicholas Serhan; Fernando Moreno Egea
- Web page: https://patentgrep.com/patent/US11077083B2

## CPC

- A61K 31/202: having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557)
- A61K 31/557: Eicosanoids, e.g. leukotrienes {or prostaglandins}
- A61K 35/60: Fish, e.g. seahorses; Fish eggs
- A61K 35/612: Crustaceans, e.g. crabs, lobsters, shrimps, krill or crayfish; Barnacles
- A61K 35/618: Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
- A61K 36/02: Algae
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention encompasses oils that have anti-inflammatory or resolution-stimulating activity that contain or are enriched with Specialized Proresolving Mediators (SPM) or SPM precursors, which originate from an oil obtained from organisms containing long chain omega-3 polyunsaturated fatty acids, such as fish, crustaceae, algae, and mollusks. The invention also encompasses a method for the production of these oils, and the utilization of the oils for nutritional supplements, pharmaceutical formulations, and cosmetic formulations, which can be employed for treating an inflammatory condition.

## Claims

### Claim 1

A composition comprising a plurality of triglycerides each having a glycerol backbone and three fatty acids chemically bound thereto, wherein
at least one of the plurality of triglycerides has 18-hydroxy-eicosapentaenoic acid (18-HEPE) as one of the fatty acids chemically bound thereto, at least one of the plurality of triglycerides has 17-hydroxy-docosahexaenoic acid (17-HDHA) as one of the fatty acids chemically bound thereto, at least one of the plurality of triglycerides has 14-hydroxy-docosahexaenoic acid (14-HDHA) as one of the fatty acids chemically bound thereto, at least one of the plurality of triglycerides has 10-hydroxy-docosahexaenoic acid (10-HDHA) as one of the fatty acids chemically bound thereto, at least one of the plurality of triglycerides has 4-hydroxy-docosahexaenoic acid (4-HDHA) as one of the fatty acids chemically bound thereto and wherein each of the plurality of triglycerides has as at least one of the fatty acids chemically bound thereto docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), or both, wherein the 17-HDHA is present in an amount of at least about 100 mg/L, and wherein the composition is encapsulated in a capsule shell.

