EP0816478B1 - Fat peroxidation process - Google Patents

Abstract

Process for peroxidation of a fatty substance comprises subjecting the fatty substance to X-ray, gamma -ray or beta -ray radiation in the presence of oxygen, such that the peroxidised product contains less than 0.30 ppm malondialdehyde (MDA) per peroxide unit.

Description

The invention relates to a process for the peroxidation of fat body. The products obtained by the process according to the invention make it possible to improve the formulations cosmetics and pharmaceuticals in which they are used.

The processes of peroxygenation of fatty substances are numerous, and pharmaceutical or cosmetic use peroxidized oils has been known for centuries.

The principle of chemical reactions of peroxidation of fatty substances is now well known. These reactions include a first initiation phase corresponding to the creation of free radicals, these the latter can then react in subsequent steps with the oxygen supplied to the medium to form the compounds peroxidation (hydroperoxides, endoperoxides).

The products obtained by all these processes are characterized by their peroxide index, revealing the quantity of oxygen fixed during the reaction of peroxidation.

In all of the processes described so far, the free radical initiation phase is either continuous, or discontinuous, and is characterized by a contribution energy in the form of heat, alone or in combination with ultraviolet radiation. The employment of promoters radicals such as metal ions have also been described.

French patent FR-A-2,461,744, for example, describes peroxidation of fatty substances by blowing air, under a temperature of the order of 50 to 100 ° C, with catalysis to ultraviolet radiation.

Other peroxidation processes are described by example in the manual "Introduction to biochemistry and food technology "Vol.1 by J.C Cheftel and H.Cheftel, Techniques et documentation-Lavoisier. These processes involve, during the initiation phase, high temperatures, and catalysts such as light radiation or traces of metals.

Similarly, French patent FR-A-0 918 163, which is relates to drugs whose active ingredients are peroxides of fatty substances, specifies that these can be obtained by peroxidation processes in which ethylenic fatty substances are used either presence of oxygen at a preferred temperature higher than 20 ° C or in the presence of hydrogen peroxide.

The use of ozone was also cited, although mainly leading to the creation of compounds oxygenated of another nature (ozonides).

In all the processes mentioned, oxygen is supplied by bubbling or by simple exposure to air, to pressure atmospheric.

This has the disadvantage of prohibiting the use powerful radical initiators. Indeed, a creation too many radicals compared to oxygen present in the environment would cause reactions harmful side effects (double position changes connections, cleavages of chains, polymerizations). The radical initiators employed are therefore limited to the heat or low energy ultra violet.

In addition, in all the processes described, training lipid peroxides is usually accompanied by formation of cytotoxic degradation products.

These products are in particular aldehydes such that malondialdehyde (MDA), which is a molecule whose toxicity for the skin is now recognized.

The present invention aims for this a new fat peroxidation process which allows control the formation of toxic degradation products such as MDA by limiting them. This process is characterized, among others, by reaction conditions allowing to obtain a peroxidized fatty substance having a level of MDA less than 30 ppm, and more particularly between 10 and 30 ppm, i.e. 0.1 to 0.3 ppm per 100 of the index peroxide.

a) introduire le corps gras dans un récipient susceptible d'être fermé ;

b) irradier le corps gras par un rayonnement X, gamma ou bêta, pour initier la réaction ;
caractérisé par le fait qu'il comprend l'étape consistant, entre les étapes a) et b) à:

c) introduire de l'oxygène gazeux dans ledit récipient à une pression comprise entre 1.10⁵ et 6.10⁵ Pa (1 et 6 bars), et fermer le récipient, le corps gras une fois peroxydé présentant un taux de malondialdéhyde inférieur à 0,30 ppm par unité de peroxyde.

The process for the peroxidation of a fatty substance according to the invention comprises the steps consisting in:

a) introduce the fatty substance into a container capable of being closed;

b) irradiating the fatty substance with X, gamma or beta radiation, to initiate the reaction;
characterized by the fact that it comprises the step consisting, between steps a) and b) of:

c) introducing gaseous oxygen into said container at a pressure between 1.10 ⁵ and 6.10 ⁵ Pa (1 and 6 bars), and closing the container, the fatty substance once peroxidized having a malondialdehyde level of less than 0.30 ppm per unit of peroxide.

