WO2005087024A2

WO2005087024A2 - Product containing a highly bioavailable mineral, method for preparing and using

Info

Publication number: WO2005087024A2
Application number: PCT/FR2005/000505
Authority: WO
Inventors: Christian Leclerc; Flore Martin; André BURCKEL; Jean-Robert Rapin
Original assignee: Larena
Priority date: 2004-03-04
Filing date: 2005-03-03
Publication date: 2005-09-22
Also published as: WO2005087024A3; FR2867029B1; FR2867029A1

Abstract

The invention relates to a novel product comprising at least one type of highly bioavailable mineral, to a method for the preparation thereof, to a compound containing said product and to the uses thereof. The inventive product can be used for preparing a food compound, preferably a food additive or a dietetic product. Said compounds are particularly efficient for preventing or curing diseases related to mineral deficiency.

Description

Product comprising a highly bioavailable mineral, preparation process and uses

The present invention relates to a new product comprising at least one highly bioavailable mineral, a process for its preparation, compositions containing said product and uses of said product. Minerals are essential for metabolic functions and biological processes, for example as constituents or activators of enzymes, regulators of biological functions, protein stabilizers, or even as co-transporters. The essential minerals are generally classified into two categories, with on the one hand the macro-elements or major mineral elements such as sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), phosphorus (P) or also magnesium (Mg) and trace elements or trace elements on the other hand. These trace elements are metal ions such as iron (Fe), zinc (Zn), manganese (Mn), chromium (Cr), copper (Cu), iodine (I), fluorine (F ), selenium (Se), lithium (Li). A deficiency in one or more minerals can have serious consequences on the performance of the organism and health, even if these deficiencies are not always manifested by particular clinical signs. If a poor diet can be responsible for a mineral deficiency, this can also be due to poor bioavailability of the absorbed minerals. The bioavailability of minerals varies depending on many factors. It depends on the mode of gastrointestinal absorption, the form of the mineral, the compounds present in the intestinal lumen, factors contained in the cells of the intestinal mucosa. Low bioavailability, alone or associated with malnutrition, can lead to deficiencies with or without more or less serious clinical signs. For example, it is known that an iron deficiency can lead to anemia or asthenia. Zinc deficiency can lead to impaired immunity, impaired vision or delayed healing. A potassium deficit leads to a disturbance of the acid-base balance. Chromium deficiency decreases glucose tolerance, and can lead to the development of type II diabetes as well as dyslipidemia. It also increases the risk of cardiovascular accidents. Magnesium deficiency is associated with tetany, particularly latent tetany. It can also be responsible for metabolic disorders, in particular disorders of the metabolism of carbohydrates and / or lipids. It also increases the cardiovascular, neuromuscular, renal and bone risks. Finally, a decrease in the magnesium level in the body can result in a decrease in immune defenses. The decrease in the amount of copper in the body can lead to anemia, neutropenia or even cardiomegaly. Manganese deficiency can lead to bone disorders or a decrease in cholesterolemia. Lithium intake is particularly indicated in mood disorders, depressive disorders, as a sedative or hypnotic. The few examples of consequences on the organism linked to a deficiency of minerals clearly show how essential these are for the organism. It is therefore particularly important that the mineral contributions, generally made up by food, are effective. This therefore relates to the bioavailability of the minerals consumed. However, many factors influence the bioavailability of minerals. Among the factors influencing the absorption of minerals, phosphates, phytates and oxalates have the property of forming insoluble complexes with metals. However, the minerals must be in ionized form to be transported through the intestinal membrane. The formation of insoluble complexes therefore greatly compromises the absorption and subsequent use of minerals. On the other hand, competition between chemically close minerals can be established at the level of transport across the intestinal barrier. This phenomenon can be observed with the transporter of divalent cations, the Transporter of Divalent Metals type 1, (DMT-1, Divalent Metal Transporter -1). This transporter contained in the villi of the enterocytes allows the capture of trace elements such as iron, manganese, copper, zinc. This is another path that can lead to deficiencies in essential minerals. In addition, to avoid the toxicity of heavy metals, the body has proteins capable of binding these compounds. However, these proteins are not specific to toxic minerals. They can capture trace elements and thus reduce their absorption. We also know that minerals are co-regulators of digestion enzymes.