### Claim 2 (depends on 1)

The composition of claim 1, wherein each of the plurality of triglycerides has one of the fatty acids chemically bound thereto selected from the group consisting of:
resolvin E1 (RvE1; 5S,12,18-trihydroxy-eicosa-6Z,8E,10E,14Z,16E-pentaenoic acid);
18S-resolvinE1 (18S-RvE1; 5S,12R,18S-trihydroxy-eicosa-6Z,8E,10E,14Z,16E-pentaenoic acid);
20-hydroxy-RvE1 (5S,12R,18R,20-tetrahydroxy-eicosa-6Z,8E,10E,14Z,16E-pentaenoic acid);
resolvin E2 (RvE2; 5S,18-dihydroxy-eicosa-6E,8Z,11Z,14Z,16E-pentaenoic acid);
resolvin E3 (RvE3; 17,18R-dihydroxy-eicosa-5Z,8Z,11Z,13E,15E-pentaenoic acid);
18S-resolvinE3 (18S-RvE3; 17,18S-dihydroxy-eicosa-5Z,8Z,11Z,13E,15E-pentaenoic acid);
17,18-epoxy-eicosa-5Z,8Z,11Z,13E,15E-pentaenoic acid;
lipoxin A5 (LXA5; 5S,6R,15S-trihydroxy-eicosa-7E,9E,11Z,13E,17Z-pentaenoic acid);
15-epi-lipoxin A5 (LXA5; 5S,6R,15R-trihydroxy-eicosa-7E,9E,11Z,13E,17Z-pentaenoic acid);
maresin 1 (MaR1; 7R,14S-dihydroxy-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid);
7S-maresin 1 (7S-MaR1; 7S,14S-dihydroxy-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid);
7S,14S-diHDHA (7S,14S-dihydroxy-docosa-4Z,8E,10Z,12E,16Z,19Z-hexaenoic acid);
protectin D1 (PD1; 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid);
10S,17S-diHDHA (10S,17S-dihydroxy-docosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic acid);
14S,21S-diHDHA (14S,21S-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid);
14S,21R-diHDHA (14S,21R-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid);
14R,21S-diHDHA (14R,21S-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid);
14R,21R-diHDHA (14R,21R-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid);
13S,14S-epoxy-DHA (13S,14S-epoxy-docosa-4Z,7Z,9E,11E,16Z,19Z-hexaenoic acid);
16,17S-diHDHA (16,17S-dihydroxy-docosa-4Z,7Z,10Z,12E,14E,19Z-hexaenoic acid);
16,17-epoxy-DHA (16,17-epoxy-docosa-4Z,7Z,10Z,12E,14E,19Z-hexaenoic acid);
resolvin D1 (RvD1; 7S,8R,17S-trihydroxy-docosa-4Z,9E,11E,13Z,15E,19Z-hexaenoic acid);
resolvin D2 (RvD2; 7S,16R,17S-trihydroxy-docosa-4Z,8E,10Z,12E,14E,19Z-hexaenoic acid);
resolvin D3 (RvD3; 4S,11R,17S-trihydroxy-docosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid);
resolvin D4 (RvD4; 4S,5,17S-trihydroxy-docosa-6E,8E,10Z,13Z,15E,19Z-hexaenoic acid);
resolvin D5 (RvD5; 7S,17S-dihydroxy-docosa-5Z,8E,10Z,13Z,15E,19Z-hexaenoic acid);
resolvin D6 (RvD6; 4S,17S-dihydroxy-docosa-5E,7Z,10Z,14Z,16E,19Z-hexaenoic acid);
aspirin-triggered resolvin D1 (AT-RvD1; 7S,8R,17R-trihydroxy-docosa-4Z,9E,11E,13Z,15E, 19Z-hexaenoic acid);
aspirin-triggered resolvin D2 (AT-RvD2; 7S,16R,17R-trihydroxy-docosa-4Z,8E,10Z,12E,14E,19Z-hexaenoic acid);
aspirin-triggered resolvin D3 (AT-RvD3; 4S,11,17R-trihydroxy-docosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid);
aspirin-triggered resolvin D4 (AT-RvD4; 4S,5,17R-trihydroxy-docosa-6E,8E,10Z,13Z,15E,19Z-hexaenoic acid);
aspirin-triggered resolvin D5 (AT-RvD5; 7S,17R-dihydroxy-docosa-5Z,8E,10Z,13Z,15E,19Z-hexaenoic acid);
aspirin-triggered resolvin D6 (AT-RvD6; 4S,17R-dihydroxy-docosa-5E,7Z,10Z,14Z,16E,19Z-hexaenoic acid);
7S,17S-diHDPA n-3 (7S,17S-dihydroxy-docosa-8E,10Z,13Z,15Z,19Z-pentaenoic acid (ω-3));
lipoxin A4 (LXA4; 5S,6R,15S-trihydroxy-eicosa-7E,9E,11Z,13E-tetraenoic acid);
15-epi-lipoxin A4 (15-epi-LXA4; 5S,6R,15R-trihydroxy-eicosa-7E,9E,11Z,13E-tetraenoic acid);
delta 12-prostaglandin J2 (delta12-PGJ2; 11-oxo-15S-hydroxy-prosta-5Z,9,12E-trienoic acid);
15-deoxy-delta12,14-prostaglandin J2 (15-deoxy-delta12,14-PGJ2; 11-oxo-prosta-5Z,9,12E,14E-tetraenoic acid);
11(12)-epoxy-eicosatetraenoic acid (11(12)-EpETE; 11(12)-epoxy-eicosa-5Z,8Z,14Z,17Z-tetraenoic acid);
17(18)-epoxy-eicosatetraenoic acid (17(18)-EpETE; 17(18-epoxy-eicosa-5Z,8Z,11Z,14Z-tetraenoic acid);
19(20)-epoxy-docosapentaenoic acid (19(20)-EpDPE; 19(20)-epoxy-docosa-4Z,7Z10Z,13Z,16Z-pentaenoic acid);
10S,17S-diHDPA n-6 (10S,17S-dihydroxy-docosa-4Z,7Z,11E,13Z,15E-pentaenoic acid);
7,17-diHDPA n-6 (7,17-dihydroxy-docosa-4Z,8E,10Z,13Z,15E-pentaenoic acid);
7,14-diHDPA n-6 (7,14-dihydroxy-docosa-4Z,8E,10Z,12Z,16Z-pentaenoic acid);
10S,17S-diHDPA n-6 (10S,17S-dihydroxy-docosa-7Z,11E,13Z,15E,19Z-pentaenoic acid); and
7, 17-diHDPA n-6 (7,17 dihydroxy-docosa-8E,10Z,13Z,15E,19Z-pentaenoic acid).

