Abstract:
Foods, cosmetics and pharmaceuticals containing a lipid susceptible to oxidation are protected from oxidation by incorporating an effective amount of a coenzyme Q in a lipid phase of the food, cosmetic or pharmaceutical. Ascorbic acid and a phospholipid may be incorporated in combination with the coenzyme Q to provide synergistic protection from oxidation.

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This is a continuation application of application Ser. No. 07/589,047, filed Sep. 27, 1990, now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     This invention relates to a process for the protection of a fat or a food, cosmetic or pharmaceutical product containing a fat against oxidation and to the use of coenzyme Q as an antioxidant in a food, cosmetic or pharmaceutical product containing a fat. 
     It is known that the coenzyme Q (CoQ), or ubiquinone, which has been isolated from the lipids of mitochondria, is involved in the basic mechanisms of energy production by respiration, in the transport of electrons in mitochondria and in oxidative phosphorylation. Its antioxidant activity in biological media is known, cf. for example Littarru et al., Fats and Perspectives, Drugs exptl. clin. Res. X (7), 1491-496. However, in a different environment, such as a food, cosmetic or pharmaceutical product containing lipids, the oxidized form, namely quinone, could be expected to have no antioxidant activity because quinones are normally considered to be deactivation products of antioxidants of the hydroquinone type. 
     SUMMARY OF THE INVENTION 
     It has now unexpectedly been found that ubiquinone in its quinone form has a significant antioxidant activity in food, cosmetic or pharmaceutical products containing lipids, more particularly in oils rich in polyunsaturated fatty acids. 
     The process according to the invention is characterized in that an effective quantity of coenzyme Q is incorporated in the fat or in the food, cosmetic or pharmaceutical product. 
     DETAILED DESCRIPTION OF THE INVENTION 
     In the context of the invention, the term &#34;food product&#34; is to be understood in a broad sense encompassing products intended for human or animal consumption providing they contain lipids susceptible to oxidation. Similarly, a cosmetic or pharmaceutical product is to be understood in a broad sense intended for topical application or for oral, enteral or parenteral administration providing the product in question contains lipids susceptible to oxidation. 
     According to the invention, CoQ is understood to be a quinone derivative corresponding to the following formula ##STR1## in which n=6-10. The compound CoQ 10 , in which n=10, is preferred because it is the most common and, at present, is the only industrially available derivative. 
     In the process or the use according to the invention, the CoQ is incorporated in the lipid phase of the food, cosmetic or pharmaceutical product in a quantity of 0.1 to 5% by weight, based on the lipids present in the product. If less than 0.1% is added or used, there is a risk that the lipids of the product in question might not be adequately protected. If more than 5% is added or used, the level of protection obtained is not significantly greater than can be obtained by adding quantities in the range indicated. 
     In one preferred embodiment of the process according to the invention, the CoQ, which is liposoluble, is used in admixture with other antioxidants capable of producing a synergistic effect, for example water-soluble ascorbic acid (AA), in the presence of a natural emulsifier. 
     In the context of the invention, a &#34;natural emulsifier&#34; is understood to be any of the naturally occurring nonionic surfactants, for example saponins, or ionic surfactants, for example phospholipids, of animal or vegetable origin of milk, egg or soya, preferably lecithins, for example commercial lecithins, purified lecithins, soya lecithin fractions. The nature of the emulsifier used has only a secondary effect on the effect observed providing it is capable of forming a stable dispersion of AA in an anhydrous product, for example a fat or a food containing a fat or a cosmetic or pharmaceutical product containing a fat. It is preferred to use soya lecithins or fractions thereof which are abundant and economical. 
     The preferred antioxidant mixture suitable for use in accordance with the invention advantageously contains 2.5 to 10% and preferably around 5% of CoQ and 2.5 to 20% and preferably 5 to 20% of AA, based on the weight of natural emulsifier. 
     It is of course possible to use the mixture as such or to incorporate the various components of the mixture separately from the fat to be protected. In cases where, for example, the fat is a vegetable oil already naturally containining lecithin (LC), for example soybean oil, it is sufficient to add the CoQ and the AA in effective quantities. 
     In one advantageous embodiment of the preferred variant described above, the mixture is prepared by combining LC and CoQ with stirring at a temperature below or equal to 60° C., preferably while an inert gas, for example nitrogen, is bubbled through. The AA dissolved in a polar solvent, preferably of low boiling point, for example ethanol, is then progressively added to this premix, after which the solvent is eliminated at a temperature of 60° C., for example in a light vacuum. The mixture obtained is in the form of a transparent and viscous liquid. It may be used in different ways, for example by incorporation in a fat to be protected, preferably with heating, the mixture being at approximately 60° C., with vigorous stirring. 
     In another advantageous embodiment of the preferred variant described above, the AA and the CoQ are incorporated in the fat to which the lecithin has previously been added, preferably in the form of a solution in a polar solvent, for example ethyl alcohol, after which the solvent is eliminated. 
     The fats to be protected in accordance with the invention are preferably those most sensitive to oxidation, for example fats rich in unsaturated, particularly polyunsaturated, fatty acids, such as vegetable oils, for example wheat germ oil, grape seed oil, corn oil, soybean oil, safflower oil, olive oil, evening primrose oil, borage oil and, in particular, black currant seed oil. Animal fats susceptible to oxidation include chicken fat, butter oil, oils of marine animals, particularly fish oil. 
     The foods, cosmetic products or pharmaceutical products to be protected are preferably those containing such fats. 
     The invention is illustrated by the following Examples in which percentages and parts are by weight, unless otherwise indicated. 
    