Certain minerals replace other minerals within these enzymes, thus modifying their digestive activity. This competition between different minerals for these enzymes also influences their own absorption. We understand from the above, in addition to the importance of minerals for the body, the importance of effectively maintaining the supply of bioavailable minerals. One of the ways of this effective maintenance is the daily food intake. A variation in food intake can modify the balance between the different minerals and / or promote the absorption of certain minerals to the detriment of others. However, human nutrition has changed a lot in recent decades. For example, among the French, the decrease in energy expenditure has led to a reduction in food intake. At the same time, the structure of the ration has been modified with an increase in the quantity of so-called "empty calorie foods" (1000 kcal consumed today generally provide less vitamins and minerals than they do brought a few decades ago). Food supplementation can help prevent these deficiencies. However, it must take into account the bioavailability of minerals and their contribution must be in a form allowing the best possible absorption. For food supplementation, the current intake of minerals is essentially in the form of salts. However, the bioavailability of these intakes can be impaired by the many factors mentioned above. New forms could allow better absorption of minerals and therefore guarantee their physiological or therapeutic effectiveness. Although forms of bioavailable minerals are known in the prior art, a large and growing need for a new form of bioavailable minerals, if possible without modification of chemical nature but having increased bioavailability, persists. Likewise we are always looking for compositions effective and without side effects for treating biological disorders linked to mineral deficiencies. One of the objectives of the present invention is to provide a product comprising at least one mineral with increased bioavailability and compositions containing such a product. Surprisingly, the applicant has shown that a particular treatment, object of the present invention, of a mixture comprising an extract of microorganisms and at least one mineral, makes said mineral highly bioavailable. Subsequently in the text, the term "product according to the invention" means the product comprising an extract of microorganisms and at least one mineral, having undergone the treatment according to the invention which makes the mineral highly bioavailable. By "highly bioavailable" is meant according to the invention that the mineral present in the product has an availability for the organism greater than what its availability would have been if it were not contained in the composition according to the invention . We will see later in the text that said mineral contained in the product according to the invention has a bioavailability for the organism, greater than what would have been its bioavailability if it were not contained in the product according to invention. The Applicant has found that the product according to the invention allows better assimilation and bioavailability of minerals by the body, thereby increasing the chances of their use. Consequently, it is possible to envisage the preparation of compositions useful inter alia as a food supplement or as a dietetic product, comprising the product according to the invention, making it possible to prevent or combat with better efficacy the biological disorders linked to a deficiency in minerals. Thus, the present invention firstly relates to a process for increasing the bioavailability of minerals, characterized in that: - in a first step, an extract of microorganisms and at least one mineral are mixed, - in a second step, the mixture obtained in the first step, and - in a third step, the concentrated product obtained in the second step is atomized. According to the invention, the extract of microorganisms can advantageously be obtained from any yeast strain known from the prior art. In this regard, mention may be made of strains of the genus Saccharomyces. According to the invention, the species Saccharomyces cerevisiae or Saccharomyces boulardii are preferably used in the process. According to the invention, the extract of microorganisms can be any extract of microorganisms known from the prior art. Yeast extracts exemplary include marketed by Bio Springer under the names "2006 extract" and "extract 2012", or a yeast extract marketed by DSM Food Specialties under the name Maxarome ^® premium, or Aromild ^® marketed by KYOWA (KOHJIN Co Ltd). These extracts are produced after culture of the yeasts and release of their nucleotides by an enzyme (ribonuclease P) and can be optionally purified. The microorganism extract can be in any form known from the prior art. In particular, it can be in hydrated form or else in the form of a powder or of microgranules, dried by atomization or lyophilization. Preferably, the microorganism extract is in the form of a spray-dried powder or microgranules. In the first step of the process, the mixture of the microorganism extract and the mineral is preferably carried out in demineralized water. According to the invention, the mineral can be a mineral chosen from macro-elements (or major mineral elements) such as, for example, calcium (Ca), potassium (K) or magnesium (Mg), and oligo- elements (or trace elements) such as, for example, metallic cations mono-, di-, tri-, or hexavalent, such as iron (Fe), zinc (Zn), manganese (Mn), chromium (Cr) , copper (Cu), or lithium (Li). According to the invention, the mineral can be in any form known from the prior art. Advantageously, a mineral is used in the form of a water-soluble inorganic salt such as for example a chloride, a sulfate, or an organic such as a citrate, a fumarate, a gluconate, a lactate or an acetate. Preferably, a chloride or a sulfate will be used. Table 1 below presents the salt forms of some minerals used in the process according to the invention. Table 1

