PROCESS FOR INCREASING THE STABILITY OF A COMPOSITION COMPRISING POLYUNSATURATED OMEGA-3 FATTY ACIDS

Abstract

A process for increasing the stability of a composition containing a polyunsaturated omega-3 fatty acid against oxidation proceeds by (i) providing a starting composition containing at least one polyunsaturated omega-3 fatty acid component; (ii) providing a lysine composition; (iii) admixing an aqueous, an aqueous-alcoholic or an alcoholic solution of starting composition and lysine composition, and subjecting resulting admixture to spray drying conditions subsequently, thus forming a solid product composition containing at least one salt of a cation derived from lysine with an anion derived from a polyunsaturated omega-3 fatty acid; the product composition exhibiting a solvent content SC selected from the following: SC<5 wt %, SC<3 wt %, SC<1 wt %, or SC<0.5 wt %.

Claims

1. A process for increasing the stability towards oxidation of a composition comprising a polyunsaturated omega-3 fatty acid, said process comprising: (i) providing a starting composition comprising at least one polyunsaturated (i) omega-3 fatty acid component; (ii) providing a lysine composition; (iii) admixing an aqueous, an aqueous-alcoholic or an alcoholic solution of starting composition and lysine composition, and subjecting a resulting admixture to spray drying conditions subsequently, thus forming a solid product composition comprising at least one salt of a cation derived from lysine with an anion derived from a polyunsaturated omega-3 fatty acid; the product composition exhibiting a solvent content SC selected from the following: SC<5 wt %, SC<3 wt %, SC<1 wt %, or SC<0.5 wt %.

2. The process according to claim 1, wherein lysine composition in (ii) is provided in such a manner that the ratio R=n(ca)/n(lys) of the amount of carboxylic acid functions n(ca) in the starting composition provided in (i) and the amount of lysine n(lys) in the lysine composition provided in (ii) is in a range selected from 0.9<R<1.1, 0.95<R<1.05, or 0.98<R<1.02.

3. The process according to claim 1, wherein the starting composition provided in (i) does not contain more than x(fe) wt % of fatty acid esters, wherein x(fe) is selected from 5, 3, 2, 1, 0.3, or 0.

4. The process according to claim 1, wherein starting composition in (i) and lysine composition in (ii) are provided in such a manner that at least sp wt % of the product composition consist of one or more salts of cations derived from lysine with anions derived from one or more polyunsaturated omega-3 fatty acids and other naturally occurring fatty acids, wherein sp is selected from 90, 95, 97, 98, 99, or 100.

5. A composition obtainable by a process according to claim 1.

6. The process according to claim 1, wherein said starting composition is a food comprising a polyunsaturated omega-3 fatty acid.

7. The process according to claim 1, wherein said starting composition is a nutritional product comprising a polyunsaturated omega-3 fatty acid.

8. The process according to claim 1, wherein said starting composition is a pharmaceutical product comprising a polyunsaturated omega-3 fatty acid.

Description

EXPERIMENTS

[0166] Analytical Methods:

[0167] Primary oxidation products (hydroperoxides at double bonds) were quantified by determining the Peroxide Value (PV) according to Ph. Eur. 2.5.5 (01/2008:20505). Secondary oxidation products (carbonyl compounds) were quantified by determining the Anisidine Value (AV) according to Ph. Eur. 2.5.36 (01/2008:20536).

[0168] Oligomeric PUFA constituents as well as their derivatives (collectively referred to as oligomer content) were quantified by gel-chromatographic means (GPC, styroldivinylbenzene-phase with tetrahydrofuran containing trifluoroacetic acid used as eluent). A refractive index (RI) detector was used for detection. Due to the fact that specific response factors of the constituents of the samples were unknown, proportions were calculated based upon fractional proportions of the total area of chromatograms.

[0169] Water content was determined by Karl-Fischer titration.

[0170] Ethanol content was determined by 1-H-NMR spectroscopy.

[0171] Acid values were determined by titration with potassium hydroxide.

