USOO6428461B1 (12) United States Patent (10) Patent No.: US 6,428,461 B1 Marquez et al. (45) Date of Patent: Aug. 6, 2002 (54) METHOD FOR INHIBITING OXIDATION OF 5,891,491 A 4/1999 Owens et al. POLYUNSATURATED LIPIDS FOREIGN PATENT DOCUMENTS (75) Inventors: Manuel Marquez, Prospect Heights; EP 209509 * 1/1987 Ahmad Akashe, Mundelein, both of IL EP O 209 SO9 9/1991 (US) JP 6-305956 11/1994 (73) Assignee: Kraft Foods Holdings, Inc., Northfield, " by *" IL (US) Primary Examiner Deborah D. Carr - 0 (74) Attorney, Agent, or Firm-Fitch, Even, Tabin & (*) Notice: Subject to any disclaimer, the term of this Flannery patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. (57) ABSTRACT The present invention generally relates to inhibition of (21) Appl. No.: 09/841,878 oxidation of polyunsaturated lipids by mixing the polyun (22) Filed: Apr. 24, 2001 Saturated lipids with a combination of polyamines providing 7 a unique anti-oxidative effect on the polyunsaturated lipids. (51) Int. Cl." .............................. C07C 1/00; C11B5/00 A especially advantageous combination of polyamines used (52) U.S. Cl. ............................................ 584/5; 426/541 in this regard includes Spermine and a different linear (58) Field of Search ............................... 584/5; 426/541 aliphatic polyamine, Such as Spermidine, putrescine, or mixtures thereof. The rate of off-flavor development is (56) References Cited Significantly reduced in polyunsaturated lipids blended with U.S. PATENT DOCUMENTS Such combinations of different polyamines. In addition, polyunsaturated lipid-containing materials and composi 4,253.848 A 3/1981 Porter tions can be Stabilized using edible, non-toxic anti-oxidants 4,957,757 A 9/1990 Law et al. based on Such polyamine combinations. Omega-3 fatty acids 4,975,290 A 12/1990 Artz et al. and compositions containing them are especially well-Suited 5,015.483. A 5/1991 Haynes et al. for processing in this manner. The Stabilized polyunsatu 5,077,0695,118,665 A 12,6/1992 1991 ChangPickart et al. rated lipid-containing products obtained in this manner have 5,230,91624-Y-2 A 7/1993 Ch ang et al. extended shelf-life while permitting the health and nutri 5,304.679 A 4/1994 McEvily et al. tional value of the treated lipids to be more fully accessed. 5,733,524 A 3/1998 Bucala et al. 5,801.200 A 9/1998 Bucala et al. 38 Claims, 2 Drawing Sheets 3OOOO 2 mM Spermine 1 mM Spermidine 1.5 mM Spermine 20000 1.5 mM Spermidine 2mM SpermineO 2 1 mM Putrescine w CD 5 1 mM Spermine Os 2 mM Spermidine 1 mM Spermip ine O 2mM Putrescine 1 OOOO / 1.5mM Putrescine O st is U.S. Patent Aug. 6, 2002 Sheet 1 of 2 US 6,428,461 B1 3OOOO Control Fig. 1A 20000 / 3 "suimM Peutriscine. s'. as2 / (----- ------------ / - 3 / - 3 mM Spermidine / P 10000 ODT O 4 8 12 16 2O 24 Hours 30000 2 mM Spermine Fig 1 B 1 mM Spermidine 2OOOO 1.5 mM Spermine 2mM Spermine g 1.5 mM Spermidine 1 mM Putrescine 5 gO 2 mMEMSE Spermidine 2mM1 mM PutreSCineSpermine C 10000 U.S. Patent Aug. 6, 2002 Sheet 2 of 2 US 6,428,461 B1 30000 1.5 mM"Sprine SOermindine Fig. 1 C 20000 1 mM Spermindine s 1 2 mM Putrescine O O C C O O 1 OOOO 2 mM Spermidine 1 mM Putrescine Hours US 6,428,461 B1 1 2 METHOD FOR INHIBITING OXDATION OF they further decompose, they form volatile aldehydes or POLYUNSATURATED LIPIDS ketones responsible for Strong unpleasant Smell and taste. In addition, free radicals formed during oxidation of the unsat FIELD OF THE INVENTION urated fatty acids may participate in the development of arteriosclerosis and other pernicious diseases in the con The present invention generally relates to a method for SUC. inhibiting the oxidation of polyunsaturated lipids using The susceptibility and rate of oxidation of the unsaturated uniquely effective combinations of two or more polyamines, fatty acids can rise dramatically as a function of increasing and the stabilized products obtained therefrom. degree of unsaturation in particular. In this regard, EPA and BACKGROUND OF THE INVENTION DHA contains five and six double bonds, respectively. This high level of unsaturation renders the omega-3 fatty acid fish Recent trends in food processing and preparation include oils readily oxidizable. The natural instability of such fish efforts to reduce the Saturated fatty acid content of many oils gives rise to their unpleasant odor and unsavory flavor foods in favor of unsaturated fatty acids. Among other characteristics where oxidation of the fish oils has occurred, things, the replacement of Saturated fats in a diet with even after a relatively short period of Storage time. The odor polyunsaturated fats can help to reduce cholesterol levels. 