    
     EXAMPLES 
     Example 1 
     Preparation of samples 
     Samples of 20 g oil stabilized by addition of ubiquinone CoQ 10  (formula I, n=10) in the quantity indicated are prepared and mixed while stirring, after which the samples are placed in lacquered, sterilized 200 ml tinplate cans in a quantity of 0.5 g stabilized oil per batch per can. The cans are hermetically sealed and stored at 37° C. 
     Accelerated oxidation test 
     The head space of the cans containing the samples are analyzed after a certain time (in days) by determining the contents of pentane and ethane as the respective degradation products of linoleic and α-linolenic acid by oxidation and also the residual oxygen content. For comparison, the same analyses are conducted with samples prepared without antioxidant. The pentane and ethane contents are determined by gas-phase chromatography while the oxygen content is determined by measurement of the paramagnetic susceptibility. 
     The results of this test are set out in Tables 1 and 2 below. 
     
                                           TABLE 1__________________________________________________________________________    Storage time (days)    9              13              14Fish oil Pentane          Ethane                O.sub.2                   Pentane                          Ethane                                O.sub.2                                   Pentane                                         Ethane                                               O.sub.2sample   M     M     %  M      N     %  M     M     %__________________________________________________________________________With 0.1% CoQ.sub.10    9.55 · 10.sup.-12          7.99 · 10.sup.-11                14.7                     9 · 10.sup.-10                           1.6 · 10.sup.-8                                0  --    --    0With 1% CoQ.sub.10     2.9 · 10.sup.-12          1.88 · 10.sup.-11                15.7                   2.7 · 6.sup.-10                          3.64 · 10.sup.-9                                5.9                                   3.39 · 10.sup.-10                                          4.5 · 10.sup.-10                                               4.7With 5% CoQ.sub.10    2.27 · 10.sup.-12          6.45 · 10.sup.-12                16.2                   2.8 · 10.sup.-11                          .sup. 2.42 · 10.sup.-10                                12.7                                   4.99 · 10.sup.-11                                         4.56 · 10.sup.-10                                               11.6Without CoQ.sub.10    1.52 · 10.sup.-10          1.54 · 10.sup.-10                14.3                     9 · 10.sup.-10                          1.61 · 10.sup.-8                                0  --    --    0(comparison)__________________________________________________________________________    15             16              17Fish oil Pentane          Ethane   Pentane                          Ethane   Pentane                                         Ethanesample   M     M     O.sub.2                   M      M     O.sub.2                                   M     M     O.sub.2__________________________________________________________________________With 0.5% CoQ.sub.10    --    --    0  --     --    0  --    --    0With 1% CoQ.sub.10    4.22 · 10.sup.-10          6.51 · 10.sup.-10                4  6.62 · 10.sup.-10                          1.06 · 10.sup.-8                                1.7                                   --    --    0With 5% CoQ.sub.10     6.1 · 10.sup.-11          5.51 · 10.sup.-10                11.5                   1.17 · 10.sup.-10                          1.05 · 10.sup.-9                                9.6                                   1.62 · 10.sup.-10                                         1.83 · 10.sup.-9.su                                         p.    7.8Without CoQ.sub.10    --    --    0  2.3    --    0  --    --    0(comparison)__________________________________________________________________________                                   20                          Fish oil Pentane                                          Ethane                                               O.sub.2                          sample   M     M     %__________________________________________________________________________                          With 0.1% CoQ.sub.10                                   --    --    0                          With 1% CoQ.sub.10                                   --    --    0                          With 5% CoQ.sub.10                                   3.76 · 10.sup.-10                                         5.96 · 10.sup.-9.su                                         p.    0.6                          Without CoQ.sub.10                                   --    --    0                          (comparison)__________________________________________________________________________ Legend: --: not determined, excessively high value 
    