Experiment 1: Eicosapentaenoic Acid (EPA) from Eicosapentaenoic Acid Ethyl Ester (EPA-OEt)

[0172] 5.00 kg of (commercially available, standard quality) eicosapentaenoic acid ethyl ester (EPA-OEt) with calculated EPA-content of 92.0% (92.0 wt % free EPA of total weight), an Anisidine Value of 5.0 A/g, a Peroxide Value of 6.5 mmol/kg and an oligomer content of 0.2 area-% (gel-chromatography, RI-detector) was placed in a 30 L double jacket vessel (rendered inert with nitrogen) and diluted with 5.0 L ethanol. 1.6 kg of NaOH (50%) solution was added and the resulting solution stirred for 30 min at 30° C.-50° C. Subsequently, the reaction mixture was diluted with 15 L of water and 1.4 L of phosphoric acid (85%) was added thereafter. Phases were separated after 10 min of subsequent stirring and the product phase was washed with 5 L of water. 4.639 kg eicosapentaenoic acid was obtained as an oil with an Anisidine Value of 3.1 A/g and a Peroxide Value of 8.6 mmol/kg. Oligomer content was not determined.

Experiment 2: Docosahexaenoic Acid (DHA) from Docosahexaenoic Acid Ethyl Ester (DHA-OEt)

[0173] 5.00 kg of docosahexaenoic acid ethyl ester (commercially available, standard quality) with a calculated DHA content of 82.8% (82.8 wt % free DHA of total weight) and a total omega-3 PUFA content of 92.8% (92.8 wt % free omega-3PUFAs of total weight), an Anisidine Value of 16.0 A/g, a Peroxide Value of 26.1 mmol/kg and an oligomer content of 0.4 area-% (gel-chromatography, RI-detector) was placed in a 30 L double jacket vessel (rendered inert with nitrogen) and diluted with 5.0 L ethanol. 1.6 kg of NaOH (50%) solution was added and the resulting solution stirred for 30 min at 30° C.-50° C. Subsequently, the reaction mixture was diluted with 15 L of water and 1.4 L of phosphoric acid (85%) was added thereafter. Phases were separated after 10 min of subsequent stirring and the product phase was washed with 5 L of water. 4.622 kg docosahexaenoic acid was obtained as an oil with an Anisidine Value of 1.7 A/g and a Peroxide Value of 7.9 mmol/kg. Oligomer content was not determined.

Experiment 3: Eicosapentaenoic Acid-L-Lysine Salt (EPA-Lys) from Eicosapentaenoic Acid (EPA) and L-lysine (L-Lys)

[0174] 2.00 kg of eicosapentaenoic acid from experiment 1, exhibiting an acid value of 177.8 mg KOH/g upon titration, was dissolved in 2 kg of ethanol and combined with 1.69 kg of an aqueous L-lysine solution (51.3 wt-%). The homogenous solution obtained was spray dried with a custom built spray drier equipped with a two-substance nozzle and a 300 mm×900 mm drying chamber with an inlet temperature of 170° C. and an outlet temperature of 80° C. 1.798 kg of a beige powder with a water content of 0.24% and an ethanol content of <0.1% were obtained. The salt exhibited an Anisidine Value of 2.1 A/g and a Peroxide Value of 1.3 mmol/kg. Oligomer content was not determined.

Experiment 4: Docosahexaenoic Acid-L-Lysine salt (DHA-Lys) from Docosahexaenoic Acid (DHA) and L-lysine (L-Lys)

[0175] 2.00 kg of docosahexaenoic acid from experiment 2, exhibiting an acid value of 166.3 mg KOH/g upon titration, was dissolved in 2.0 kg of ethanol and combined with 1.81 kg of an aqueous L-lysine solution (51.3 wt-%). The homogenous solution obtained was spray dried with a custom built spray drier equipped with a two-substance nozzle and a 300 mm×900 mm drying chamber with an inlet temperature of 170° C. and an outlet temperature of 80° C. 1.892 kg of a beige powder with a water content of 0.27% and an ethanol content of <0.1% were obtained. The salt exhibited an Anisidine Value of 3.1 A/g and a Peroxide Value of 1.7 mmol/kg. Oligomer content was not determined

