Novel use of an extract of the microalga phaeodactylum tricornutum

Abstract

The invention relates to a Phaeodactylum tricornutum extract or to a composition comprising same for facilitating the resumption of a physical activity, advantageously a sports activity, and / or reducing cardiovascular risks and / or risks related to fragile bones and / or joints when resuming a physical activity, advantageously a sports activity.

Description

New use of an extract of the microalgae Phaeodactyium tricornutum Technical Field

[0001] The present invention relates to new uses of the microalgae Phaeodactylum tricornutum to facilitate the resumption of physical activity, advantageously sporting, and / or to reduce cardiovascular risks and / or risks linked to bone and / or joint fragility when resuming physical activity, advantageously sporting. Prior art

[0002] Sedentary lifestyle is a global scourge affecting all age groups of the population and particularly affecting urban and active populations. Sedentary lifestyle, in the sense of the absence of physical exercise, combined with poor diet and / or poor lifestyle, can result first in the appearance of excess weight, but also more gradually in more severe metabolic deficiencies such as atherosclerosis, hypercholesterolemia, hyperlipidemia, high blood pressure, or even diabetes, which ultimately promote cardiovascular problems. Stress and anxiety have also been shown to have harmful effects on the cardiovascular system.

[0003] As such, one of the cardiovascular markers most easily controlled and affected by these deficiencies and more generally by overweight, lack of physical exercise or poor lifestyle is resting heart rate, defined as the minimum heart rate measured in an individual at rest, in the morning, in the absence of any physical exercise. While resting heart rate is a function of the age of individuals, it also reflects the state of heart health. As such, it constitutes a therapeutic target in its own right.

[0004] Several medications have been available for many years to control the metabolic disorders mentioned above and reduce the occurrence of cardiovascular accidents. Certain beta-blockers, specific competitive antagonists of p-adrenergic receptors, have notably shown their effectiveness in reducing heart rate. In addition, calcium channel blockers or potassium or sodium, allowing the blocking of the corresponding channels and inducing a decrease in cardiac activity. On the other hand, few natural solutions exist. In this respect, we can cite garlic (AHium sativum), omega-3 fatty acids from fish oils or even phytosterols and phytostanols, particularly known for their beneficial effect on blood cholesterol levels.

[0005] Furthermore, as part of a program to resume physical activity, particularly sport, possibly coupled with a slimming diet, with the aim of reducing the resting heart rate and therefore the cardiovascular risk mentioned above, a significant parameter will be modified: the bone mineral level. We know that weight loss, often associated with a resumption of physical activity, particularly sport, is accompanied by a drop in this bone mineral level, with the obvious consequence of bone and joint fragility, bone fragility also impacting the joints.

[0006] Natural solutions capable of reducing resting heart rate, thereby reducing cardiovascular risk, which are also suitable for resuming physical activity, particularly sport, and in particular maintaining bone mineral levels, are rare. There is therefore a significant need in the nutraceutical field for natural solutions of this type.

[0007] Fish oil-based dietary supplements are known to have an effect on the prevention and / or treatment of hypercholesterolemia or hypertriglyceridemia (WO9733599).

[0008] Application WO2020065402A1 also described a method for preventing and treating several metabolic deficiencies caused by air pollution or the inhalation of particles such as oxidative stress, endothelial dysfunction, narrowing and / or thickening of the arteries and / or inflammation and in particular a method for reducing cardiac risks in patients suffering from these deficiencies by using eicosapentaenoic acid (EPA). This application mentions the possibility of an action on the heart rate which can be measured among other things by the levels of the heart rate. However, this application recommends the use of a high dose of EPA (4g / day) and has only considered in these examples tests with 96% pure E-EPA (ethyl EPA / ethyl eicosapentaenoate), without providing the results of these tests. Thus, the applicant of this application (AMARIN PHARMACEUTICALS) has only obtained marketing approval for the product called Vazkepa® which consists of E-EPA at a dosage of 4g per day for a very limited application: reducing cardiovascular risk in adult patients treated with statins presenting a high cardiovascular risk with high triglycerides (> 150 mg / dL) and either established cardiovascular disease or diabetes and at least one other cardiovascular risk factor.The European Medicines Agency (EMA) assessment report of January 28, 2021 on this product also mentions that during the tests carried out with this product, there was no significant change in heart rate between people treated with this product or with the placebo. Thus, in addition to the fact that the recommended dosages of EPA and especially E-EPA are very high and that the patients to be treated cannot be considered healthy patients, there is no relevant information on the effect of this product on heart rate and in particular on its use to facilitate the resumption of physical activity, advantageously sporting, and / or reduce cardiovascular risks when resuming physical activity in healthy patients.

[0009] Application EP3906920 describes a marine oil comprising, among other things, omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for reducing resting heart rate. However, the amount of DHA is greater than the amount of EPA since the DHA / EPA ratio is between 3 / 2 and 4 / 1 and the recommended amount of EPA to be administered is very high (at least 700mg / day) and that of DHA even higher (at least 1800mg / day), the dosage form thus comprising at least 150mg of EPA and at least 450mg of DHA to be administered several times a day.

[0010] Several clinical studies involving oral administration of fish oils or combinations of EPA and DHA have been published (Hidayat et al., 2018). But none of these studies have demonstrated the effectiveness of EPA in reducing resting heart rate, especially at doses of EPA below 100 mg / day in human equivalent. Some studies have even shown that EPA has no effect on resting heart rate. In any case, all of these clinical studies report a very high daily dose of omega-3 fatty acids administered (from 0.5 to 1.5 g / day of EPA+DHA).

[0011] Furthermore, application WO2014184484 describes a synergistic combination of DHA and fisetin for the treatment and prevention of bone pathologies, including Paget's disease or osteoporosis. However, it appears that the pathologies in question are associated with aging, menopause or resulting from metabolic diseases such as obesity or diabetes. The populations targeted by the administration of this combination of molecules in this application are therefore distinct from those targeted by the present invention. It should also be noted that in this application only fisetin was tested in vivo. This application also does not teach that DHA alone can have an effect on bone pathologies.

[0012] Furthermore, application FR3118967 describes a composition of microorganism oil enriched with polyunsaturated fatty acids comprising a quantity of EPA greater than or equal to 5% by weight relative to the total weight of the composition and a quantity of DHA greater than or equal to 6% by weight relative to the total weight of the composition. It is used in the treatment or prevention of obesity, reduction of cholesterol levels and bone diseases in particular. However, the EPA and DHA contents described in this application are significantly higher than those of the composition according to the present invention.

