WO2007003762A1

WO2007003762A1 - Food supplement and use thereof for the prevention or control of the effects of articular disorders

Info

Publication number: WO2007003762A1
Application number: PCT/FR2006/001512
Authority: WO
Inventors: Jean-Luc Charagnac; Cédric Bourges
Original assignee: Physcience
Priority date: 2005-06-29
Filing date: 2006-06-28
Publication date: 2007-01-11
Also published as: FR2887748B1; FR2887748A1

Abstract

The invention relates to a food supplement comprising unsaponifiable fractions of vegetable oils, curcumin and omega-3 polyunsaturated fatty acids originating from animal or vegetable oils and to the use thereof for the prevention or control of the effects of degenerative disorders affecting the cartilage, in particular osteoarthritis and rheumatoid polyarthritis.

Description

FOOD SUPPLEMENT AND USE THEREOF FOR THE PREVENTION OR CONTROL OF THE EFFECTS OF JOINT DISEASES

The present invention relates to a dietary supplement and its use to prevent or combat the effects of degenerative joint diseases including osteoarthritis and rheumatoid arthritis.

Osteoarthritis is a pathology that affects mostly the elderly. In fact, 85% of people over 70 have radiological signs of osteoarthritis. This pathology affects more than 5 million people in France, which makes it a major public health problem.

Osteoarthritis is a degenerative condition that primarily affects the articular cartilage and may subsequently affect the entire joint, and even reach the underlying bone as well as the joint capsule and the joint. synovial membrane.

The consequences of this affection are various. First, the cartilage that supports the constraints related to the weight of the body, is damaged when affected by this condition. This deterioration results in a decrease in the thickness of the cartilage which exposes the underlying bone to stresses greater than the usual constraints, and which causes a remodeling of the bone with appearance of osteoporosis zones and zones of osteoporosis. bone condensation. This inhomogeneity of the bone tissue not only causes pain in the surrounding tissues but also induces a great fragility of the bone tissues.

In addition, tissue debris is formed and accumulates within the joint, resulting in increased synthesis of cartilage degradation proteolytic enzymes such as collagenases, elastases, hyaluronidases, aggrecanases, and metalloproteinases. These enzymes also act on the cartilage not yet affected by the condition, resulting in lesions like cracking or ulceration. The action of these enzymes can even involve the total and definitive disappearance of the cartilage exposing the underlying bone to bare. Finally, the intervention of the aforementioned enzymes induces the secretion by the surrounding tissues of chemical mediators: Cytokines such as interleukin type 1 or 8 (IL-1 or IL-8) or tumor necrosis factor α (TNF-α) which are responsible for the appearance of an inflammatory reaction at the level of the synovial membrane. The inflammatory reaction also causes pain and joint stiffness.

In addition, cytokines can not only cause pain but also edemas

Eicosanoids such as prostaglandins, for example prostaglandins E (PGE) and leukotrienes, for example of type B4 and C4, which are algogenic

Leukocyte adhesion protein type such as intercellular adhesion molecules type 1 (ICAM-I)

The use of anti-inflammatory pharmaceutical compositions for relieving effects related to osteoarthritis is known. However, the use of such compositions causes a number of side effects such as upset stomach, intestinal problems, skin reactions, fluid retention, effects on the liver and blood.

In addition, the anti-inflammatory pharmaceutical compositions do not promote the reconstruction of the cartilage affected by osteoarthritis nor do they make it possible to fight against the degradation of the cartilage.

Finally, there is currently no composition to prevent synovial inflammatory reaction, effectively fight against cartilage and bone degradation or even stimulate the construction or reconstruction of cartilage affected by osteoarthritis.