According to the invention, the mixing of the first step can be carried out with one or more extracts of different microorganisms and one or more minerals. For example, a mixture according to the invention can comprise an extract of particular microorganisms and two particular minerals. The mixing of the first step can be carried out by any method known from the prior art. In particular, the mixing can be carried out by simple mechanical stirring for a time sufficient to obtain good homogenization of the mixture. Those skilled in the art know how to adjust the time and the strength of the agitation in order to obtain the desired homogenization. The mixing (first step) is carried out using any proportion by weight, defined between the extract of microorganism, particularly yeast, and the mineral. This ensures in the final product an optimal degree of complexation between the mineral (s) and the nucleotides or peptides present in the extract. As an example, Table 2 presents the quantities of minerals and microorganism extracts (extract 2012 BIOSPRINGER) to obtain a quantity of mineral equivalent to 100% of the Complexed Recommended Daily Allowances. Table 2

* Corresponding to 100% of the recommended daily allowance (RDA) for each mineral. According to the invention, the mixing of the first step can be carried out at room temperature, that is to say at a temperature between 18 ° C and 35 ° C, preferably between 20 ° C and 30 ° C. Concentration during the second step can be carried out by any concentration process known from the prior art, such as, for example, vacuum evaporation or filtration using a nanofiltration or reverse osmosis membrane, or another diafiltration (nanofiltration at constant volume). The membrane can be a polyamide, polysulfone or polyethersulfone membrane. It can have a cutoff threshold between 100 and 300 Daltons (Da), preferably between 150 and 250 Da. Preferably, a polyamide membrane filtration process is used. During diafiltration, the molecules in solution, depending on their molar mass and their steric bulk, may or may not pass through the membrane. Filtering at constant volume amounts to supplying the retentate with a flow of demineralized water equal to the flow of solution passing through the membrane. If the volume of demineralized water added is IX, the concentration in the retentate of the molecules likely to pass through the membrane will be divided by 2; if the volume is 2X, the content will be further divided by 2, etc. In general, to reduce the concentration of molecules likely to pass through the membrane, the number of volumes must be between 2X and 10X. The molecules not passing through the membrane will keep the same concentration in the retentate. By atomization (third step of the process) is meant according to the invention, any process of the known prior art allowing the drying of the product obtained during the second step of the process according to the invention. The product to be dried obtained in the second step can be brought into contact with a large flow of superheated air at a temperature between 150 ° C and 200 ° C, preferably between 170 ° C and 190 ° C. The water contained in the product to be dried is then vaporized and entrained outside. The dried product is collected in a tower in the form of a powder. A second object of the invention is a product comprising at least one mineral whose bioavailability is high, said product being capable of being obtained by the process described above. Thus, the subject of the invention is: - a product comprising at least iron whose bioavailability is high, said product being capable of being obtained by the process described above in which the mineral is iron, or - a product comprising at less calcium with high bioavailability, said product being capable of being obtained by the process described above in which the mineral is calcium, or - a product comprising at least potassium with high bioavailability, said product being capable of '' be obtained by the process described above in which the mineral is potassium, or a product comprising at least zinc whose bioavailability is high, said product being capable of being obtained by the process described above in which the mineral is zinc , or - a product comprising at least manganese whose bioavailability is high, said product being susceptible e to be obtained by the process previously described in which the mineral is manganese, or a product comprising at least copper whose bioavailability is high, said product being capable of being obtained by the process previously described in which the mineral is copper, or - a product comprising at least chromium whose bioavailability is high, said product being capable of being obtained by the process described above in which the mineral is chromium, or - a product comprising at least magnesium whose bioavailability is high, said product being capable of being obtained by the process described above in which the mineral is magnesium. - A product comprising at least lithium whose bioavailability is high, said product being capable of being obtained by the process described above in which the mineral is lithium. Of course, the product according to the invention may comprise more than one mineral whose bioavailability is high. It may also include more than one microorganism extract. A third subject of the invention is a food composition which can be a food supplement, or a dietetic product comprising at least one product comprising at least one mineral whose bioavailability is high, said product being capable of being obtained by the process according to the invention previously described. A fourth object of the invention is the use of at least one product according to the invention in the preparation of a food composition, preferably a food supplement, or a dietetic product. A fifth object of the invention is also the use of at least one product according to the invention, in the preparation of a food composition, preferably a food supplement, or of a dietetic product, intended to prevent or compensate any mineral deficiency. A sixth object of the invention is also the use of at least one product according to the invention, in the preparation of a food composition, preferably a food supplement, or of a dietetic product, intended for the treatment of related affections. a deficiency, or even a deficiency, in mineral, such as for example - a disturbance of the acid-base balance linked to potassium deficiency or, anemia linked to a deficiency or deficiency in iron and / or copper or, - asthenia linked to an iron deficiency or deficiency or, an immunity disorder and / or a vision disorder and / or delayed healing linked to a zinc deficiency or deficiency or, - a decrease in glucose tolerance and / or the appearance of type II diabetes and / or dyslipidemia and / or an increased risk of cardiovascular accidents linked to chromium deficiency or, - tetany, particularly latent tetany and / or a t metabolic ruble, in particular a metabolism of carbohydrates and / or lipids, and / or an increased risk of cardiovascular and / or neuromuscular and / or renal and / or bone accidents and / or a decrease in the immune defenses linked to a magnesium deficiency or, - neutropenia and / or cardiomegaly linked to a copper deficiency or deficiency or, a bone disorder and / or a reduction in cholesterolemia linked to a deficiency or manganese deficiency or, - mood disorders and / or sleep linked to too little lithium intake. It is understood that in the uses of at least one product envisaged according to the invention, the final composition may contain either several products according to the invention, each comprising one or more minerals having a high bioavailability, or a single product according to the invention comprising several minerals with high bioavailability. It is obvious that said composition can also be a combination of several products according to the invention comprising several minerals having a high bioavailability. Other characteristics of the invention will appear in the exemplary embodiments of the invention, without, however, these constituting any limitation of the invention. EXAMPLES: 1) Example 1: preparation of a product comprising highly bioavailable magnesium (GUANYLOR ^® Mg): • 2100 liters of demineralized water are pasteurized beforehand (85 ° C, lh); • The following weighings are carried out: 1025 kg of pasteurized demineralized water; - 120 kg of yeast extract 2012; 51.2 kg of magnesium chloride hexahydrate (containing 251.8 moles of magnesium). • The yeast extract and the magnesium chloride are mixed by mechanical stirring in the 1025 kg of demineralized water. Mechanical stirring is maintained for 30 minutes in order to obtain homogenization of the mixture. • The homogeneous mixture obtained (volume of 1100 1) is then diafiltered at constant volume on a polyamide membrane with a cut-off threshold at 200 Da, for 4 h at a temperature between 25 ° C and 30 ° C. • The diafiltered solution obtained previously (initial volume 1100 1) is concentrated by filtration on a polyamide membrane with a cutoff threshold of 200 Da, at a temperature between 25 ° C and 30 ° C, for 3 h. After concentration, the final volume is 4501. The content of chloride ions is further divided by a factor of 2.5. This step also makes it possible to have a concentrated solution which will make it possible to obtain a dense powder during the atomization. ^" The concentrated solution obtained is then spray-dried (rotation of the turbines 30 to 34 Hz, 4 h, inlet temperature of the atomizer 180 ° C and outlet temperature of the atomizer from 85 ° C to 90 ° C) .