[0013] Finally, application WO2006085144 describes compositions used in diets intended to treat or prevent in particular cardiovascular disorders or osteoporosis. However, the present invention describes EPA and DHA contents much lower than those described in application WO2006085144.

[0014] The inventors surprisingly discovered that Phaeodactylum tricornutum extract had an impact on both resting heart rate and bone mineral levels, thereby maintaining and / or reducing resting heart rate and preventing a decrease in bone mineral levels. These two properties are highly sought after when resuming physical activity, particularly in overweight people, especially those who have followed a slimming diet.

[0015] The applicant already knows of a microalgae extract of the species Phaeodactylum tricornutum for the preparation of a composition in the form of a food supplement to prevent or combat cognitive disorders linked to aging or cognitive disorders in children or young adults who have suffered prenatal stress (FR3092968A1).

[0016] However, it has never been described or suggested that such an extract not only has the capacity to maintain and / or decrease the resting heart rate in mammals without cardiovascular pathology or deficiency in generating it, but also the capacity to prevent a decrease in bone mineral content and to increase bone mineral density in these same mammals.

[0017] An advantage of the present invention is that the microalgae extract is a completely natural extract, obtained from biomass produced in photobioreactors under controlled conditions of temperature and light, without the addition of any chemical or hormone. The extract can be ingested orally without any proven side effects. Compared to the processes for obtaining fish oils involving relatively heavy concentration and purification steps, or even refining, the process for obtaining the microalgae extract is simple, and can be easily implemented at the industrial level at a lower cost.

[0018] It is certainly known that Phaeodactylum tricornutum extract contains DHA and EPA. However, DHA is present in small quantities of at most 4% by weight relative to the total weight of the extract, advantageously at most 2%. by weight relative to the total weight of the extract, more advantageously at most 1% by weight, which does not allow it to play a role in the newly discovered effects. In addition, the EPA / DHA weight ratio is greater than 1, in particular between 5 / 4 and 50 / 1. The extract thus comprises more EPA than DHA. However, the quantity of EPA is also low, between 4% and 20% by weight, preferably between 5% and 15%, still preferentially between 7% and 13%, still preferentially 12.4%, by weight relative to the total weight of the extract. Thus, the overall content of EPA + DHA is at most 24% by weight, advantageously at most 17% by weight, in particular at most 14% by weight, relative to the total weight of the extract.

[0019] Finally, the extract includes other components such as fucoxanthin, sterols, and phycoprostane.

[0020] The microalga Phaeodactylum tricornutum is a microalga belonging to the genus Phaeodactylum and the family Phaeodactylaceae. It is present in 3 distinct morphotypes (fusiform, oval, triradiate); it is found in many oceanic regions of the world, including northern Europe, Oceania, and the Atlantic. Statement of the invention

[0021] A first subject matter relates to an extract of P. tricornutum or a composition comprising it for its use to facilitate the resumption of physical activity, advantageously sporting, and / or reducing cardiovascular risks and / or risks linked to bone and / or joint fragility when resuming physical activity, advantageously sporting, advantageously to maintain and / or reduce heart rate, and / or to prevent a decrease in bone mineral content and / or increase bone mineral density, more advantageously in healthy mammals, very advantageously in overweight mammals and / or following a slimming diet, advantageously healthy humans. Advantageously, the extract or composition is used for: - strengthen cardiovascular capacities and / or - reduce cardiovascular risk and / or - prevent bone and / or joint fragility and / or - preserve bone capital and / or joints.

[0022] Here, "mammals" means humans and non-human mammals, in particular non-human mammals chosen from horses, cows, pigs, swine, domestic animals such as cats and dogs, advantageously domestic animals and humans, again advantageously humans.

[0023] "Healthy mammals" means mammals that do not have any cardiovascular deficiency or pathology or deficiency generating them and that are not obese. Cardiovascular pathologies include, but are not limited to, heart failure, venous insufficiency, atherosclerosis, cardiac amyloidosis, myocardial infarction, angina pectoris, atrial fibrillation, tachycardia, Bouveret's disease.

[0024] The deficiencies generating these cardiovascular pathologies from which the healthy mammals of the present invention are excluded include in particular hypertension, diabetes, dyslipidemias including hypercholesterolemia and hypertriglyceridemia, in particular with triglycerides > 150 mg / dL, cancer, active smoking, depression, stress and anxiety.

[0025] In particular, healthy mammals according to the invention do not suffer from oxidative stress, endothelial dysfunction, narrowing and / or thickening of the arteries and / or inflammation. They also do not suffer from bone pathologies, including Paget's disease or osteoporosis.

[0026] More advantageously, healthy mammals according to the invention are not treated with statins.

[0027] More particularly, the healthy mammals according to the invention do not suffer from cognitive disorders linked to aging, defined as a non-pathological decrease in cognitive functions, or from cognitive disorders in children or young adults having undergone prenatal stress inducing non-pathological disorders, such as hyperactivity, attention and memory deficit, language delay and anxious behavior.

[0028] Healthy mammals as defined herein are mammals whether or not they are overweight, without any other deficiency or pathology such as above that could generate a cardiovascular pathology. Overweight is not considered a pathology within the meaning of the invention. Indeed, overweight has nothing to do with obesity. Advantageously, healthy mammals, advantageously healthy humans, are overweight. “Healthy overweight humans” means individuals with a body mass index (BMI) greater than or equal to 25 kg / m2 and less than or equal to 29.9 kg / m2, and / or with a waist circumference greater than or equal to 80 cm for a woman, or 94 cm for a man. Finally, healthy mammals as defined herein are not mammals exposed to air pollution, are not menopausal, and do not have osteolytic diseases.In particular, healthy mammals and advantageously healthy humans are not old, "old" being understood here as humans over 50 years old. Similarly, healthy domestic animals are not old, "old domestic animals" being understood here as domestic animals over 7 years old. Advantageously, the healthy humans according to the invention are not children or young adults who have suffered prenatal stress. In particular, the healthy humans according to the invention are aged from 25 to 50 years, in particular from 30 to 50 years, more particularly from 30 to 40 years.

[0029] For the purposes of the present invention, "physical activity" means all body movements produced by the muscles, resulting in an expenditure of energy greater than that expended at rest. It therefore includes, in addition to sporting activities, daily physical activities and exercises.