The invention aims to provide a dietary supplement that has many qualities and avoids the aforementioned side effects. In particular, the invention aims to:

to stimulate the construction and / or reconstruction of the cartilage affected by osteoarthritis or any other cause of cartilage degradation,

to fight against the cartilaginous and bone degradation which involves the aforementioned proteolytic enzymes and to prevent the synovial inflammatory reaction which implements the aforementioned chemical mediators. For this purpose, the invention relates to a dietary supplement comprising from 5 to 30% by weight of unsaponifiable fractions of vegetable oils relative to the total weight of the food supplement, from 5 to 30% by weight of curcumin relative to the total weight of the dietary supplement, and from 5 to 30% by weight of polyunsaturated fatty acids of the omega 3 series relative to the total weight of the food supplement. These three main compounds interact to fight effectively against the effects of degenerative cartilage disorders including osteoarthritis. In fact, the combination of these three compounds simultaneously makes it possible to prevent the synovial inflammatory reaction and to fight effectively against the cartilaginous degradation or even to reconstruct the affected cartilage.

Advantageously, the dietary supplement further comprises piperine and / or anti-radical agents. These secondary compounds make it possible to amplify the action of the abovementioned main compounds.

Preferably, the unsaponifiable fractions of vegetable oils come from rapeseed oil and / or soybean oil.

In an advantageous embodiment of the invention, the polyunsaturated fatty acids of the omega 3 series come from an animal oil.

Preferably, the anti-radical agents are selected from the group consisting of metals such as manganese and copper. Advantageously, the compounds used in the formulation of said food supplement are packaged together or separately, in the form of capsules and / or capsules.

In an even more advantageous embodiment, unsaponifiable fractions of vegetable oils and polyunsaturated fatty acids of the omega 3 series are packaged in capsules and curcumin, and optionally piperine and anti-radical agents, are packaged in capsules.

The invention also relates to said dietary supplement applied to the prevention or the fight against the effects of degenerative disorders of cartilage and in particular osteoarthritis. The dietary supplement can also be used for populations of individuals, who have premature wear of their cartilage, for example the great sportsmen or people whose activity involves the execution of repetitive actions. In addition, the dietary supplement according to the invention can also be applied to preventing or combating the effects of rheumatoid arthritis.

The invention will be better understood, and other objects, details, features and advantages thereof will appear more clearly in the following description of a particular embodiment of the invention, given solely for illustrative purposes and not limiting, with reference to the accompanying drawings in which:

FIG. 1 is a graph allowing comparison of IL1 release from the "control" group and the "induced" group;

FIG. 2 is a graph allowing the comparison of IL1 release results in the product group.

1 "tested at different concentrations with the results of the" control "and" induced "groups; FIG. 3 is a graph allowing the comparison of IL1 release results in the product group.

2 "tested at different concentrations with the results of the" control "and" induced "groups.

As indicated above, the food supplement according to the invention comprises at least three main compounds which are unsaponifiable fractions of vegetable oils, polyunsaturated fatty acids of the omega 3 series derived from vegetable or animal oils and curcumin.

The unsaponifiable fractions of vegetable oils come from vegetable oils which are preferably soybean, avocado or rapeseed oils. Illustrative examples of these unsaponifiable fractions are phytosterols from soybean or rapeseed and in particular β-sitosterol from soybean or rapeseed. Unsaponifiable fractions of different vegetable oils can be used simultaneously for the manufacture of a food supplement. The percentage by weight of active ingredient (phytosterol) in the food supplement relative to the raw component used (soy extract and / or rapeseed, for example) is preferably greater than 80% and even more advantageously greater than 90%. Phytosterols are preferably present in the food supplement in an amount ranging from 5 to 30% by weight of the total weight of the food supplement.

It has surprisingly been found that unsaponifiable fractions of such vegetable oils have a role in stimulating collagen synthesis within connective tissues and inhibit the production of interleukin 1.

The polyunsaturated fatty acids of the omega 3 series used in the context of the present invention are either of plant origin and come for example from flax, hemp, walnut, or of animal origin and come from the oil of certain fish, for example, some fish from cold seas such as salmon, herring, mackerel and sardines.

The polyunsaturated fatty acids of the omega 3 series are, for example, α-linoleic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

The percentage by weight of active ingredient (omega 3: DHA and / or EPA and / or ALA polyunsaturated fatty acids) in the food supplement relative to the raw component used (extract of plant oil and / or fish) is preferably greater than 10% and even more preferably greater than 15%.