     
                                           TABLE 2__________________________________________________________________________      Storage time (days)      25                     27black currant seed oil      Pentane  Ethane   O.sub.2                             Pentane Ethane   O.sub.2sample     M        M        %    M       M        %__________________________________________________________________________With 0.1% CoQ.sub.10      5.44 · 10.sup.-11               3.51 · 6.sup.-11                        13.6 4.09 · 10.sup.-11                                      2.9 · 10.sup.-11                                              13.6With 1% CoQ.sub.10       1.4 · 10.sup.-11               9.42 · 10.sup.-12                        14.4  4.6 · 10.sup.-10                                     2.61 · 10.sup.-10                                              11.2With 5% CoQ.sub.10      x        x        x    6.55 · 10.sup.-11                                     4.17 · 10.sup.-11                                              13.1Without CoQ.sub.10      2.71 · 10.sup.-10               1.64 · 10.sup.-10                        12.1 1.01 · 10.sup.-8.sup.                                     4.35 · 10.sup.-9.sup.                                               4.6(comparison)__________________________________________________________________________      28             30             31black currant seed oil      Pentane            Ethane   Pentane                           Ethane   Pentane                                          Ethanesample     M     M     O.sub.2                     M     M     O.sub.2                                    M     M     O.sub.2__________________________________________________________________________With 0.5% CoQ.sub.10      4.76 · 10.sup.-9.sup.            2.2 · 10.sup.-9                  5.9                     --    --    0  --    --    0With 1% CoQ.sub.10       1.9 · 10.sup.-10            1.14 · 10.sup.-10                  12.6                     3.68 · 10.sup.-9.sup.                           1.65 · 10.sup.-9.sup.                                  7.1                                    3.11 · 10.sup.-8.sup.                                          1.15 · 10.sup.-8.s                                          up.   0With 5% CoQ.sub.10      3.38 · 10.sup.-10            1.76 · 10.sup.-10                  11.7                     8.44 · 10.sup.-11                           4.97 · 10.sup.-11                                 12.8                                    8.38 · 10.sup.-10                                          4.12 · 10.sup.-10                                                9Without CoQ.sub.10      1.31 · 10.sup.-8.sup.            5.47 · 10.sup.-9.sup.                  2.9                     --    --    0  --    --    0__________________________________________________________________________                                    34                         black currant seed oil                                    Pentane                                          Ethane                                                O.sub.2                         sample     M     M     %__________________________________________________________________________                         With 0.1% CoQ.sub.10                                    --    --    0                         With 1% CoQ.sub.10                                    --    --    0                         With 5% CoQ.sub.10                                    5.58 · 10.sup.-9                                          2.15 · 10.sup.-9                                                4.4                         Without CoQ.sub.10                                    --    --    0                         (comparison)__________________________________________________________________________ Legend: --: not determined, excessively high value x: not measured 
    
     The above results clearly demonstrate the antioxidant activity of CoQ 10  in fish oil and black currant seed oil by comparison with the same oils without CoQ 10 . 
     Example 2 
     The procedure described in Example 1 is again used to measure the pentane, ethane and oxygen contents of the head space of 200 ml cans containing 0.5 g fish oil stabilized with 
     2.1 0.1% CoQ 10   
     2.2 0.1% CoQ 10  and 1% purified soya lecithin (Topcithin®, LC) 
     2.3 0.1% CoQ 10 , 1% Topcithin® and 1,000 ppm (parts per million) ascorbic acid (AA) 
     and stored at 37° C. for the period indicated (days). 
     The pentane, ethane and oxygen contents of the head space of the cans containing the fish oil without stabilizer (C 1 ), with 1,000 ppm AA (C 2 ) and finally with 1,000 ppm AA+1% LC (C 3 ) are determined for comparison. 
     The results obtained are shown in Table 3 below. 
     
                                           TABLE 3__________________________________________________________________________Storage time (days)12                  19              41Fish oilPentane      Ethane            O.sub.2               Pentane                     Ethane O.sub.2                               Pentane                                     Ethane                                           O.sub.2SampleM     M     %  M     M      %  M     M     %__________________________________________________________________________2.1  1.38 · 10.sup.-11      9.77 · 10.sup.-11            13.3               4.96 · 10.sup.-10                     6.76 · 10.sup.-9                            2  --    --    02.2  1.21 · 10.sup.-12      1.04 · 10.sup.-11            14.6               2.01 · 10.sup.-11                     .sup. 2.55 · 10.sup.-10                            12.2                               --    --    02.3  5.53 · 10.sup.-12      3.59 · 10.sup.-12            15.4                 8 · 10.sup.-12                       8 · 10.sup.-12                            15.4                               1.73 · 10.sup.-10                                     3.14 · 10.sup.-9                                           8C.sub.12.02 · 10.sup.-11      1.21 · 10.sup.-10            13.1               8.56 · 10.sup.-10                     1.38 · 10.sup. -8                            0  --    --    0C.sub.2  2 · 10.sup.-11      1.01 · 10.sup.-11            13   8 · 10.sup.-10                     0.67 · 10.sup.-8                            0.5                               --    --    0C.sub.3 1.8 · 10.sup.-11       0.9 · 10.sup.-10            12.9                7.8 · 10.sup.-10                      0.9 · 10.sup.-8                            0.6                               --    --    0__________________________________________________________________________ Legend: --: not determined, excessively high value 
    
     The above results clearly show that the combination of CoQ 10 , AA and LC in the quantities used affords fish oil effective protection against oxidation, even after storage for 41 days, whereas without stabilizer (C 1 ) fish oil oxidizes rapidly from the 12th day. In addition, the use of AA alone (C 2 ) or in admixture with LC (C 3 ) no longer affords fish oil protection against oxidation from the 19th day.