[0030] Daily physical activities include: - active travel: walking, cycling, going up and down stairs, - domestic activities: cleaning, DIY, gardening, - professional activities (physical work for example) or school activities.

[0031] Physical activity is characterized by its intensity. Depending on the consequences it produces on the body, physical activity can be defined as light intensity, moderate or high.

[0032] During low intensity physical activity: - breathing is almost normal without shortness of breath, - conversation is possible, - the heart is not accelerated.

[0033] During moderate-intensity physical activity: - breathing is slightly accelerated and shortness of breath is slight, - conversation is possible, - heartbeat is a little faster.

[0034] During high intensity physical activity: - breathing is accelerated and shortness of breath is high, - the conversation is difficult, made up of short sentences, - the heart beats fast.

[0035] "Resuming physical activity, preferably sporting activity" means restarting physical activity, in particular of low, moderate or high intensity, more preferably moderate or high, after a period of inactivity and / or sedentary lifestyle. The period of inactivity and / or sedentary lifestyle may have lasted from a few days (1 to 7 days for example) to a few months (12 months for example) or even a few years (1 to 10 years for example), passing through a few weeks (1 to 5 weeks for example) and may be due to various factors such as injuries, fractures, operations, illnesses, pregnancies, childbirth, lifestyle, overweight etc.

[0036] By "facilitating the resumption of physical activity, advantageously sporting activity" is meant avoiding physical problems linked to this resumption such as injuries, cardiovascular problems (discomfort, chest pain, heart palpitations, abnormal shortness of breath), fractures, joint problems and / or excessive fatigue, in particular by maintaining and / or reducing the heart rate, and / or preventing a decrease in bone mineral content through the administration of the extract according to the invention or the composition comprising it.

[0037] By "reducing cardiovascular and / or related risks" we mean bone and / or joint fragility when resuming physical activity, advantageously sporting activity”, reduce the probability of occurrence of cardiovascular problems (such as discomfort, chest pain, heart palpitations, abnormal shortness of breath, cardiac arrest) and / or fractures and / or tendonitis, in particular by maintaining and / or reducing the heart rate, and / or preventing a decrease in bone mineral content through the administration of the extract according to the invention or the composition comprising it.

[0038] "Decreasing heart rate" means reducing the resting heart rate and / or maximum heart rate, i.e., respectively, the minimum heart rate measured at rest, without any physical effort and in the morning, and the maximum heart rate at which the heart can beat, typically reached during progressive and maximum endurance exercise. Resting and maximum heart rates are advantageously measured by a specialist doctor, a cardiologist.

[0039] Advantageously, "reducing the heart rate" means reducing the resting heart rate. In one embodiment, this is a reduction in the resting heart rate of at least 5%, advantageously at least 9% in the presence of the composition according to the invention, compared to the resting heart rate measured in the absence of the composition. Advantageously, this is a reduction in the resting heart rate measured in the context of a clinical trial conducted on a population of humans qualified as healthy within the meaning of the invention, the clinical trial consisting of the daily oral administration of the composition according to the invention or a placebo, for a total period of 12 weeks, under the conditions described in detail in Example 2.

[0040] The extract according to the invention is further used to prevent a decrease in bone mineral content and / or to increase bone mineral density, advantageously in healthy mammals, particularly when resuming physical activity, advantageously sporting, and very advantageously in mammals who are overweight and / or following a slimming diet, advantageously healthy humans. It is known in fact that weight loss, associated or not with a slimming diet and / or a resumption of physical activity, can cause a reduction in the quantities of minerals present in the bones in mammals, particularly in humans.

[0041] Thus, the expression "preventing a decrease in bone mineral content" means maintaining at least 1%, preferably at least 1.5%, of the bone mineral content in healthy mammals, in particular healthy humans in the presence of the composition according to the invention and in comparison with that measured in the absence of the composition. In an advantageous embodiment, the bone mineral content is measured within the population of healthy humans following the 12-week physical exercise program in the clinical study described in detail in Example 2. The results are presented in Example 3 and confirm a maintenance of the bone mineral content within the population having received the oral supplementation comprising the composition, in comparison with the placebo supplementation, with both populations showing significant weight loss.

[0042] Furthermore, the term "increasing bone mineral density" means increasing by at least 1% the bone mineral density in healthy mammals, in particular healthy humans, in the presence of the composition according to the invention and in comparison with the bone mineral density measured in the absence of the composition. Advantageously, the bone mineral density is measured within the population of healthy humans following the 12-week physical exercise program in the clinical study described in detail in Example 2.

[0043] In this application, the expressions "between ... and ..." and "from ... to ..." must be understood to include the limits unless explicitly stated otherwise.

[0044] The extract according to the invention, by reducing the heart rate, advantageously at rest, is useful for strengthening cardiovascular capacities in mammals, in particular humans and preferably healthy humans. It is also useful for reducing cardiovascular risk, in particular when resuming physical activity, advantageously sporty. By "strengthening cardiovascular capacities" we mean increasing endurance and physical capacities. In addition, by "reducing cardiovascular risk" we mean reducing the risks of cardiovascular events induced by exertion increasing the heart's oxygen requirements and chosen from myocardial infarction and angina pectoris. Also included are cardiovascular events affecting the arteries and veins such as thrombosis, atherosclerosis, stroke.

[0045] On the other hand, by preventing a decrease in the bone mineral level inherent in the resumption of physical activity, in particular sporting activity, and in particular accompanied by weight loss, as well as by increasing bone mineral density, the extract according to the invention is useful for preventing bone and / or joint fragility, advantageously in healthy mammals, and even more advantageously in healthy humans. Here, the term "preventing bone fragility" means preventing bone demineralization leading to a loss of bone density for a given bone, and which may in particular lead to a risk of bone lesions, in particular stress fracture or fracture, in particular in humans resuming physical activity, in particular sporting activity. The term "preventing joint fragility" means preventing joint lesions, in particular at the level of the cartilages, due to the indirect effect of a bone lesion.By preventing bone demineralization and / or increasing bone mineral density, the extract according to the invention can thus be used to preserve bone capital and / or the joints of mammals, advantageously healthy mammals, even more advantageously healthy humans, in particular healthy non-elderly humans as defined in the context of the invention.

[0046] The extract is in fact particularly dedicated to facilitating the resumption of physical activity, advantageously sporting.