Thus, the method according to the invention implements more energetic radiation than radiation ultraviolet, like for example, x-rays, rays gamma, beta rays.

However, alpha rays and neutrons are difficult to use because the energy of radiation must be such that it does not induce reactions significant nuclear power.

The fatty substances are peroxidized in the presence of the required amount of oxygen quickly and controlled, avoiding the formation of degradation products that appear if the reaction is conducted beyond the creation of peroxide compounds.

To implement the method according to the invention, the fatty substance is placed in a transparent container radiation selected and partially filled so as to trap a sufficient volume of oxygen or air at the above the fat. The volume of oxygen is calculated for correspond to the value of the desired peroxide index. This oxygen (or the volume of air containing it) can be in liquid or gaseous form and is put under pressure because it is then directly dissolved within the fatty substance and can react instantly with radicals created by radiation.

The oxygen will advantageously be introduced under a pressure of 2.10 ⁵ Pa (2 bars).

Initial pressurization is controlled by a pressure gauge. At the end of the reaction, the pressure indicated by the pressure gauge (taken at initial temperature), must have returned to a value indicating consumption total oxygen present by the fatty substance. In the case of the use of pure oxygen under pressure, this value will be close to zero.

An intense automatic stirring device can also be used during the ionization phase and just after.

Advantageously, the ionizing radiation is basically applied to initiate the reaction of peroxidation. However, it can also be applied throughout the duration of the reaction.

In a variant of the invention, the addition, to a untreated fat, part of fat as well peroxidized and then playing the role of primer, allows reduce the duration of a peroxidation carried out according to conventional processes, and therefore to limit the formation of secondary degradation compounds.

In the method according to the present invention, the use of gamma radiation, in particular, allows advantageously to obtain a peroxidized fatty substance having a rate of MDA lower than that obtained with the techniques already described and under more reaction conditions economical due to the reduction in operating time.

In practical terms, the invention preferably uses ionization parameters of sterilization units industrial particles (beta rays or electrons accelerated) or electromagnetic waves (gamma rays, X-rays).

The energy used is a function of the radiation employee. The ionization parameters are calculated in order to allow the emission of a total energy between 10 and 100 Kgy.

The relatively short duration of the reaction, understood between 4 and 10 hours avoids the formation of secondary degradation compounds of peroxides lipid. At the end of the reaction, the absence of oxygen within of the container is advantageous because it makes it possible to obtain a stable product.

A peroxidized fatty substance is obtained having a rate of MDA less than 30 ppm, and more particularly understood between 10 and 30 ppm, i.e. 0.1 to 0.3 ppm per 100 of the index peroxide.

The products thus obtained can be used pure or as a mixture, in particular in the constitution of products to therapeutic, cosmetic, dietetic use.

In a particularly embodiment advantageous of the process, it is planned to add an active thermosensitive to fatty substances, before ionization of this latest. We can then benefit from sterilizing effects radiation used in applications requiring a sterile product.

This heat-sensitive active agent can be chosen in particular from the groups of antibiotics, fat-soluble vitamins, enzymes or proteins.
The peroxidized oils used in the process according to the invention are vegetable and / or animal. They are chosen from the group of ethylenic fatty substances such as olive oil, peanut, sesame, corn, sunflower, sweet almond, or from the group of polyunsaturated fatty acids such as olive oil. evening primrose, borage, blackcurrant, wheat germ, or in the group of animal oils such as those from fish. This list is not exhaustive.

The following examples illustrate the present invention without limiting the possibilities and variants in action.

Example 1

In a cylindrical polyethylene shell of 20 liters and 20 cm in diameter, equipped with an orifice provided with a tap allowing its filling, and a manometer, there are 15 kg of sunflower oil. 10 liters of gaseous oxygen are introduced. The pressure indicated is very slightly higher than 2.10 ⁵ Pa (2 bars). The shell is placed on the sterilization gamma cart. The duration of exposure is 8 hours, in four passages of 2 hours on the emitting source.