Finally, the polyunsaturated fatty acids of the omega 3 series are preferably present in the food supplement in an amount ranging from 5 to 30% by weight of the total weight of the food supplement. The role of polyunsaturated fatty acids of the omega 3 series is known in human nutrition because it makes it possible to limit the risk of cardiovascular accidents such as atherosclerosis.

It has surprisingly been found that the polyunsaturated fatty acids of the omega 3 series inhibit the action of cyclooxygenases-1 and 2 (COX-I and COX-2) and 5-lipoxygenase which synthesise the eicosanoids, thereby decreasing the activation of inflammation. The mechanisms of action are as follows:

^Coχ arachidonic acid - ^{the ouCOχ} - ^_2> p _ros t _ag Landine E 2 (PGE-2) arachidonic acid ^s - ^{'ipoxygénase>} Leukotriene B 4 (LTB-4)

Inhibition of COX-I or COX-2 induces a decrease in the production of PGE-2 which is a vasodilatory and algogenic chemical mediator. Inhibition of 5-lipoxygenase induces a decrease in the production of LTB-4 which is a chemotactic activator of polynuclear cells and therefore of inflammation, and which is also involved in the maintenance of edema in the lymph node. 'inflammation.

It has also been shown that the omega 3 fatty acids allow the inhibition of the production of interleukins lβ and TNF-α and a decrease in the proteolitic effect of enzymes such as collagenase, aggrecanase and metalloproteinases.

Finally, the omega 3 polyunsaturated fatty acids inhibit all the aforementioned enzymes without affecting the expression of other proteins involved in the maintenance of healthy cartilage tissue.

The dietary supplement according to the present invention may also comprise curcumin.

Curcumin is present in the rhizomes of Curcuma longa, a plant close to ginger, also known as Indian saffron. Curcumin is a diferuloylmethane. It presents the chemical formula below:

The percentage by weight of active ingredient (curcumin) in the food supplement relative to the raw component used (Curcuma longa extract) is preferably greater than 80% and even more advantageously greater than 90%. Curcumin is preferably present in the dietary supplement in an amount ranging from 5 to 30% by weight of the total weight of the dietary supplement.

Advantageously, curcumin is used in the form of micro-granules in the preparation of the food supplement.

Turmeric longa has been used for centuries as a spice and as a food additive to improve the palatability, appearance and preservation of perishable foods.

Furthermore, the use of curcumin as an antioxidant molecule is known with reference to the article by Mohandas K.M. et al. "Epidemiology of Digestive Tract Cancers in India", Indian Journal of Gastroenterology, 1999; 18: 118-21. Curcumin thus makes it possible, thanks to its anti-radical power, to reduce the incidence of cardiovascular and cancerous infections. Surprisingly, it has been discovered that curcumin initially has an effect on certain cytokines and in particular on TNF-α. Indeed, curcumin inhibits the production of TNF-α in vitro. However, TNF-α induces the production of interleukin 1 (IL-1), prostaglandin E (PGE) as well as leukocyte adhesion proteins such as ICAM-I. Therefore, inhibition of TNF-α production induces inhibition of IL-1, PGE, and ICAM-1 production, resulting in decreased risk of spread of inflammation , oedemas and pain related to the activation of these chemical mediators. It has also been discovered that curcumin also inhibits the production of interleukin-8 (IL-8), which has the consequence of reducing the inflammation reaction, since interleukins 8 are chemotactic pro-inflammatory peptides involved in the production of interleukin-8 (IL-8). polynuclear attraction at the site of inflammation. It has also been found that curcumin also reduces the formation of the aforementioned pro-inflammatory eicosanoids. Indeed, it inhibits the release of arachidonic acid which is used as a substrate for the formation of these eicosanoids.

In addition, curcumin inhibits lipoxygenase 1, the enzyme that produces the leukotriene B4 and C4 eicosanoids that are algogenic. In addition, it also inhibits the expression of cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandin-type eicosanoids.