### Claim 3 (depends on 1)

The composition of claim 1, wherein each of the plurality of triglycerides has as one of the fatty acids chemically bound thereto selected from the group consisting of:
5S-HEPE (5S-hydroxy-eicosa-6E,8Z,11Z,14Z,17Z-pentaenoic acid);
11S-HEPE (11S-hydroxy-eicosa-5Z,8Z,12E,14Z,17Z-pentaenoic acid);
12S-HEPE (12S-hydroxy-eicosa-5Z,8Z,10E,14Z,17Z-pentaenoic acid);
12R-HEPE (12R-hydroxy-eicosa-5Z,8Z,10E,14Z,17Z-pentaenoic acid);
15S-HEPE (15S-hydroxy-eicosa-5Z,8Z,11Z,13E,17Z-pentaenoic acid);
7S-HDHA (7S-hydroxy-docosa-4Z,8E,10Z,13Z,16Z,19Z-hexaenoic acid);
20S-HDHA (20S-hydroxy-docosa-4Z,7Z,10Z,13Z,16Z,19Z-hexaenoic acid);
17S-HDPAn-6 (17S-hydroxy-docosa-4Z,7Z,10Z, 13Z, 15E-pentaenoic acid);
14S-HDPAn-6 (14S-hydroxy-docosa-4Z,7Z,10Z,12E,16Z-pentaenoic acid);
10S-HDPAn-6 (10S-hydroxy-docosa-4Z,7Z,11E,13Z,16Z-pentaenoic acid);
17S-HDPAn-3 (17S-hydroxy-docosa-7Z,10Z,13Z,15E,19Z-pentaenoic acid);
14S-HDPAn-3 (14S-hydroxy-docosa-7Z,10Z,12E,16Z,19Z-pentaenoic acid);
10S-HDPAn-6 (10S-hydroxy-docosa-7Z,11E,13Z,16Z,19Z-pentaenoic acid);
15S-HETE (15S-hydroxy-eicosa-5Z,8Z,11Z,13E-tetraenoic acid); and
15R-HETE (15R-hydroxy-eicosa-5Z,8Z,11Z,13E-tetraenoic acid).

### Claim 4 (depends on 1)

The composition of claim 1, wherein the 17-HDHA includes both 17S-HDHA (14S-hydroxy-docosa-4Z,7Z,10Z,13Z,15E,19Z-hexaenoic acid) and 17R-HDHA (17R-hydroxy-docosa-4Z,7Z,10Z,13Z,15E,19Z-hexaenoic acid).

### Claim 5 (depends on 1)

The composition of claim 1, wherein the 18-HEPE includes both 18S-HEPE (18S-hydroxy-eicosa-5Z,8Z,11Z,14Z,16E-pentaenoic acid) and 18R-HEPE (18R-hydroxy-eicosa-5Z,8Z,11Z,14Z,16E-pentaenoic acid).

### Claim 6 (depends on 1)

The composition of claim 1, wherein the 10-HDHA includes both 10S-HDHA (10S-hydroxy-docosa-4Z,7Z,11E,13Z,16Z,19Z-hexaenoic acid) and 11S-HDHA (11S-hydroxy-docosa-4Z,7Z,9E,13Z,16Z,19Z-hexaenoic acid).

### Claim 7 (depends on 1)

The composition of claim 1, wherein the 4-HDHA is 4S-HDHA (4S-hydroxy-docosa-5E,7Z,10Z,13Z,16Z,19Z-hexaenoic acid).

### Claim 8 (depends on 1)

The composition of claim 1, wherein the 14-HDHA includes both 14S-HDHA (14S-hydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic) and 14R-HDHA (14R-hydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid).

### Claim 9 (depends on 1)

The composition of claim 1, further comprising a carrier or an excipient.

### Claim 10 (depends on 1)

The composition of claim 1 having anti-inflammatory or resolution-stimulating activity.

### Claim 11 (depends on 1)

A method of lowering macroscopic and physical signs of inflammation in a subject in need thereof comprising, administering an effective amount of the composition of claim 1 to the subject.

### Claim 12 (depends on 1)

A method of treating an inflammatory condition in a subject in need thereof comprising, administering an effective amount of the composition of claim 1 to the subject.

### Claim 13 (depends on 1)

The composition of claim 1, wherein the composition is a pharmaceutical composition or a dietary supplement.

### Claim 14 (depends on 1)

The composition of claim 1 having anti-inflammatory and resolution-stimulating activity.

### Claim 15 (depends on 1)

The composition of claim 1, wherein the plurality of triglycerides are remodeled triglycerides.

### Claim 16 (depends on 1)

The composition of claim 1 having resolution-stimulating activity.