15 and flavor of rancid fish oils are Strong and pungent. Omega-3 long chain polyunsaturated fatty acids. in Consequently, elimination of these odors and tastes, once generated, has been difficult if not impossible. Moreover, the particular, have been viewed as highly attractive potential off-flavor odor or taste can be So malodorous that even a additives for foods and dietary Supplements. Omega-3 poly Small level of rancidity in a fish oil-containing product can unsaturated fatty acids are found naturally in marine oils, be negatively perceived by a consumer. Linolenic acid and also in certain vegetable oils. Certain fish oils, Such as (ALA) derived from plant oils is also very Susceptible to capelin oil, cod liver oil, and menhaden oil, contain large off-flavor development. Dietary Supplements containing amounts of highly unsaturated long chain fatty acids, Such as omega-3 oils often are packaged in dark, light-blocking eicosapentaenoic acid (EPA), docosahexaenoic (DHA), and containers in either encapsulated form; free liquid forms eicosatetraenoic acid (arachidonic acid). EPA and DHA are 25 generally require chilled Storage once opened. Despite Such omega-3 fatty acids. Many vegetable oils contain linoleic precautions, they still tend to have a strong fish-like flavor acid, an essential fatty acid, which is classified as an and/or smell. Consequently, it has been very difficult in the omega-6 fatty acid. However, unlike many other vegetable past to produce Omega-3 fatty acid containing products or oils, flaxseed oil also contains significant amounts (generally Supplements having an extended Shelf life. about 55 to about 65 percent) alpha linolenic acid (ALA), Previous proposals or practices for addressing lipid oxi which is another essential fatty acid. ALA also is an omega-3 dation include, for example, U.S. Pat. No. 4,975,290 which fatty acid. Small amounts of ALA also can be found, for describe a method of inhibiting lipid oxidation in food example, in walnut oil, canola oil, Soybean oil, and black products Such as uncured meat and extruded food products currant. The body metabolizes ALA, at least in part, into using an aqueous Solution of organic iron Salt. U.S. Pat. No. EPA, and, to a lesser extent, DHA and 3-Series prostaglan 35 5,015,483 describes means for stabilizing oxidizable lipo dins. philic components Such as fish oils by encapsulation of the The omega-3 fatty acids obtained directly from fish oils components in a lipidic bilayer of liposomes (preferably (i.e., EPA and DHA) are thought to offer a wide range of saturated phospholipids). U.S. Pat. No. 5,077,069 describes possible nutritional and health benefits. These benefits use of natural antioxidants including tocopherols, ascorbic include reductions in cholesterol levels, anti-thrombotic 40 acid, citric acid, and phospholipids, and optionally rosemary effects, anti-arthritic effects in joints, and enhancement of extract, for stabilizing polyunsaturated oils. U.S. Pat. No. mental and Visual acuity. ALA has been reported to be useful 5,230,916 describes use of an ascorbic acid complex for in lowering blood pressure, controlling inflammatory stabilizing polyunsaturated oils. U.S. Pat. No. 5,304,679 conditions, inhibiting autoimmune reactions, and protecting describes a composition for inhibiting the enzymatic brown against cardiovascular disease. 45 ing of foods and beverages by using certain resorcinol While foods and dietary supplements prepared with Such derivatives in place of earlier enzymatic browning inhibitors polyunsaturated fatty acids may be healthier, they also have Such as Sodium bisulfite. U.S. Pat. No. 5,891,491 describes an increased Vulnerability to rancidity. Rancidity in lipids, use of certain dihydroxyquinoline compounds to extend the Such as unsaturated fatty acids, is associated with oxidation shelf life of products derived from mammals and fish fed a off-flavor development. The off-flavor development 50 diet including such compounds. Also, EPO 0 209 509 involves food deterioration affecting flavor, aroma, color, describes protecting easily oxidizable compounds, espe texture, and the nutritional value of the particular food. A cially polyunsaturated fatty acids, against oxidation, in primary Source of off-flavor development in lipids, and which the anti-oxidant is a compound containing primary or consequently the products that contain them, is the chemical Secondary amino-groups linked to carbon in an aliphatic reaction of lipids with oxygen. The rate at which this 55 residue of a certain described formula. The antioxidants are oxidation reaction proceeds has generally been understood Specifically characterized therein as being either Spermine or to be affected by factorS Such as temperature, degree of Spermidine. Also, comparative reference is made to BHA unsaturation of the lipids, oxygen level, ultraViolet light (butylated hydroxyanisole) and TBHQ (tertiary exposure, presence of trace amounts of pro-Oxidant metals butylhydroquinone) as anti-oxidants. Although not directed (Such as iron, copper, or nickel), lipoxidase enzymes, and So 60 to anti-oxidants for lipids, Japanese Pat.