The characteristics of the final product obtained, measured by the usual techniques used in the matter are as follows: - Dry matter (2h at 105 ° C): 93% - Unpacked density: 0.44% / DM - Chloride content (dosage colorimetric): 5.7 - Magnesium content (atomic absorption): 4.1

2) Example 2 Preparation of a product comprising highly bioavailable iron and copper (Fe-Cu Guanylor ^®): • 1500 liters of demineralized water are previously pasteurized (85 ° C, 1 h); • The following weighings are carried out: - 600 kg of pasteurized demineralized water; - 70 kg of yeast extract 2012; - 30 kg of iron sulphate heptahydrate (i.e. 108 moles of iron); - 0.9 kg of copper sulphate pentahydrate (i.e. 3.6 moles of copper). • The yeast extract and the 600 kg of demineralized water are mixed by mechanical stirring. Mechanical stirring is maintained for 1 hour in order to obtain homogenization of the mixture. • The homogeneous mixture obtained (volume of 600 l) is then diafiltered at constant volume on a polyamide membrane with cut-off threshold at 200 Da, for 3 h at a temperature between 25 ° C and 30 ° C. • The iron sulphate and the copper sulphate are then incorporated by mechanical stirring into the homogeneous mixture obtained, for 1 h, until the mixture is homogenized. • The homogeneous mixture obtained previously (initial volume 600 1) is concentrated by filtration on a polyamide membrane with a cut-off threshold of 200 Da, at a temperature between 25 ° C and 30 ° C, for 2 h. After concentration, the final volume is 4501. The content of chloride ions is further divided by a factor of 2. • The concentrated solution obtained is then spray-dried (turbine rotation 30 to 34 Hz, 4 h, inlet temperature of atomizer 180 ° C and outlet temperature of the atomizer 85 ° C to 90 ° C). The characteristics of the final product obtained, measured by the usual techniques used in the matter are as follows: - Dry matter (2h at 105 ° C): 98% Unpacked density: 0.46% / DM Chloride content (colorimetric dosage) 2.9 Iron content (atomic absorption): 4.6 Copper content (atomic absorption): 0.17

3) Example 3: preparation of products comprising other minerals or mixtures of highly bioavailable minerals: Products comprising other minerals or mixtures of highly bioavailable minerals are prepared according to the same protocol as that of Example 2. Table 3 following presents the respective amounts of minerals and extracts of microorganisms to be mixed in order to obtain different products according to the invention.