Finally, it has surprisingly been found that curcumin decreases the secretion of enzymes involved in the remodeling and destruction of joint tissues such as collagenases, elastases, hyalurodinases and metalloproteinases.

In addition, the dietary supplement according to the present invention may comprise piperine, which is an alkaloid present in black pepper and whose chemical formula is as follows:

The percentage by weight of active ingredient (piperine) in the food supplement relative to the raw component used (black pepper seed extract) is preferably greater than 80% and even more advantageously greater than 90%.

Piperine is preferentially present in the food supplement at a level ranging from 1-5% by weight of the total weight of the food supplement.

It has been found that, surprisingly, piperine makes it possible to increase the bioavailability of certain compounds, in particular curcumin, by a factor of 20 in humans. Finally, the food supplement can comprise anti-radical agents, preferably of a metallic nature, advantageously based on copper and manganese.

The percentage by weight of active ingredient (for example copper or manganese ion) in the food supplement relative to the raw component used (for example copper sulfate or manganese) is preferably between 15 and 50%.

The anti-radical agent is preferably present in the food supplement at a quantity ranging from 0.5 to 3% by weight of the total weight of the dietary supplement. It is preferably chosen so as to correspond to the daily contributions in corresponding mineral salts.

Copper and manganese are respectively the co-factors of cytoplasmic and myocondrial superoxide dismutase. Superoxide dismutase is an enzyme that neutralizes superoxide ions released during an inflammatory process, for example, which damages collagen and disrupts membrane permeability of synovial membrane cells and causes depolymerization of hyaluronic acid. As a result, copper and manganese inhibit the detrimental effects of superoxide ions in the inflammatory process associated with osteoarthritis. In addition, it has surprisingly been found that copper itself has a certain anti-inflammatory power and that it is likely to increase, by being associated with it, the potency of certain anti-inflammatories.

The dietary supplement may also include adjuvants.

Among the adjuvants are advantageously cited the excipients, the use of which varies according to the shape of the food supplement (capsule, soft or rigid capsule, tablet, syrup). Indeed, microcrystalline cellulose, hydroxypropyl methylcellulose (to form the shell), and magnesium stearate (to bind the liquid compounds in a capsule) are preferentially used for capsules. Glycerol (as binding agent) is advantageously used for capsules or tablets.

Other adjuvants, such as flavors (natural or chemical flavors, fruit or other), pigments (such as titanium dioxide or other) are advantageously incorporated into the preparation of the food supplement. Finally, proteins of animal origin (such as fish gelatin) or of plant origin (such as soy lecithin) can be used as a basic component for reconstituting the proteoglycans of the intercellular matrix.

Likewise, vitamins may be incorporated into the dietary supplement (eg natural vitamin E, A or C) as an anti-radical agent. An example of a food supplement formulation is shown in Table 1 below:

Table I: Composition of a daily portion (minimum recommended) of dietary supplement consisting of a capsule of 833.5 mg and a capsule of

The above values are given to an accuracy of 0.01.

Finally, the dietary supplement according to the invention may be used alone or in combination with a medical treatment intended to relieve the effects of osteoarthritis. In vitro evaluation of the effect of dietary supplement on the protection of degradation of glycosaminoglycans and collagens has been performed on human cartilage according to the following protocols.

Indeed, we know that cartilage is a connective tissue consisting of cells, the chondrocytes that are located within an extracellular matrix. However, the extracellular matrix is formed of collagen, elastin, and glycosaminoglycans and collagen and glycosaminoglycans are degraded in the first place during a condition of the joint by osteoarthritis. This degradation induces a release of glycosaminoglycans in the surrounding medium of the cartilage, the quantity of which is evaluated by the following protocol.

Protocol for Evaluating the Effect of the Combination of Unsaponifiable Fractions of Vegetable Oils, Omega 3 Fatty Acids and Curcumin on the Degradation of Glycosaminoglycans: In the description that follows, all the reagents used in the compositions the following tables are of analytical quality.