At each pass the energy transmitted is 25 KGy. At total 100 Kgy are transmitted. After each pass we read the pressure on the pressure gauge. In this case the pressure decreases roughly a quarter for each measurement, to be practically zero after the last pass. We note a reddening of the reaction medium after the second passage. This blush disappears at the end of the reaction. Sunflower oil then has a peroxide index close to 300, and an MDA level below 30 ppm, i.e. 0.1 ppm per unit of peroxide.

Example 2

The fifteen liters of Example 1 are mixed with 30 liters of untreated sunflower oil. The mixture has a peroxide number of 100, and an MDA level of 0.10 ppm per unit of peroxide.

Example 3

The reaction conditions are those of Example 1, but the shell is only subjected to a single pass under ionizing radiation at 25 kGy. The residual pressure is 1.10 ⁵ Pa (1 bar), the peroxide index of 50, the MDA content of 0.2 per unit of peroxide.

The shell is placed in a thermostated bath at 95 ° C for 8 hours. The reaction is stopped while the residual pressure is 1.10 ⁴ Pa (0.1 bar). The peroxide index is 120, and the MDA content is 0.3 ppm per unit of peroxide.

Example 4

An oil of Calophylum Inophyllum is treated with the conditions of example 1 The calculations are carried out to obtain a peroxide index of 50 and an MDA level less than 0.3 ppm per unit of peroxide. This oil applied to solar erythemas, provides a rapid sedation of painful manifestations related to erythema.

Claims (13)

1. A method for the peroxidation of a fatty substance, comprising the steps consisting in:

   a) introducing the fatty substance into a receptacle able to be closed;

   b) irradiating the fatty substance with X-rays or gamma or beta radiation in order to initiate the reaction;
   characterised by the fact that it comprises the steps consisting in, between steps a) and b):

   c) introducing gaseous oxygen into the said receptacle at a pressure of between 1.10⁵ and 6.10⁵ Pa (1 and 6 bar) and closing the receptacle,

   the fatty substance once peroxidised having a malondialdehyde content of less than 0.30 ppm per unit of peroxide.
2. A method according to Claim 1, in which the ionising radiation is applied essentially in order to initiate the peroxidation reaction.
3. A method according to Claim 1, in which the ionising radiation is applied throughout or substantially throughout the reaction.
4. A method according to Claims 1 to 3, consisting in adding to the fatty substance prior to any normal peroxidation a small quantity of ionised fatty substance fulfilling the role of initiator in order to reduce the duration of the reaction.
5. A method according to Claims 1 to 4, consisting in introducing gaseous oxygen at a pressure of 2.10⁵ Pa (2 bar).
6. A method according to Claims 1 to 5, consisting in, prior to the reaction, fixing the quantities of oxygen and radiation according to the peroxide index required in the peroxidised fatty substance.
7. A method according to Claims 1 to 6, consisting in subjecting the fatty substance to gamma radiation, the energy transmitted being between 10 and 100 kGy.
8. A method according to Claims 1 to 7, consisting in choosing the fatty substance from amongst animal and/or vegetable fatty substances.
9. A method according to Claims 1 to 8, consisting in preferably using ethylenic vegetable oils such as olive, ground nut, sesame, maize, sunflower or sweet almond oil, or polyunsaturated vegetable oils such as evening primrose, borage, blackcurrant or wheatgerm oil, or from the group of animal oils such as those coming from fish.
10. A method according to Claims 1 to 9, consisting in choosing reaction conditions making it possible to obtain a peroxidised fatty substance comprising an MDA content preferably of between 0.10 and 0.3 ppm per unit of peroxide.
11. A method according to Claims 1 to 10, consisting in adding a heat-sensitive active agent to the fatty substance, prior to subjecting it to the ionising radiation.
12. A method according to Claims 1 to 11, consisting in adding a heat-sensitive active agent chosen in particular from the groups consisting of antibiotics, liposoluble vitamins, enzymes or proteins.
13. A method according to Claims 1 to 12, consisting in stirring the fatty substance during the subjecting to the ionising radiation and/or just afterwards.