[0047] Advantageously, the extract according to the invention is not used in association with fisetin and / or in a composition comprising it. Advantageously, the composition comprising the extract according to the invention does not comprise fisetin and / or is not used in association with fisetin. Extract

[0048] The extract according to the invention is obtained by any extraction method known to those skilled in the art from any biomass of the microalga Phaeodactylum tricornutum. The biomass can be obtained from a culture of the microalga in autotrophic mode, in heterotrophic mode, or in mixotrophic mode with respect to carbon. Advantageously, the autotrophic mode is implemented. The microalga can be cultivated under controlled conditions within suitable systems such as open culture tanks of the “race-ways” or “open ponds” type or closed systems of the photobioreactor type. The photobioreactors used can be of any existing type such as horizontal tubular photobioreactors, vertical photobioreactors such as so-called “green wall panel” systems, flat or columnar photobioreactors. Preferably, biomass production is carried out within a closed culture system of the photobioreactor type. The microalgae culture is carried out according to batch, fed-batch, continuous, semi-continuous, turbidostat or chemostat culture management methods.

[0049] The extraction can be carried out from frozen or fresh biomass, preferably frozen. It may or may not be dried before extraction. It is advantageously dried. Its quantity is between 0.1% and 20% by weight, advantageously between 1% and 20%, very advantageously between 5% and 15%, and even more advantageously it is 15% by weight relative to the total weight of the material and the extraction solvent. For the purposes of the invention, the term "dry biomass" means a dehydrated biomass comprising less than 15%, advantageously less than 10%, even advantageously less than 5% and very advantageously less than 1% of water.

[0050] The biomass can be centrifuged and then filtered to remove water before extraction. A solid-liquid extraction step can be carried out subsequently. Preferably, the extract is obtained by extraction in a solvent or solvent mixture chosen from water, acetone, hexane, ethyl acetate, methyltetrahydrofuran, 2-methyloxolane, heptane, an alcohol chosen from ethanol, methanol, isopropanol, a natural or branched oil, a glycol, a polyol and a water / alcohol or water / glycol mixture in a proportion of 99 / 1 to 1 / 99 (w / w) or any other solvent allowing all or part of the compounds of a hydrophobic and amphiphilic nature to be extracted. Preferably, the extract of P. tricornutum is obtained by extraction in a water / ethanol mixture in a proportion of 40 / 60 (w / w) to 1 / 99 (w / w), including 30 / 70 (w / w) and 20 / 80 (w / w), and very preferably in ethanol as the sole solvent or in a water / ethanol mixture of 1 / 99 (w / w) (w / w means weight / weight in the context of the present invention). The solvent or solvent mixture is separated from the residual biomass after extraction by processes such as centrifugation, filtration and can subsequently be concentrated, or the solvent removed, by techniques such as vacuum evaporation or any other technique allowing the selective evaporation of the solvent in question. Alternatively, the extract of P.tricornutum according to the invention is obtained by extraction under subcritical or supercritical conditions. Advantageously in this case, the extract is obtained by supercritical CO2 extraction. Advantageously, the extract is lipophilic, in particular oily.

[0051] The extraction can be carried out at a temperature ranging from 4°C to 300°C, including room temperature, i.e. a temperature of 20°C. In a preferred embodiment of the invention, the extraction is carried out at room temperature.

[0052] In one embodiment of the invention, the extraction is carried out in water under subcritical conditions, at a temperature ranging from 100°C to 300°C, advantageously from 120°C to 250°C, still advantageously at 120°C. The extraction can be carried out at a given temperature or at successively increasing temperatures. In an advantageous embodiment of the invention, the extraction is carried out at a temperature of 120°C. In an alternative mode, it will be carried out according to a gradient of three increasing temperatures between 100°C and 200°C, such as 120°C, 140°C then 160°C or 110°C, 130°C then 150°C, or even 120°C, 145°C then 170°C.

[0053] Extraction under "subcritical conditions" means extraction in the presence of water, under conditions of temperature above 100°C and pressure below 221 bars, the water remaining in the liquid state but having a viscosity and surface tension lower than that of water at room temperature, increasing its dielectric constant. Thus, the extraction pressure is between 150 bars and 250 bars, preferably between 200 and 221 bars, advantageously in a pressure extraction autoclave.

[0054] The extraction can be carried out by any method well known to those skilled in the art, advantageously by maceration in a solvent or mixture of solvents as described above.

[0055] The extraction time can be between a few minutes and several hours, in particular from 30 minutes to 4 hours, more advantageously from 1 hour to 3 hours, in particular it is 2 hours.

[0056] In all cases, the extract obtained is filtered and is in oily form. It can be decolorized with activated carbon to remove the chlorophyll. In this case, it is filtered again. It can optionally be dried. Advantageously, in this case, the drying step is carried out by lyophilization, vacuum drying, drum drying, or atomization, by fluidized bed, coupled with any technique allowing encapsulation or microencapsulation via a support matrix and / or the formation of an emulsion. The extract according to the invention is then in powder form. It can be incorporated into a composition in powder form or in the oily form previously described.

[0057] In a first advantageous embodiment of the invention, the extract is obtained from frozen and dried biomass, which is then thawed and filtered. The extraction is carried out with a water / ethanol mixture in a proportion of 1 / 99 (w / w), under the conditions described in example 1a), from a quantity by weight of 15% of biomass relative to the total weight of the biomass and ethanol. The extract obtained is an oily extract (lipophilic), indifferently called liquid extract or oily extract in the present invention. This oily extract is then advantageously incorporated into a composition comprising at least one vegetable oil and vitamin E.

[0058] In a second advantageous embodiment of the invention, the extract is obtained by extracting a quantity of 15% by weight of biomass in a water / ethanol mixture (20 / 80; w / w) under the conditions described in example lb), making it possible to obtain the oily extract (lipophilic). This oily extract is then advantageously incorporated into a composition comprising at least one vegetable oil and vitamin E.

[0059] Advantageously, the extract of P. tricornutum according to the invention contains an amount by weight relative to the total weight of the extract of between 4% and 20% of EPA (Eicosapentaenoic acid or (5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentenoic acid; CAS number 10417-94-4; molar mass 302.451 g / mol; empirical formula C20H30O2), preferably between 5% and 15%, more preferably between 7% and 13%, more preferably 12.4%.