Human cartilage sampling:

Human cartilage disks from operative residues (67-year-old patient, left hip) were punch-cut and prepared (by cutting in the thickness direction) to be 5 mm in diameter and weigh 11 cm. , 1 mg.

Preparation of the first incubation medium:

The first incubation medium consists of MEM / M199 nutritional medium supplemented with sufficient amounts of antibiotics, sodium bicarbonate and fetal calf serum. Table II Composition of the first incubation medium

Vol *: volume of the first incubation medium

Culture of the Cartilage Fragments: The human cartilage disks prepared according to the preceding step are placed in defined volumes of 500 μl of the first incubation medium in wells of a 24-well culture plate. Incubation is maintained for 16 hours at 37 ° C in a 5% CO ₂ atmosphere. It helps stabilize the metabolism of chondrocytes.

Effect of Interleukin-1β on GAG Release: The following assays were performed to demonstrate the effects of interleukin 1-β on GAG release.

A second incubation medium comprising a mixture of MEM and Ml 99 culture media is prepared according to a ratio MEM / M199 = 3/4 vol / vol. This medium also comprises sufficient amounts of antibiotics, sodium bicarbonate and bovine serum albumin whose fatty acids have been removed ("delipidated"). Indeed, delipidated bovine serum albumin replaces fetal calf serum because it contains natural inhibitory substances of metalloproteases that are responsible for cartilage degradation. These inhibitory substances may compete with interleukin-1 and distort the results. The amounts of each component are as indicated in the following Table III. Then, interleukin-1, which is a factor inducing the degradation of glycosaminoglycans is incorporated in a portion of the second nutritional medium so as to form the induction medium whose composition described in the following Table III. Table III. Composition of the induction medium with interleukin-1

Vol *: volume of the induction medium

A control consisting of the second incubation medium without interleukin-1-β is carried out so as to verify the effects of the induction of rinterleukin-1-β on human chondrocytes.

A volume of 500 μl of induction medium as described in Table III is deposited in six culture wells. Incubation is maintained for 120 hours at 37 ° C in a 5% CO ₂ atmosphere. It can mimic inflammation of the cartilage.

In the same manner, a volume of 500 μl of "control" solution consisting of second incubation medium without interleukin-1β is deposited in six culture wells. Incubation is maintained for 120 hours at 37 ° C in a 5% CO ₂ atmosphere. It makes it possible to constitute a negative control to prove that the induction of inflammation of the cartilage by IL1 takes place.

Effect of unsaponifiable rapeseed / self on the release of GAG, after 5 days of culture of human cartilage disks: Soybean oil is mixed with rapeseed oil and the mixture of soybean oil + oil The rapeseed formed is mixed with THF in the proportions indicated in the following Table IV. Table IV. Preparation of the basic component of product 1 (unsaponifiable colza / soya bean) without dilution

Then the "unsaponifiable vegetable oil component" is diluted in the second incubation medium to obtain the dilutions indicated in the following Table V.

Table V. Composition of Product 1 (Unsaponifiable Rapeseed / Soybean) Tested at Different Dilution Factors

Finally, a volume of 500 μl of the daughter solutions 1 to 3 is deposited in seven culture wells.

Incubation is maintained for 120 hours at 37 ° C in a 5% CO ₂ atmosphere. It makes it possible to check the effect of rapeseed / soya unsaponifiables on cartilage repair, which should result in a decrease in the release of GAGs.

Effect of the mixture constituted by unsaponifiables of rapeseed / soya, omega 3 fatty acids and curcumin on the release of GAG, after 5 days of culture of human cartilage disks:

Soybean oil is mixed with rapeseed oil and the soybean oil mixture + the rapeseed oil formed is mixed with THF in the proportions indicated in the following Table VI.

In the same way, polyunsaturated fatty acids (eicosapentaenoic acid: EPA and docosahexaenoic acid: DHA) are The resulting mixture is then mixed with THF in the proportions indicated in the following Table VI.

Finally, curcumin is mixed with THF in the proportions indicated in the following Table VI.

