RU2545651C1 - Lipid oxidation stabilisation composition - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to production of a composition which stabilises the process of oxidising lipids, lipid-containing food additives, active cosmetic and medicinal agents. The antioxidant used is N-(4'-hydroxy-3',5'-di-tert-butylphenyl)amide 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid, which is added in amount of 0.01-0.14% of the weight of lipids.

EFFECT: invention enables to obtain a composition for stabilising oxidation of lipids using an antioxidant, having high effectiveness and low toxicity.

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Description

The invention relates to the field of food technology, and in particular to methods of protecting lipids, oils, fats from oxidation and oxidative degradation, and can be used in the food, cosmetic and chemical-pharmaceutical industries to obtain stable lipid-containing food additives (nutraceuticals), medical and cosmetic products and drugs.

To inhibit the oxidation processes, antioxidants (oxidation inhibitors) are used, which are increasingly used to prevent oxidative transformations of lipids and their preparations in vitro, as well as in vivo in the complex treatment of a wide range of diseases (M.P. Gerchuk Antioxidants in the food industry / / Journal of the All-Union Chemical Society named after D.I. Mendeleev. - 1960. - N.4. - P.395-402), (Avakumov V.M., Kovler M.A., Kruglikova-Lvova R. P. Medicines for metabolic therapy based on vitamins and enzymes (Review) // Questions D. Chemistry. - 1992. - T.38. - N4. - S.14-21). (Durnev A.D., Seredenin S.V. Antioxidants as a means of protecting the genetic apparatus // Chem.-Pharm. Journal. - 1990. - N2. - S.92-100). Thus, the antioxidants present in the drug or cosmetic product are not only the active principle of these agents, but can significantly inhibit their oxidation during long-term storage, helping to maintain easily oxidized biologically active components in their native state. Known compositions for stabilizing lipids to oxidation of various origins by introducing tocopherol antioxidants (US No. 2564106, publ. 14.08.1951), (Emanuel N.M., Lyaskovskaya Yu.N. Inhibition of fat oxidation processes. M .: Pishchepromizdat, 1961. - 360 s.).

As a prototype of the selected composition for stabilization of lipids to oxidation by the introduction of tocopherols (US No. 2564106, publ. 14.08.1951). The specified composition inhibits the process of lipid oxidation due to the antioxidant action of a naturally occurring α-tocopherol inhibitor (6-hydroxy-2,5,7,8-tetramethyl-2-wick-chroman, vitamin E). It is known that α-tocopherol is characterized by an extremely high constant reaction rate with peroxyl radicals k ₇ = (3.3-3.5) × 10 ⁶ M ^-1 × s ^-1 (Burlakova EB, Krashakov S.A., Khrapova N.G. Kinetic features of tocopherols as antioxidants.Chernogolovka, 1992. - 56 p).

The disadvantage of this composition (prototype) is the complex mechanism of action of α-tocopherol in lipid substrates, its participation not only in chain termination reactions, but also in chain extension reactions, which reduces the antioxidant activity of α-tocopherol and promotes the oxidation process.

The proposed compound N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid was synthesized at the Novosibirsk Institute of Organic Chemistry named after N.N. Vorozhtsova SB RAS in order to expand the range of non-toxic biologically active oxidation inhibitors. The compound has no local and general toxic effect (Perevozkina M.G. Kinetics and the mechanism of the inhibitory effect of derivatives of phenosan, salicylic acid and their synergistic mixtures with α-tocopherol and phospholipids. Abstract. Thesis ... Candidate of Chemical Sciences. Tyumen. - 2003. - 28 p.).

The compound exhibits activity with peroxyl radicals with a reaction rate constant k ₇ = 1.69 × 10 ⁴ M ^-1 × s ^-1 and additionally has the ability to directly interact with hydroperoxides, destroying them without the formation of free radicals, which is not observed in the presence of α-tocopherol . The destruction of hydroperoxides under the influence of N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid, in turn, is the reason for the gain in periods of induction . For the proposed synthetic antioxidant, there is a positive correlation between the concentration and the magnitude of the inhibitory effect, which is not observed for α-tocopherol, this dependence is extreme and at high concentrations the antioxidant effect of α-tocopherol changes to pro-antioxidant. Additionally, N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid has a photostabilizing effect and is capable of absorbing UV radiation in the range of 301-305 nm, dangerous for the development of skin cancer, which can be used in the cosmetic industry / Porotov LG, Storozhok NM, Perevozkina MG Kinetic studies of the antioxidant and photo-stabilizing effect of osalmide - a new amide derivative of salicylic acid (Collected report of the All-Russian Scientific Conference of Young Scientists and the Second School named after Academician N.M. Emanuel “Oxidation, Oxidative Stress, Antioxidants. Moscow. (1 June 3). 2006. S.131-133).