Table 3

4) Example 4: compositions comprising at least one product according to the invention Example 4-1: food supplement of the base composition referred OLIGOBIANE Cr ^®: The basic composition of this product is a mixture of the various ingredients in powder form. Depending on the desired final formulation of the composition (capsule, sachet of powder, liquid, etc.), the final composition may contain any additive usually used to obtain the desired final formulation.

* Sold by the company DIANA VEGETAL under the name ALOIGN 5003. ** Sold by the company Européenne Herboristerie.

Example 4-2: Basic composition of the food supplement called OLIGOBIANE ^® Mn-Cu The basic composition of this product is a mixture of the various ingredients in powder form. Depending on the desired final formulation of the composition (capsule, sachet of powder, liquid, etc.), the final composition may contain any additive usually used to obtain the desired final formulation.

Example 4-3: Basic composition of the food supplement called OLIGOBIANE ^® Fe-Cu The basic composition of this product is a mixture of the various ingredients in powder form. According to the desired final formulation of the composition (capsule, sachet of powder, liquid, etc.), the final composition may contain any additive usually used to obtain the desired final formulation.

5) Example 5: Compared bioavailability of magnesium and iron in the form of salts or present in a product according to the invention: To show the advantage of the products according to the invention comprising magnesium and iron, comparative studies were carried out in animals. A) Study of the absorption of magnesium A comparative study was conducted in the WISTAR rat receiving per os the same amount of magnesium (30 mg / kg) in the form of magnesium chloride, or a mixture of magnesium oxide and protein hydrolyzate (measurement of the effect of peptides), or of a mixture of magnesium chloride and yeast extract (product according to the invention). The following Table 4 presents the results obtained during the magnesium bioavailability study: Table 4

N = 10, m ± ESM, ** p <0.01 vs GUANYLOR ^® Mg (Student's t test) Cmax: maximum plasma concentration measured after treatment; Tmax: time at which the maximum concentration was measured; B: bioavailability

The intake of magnesium by a product according to the invention based on yeast extract or by peptides (protein hydrolyzate) allows better absorption and a better fixation rate of magnesium. Nevertheless, the bioavailability values and the fixed percentage of magnesium are greater during a supply of magnesium by a product according to the invention based on yeast extract than in combination with peptides.

B) Study of the bioavailability of iron The same study was conducted with iron. Iron is provided in the form of only ferrous sulfate or iron sulfate + protein hydrolyzate, or iron sulfate + yeast extract (product of the invention, Guanylor ^® Fe-Cu (Example 2)). Table 5 presents the results obtained during the iron bioavailability study.

Table 5.

N = 10, m ± ESM, ** p <0.01 vs GUANYLOR ^® Fe-Cu (Student's t test) Cmax: maximum plasma concentration measured after treatment; Tmax: time at which the maximum concentration was measured; B: bioavailability The assay of plasma iron concentrations shows that the maximum iron concentration obtained in animals treated with a product according to the invention based on yeast extract + iron sulfate is significantly higher than that in rats having underwent the other 2 treatments. Similarly, the percentage of iron crossing the intestinal barrier is highly more significant with this iron intake (36% vs 9-13%). The addition of iron by a product according to the invention based on yeast extract allows a passage as good as that of heme iron. This sought-after effect had hitherto never been observed with commercial drug molecules.

C) Study of plasma ferritin

D0: Samples D0: The 40 rats after the stabilization period are weighed and blood is punctured in a pudental vein on heparin. The blood samples are immediately centrifuged (4000 rpm for 10 minutes). The plasma is isolated and frozen at - 0 ° C.