Table VI. Preparation of the basic components of product 2 (embodiment) without dilution

THF: tetrahydrofuran EPA: eicosapentaenoic acid DHA: docosahexaenoic acid

Table VII. Composition of the product 2 (embodiment) tested with different dilution factors:

A volume of 500 μl of daughter Y 3 'solutions is deposited in seven culture wells. Incubation is maintained for 120 hours at 37 ° C in a 5% CO ₂ atmosphere. It shows the effect of the mixture of unsaponiflables rapeseed and soy, polyunsaturated fatty acids and curcumin on the repair of cartilage, which should result in a decrease in the release of GAG.

Finally, the amount of glycosaminoglycans obtained was compared to that obtained without dilution with dietary supplement (negative control) or that obtained in the presence of dietary supplement in which some of the main compounds are omitted (comparative example), that is to say in the present case, which only includes vegetable oils (unsaponifiable rapeseed / soya).

Each of the protocols is tested at three different concentrations of dietary supplement, and each test is performed seven times. Results:

Determination of glvcosaminoglucans (GAG):

The culture medium is recovered and the amount of glycosaminoglycans (in μg) present in each culture medium was evaluated spectrophotometrically with dimethylene blue which complexes with glycosaminonglycans to form a purple colored compound. This method is of the type described in the article by Farndale and Barett "Connective Tissue Research",

1982; 9: 247-248 and the paper by Goldberg and Kolibras

"Connective Tissue Research", 1990; 24: 265-275. The optical density of this complex, determined by spectrophotometric method at the wavelength of 530 nm, is proportional to the amount of GAG of the sample.

In addition, a range of chondroitin sulfate is performed simultaneously to quantify the amount of GAG (chondroitin sulphate: SIGMA, C4384).

Then statistical tests carried out on the values in μg of GAG released (Test of KRUSKAL-WALLIS). These are non-parametric group comparison rank tests.

Effect of Finterleukine 1-β on the release of GAGs: In this test, the GAG values released in the compound groups of the second incubation medium without IL1 (designated below) by "control" group) are compared to those of the compound groups of the induction medium (i.e. with IL1, hereinafter referred to as the "induced" group).

TABLE VIII Comparison of Release of IL1 from the "Control" and "Induced" Groups:

+++ = mean significantly different from that of the "control" group (p≤ 0.01)

Figure 1 illustrates the results of Table VIII. In this figure, the +++ symbol indicates that the average obtained for the "induced" group is significantly different from that of the "control" group for a probability p <0.01.

This result confirms that interleukins IL1 actually induced cartilage destruction because significantly more GAG is released from the cartilage in the culture medium.

Effect of unsaponifiable rapeseed on the release of GAG after 5 days of culture of human cartilage disks:

In this test, the GAG values released in the groups previously called "product 1" (unsaponifiables of vegetable oils) tested at different concentrations are compared with those of the "control" and "induced" groups of Table VIII. Table IX: IL1 release results in the "product 1" group tested at different concentrations:

** = average significantly different from that of the "Induced" group (p <0.05)

The percentage of protection is indicative of the effectiveness of the fight against cartilage degradation. It is calculated by the ratio between the amount of GAG released into the culture medium of the test product and that released into the culture medium of IL1-induced controls.

Figure 2 illustrates the results of Table IX. In this figure, the +++ symbol indicates that the average obtained for the "induced" group is significantly different from that of the "control" group for a probability p <0.01.

The symbol ** indicates that the average obtained for the group "product 1 at a concentration of 40 μg / ml" is significantly different from that of the "induced" group for a probability p <0.05.

The results confirm that the presence of a mixture of vegetable oil unsaponifiables results in a slight reduction in the amount of GAG released with a probability of p <0.05. Effect of the mixture constituted by the unsaponifiables of rapeseed / soi, omega 3 fatty acids and curcumin on the release of GAG, after 5 days of culture of the human cartilage disks:

In this test, the values of the GAGs released in the groups previously called "product 2" (embodiment example of the invention) tested at different concentrations are compared with those of the "control" and "induced" groups of Table VIII.