[0060] In a particular embodiment of the invention, the extract according to the invention contains a quantity of omega-3 polyunsaturated acid DHA (docosahexaenoic acid; cas number 6217-54-5; molar mass 328.48 g / mol; empirical formula C22H32O2) by weight relative to the total weight of the extract according to the invention of at most 4%, advantageously at most 2%, very advantageously at most 1%. Thus this DHA content in the extract according to the invention is so low that the DHA is not in sufficient quantity to have an action on maintaining or reducing the heart rate, advantageously at rest, nor on preventing the reduction of the bone mineral level.

[0061] Thus, the extract according to the invention is such that the EPA / DHA weight ratio is between 5 / 4 and 50 / 1, advantageously between 7 / 4 and 40 / 1, still advantageously between 3 / 1 and 30 / 1 and particularly advantageously it is 28.33 / 1.

[0062] Thus, in particular, DHA is not responsible for the reduction of heart rate, advantageously of resting heart rate, advantageously in healthy mammals, preferentially healthy humans, and / or for the prevention of the reduction of bone mineral level or the increase of bone mineral density.

[0063] The extract according to the invention may comprise other components such as fucoxanthin, sterols, and / or phycoprostane.

[0064] In an advantageous embodiment the extract is for oral use, advantageously in the form of a food supplement. Composition

[0065] Another subject of the invention relates to a composition comprising the extract of P. tricornutum according to the invention for its use to facilitate the resumption of a physical activity, advantageously sporting, and / or reducing cardiovascular risks and / or risks linked to bone and / or joint fragility when resuming a physical activity, advantageously sporting, advantageously to maintain and / or reduce heart rate, and / or prevent a decrease in bone mineral level and / or increase bone mineral density. In one embodiment, the composition is a food supplement, whereby the term "food supplement" is understood herein to mean a food supplement, a nutritional supplement, a dietary supplement, an over-the-counter supplement, a dietary supplement or a nutritional supplement. In an advantageous embodiment, the composition according to the invention is for oral use.

[0066] The extract according to the invention is present in the composition according to the invention in an amount by weight relative to the weight of the composition of between 20% and 70% by weight relative to the total weight of the composition, preferably between 30% and 65%, more preferably between 45% and 60%, including 45%-55%.

[0067] The composition also comprises at least one vegetable oil and vitamin E, advantageously coconut oil and α-tocopherol.

[0068] By "vegetable oil" is meant any oil extracted from a plant or an algae, including a microalgae, notably chosen from olive oil, rapeseed oil, linseed oil, sunflower oil, a medium chain triglyceride (MCT) oil. By medium chain triglycerides (MCT) is meant esters of glycerol and saturated fatty acids, the hydrocarbon chain of which has 6 to 12 carbon atoms. An MCT oil can thus be chosen from coconut oil, advantageously coconut oil, palm kernel oil and palm oil but can be obtained from other fats or oils. Advantageously within the meaning of the invention, the vegetable oil is an MCT oil, more advantageously coconut oil, very advantageously coconut oil. In a particularly advantageous embodiment of the invention, the vegetable oil is present in an amount of 20% to 80%, more advantageously 30% to 60% by weight relative to the total weight of the composition, including between 40% and 50% and more advantageously 45%.

[0069] “Vitamin E” means a tocopherol selected from α-tocopherol, γ-tocopherol, α-tocopherol or δ-tocopherol, or a tocotrienol selected from γ-tocotrienol, γ-tocotrienol, γ-tocotrienol or 5-tocotrienol. Advantageously, it is α-tocopherol.

[0070] In an advantageous embodiment, vitamin E is present in the composition in an amount by weight relative to the total weight of the composition of 0.15% to 1.25%, advantageously of 0.25% to 1%, very advantageously of 0.5%.

[0071] Thus, a particularly advantageous composition of the invention comprises by weight relative to the total weight of the composition: - Between 30% and 65%, advantageously from 45% to 60% of the extract of Phaeodactylum triœrnutum according to the invention; - - Between 0.25% and 1% of vitamin E, advantageously 0.5%, and preferably α-tocopherol; - Between 30% and 60%, preferably 45% coconut oil.

[0072] In an advantageous embodiment, the composition consists essentially of, in particular consists of, the extract, vitamin E and coconut oil.

[0073] In addition, the composition may comprise at least one orally acceptable excipient selected from carrier agents, bulking agents, preservatives, acidifying agents, emulsifying agents, humectants, gelling agents, lubricating agents, coating or encapsulating agents, stabilizing or dispersing agents, sweetening agents. The excipient is non-toxic and inert. It can be ingested orally without safety and without side effects. Carrier agents include maltodextrin, acacia gum, cellulose and its derivatives (methylcellulose, ethylcellulose and microcrystalline cellulose), calcium phosphate, inulins, flours (rice flour, coconut flour or other), starches and their derivatives, talc, or carob gum. Preservatives are chosen from sodium sorbate or sodium benzoate; acidifying agents are chosen in particular from citric acid or sodium citrate; emulsifying agents are chosen from lecithin, phospholipids, polyethylene glycols; humectants are chosen from glycerin, sorbitol, dextrose.Examples of bulking agents include mannitol, lactose, sorbitol, starch, microcellulose, hydroxypropylmethylcellulose, crosscarmelose, polyvinylpyrrolidone, calcium phosphate (anhydrous or hydrated di and tribasic), citric acid or tartaric acid, sodium, potassium or calcium carbonates, siliceous cellulose, or acacia gum. Lubricating agents (anticaking agents) include magnesium stearate, stearic acid, lecithins, colloidal silica, rice extract, talc, glycerol dibehenate, or bamboo extract titrated in silica. Coating or encapsulating agents may be chosen from gelatin, hydroxypropylmethylcellulose, pululan, beeswax or carnauba wax. Gelling agents can be chosen from starches, native or pregelatinized, carrageenans, pectin, alginates, agar-agar, xanthan gum or even gelatin.Examples of stabilizing or dispersing agents include alginates, acacia gum, and phospholipids. Sweetening agents include maltitol, xylitol, sucralose, sorbitol, agave syrup, glucose syrup, sucrose, fructose, stevia extract, honey, isomalt, and maltitol.

[0074] The excipient is advantageously present in the composition in an amount of 1% to 90% by weight relative to the total weight of the composition, advantageously between 1% and 50%, still advantageously between 1.5% and 10%.

[0075] The extract of P. tricornutum according to the invention, in particular the oily extract, and advantageously the composition or the food supplement comprising it, can be put in the form of soft capsules, or can be formulated in powder form, by any technique allowing the microencapsulation of aqueous solution involving or not a support or a matrix allowing or not its homogeneous dispersibility within a polar oral solution.