D8: Samples D8: The rats then have access to iron-depleted food for 8 days, (specially prepared kibbles UAR for iron intake equivalent to half the intake required by rats). After 8 days, the rats are weighed and blood is drawn from a pudendal vein and treated as on D0. The rats are then randomly divided into 4 groups of 10: - 1 control group again receiving standard food for 21 days and per os of water which constitutes the vehicle for the treatments. - 1 group treated with iron sulfate at a dose of 14 mg of iron per day, ie 1 mg / kg of ferrous sulfate heptahydrate. - 1 group treated with yeast extract at 6% iron (product of the invention, GUANYLOR ^® Fe-Cu (example 2) for an intake equivalent to 14 mg d in humans, ie 3.3 mg / kg of yeast extract - 1 group treated with 6% iron yeast extract (product of the invention, GUANYLOR ^® Fe-Cu (example 2) taking into account the bioavailability 3.3 times greater according to the results previously obtained, ie 1 mg / kg / day All the treatments are carried out in the morning between 9 and 10 am Administration is carried out by oral route The products are dissolved or suspended in water. of water administered is lml / kg D29: Samples D29: The rats are again weighed and blood is drawn from a pudendal vein on heparin. The sample is taken 2 hours after the last administration of the product. are frozen until the determination of iron (by a reaction with ferrozine according to the method of ABX diagnostics) and ferritin (immunoturbidimetric reaction after mixing the plasma with the reagent ABX diagnostics ferritin latex).

Table 6: Results of the study

N = 40, fp vs D0 and * vs the control group Ferritin is considered to be the best current marker of iron deficiency. In rats, a partial iron deficiency implemented by a food containing half as much iron as the recommended intakes leads to a reduction in plasma ferritin. Returning to a normal diet does not normalize the plasma ferritin. For an equivalent iron content, supplementation with iron sulphate for 21 days induces elevations of plasma iron and ferritin less than those induced by the product according to the invention. The administration of three times less iron by a treatment with a product according to the invention based on yeast-iron (lmg / kg) during this period makes it possible to increase the plasma concentrations of iron and ferritin to values slightly higher than those obtained with iron sulphate. The better bioavailability of iron present in a product according to the invention based on brewer's yeast and iron sulphate therefore allows the administration of iron in a quantity less than that required by other treatments to suppress the effects of the deficiency.

6) Example 6: Anti-Fatigue Effects of the Product According to the Invention Introduction Magnesium guanylate is a patented product (FR 2 721 315) having, as properties described in the patent, an anti-asthenic effect. This molecule has also been shown to have anti-ischemic activities, whether in the heart or the brain.

The first symptoms of a deficiency or simply of a deficit are hyperexcitability followed by periods of fatigue, even exhaustion. The intake of magnesium calms in the same way as tranquilizers but unlike the latter eliminates the feeling of fatigue.

The objective of this protocol is to verify the anti-fatigue effects of the product according to the invention and to compare them with a simple magnesium salt and with a yeast association free of nucletotides / magnesium. The comparison of the three compounds will make it possible to highlight a possible potentiation of the effects of magnesium by the product according to the invention.

The fatigue model chosen is that of forced swimming, which is reproducible. Furthermore, and concomitantly, the reactivity of the rats and the various types of motility were tested. D0. The 60 rats after the housing period are weighed and randomly distributed into six batches of 10 rats. - 1 control group (Control 1) receiving standard food for 17 days, having undergone no treatment, and having not undergone any test. - 1 control group (Control 2) receiving standard food for 17 days, treated per os with distilled water which constitutes the vehicle for the treatments and having undergone the tests; - one group treated with the product according to the invention (yeast extract-Mg Mg Guanylor ^® (Example 1)) at a dose of 125 mg / kg orally (7.5 mg / kg of Mg); - one group treated with the product according to the invention (yeast extract-Mg, Mg Guanylor ^® (Example 1)) at a dose of 250 mg / kg per os (or 15mg / kg of Mg); - one group treated with the product according to the invention (yeast extract-Mg, Mg Guanylor ^® (Example 1)) at a dose of 500 mg / kg per os (or 30mg / kg of Mg); - 1 group treated with magnesium chloride alone at a dose of 127 mg / kg (i.e. 15 mg / kg Mg); - 1 group treated with a yeast extract without nucleotides and magnesium chloride at a dose of 250 mg / kg (i.e. 15 mg / kg Mg).

All treatments are carried out in the morning between 9 and 10 am and last 17 days.

Administration is carried out orally. The products are dissolved or suspended in distilled water. The amount of water administered is lml / kg. Comparable doses of magnesium are therefore with the product according to the invention at

250mg / kg.

Behavioral experimentation

D10: After ten days of treatment and between 2 and 4 hours after the administration of one of the products, the animals are placed in forced swimming.