Table X: Release Results of IL1 in the "Product 2" Group Tested at Different Concentrations:

* = mean significantly different from that of the group "Induced" (p <0.1) ** = average significantly different from that of the group "Induced" (p <0.05) *** = average significantly different from that of the group "Induced" (p <0.01)

Figure 3 illustrates the results of Table X.

In this figure, the +++ symbol indicates that the average obtained for the "induced" group is significantly different from that of the "control" group for a probability p <0.01.

The symbol *** indicates that the average obtained for the group "product 2 at the highest concentration (that is, rapeseed / soybean at 40 μg / ml + omega 3 at 80 μg / ml + curcumin at 40 μM) ", is significantly different from that of the" induced "group for a probability p <0.01.

The symbol ** indicates that the average obtained for the group "product 2 at the average concentration (that is to say, rapeseed / soybean at 10 μg / ml + omega 3 at 20 μg / ml + curcumin at 10 μM)" is significantly different from that of the "induced" group for a probability p <0.05. The symbol * indicates that the average obtained for the group "product 2 at the lowest concentration (that is, rapeseed / soybean at 2.5 μg / ml + omega 3 at 5 μg / ml + curcumin at 2 , 5 μM) "is significantly different from that of the" induced "group for a probability p <0.1.

The results of Table X above demonstrate that the decrease in the release of GAG is significantly greater with the unsaponifiable mixture of vegetable oils, unsaturated fatty acids and curcumin (embodiment) than with the mixture only constituted unsaponifiables of vegetable oils (comparative example).

Finally, the percentage of protection is also significantly higher with the unsaponifiable mixture of vegetable oils, unsaturated fatty acids and curcumin (embodiment) than with the mixture consisting solely of unsaponifiable vegetable oils ( comparative example).

In conclusion, significantly lower amounts of glycosaminoglycans and therefore collagen are obtained when the cartilage elements are brought into contact with formulations comprising both unsaponifiable fractions of vegetable oil, omega 3 fatty acids and curcumin in comparison with the amounts obtained with the formulations constituting the comparative example or the negative control. This decrease in the amounts of glycosaminoglycans is indicative of a halt in cartilage degradation or even in cartilage repair.

Although the invention has been described in connection with a particular embodiment, it is obvious that it is not limited thereto and that it comprises all the technical equivalents of the means described and their combinations if they are within the scope of the invention.

Claims

1. Food supplement characterized in that it comprises from 5 to 30% by weight of unsaponifiable fractions of vegetable oils relative to the total weight of the food supplement, from 5 to 30% by weight of curcumin relative to the total weight of the supplement 5 to 30% by weight of polyunsaturated fatty acids of the omega 3 series relative to the total weight of the dietary supplement.

2. Dietary supplement according to claim 1, characterized in that it further comprises piperine.

3. Supplement according to claim 1 or 2, characterized in that it further comprises anti-radical agents.

4. Food supplement according to one of the preceding claims, characterized in that the unsaponifiable fractions of vegetable oils come from rapeseed oil and / or soybean.

5. Dietary supplement according to one of the preceding claims, characterized in that the polyunsaturated fatty acids of the omega 3 series come from an animal oil.

6. Dietary supplement according to one of the preceding claims, characterized in that the anti-radical agents are selected from the group consisting of metals such as manganese and copper.

7. Food supplement according to one of the preceding claims, characterized in that the compounds used in the formulation of said food supplement are packaged together or separately, in the form of capsules and / or capsules.

8. Dietary supplement according to the preceding claim, characterized in that unsaponifiable fractions of vegetable oils and polyunsaturated fatty acids of the omega 3 series are packaged in capsules and curcumin, and optionally piperine and anti-radical agents, are packaged in capsules.

9. Food supplement according to one of the preceding claims, applied to the prevention or the fight against the effects of degenerative diseases of cartilage and in particular osteoarthritis.

10. Dietary supplement according to one of the preceding claims, applied to the prevention or control of the effects of rheumatoid arthritis.