[0076] Thus, advantageously, the composition according to the invention is in solid form, advantageously in powder form, still advantageously in the form of cold-dispersible powder, or alternatively in liquid form.

[0077] Advantageously, the composition according to the invention is in the form of a gel cap, a capsule, a tablet, a tablet, a candy, a chewing gum, a granule, a lozenge, a pill, an energy bar, a kibble, a pâté, a treat, granules, a soft capsule, a syrup, a spray, an ampoule, a suspension, an emulsion, a hot or cold drink such as a fruit juice, in particular an energy drink.

[0078] The composition according to the invention can therefore be in the form of a powder, advantageously in the form of a cold-dispersible powder, and advantageously in this case in the form of a capsule, a capsule, a tablet, a tablet, a candy, a chewing gum, a granule, a pill, a lozenge, an energy bar, a kibble, a pâté, a food supplement for animals, a treat, granules. It is advantageously packaged in doses having a unit weight of between 1 lmg and 2g, advantageously between 20mg and 2g.

[0079] Alternatively, the composition of the invention is in liquid (oily) form. In this case it is advantageously in the form of a soft capsule, a syrup, a spray, an ampoule, a suspension, an emulsion, a hot or cold drink such as a fruit juice, in particular an energy drink.

[0080] In a preferred embodiment of the invention, the composition according to the invention is used in humans. In this case, it can be administered orally in oily (liquid) form at a daily dose equivalent human (70kg human) between 50mg and 1250mg, advantageously between 100mg and 850mg, still advantageously between 150mg and 700mg, particularly between 200mg and 500mg, and still preferentially between 218mg and 650mg, including 436mg and 630mg. This therefore corresponds respectively to a daily dose administered between 0.71mg / kg and 17.85mg / kg, advantageously between 1.42mg / kg and 12.14mg / kg, still advantageously between 2.14mg / kg and 10mg / kg, particularly between 2.85mg / kg and 7.14mg / kg, and still preferentially between 3.11mg / kg and 9.28mg / kg, including 6.24mg / kg and 9mg / kg.

[0081] Alternatively, the composition according to the invention is administered orally in powder form at a daily dose in human equivalent (70kg human) of between 100mg and 125mg, advantageously between 200mg and 2125mg, advantageously still between 300mg and 1750mg, particularly between 400mg and 1250mg, and even more preferably between 436mg and 1625mg, including 872mg and 1575mg. In all cases, the humans are advantageously healthy humans.

[0082] Alternatively, the composition according to the invention is administered to mammals in oily form at a daily dose of between 2.5 and 10 mg per kg of body mass, advantageously between 5 mg and 7.5 mg, and very advantageously between 5.5 mg and 6.5 mg, including 5.8 mg. Advantageously, the mammals are domestic animals, preferably healthy, and even more advantageously it is the dog, preferably the healthy dog. The composition according to the invention may be presented in this case in the form of pâté, animal food supplement, kibble, granules, treats, or chew bones.

[0083] Alternatively, the composition according to the invention is administered to mammals in powder form at a daily dose of between 6 mg and 30 mg per kg of body mass, advantageously between 10 mg and 19 mg, and very advantageously between 12 mg and 16 mg, including 14.6 mg. Advantageously, the mammals are domestic animals, preferably healthy ones, and even more advantageously it is the dog, preferably the healthy dog. The composition may be in this case in the form of pâté, animal food supplement, kibble, granules, treats, chew bones.

[0084] The composition according to the invention can be used to strengthen cardiovascular capacities and / or reduce cardiovascular risk, in particular when resuming physical activity, advantageously sporting. The composition according to the invention is also useful for preventing bone and / or joint fragility, advantageously in healthy mammals, still advantageously in healthy humans, very advantageously in healthy non-elderly humans. The composition according to the invention can thus be used to preserve bone capital and / or joints in mammals, advantageously in humans, particularly in non-elderly humans. Alternatively, it is used to preserve bone capital and / or joints in domestic animals, advantageously healthy animals, still advantageously in dogs, and particularly in non-elderly dogs.

[0085] The composition according to the invention is thus used to facilitate the resumption of physical activity, advantageously sporting.

[0086] In a particular embodiment of the invention, the extract of P. tricornutum according to the invention or the composition according to the invention is used within a population of mammals that are overweight and / or following a slimming diet, preferably healthy humans.

[0087] Thus, the extract according to the invention or the composition comprising it can be used in combination with ingredients known to reduce body weight and / or induce a satiety effect. Examples include L-carnitine or any of its salts, caffeine, a green tea extract, a fenugreek extract, an artichoke extract, a raspberry extract, a cactus extract, soy proteins, soluble fibers of the konjac glucomannan type, a prickly pear extract, chromium picolinate, a guarana extract (Paulina cupana), a Citrus aurantium extract, a Garcinia cambodia extract, lysine and / or magnesium, vitamin B3 (also called niacin) and / or any of their combinations.

[0088] The extract of P. tricornutum according to the invention, in particular included in the composition according to the invention, and these ingredients may have a synergistic or complementary effect so that the induced weight loss facilitates the action of the extract according to the invention or of the composition comprising it to facilitate the resumption of physical activity, in particular sporting activity, in particular on the maintenance and / or reduction of heart rate, to strengthen cardiovascular capacities.

[0089] Likewise, the extract according to the invention or the composition comprising it can be combined with any extract or ingredient or molecule known for its effectiveness on muscular and / or endurance capacities, allowing by synergy or complementary effect to facilitate the resumption of a physical activity, in particular a sporting activity. In this respect, the extract according to the invention or the composition which comprises it can for example be combined with an extract of the microalga Porphyridium cruentum, in particular with an aqueous extract of P. cruentum marketed by the Applicant, useful for increasing recovery or muscular endurance but also muscular relaxation. Mention will also be made of an extract of the microalga Tetrase / mis suecica, advantageously an aqueous extract, or astaxanthin or any microalga extract comprising and in particular an extract of Haematococcus pluvialis.

[0090] In a particular embodiment of the invention, the composition according to the invention comprises a quantity of DHA by weight relative to the total weight of the composition of at most 2%, advantageously at most 1%, very advantageously at most 0.5%. Thus this DHA content in the composition according to the invention is so low that the DHA is not in sufficient quantity to have an action on maintaining or reducing the heart rate, advantageously at rest, nor on preventing the reduction of the bone mineral level nor on increasing the bone mineral density.