A weight of 51.5 grams is attached under the belly of the animal to increase the physical effort of the rat in the forced swimming test. Swimming time is measured. When the animals let themselves flow, they are immediately taken out of the swimming pool, wiped, dried and placed in an open field (square plate on which are drawn 16 squares of 13.125 cm side and placed at 1 m from the ground). The rat remains one minute on this open field and we measure during this time the number of square explored (actimetry) and the number of times that the animal leans outside (curiosity). The animals are then replaced in their cage (n = 5 per cage) and continue to receive their treatment daily. D17: The rats are fasted the previous evening at 8 p.m. and 2 to 4 hours after the last administration of the treatment are placed in different experimental conditions in the following order and without interruption between the tests: - Optovarimex (Columbus instruments). Actimetry, anxiety and depression tests; - T-Maze. Attention test; - Inclined plane. Physical performance test; - Aggression test. The following Table 7 presents the average results obtained concerning the swimming times on D10. Table 7

m +/- ESM * p <0.05 ** p <0.01 comparison with controls All the magnesium salts used cause an extension of the swimming time. It is the anti-asthenic effect. Nevertheless, at a comparable dose of magnesium administered (250 mg / kg), the product according to the invention proves to be the most active.

The following Table 8 presents the results concerning the actimetry and the curiosity of the 6 groups of animals. Table 8

** p <0.01 comparison with controls (t test) m +/- ESM After forced swimming and due to fatigue, motor activity is reduced (control animals vs animals not subjected to treatment). Only the doses of 250 mg / kg and 500 mg / kg of the product of the invention improve the performance of the rats. At an equivalent dose of magnesium, only the product according to the invention is active.

On curiosity, the result obtained in the witnesses is very weak in comparison with naive animals. The administration of magnesium restores this curiosity and the results are in all cases statistically superior to the controls. These results are related to the amount of magnesium ingested and not to the form. In both cases, actimetry and curiosity, there is a dose effect with the product according to the invention.

The following Table 9 represents the results corresponding to the study of the number of large movements, the grooming time and the immobility time in an Optovarimex for three minutes. Table 9

m +/- ESM * p <0.05 ** p <0.01 Comparison with controls °° p <0.01 comparison with the same amount of magnesium administered.

Large movements often called the walking perimeter are a good assessment of motility (actimetry). The product according to the invention, and this as a function of the dose administered (effect / dose relationship) increases the motility of the animals. Magnesium alone is ineffective. Small movements and more specifically grooming movements are a good reflection of anxiety. Here, the duration of grooming is significantly improved with the product according to the invention. In this test, magnesium alone is ineffective. On the time of immobility representative of a depressive tendency, the same conclusions are obvious.

Table 10 below presents the results corresponding to a vigilance test (immobility time of animals subjected to 16 h of fasting when they are placed in a labyrinth containing a kibble). Table 10 Treatment of animals Time of immobility (seconds) Controls 2 2.3 +/- 0.14 MgC12 127 mg / kg 2.5 +/- 0.12 GUANYLOR ^® Mg (example 1)) 125mg / kg 1, 8 +/- 0.16 * GUANYLOR ^® Mg (example 1)) 250 mg / kg 1.4 +/- 0.14 ** °° GUANYLOR ^® Mg (example 1)) 500mg / kg 1.1 +/- 0.12 ** Yeast extract without nucleotides and MgC12 250 mg / kg 2.6 +/- 0.17 m +/- ESM, * p <0.05, ** p <0.01 comparison with controls. °° p <0.01 comparison between the same magnesium intakes.

On alertness, magnesium has no effect, there is even a slight decrease with larger doses. It is the calming action of magnesium. The product according to the invention significantly improves, in a dose-dependent manner, the alertness of rats.

Table 11: Rat coordination and fatigue (grip capacity on a surface with roughness).

m +/- ESM, * p <0.05 ** p <0.01. Comparison with controls °° p <0.01 comparison with the same amounts of magnesium ingested. Magnesium regardless of the salt used is active on this movement coordination and fatigue test. Nevertheless, it can be observed that the product according to the invention proves to be the most active. Table 12: Measurement of aggressiveness (bites in response to contact behind the ear).

m +/- ESM, * p <0.05 ** p <0.01 comparison with controls °° p <0.01 comparison for the same amount of magnesium ingested The aggressiveness test corresponds to the irritability in l 'man. Magnesium is not active on this parameter at therapeutic doses. It becomes so in higher doses. Under the experimental conditions used, the magnesium chloride and the magnesium added to the yeast extract are inactive. Only the product according to the invention appears to be active.

Conclusion

All the results obtained demonstrate that with the product according to the invention, a greater magnesium effect is obtained for an equivalent amount of magnesium. It is therefore a question of better bioavailability of the cation with the product according to the invention. The product according to the invention proves to be an anti-asthenic substance superior to magnesium salts. This anti-fatigue effect is proportional to the dose used. In addition, this preparation has intrinsic properties, not attributable to the mineral magnesium alone. Thus, this product, comprising magnesium whose bioavailability is increased, has an anxiolytic, anti-depressant, anti-irritability effect which are specific to it. These properties are very interesting for dealing with the many stresses of everyday life.

