Oils with anti-inflammatory activity containing natural specialized proresolving mediators and their precursors
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.
1. A method of reducing inflammation or stimulating resolution of inflammation in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising 18-hydroxy-eicosapentaenoic acid (18-HEPE), 17-hydroxy-docosahexaenoic acid (17-HDHA), 14-hydroxy-docosahexaenoic acid (14-HDHA), 10-hydroxy-docosahexaenoic acid (10-HDHA), and 4-hydroxy-docosahexaenoic acid (4-HDHA), wherein 17-HDHA is present in an amount of at least 100 mg/L.
2. The method of claim 1 , wherein the composition further comprises eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA).
3. The method of claim 1 , wherein 18-HEPE, 17-HDHA, 14-HDHA, 10-HDHA, and 4-HDHA are in a form selected from the group consisting of a free fatty-acid, an ester, a phospholipid, a mono-glyceride, a di-glyceride, a tri-glyceride, a remodeled tri-glyceride, and combinations thereof.
4. The method of claim 1 , wherein 18-HEPE, 17-HDHA, 14-HDHA, 10-HDHA, and 4-HDHA are in are in a form selected from the group consisting of an ethyl ester, a remodeled tri-glyceride, and combinations thereof.
5. The method of claim 4 , wherein 18-HEPE, 17-HDHA, 14-HDHA, 10-HDHA, and 4-HDHA are in the ethyl ester form.
6. The method of claim 4 , wherein 18-HEPE, 17-HDHA, 14-HDHA, 10-HDHA, and 4-HDHA are in the remodeled tri-glyceride form.
7. The method of claim 1 , wherein the composition further comprises a compound 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,6Z,19Z-hexaenoic acid),
11S-HDHA (11S-hydroxy-docosa-4Z,7Z,9E,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-4Z, 7Z,11E,13Z,16Z-pentaenoic acid),
15S-HETE (15S-hydroxy-eicosa-5Z,8Z,11Z,13E-tetraenoic acid).
8. The method of claim 1 , wherein said administration lowers macroscopic and physical signs of inflammation.
9. The method of claim 1 , wherein said administration treats pain relating to an inflammatory condition.
10. The method of claim 1 , wherein said administration stimulates resolution of inflammation.
11. A method of stimulating resolution of inflammation in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising fatty acids including 18-hydroxy-eicosapentaenoic acid (18-HEPE), 17-hydroxy-docosahexaenoic acid (17-HDHA), 14-hydroxy-docosahexaenoic acid (14-HDHA), 10-hydroxy-docosahexaenoic acid (10-HDHA), 4-hydroxy-docosahexaenoic acid (4-HDHA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), wherein the fatty acids are in ethyl ester form and the 17-HDHA is present in an amount of at least 100 mg/L.
12. The method of claim 11 , wherein the composition further comprises a compound 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,6Z,19Z-hexaenoic acid),
11S-HDHA (11S-hydroxy-docosa-4Z,7Z,9E,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-4Z, 7Z,11E,13Z,16Z-pentaenoic acid),
15S-HETE (15S-hydroxy-eicosa-5Z,8Z,11Z,13E-tetraenoic acid).
13. The method of claim 11 , wherein said administration lowers macroscopic and physical signs of inflammation.
14. The method of claim 11 , wherein said administration treats pain relating to an inflammatory condition.