[0091] Thus, in a particularly advantageous embodiment, DHA is not responsible for the reduction in heart rate, advantageously the resting heart rate, advantageously in healthy mammals, preferably healthy humans and / or the prevention of the reduction in bone mineral level and / or the increase in bone mineral density.

[0092] Thus, in particular, the daily oral administration of the composition in oily (liquid) form as defined above, that is to say in humans at a human equivalent dose of between 50 mg and 1250 mg, advantageously between 100 mg and 850 mg, still advantageously between 150 mg and 700 mg, particularly between 200 mg and 500 mg, and still preferentially between 218 mg and 650 mg, including 436 mg and 630 mg, provides a quantity of DHA of between 0.25 mg and 6.25 mg, advantageously between 0.5 mg and 4.25 mg, still advantageously between 0.75 mg and 3.5 mg, particularly between 1 mg and 2.5 mg, and still preferentially between 1.09 mg and 3.25 mg, including 2.18 mg and 3.15 mg.

[0093] Alternatively, oral administration of the composition in powder form as defined above, i.e. in humans at a human equivalent dose (70kg human) of between 100mg and 3125mg, advantageously between 200mg and 2125mg, advantageously still between 300mg and 1750mg, particularly between 400mg and 1250mg, and even more preferably between 436mg and 1625mg, including 872mg and 1575mg, provides a quantity of DHA respectively of between 0.5mg and 15.625mg, advantageously between 1mg and 10.625mg, advantageously still between 1.5mg and 8.75mg, particularly between 2mg and 6.25mg, and even more preferably between 2.18mg and 8.125mg, including 4.36mg and 7,875mg .

[0094] Alternatively, in the context of daily administration to domestic animals, advantageously in dogs, advantageously in healthy dogs, of the composition in oily (liquid) form of between 2.5 and 10 mg per kg of body mass, advantageously between 5 mg and 7.5 mg, and very advantageously between 5.5 mg and 6.5 mg, including 5.8 mg, the daily dose of DHA by weight is very advantageously respectively between 0.0125 mg and 0.2 mg per kg of body mass, advantageously between 0.025 mg and 0.0375 mg, and very advantageously between 0.0275 mg and 0.0325 mg per kg of body mass.

[0095] Alternatively, when the composition according to the invention is administered to domestic animals, advantageously to dogs, advantageously in healthy dogs, in powder form at a daily dose of between 6 mg and 30 mg per kg of body mass, advantageously between 10 mg and 19 mg, and very advantageously between 12 mg and 16 mg, including 14.6 mg, the daily dose of DHA provided is very advantageously respectively between 0.03 mg and 0.15 mg per kg of body mass, advantageously between 0.05 mg and 0.095 mg, and very advantageously between 0.06 mg and 0.08 mg, including 0.073 mg per kg of body mass.

[0096] The composition according to the invention contains an amount by weight relative to the total weight of the composition of eicosapentaenoic acid (EPA) of between 4% and 10%, advantageously between 5% and 8%, very advantageously it is 6.2%. Thus, the EPA / DHA weight ratio of the composition according to the invention is between 5 / 4 and 50 / 1, advantageously between 7 / 4 and 40 / 1, still advantageously between 3 / 1 and 30 / 1 and particularly advantageously it is 28.33 / 1.

[0097] A third subject of the present invention relates to a method for facilitating the resumption of physical activity, advantageously sporting, and / or reducing cardiovascular risks and / or risks linked to bone and / or joint fragility when resuming physical activity, advantageously sporting, and / or maintaining and / or reducing heart rate, in particular at rest, and / or preventing a decrease in bone mineral content and / or increasing bone mineral density, in particular for: - strengthen cardiovascular capacities and / or - reduce cardiovascular risk and / or - prevent bone and / or joint fragility and / or - preserving bone capital and / or joints, comprising the administration, in particular orally, to a healthy mammal, in particular one who needs it and / or wants it, more particularly one who is overweight, of an effective quantity of an extract of Phaeodacty / um tricornutum according to the invention or of a composition comprising it according to the invention.

[0098] The effective amounts are as described above.

[0099] Advantageously, the method according to the invention comprises the following steps: - the selection of a healthy mammal, in particular one that needs it and / or wants it, especially one that is overweight, - the administration, in particular by oral route, of an effective quantity of an extract of Phaeodactyium tricornutum according to the invention or of a composition comprising it according to the invention to facilitate the resumption of a physical activity, advantageously sporting, and / or reduce cardiovascular risks and / or risks linked to bone and / or joint fragility when resuming a physical activity, advantageously sporting, and / or maintaining and / or reducing heart rate, in particular at rest, and / or preventing a decrease in bone mineral content, and / or increasing bone mineral density, in particular for: - strengthen cardiovascular capacities and / or - reduce cardiovascular risk and / or - prevent bone and / or joint fragility and / or - preserve bone capital and / or joints.

[0100] Examples referring to the description are presented below. These examples are illustrative and do not limit the scope of the invention. The examples are an integral part of the present invention and any new feature compared to a state of the prior art from the description taken as a whole is an integral part of the invention.

[0101] Unless otherwise stated, percentages are expressed as weight / weight, temperature is given in degrees Celsius and time is given in milliseconds (ms). Bibliographic references:

[0102] Hidayat K, Yang J, Zhang Z, Chen GC, Qin LQ, Eggersdorfer M, Zhang W. Effect of omega-3 long-chain polyunsaturated fatty acid supplementation on heart rate: a meta-analysis of randomized controlled trials. European Journal of Clinical Nutrition. 2018; 72:805-817.

[0103] Klesges RC, Ward KD, Shelton ML, Applegate WB, Cantier ED, Palmieri GM, et al. Changes in bone mineral content in male athletes. Mechanisms of action and intervention effects. JAMA. 1996 ;276(3):226-230. (doi: 10.1001 / jama.1996.03540030060033). EXEMPLES

[0104] Example 1a): A biomass was obtained from a strain of Phaeodactylum tricornutum originating in France and cultivated in a photobioreactor in autotrophic mode under controlled conditions of pH, light and temperature. The biomass obtained was frozen and then dried. It was then pre-centrifuged and then filtered to remove the water. A solid-liquid extraction step was then carried out using a quantity by weight of 15% of biomass relative to the total weight of the biomass and the solvent. The extract was thus obtained by extraction by maceration in a water / ethanol mixture in a proportion of 1 / 99 (w / w), at a temperature of 20°C, i.e. at room temperature, for a period of 2 hours. The oily extract thus obtained is then incorporated into a composition as below.