The task of the invention is to develop a composition for stabilizing lipids to oxidation using an antioxidant with high efficiency and low toxicity.

The technical result is a simple composition that does not require large material costs, based on the ability of the low-toxic antioxidant N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy-3-tert-butyl-5- ethylbenzoic acid to interact with peroxyl radicals and destroy the products of oxidative destruction of lipids (hydroperoxides) in a non-radical way, absorb UV radiation in the range of 301-305 nm and have a photostabilizing effect.

The technical result is achieved by adding to the lipids as an antioxidant N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid in an amount of 0 , 01-0.14% by weight of lipids.

The essence of the invention is the use of N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide of 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid as an antioxidant, the chemical structure of the compound is presented below:

The effectiveness of the stabilizers was evaluated by several independent methods (Storozhok N.M. Intermolecular interactions of the components of natural lipids in the oxidation process. Thesis ... Dr. of Chemical Sciences. M: Institute of Biochemical Physics named after N.M. Emanuel RAS, 1996.360 s. .), (Tsepalov V.F., Kharitonova A.A., Gladyshev G.P. et al. Determination of rate constants and inhibition coefficients of phenol antioxidants using a model chain reaction // Kinetics and Catalysis. - 1977. - T. 18. - issue 5. - S.1261-1267):

- studied the kinetics of oxygen absorption in the initiated oxidation of lipid substrates in the presence of the proposed composition and prototype;

- the kinetics of accumulation of the primary oxidation products — hydroperoxides — by iodometric titration (IF) during lipid autooxidation at elevated temperatures (60 ± 0.2 ° C) was tested.

Antioxidant activity (AOA) was tested by the volumetric method of oxygen absorption in a modified Warburg type apparatus during the oxidation of methyl oleate (MO) in an inert solvent of chlorobenzene, the process was initiated due to thermal decomposition of AIBN at a concentration of 3 × 10 ^-3 M. As criteria for assessing the antioxidant properties of compounds used periods of induction, initial and maximum oxidation rates. The magnitude of the induction period (τ _i ) was determined by a graphical method, which is a segment of the abscissa axis cut off by a perpendicular omitted from the intersection point of the tangents drawn to the kinetic curve. The effectiveness of inhibition of the oxidation of a lipid substrate is determined by the set of reactions of the inhibitor and denotes its antioxidant activity, quantitatively determined by the formula AOA = τ _i -τ _S / τ _S , where τ _S and τ _i are the periods of induction of substrate oxidation in the absence and in the presence of the studied antioxidant ( AO), respectively. The criterion of antioxidant action was the initial (Wo _{2 beg} ) and maximum (Wo _{2 max} ) oxidation rate in the presence and absence of an antioxidant. The initiation rate was determined by the equation Wi = f [InH] / τ _i , where f is the stoichiometric coefficient of inhibition, [InH] is the concentration of the reference inhibitor, and τ _i is the induction period.

; где a - объем Na₂S₂O₃, пошедший на титрование пробы; b - объем Na₂S₂O₃, пошедший на титрование контрольного опыта; d - масса навески субстрата окисления.The kinetics of the accumulation of hydroperoxides in the model substrate was studied under autooxidation by the method of reverse iodometric titration in chlorobenzene medium at t = (60 ± 0.2) ° C. A portion of the oxidizable model substrate was dissolved in a mixture of glacial acetic acid and chloroform in the ratio 3: 2, potassium iodide saturated in the cold was added, the mixture was stirred and left in the dark. At regular intervals, samples were taken and the peroxide number was determined in them: $$PH=\frac{0.1269\times (a-b)}{d}$$

; where a is the volume of Na ₂ S ₂ O _{3 used} for titration of the sample; b is the volume of Na ₂ S ₂ O _{3 used} for titration of the control experiment; d is the mass of the sample of oxidation substrate.

The invention is illustrated by the following examples.

