Composition containing eicosapentaenoic acid alkyl ester, and method for producing same

Patent metadata

Field	Value
Publication number	US-9918953-B2
Application number	US-201515511757-A
Country	US
Kind code	B2
Filing date	Sep 17, 2015
Priority date	Sep 17, 2014
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

Provided are: an eicosapentaenoic acid alkyl ester-ontaining composition which comprises 96-99 area % of an eicosapentaenoic acid alkyl ester, wherein the content of an arachidonic acid alkyl ester is 0.7 area % or less, and the content of mono-trans forms of the eicosapentaenoic acid alkyl ester is 2.5 area % or less; a method for producing a high-concentration eicosapentaenoic acid alkyl ester-containing composition, which comprises performing rectification on an eicosapentaenoic acid alkyl ester-containing composition with the degree of vacuum being 0.2 Torr or less and at a whole-column temperature 190° C. or less, and performing a concentration treatment on the rectified composition using chromatography, the eicosapentaenoic acid alkyl ester-containing composition being obtained by alkyl esterifying a feed oil containing eicosapentaenoic acid.

First claim

The invention claimed is:

1. An eicosapentaenoic acid alkyl ester-containing composition which, upon measurement by gas chromatography, comprises 96-99 area % of an eicosapentaenoic acid alkyl ester, wherein the content of an arachidonic acid alkyl ester is 0.7 area % or less, and the content of mono-trans forms of the eicosapentaenoic acid alkyl ester is 2.5 area % or less.

2. The composition of claim 1 , wherein the sum of the contents of mono-trans forms and di-trans forms of the eicosapentaenoic acid alkyl ester is 2.5 area % or less.

3. The composition of claim 1 , wherein the sum of the contents of mono-trans forms, di-trans forms and tri-trans forms of the eicosapentaenoic acid alkyl ester is 2.5 area % or less.

4. The composition of claim 1 , wherein the sum of the contents of mono-trans forms, di-trans forms, tri-trans forms and tetra-trans forms of the eicosapentaenoic acid alkyl ester is 2.5 area % or less.

5. The composition of claim 1 , wherein the content of any one of the mono-trans forms of the eicosapentaenoic acid alkyl ester in which any one of the double bonds at 5-, 14-, and 17-positions thereof is trans is 0.5 area % or less.

6. The composition of claim 1 , wherein the content of a mono-trans form of the eicosapentaenoic acid alkyl ester in which the double bond at 11-position thereof is trans is 1.0 area % or less.

7. A composition which, upon measurement by gas chromatography under the following analytical conditions, comprises 96-99 area % of ethyl eicosapentaenoate, wherein the content of an ethyl arachidonate is 0.7 area % or less, and wherein the sum of the contents of substances whose relative retention times appear as peaks at about 0.955, 1.027, 1.062 or 1.077, with the mean retention time of ethyl eicosapentaenoate being taken as unity, is 2.5 area % or less:
[gas chromatographic analysis conditions: GC-FID measurement conditions]
GC: 6890N (Agilent Technologies)
Column: DB-WAX (Agilent Technologies)
30 m x 0.25 mm ID, 0.25 μm in film thickness

Carrier gas: helium, 0.5 mL/min
Injection port: 300° C., 1μL, Split (1:100)
Column temperature: 200° C. (constant)
Detector: FID, 300° C.
Makeup gas: nitrogen, 40 mL/min.

8. The composition of claim 1 , wherein the arachidonic acid alkyl ester content is 0.1 area % or less.

9. The composition of claim 1 , wherein the content of an eicosatetraenoic acid alkyl ester is 0.7 area % or less.

10. The composition of claim 1 , wherein the content of an octadecatetraenoic acid alkyl ester is 0.4 area % or less.

11. The composition of claim 1 , wherein the content of a nonadecapentaenoic acid alkyl ester is 0.2 area % or less.

12. The composition of claim 1 , wherein the eicosapentaenoic acid alkyl ester is ethyl eicosapentaenoate or methyl eicosapentaenoate.

13. The composition of claim 1 , wherein the content of a n-nonadecanoic acid (C19:0) alkyl ester is 0.1 area % or less.

14. The composition of claim 1 , wherein the content of an arachidic acid (C20:0) alkyl ester is 0.2 area % or less.

15. The composition of claim 1 , wherein the content of alkyl esters of saturated fatty acids is 0.5 area % or less.

16. The composition of claim 1 , wherein the content of an icosa-5,9,11,14,17-pentaenoic acid (C20:5n-3(5,9,11,14,17)) alkyl ester is 0.2 area % or less.

17. The composition of claim 1 , wherein the content of a henicosapentaenoic acid alkyl ester is 0.2 area % or less.

18. The composition of claim 1 , wherein the content of the eicosapentaenoic acid alkyl ester is 96-98 area %.

19. The composition of claim 1 , wherein the content of a dihomo-γ-linolenic acid alkyl ester is 0.05 area % or less.

20. The composition of claim 1 , wherein the content of alkyl esters of monounsaturated fatty acids with carbon number of 20 or more is 0.05 area % or less.

21. A pharmaceutical composition comprising the eicosapentaenoic acid alkyl ester-containing composition of claim 1 as an effective component.

22. The pharmaceutical composition of claim 21 further comprising a pharmaceutically acceptable additive component.

23. The pharmaceutical composition of claim 21 which is a therapeutic agent for at least one disease selected from the group consisting of arteriosclerosis, cerebral infarct, cardiovascular infarct, thrombosis, lifestyle-related diseases, allergies, and inflammatory diseases.

24. A method for producing high-concentration ethyl eicosapentaenoate, comprising ethyl esterifying a feed oil containing eicosapentaenoic acid and thereafter performing distillation and chromatography, wherein the distillation is carried out by performing rectification with the degree of vacuum being 0.2 Torr or less and at a whole-column temperature of 190° C. or less, whereby the content of ethyl arachidonate is reduced while suppressing the generation of a trans form due to heat.

25. A method for producing a high-concentration eicosapentaenoic acid alkyl ester-containing composition, which comprises:
performing rectification on an eicosapentaenoic acid alkyl ester-containing composition with the degree of vacuum being 0.2 Torr or less and at a whole-column temperature 190° C. or less, the eicosapentaenoic acid alkyl ester-containing composition being obtained by alkyl esterifying a feed oil containing eicosapentaenoic acid; and
performing a concentration treatment on the rectified composition using chromatography.

26. The method of claim 25 , wherein the alkyl esterification is performed using a lower alcohol with carbon number 1 or carbon number 2.

27. The method of claim 24 , wherein the eicosapentaenoic acid alkyl ester-containing composition of claim 1 is obtained by carrying out rectification and chromatography.

28. The method of claim 24 , wherein the rectification is continuous rectification using two or more distillation columns.

29. The method of claim 24 , wherein the chromatography is reverse-phased chromatography.

30. The method of claim 24 , wherein the feed oil is an oil or fat derived from a marine product as a feed.

31. A food comprising the eicosapentaenoic acid alkyl ester-containing composition of claim 1 .

32. A method of disease treatment, or relief comprising administering the pharmaceutical composition of claim 21 to a subject who is affected with at least one disease selected from the group consisting of arteriosclerosis, cerebral infarct, cardiovascular infarct, thrombosis, lifestyle-related diseases, allergies, and inflammatory diseases.

Assignees

• Nippon Suisan Kaisha Ltd
• Mochida Pharm Co Ltd

Inventors

• Doisaki Nobushige
• Arato Shingo
• Fukae Takuro

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title