Experiment 5: Eicosapentaenoic Acid-Sodium Salt (EPA-Na) from Eicosapentaenoic Acid (EPA) and NaOH

[0176] 50 g of eicosapentaenoic acid obtained analogously to experiment 1, exhibiting an acid value of 183.3 mg KOH/g upon titration, was dissolved in 50 ml of ethanol and combined under stirring with 6.54 g sodium hydroxide in 30 ml of water. The homogenous solution obtained was spray dried with a Buchi B190 laboratory-spray drier with an inlet temperature of 140° C. and an outlet temperature of about 80° C. 28.6 g of a faintly beige powder were obtained. After storage for 3 months at room temperature the salt had obtained grey-coloured appearance and at that point exhibited an Anisidine Value of 41.1 A/g and a Peroxide Value of 5.0 mmol/kg. Oligomer content was determined as 2.4 area-% (gel-chromatography, RI-detector).

Experiment 6: Docosahexaenoic Acid—Sodium Salt (DHA-Na) from Docosahexaenoic Acid (DHA) and NaOH

[0177] 50 g of docosahexaenoic acid obtained analogously to experiment 2, exhibiting an acid value of 169.5 mg KOH/g upon titration, was dissolved in 50 ml of ethanol and combined under stirring with 6.04 g sodium hydroxide in 30 ml of water. The homogenous solution obtained was spray dried with a Büchi B190 laboratory-spray drier with an inlet temperature of 140° C. and an outlet temperature of about 80 ° C. 27.5 g of a faintly beige powder were obtained. After storage for 3 months at room temperature the salt had obtained grey-coloured appearance and at that point exhibited an Anisidine Value of 77.9 A/g and a Peroxide Value of 6.9 mmol/kg. Oligomer content was determined as 3.4 area-% (gel-chromatography, RI-detector).

Experiment 7: Examination of Stability of PUFAs and Derivatives Thereof as to the Storage at Elevated Temperature (50° C.) and Exposure to Air

[0178] About 50 g each of the liquid ethyl esters EPA-OEt and DHA-OEt used in experiments 1 and 2 as well as of the liquid fatty acids EPA and DHA obtained in experiments 1 and 2 were filled into 250 ml Schott Duran bottles with an inner diameter of about 60 mm (filling height about 20 mm). About 50 g each of the solid lysine-salts EPA-Lys and DHA-Lys obtained in experiments 3 and 4 were filled into 250 ml polyethylene wide-neck bottles (55 mm*55 mm*80 mm) (filling height about 60 mm-70 mm).

[0179] All of the bottles were placed together with opened lids in a drying oven with an opened ventilation valve at 50° C. and stored under these conditions for 26 days. Results of the analyses performed subsequently as well as the results obtained for the sodium-salts which were stored at room temperature (cf. experiments 5 and 6) are summarized in the following table (Table 1).

TABLE-US-00001 TABLE 1 Anisidine Value (AV) Peroxide Value (PV) Oligomer content [A/g] [mmol/kg] [area-%]* t = 26 t = 26 t = 26 Experiment t = 0 days t = 0 days t = 0 days EPA-OEt 1 - starting 5.0 1843    6.5 267.7  0.2 37.0 material DHA-OEt 2 - starting 16.0 1732    26.1 282.0  0.4 32.6 material EPA-OH 1 3.1 424   8.6 14.7 n.d. 20.6 DHA-OH 2 1.7 894   7.9 20.6 n.d. 34.7 EPA-Lys 3 2.1 <1.0 1.3 <1.0 n.d.  0.6 DHA-Lys 4 3.1 <1.0 1.7 <1.0 n.d.  0.9 EPA-Na 5 n.d.   41.1 ** n.d.    5.0 ** n.d.    2.4 ** DHA-Na 6 n.d.   77.9 ** n.d.    6.9 ** n.d.    3.4 ** *gel-chromatography, Rl-detector ** after 3 months at room temperature n.d. = not determined