Example 1

1. Take 1 g (accurately weighed) of methyl oleate (MO) and place in a pressure cell, add N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy-3-tert-butyl -5-ethylbenzoic acid in an amount of 0.03% by weight of lipids, a solution of 3 × 10 ^-3 M AIBN oxidation initiator in chlorobenzene, adjusted with chlorobenzene to a total sample volume of 2 ml. Oxygen absorption is estimated by the volumetric method in a thermostatted Warburg type apparatus at a temperature t = (60 ± 0.2) ° C with stirring on a magnetic stirrer. Measure the volume (mm ³ ) of absorbed oxygen over time, build a graph in the coordinates dV / dt. The graphical method of the kinetic curves determine the magnitude of the induction period (τ _i ). From the slope of the kinetic curves, the initial (W _{O2 beginning} ) and maximum (W _{O2 max.} ) Oxidation rates of the lipid substrate are determined in the control experiment and with the addition of antioxidants. The indicators are compared with the prototype (Table 1.).

Kinetic parameters of the oxidation of methyl oleate in an anhydrous medium in the presence of 3 × 10 ^-3 M AIBN depending on the concentration of 2- hydroxy-3-tert-butyl N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide -5-ethylbenzoic acid and α-tocopherol (prototype), W _i = 4,2 × 10 ^-8 M × s ^-1 , t = 60 ° C. Note * - AO antioxidant, "-" - lack of effect. Each digit is the result of 10 experiments, p <0.05.

Table 1 No. p / p The content of AO *, wt.% τ min W _{O2 starting} × 10 ⁻⁷ , M × s ⁻¹ W _O2max × 10 ^-7 M × s ^-1 W _O2max MO W _O2max AO Oxidation substrate - methyl oleate (control) one 0 0 1.90 8.00 - α-tocopherol (prototype) 2 0.01 70 0.82 6.50 1,2 3 0,03 150 0.78 6.50 1,2 four 0.05 250 0.76 6.40 1,2 5 0.08 400 0.77 6.50 1,2 6 0.11 480 0.76 6.30 1,2 7 0.14 590 0.76 6.40 1,2 N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid 8 0.01 150 1.06 7.14 1,1 9 0,03 200 0.62 4.60 1.7 10 0.05 280 0.47 3.40 2,4 eleven 0.08 420 0.32 3.39 2,4 12 0.11 500 0.29 3.26 2,5 13 0.14 620 0.27 2,38 3.4

Example 2

2. Take 10 g (accurately weighed) of linoleic acid (LA), add N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid in an amount of 0.03% by weight of lipids, stirred with a magnetic stirrer in a lightproof thermostatic cell at a temperature of t = (60 ± 0.2) ° C. At regular intervals, samples are taken and the peroxide value (IF) is determined in them.

The values of the initial, maximum oxygen absorption rates during the initiated oxidation of methyl oleate (MO), the destruction of hydroperoxides during the autooxidation of linoleic acid (LA) in the presence of N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy -3-tert-butyl-5-ethylbenzoic acid and α-tocopherol (prototype), t = 60 ° C.

Note * - lipids; “-” - lack of effect. Each digit is the result of 10 experiments, p <0.05.

table 2 Mixture composition Initiated oxidation of MO, W _i = 4.2 × 10 ^-8 M × s ^-1 Autooxidation of LC ROOH failure rate in 7 hours W _{O2 beg} × 10 ^-7 M × s ^-1 W _{O2 max} × 10 ⁻⁷ M × s ^-1 W _{accumulation ROOH} × 10 ^-4 ; g I _2/100 g Jul. * × s ^-1 W _{destruction ROOH} × 10 ^-4 g I _2/100 g Jul. * × s ^-1 LIPIDS (control) 1.90 8.00 5.52 - - LIPIDS + α-tocopherol (0.03 wt.%) (Prototype) 0.78 6.50 5.52 - - LIPIDS + N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) -amide 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid (0.03 wt.%) 0.62 4.60 - 3.33 71.7

Claims (1)

Composition for stabilizing lipids, including an antioxidant, characterized in that N- (4′-hydroxy-3 ′, 5′-di-tert-butylphenyl) amide 2-hydroxy-3-tert-butyl-5-ethylbenzoic is used as an antioxidant acid added in an amount of 0.01-0.14% by weight of lipids.