Claims

1. Method for increasing the bioavailability of minerals, characterized in that - in a first step, an extract of microorganisms and at least one mineral are mixed, - in a second step, the mixture obtained in the first step is concentrated, and - in a third step the concentrated product obtained in the second step is atomized.

2. Method according to claim 1, characterized in that the microorganism extract is a yeast extract, particularly an extract obtained from a Saccharomyces strain, very particularly from the Saccharomyces cerevisiae or Saccharomyces boulardii strain.

3. Method according to any one of claims 1 or 2, characterized in that the extract of microorganisms is in hydrated form or in the form of a powder or of microgranules, lyophilized or atomized, preferably in the form of lyophilized or atomized powder or microgranules.

4. Method according to any one of claims 1 to 3, characterized in that the mineral is chosen from macro-elements (or major mineral elements) such as, for example, calcium (Ca), potassium (K) or magnesium (Mg), and trace elements (or trace elements) like, mono-, di-, tri-, or hexavalent metal cations like iron (Fe), zinc (Zn), manganese (Mn) , chromium (Cr), copper (Cu), or lithium (Li).

5. Method according to any one of claims 1 to 4, characterized in that the mineral is in the form of a water-soluble inorganic salt chosen from a chloride or a sulfate, or organic chosen from a citrate, a fumarate, a gluconate or a lactate.

6. Method according to claim 5, characterized in that the mineral is in the form, - for iron, of iron sulfate heptahydrate; - for zinc, zinc sulphate heptahydrate; - for manganese, manganese sulfate monohydrate; - for copper, copper sulphate pentahydrate; - for chromium, chromium chloride hexahydrate; - for magnesium, magnesium chloride hexahydrate; - for lithium, lithium chloride.

7. Method according to any one of claims 1 to 6, characterized in that the mixing of the first step is carried out at room temperature, that is to say at a temperature between 18 ° C and 35 ° C, preferably between 20 ° C and 30 ° C.

8. Method according to any one of claims 1 to 7, characterized in that the concentration carried out during the second step is carried out by evaporation under vacuum or by filtration of the mixture with a nanofiltration or reverse osmosis membrane or a diafiltration at constant volume.

9. Method according to claim 8, characterized in that the membrane has a cutoff threshold between 100 and 300 Daltons, preferably between 150 and 250 Da.

10. Method according to any one of claims 1 to 9, characterized in that the atomization (third step) is carried out by bringing the product to be dried into contact with a flow of superheated air at a temperature between 150 ° C and 200 ° C, preferably between 170 ° C and 190 ° C.

11. Product comprising at least one mineral whose bioavailability is high, said product being capable of being obtained by the process described according to any one of claims 1 to 10.

12. Product according to claim 11, in which the mineral whose bioavailability is high is calcium, potassium, iron, zinc, manganese, copper, chromium, magnesium, lithium or a mixture.

13. Food composition or food supplement or dietetic product comprising at least one product as described in any one of claims 11 or 12.

14. Use of at least one product according to any one of claims 11 or 12, in the preparation of a food composition, preferably a food supplement, or a dietetic product.

15. Use of at least one product according to any one of claims 11 or 12, in the preparation of a food composition, preferably a food supplement, or of a dietetic product, intended to prevent or compensate for any deficit in mineral.

16. Use of at least one product according to any one of claims 11 or 12, in the preparation of a food composition, preferably a food supplement, or of a dietetic product, intended for the preventive and / or curative treatment of conditions linked to a deficiency, even a deficiency, in mineral,

17. Use according to claim 16, characterized in that the composition is intended for the curative and / or preventive treatment - of a disturbance of the acid-base balance linked to the potassium deficit or - of an anemia linked to a deficiency or iron and / or copper deficiency, or - asthenia related to deficiency or iron deficiency, or - immunity disorder and / or vision disorder and / or delayed healing linked to zinc deficiency or deficiency, or - a decrease in glucose tolerance and / or the onset of type II diabetes and / or dyslipidemia and / or an increased risk of cardiovascular accidents linked to a chromium deficiency, or - tetany, particularly latent tetany and / or a metabolic disorder, in particular a carbohydrate metabolism disorder and / or lipids, and / or an increased risk of cardiovascular and / or neuromuscular accidents and / or renal and / or bone and / or a decrease in the immune defenses linked to a deficiency in magnesium, or - neutropenia and / or cardiomegaly linked to a deficiency or a copper deficiency, or - a bone disorder and / or a decrease in cholesterolemia linked to a manganese deficiency or deficiency; - mood or sleep disturbances linked to too little lithium intake.