[0105] Composition or food supplement comprising the extract according to the example

[0106] The oily extract obtained was mixed with a final amount by weight relative to the total weight of the coconut oil composition of 45%. A final amount (w / w composition) of 0.5% o-tocopherol was added to the mixture. At least one orally acceptable excipient was added to the composition thus obtained. The composition thus obtained is in oily (liquid) form.

[0107] Example 1b): The microalgae extract of P. tricornutum is obtained under the same culture conditions of the same strain as those of example 1a). The biomass was extracted in a water / ethanol mixture of 20 / 80 (w / w) at a temperature of 20°C, i.e. at room temperature, for a period of 2 hours. It was then filtered. The oily extract thus obtained is then incorporated into a composition or food supplement under the same conditions as those of example 1a). : m nu on ea de renos in healthy humans in the presence of a composition according to the invention the extract of tricornutum [01081 Protocol: A double-blind randomized clinical trial was conducted as follows: 35 Caucasian female volunteers aged 18 to 50 years, healthy, i.e. not presenting any deficiency or cardiovascular pathology or situation generating them and who are also not in a situation of obesity, as defined in the context of the present invention, subject in addition to the inclusion and exclusion criteria defined below, were administered orally before breakfast, each day for a period of 12 weeks, a supplement consisting of a soft capsule consisting of 218 mg of the composition according to the invention (containing 1.09 mg of DHA and 13.5 mg of EPA) or a placebo capsule consisting of 218 mg of sunflower oil and having the same appearance as the capsule comprising the composition.

[0109] Inclusion criteria: 1. Informed and written voluntary consent to the clinical trial; 2. Not pregnant or not wishing to become pregnant within the period corresponding to the trial; 3. Non-breastfeeding; 4. Body Mass Index between 25 - 35 kg / m2 and / or fat mass > 30%; preferably BMI between 25-32 kg / m2, the average BMI of each of the 2 groups (Composition and placebo) must be between 25-29.9 kg / m2; 5. Living in a private home, alone or with family, independent in terms of hygiene (without assistance); 6. In good health; 7. Willing to maintain a consistent sleep cycle daily before visits.

[0110] Exclusion criteria: 1. Programmed lifestyle change (Diet, level change exercise, travel) during the clinical trial; 2. Recent history (<3 months) of weight loss (>5%) or exercise; 3. Presence of an orthopedic limitation compromising participation in the exercise program; 4. Presence of cardiac impairment, hypertension, diabetes, thyroid impairment, cancer, neurological impairment, severe depression or untreated psychotic disorder; 5. Taking food supplements or medications for slimming / weight loss during the 4 weeks preceding the start of the clinical study; 6. Taking oral or injectable corticosteroids during the 12 months preceding the start of the clinical study; 7. Excessive alcohol or drug use during the 12 months preceding the start of the clinical study; 8. Severe active smoking (> 1 pack / day during the 3 months preceding the start of the study); 9. Consumption of caffeinated products at a dose greater than 400mg caffeine / day during the 2 weeks preceding the study; 10. Known allergy to one of the ingredients contained in the composition according to the invention or the placebo.

[0111] All participants followed a supervised exercise program 3 days per week consisting of 5 minutes of warm-up, stretching, resistance exercise corresponding to 3 sets of 10 repetitions and cardiovascular exercise (walking or cycling for 20 to 30 minutes at a heart rate reserve of 60% to 80%). Finally, participants were asked to walk 10,000 steps on the days outside the supervised exercise program above (total duration greater than 100 minutes per week; in the form of moderate exercise). Exercise was recorded by pedometer or equivalent (iPhone or FitBit).

[0112] Resting heart rate was measured by ECG (Electrocardiogram) for each participant in each of the 2 groups at time TO, at 6 and 12 weeks after the start of the clinical trial. The results presented in Table 1 below correspond to the average of the 18 measurements (placebo) or 17 measurements (composition according to the invention) of resting heart rate, expressed as a percentage relative to the resting heart rate measured at time TO at the start of the clinical study. [01131 Results: The results are collected in Table 1.

[0114] [Table 1]

[0115] (*pairwise comparison statistical test) p <O,O5)

[0116] Conclusion: The clinical trial conducted showed a significant decrease in resting heart rate of more than 9% in the group that consumed the composition according to the invention daily from 6 weeks, compared to the placebo group. The composition comprising the P. tricornutum extract is therefore effective in reducing resting heart rate in healthy human populations at doses of EPA and DHA well below the daily doses known to be effective in reducing resting heart rate. Example 3: Effect of an oral administration of the composition according to the invention comprising the extract of Phaeodactylum tricornutum sux la prevention of bone and / or joint fragility: maintenance of bone mineral levels in healthy humans and increase in bone mineral density [01171 Protocol: The clinical trial protocol conducted is as described in Example 2. Overall bone mineral content and bone mineral density were measured at the 6-week and 12-week visits by dual-energy x-ray absorptiometry (DEXA); Hologic Inc., Waltham, MA, USA (Diagnostic and therapeutic technology assessment (datta). JAMA. 1992; 267(2):286-94. doi:10.1001 / jama.1992.03480020096040; Klesges et al., 1996) in the 35 participants. [01181 Results: The results are presented in Table 2.

[0119] [Table 2]

[0120] (*pairwise comparison statistical test p<0.05)

[0121] Conclusion: The clinical trial conducted showed a maintenance of bone mineral content in individuals who received the supplementation comprising the composition according to example 1a), while this content decreased by almost 1.5% at 6 weeks in the placebo group. In addition, the composition according to example 1a) increased bone mineral density after 12 weeks. The composition according to the invention is therefore capable of preventing bone and / or joint fragility, presenting a clear advantage in comparison with compositions optionally comprising EPA and / or DHA used in the treatment or prevention of disorders associated with bone loss, the composition according to the invention comprising doses of DHA and EPA much lower than said compositions. Example 4: Examples of compositions comprising the composition according to the invention

[0122] The percentages are expressed by weight relative to the total weight of the composition.

[0123] Example 4a) Composition in capsule form:

[0124] [Table 3]

[0125] Example 4b): Composition in tablet form:

[0126] [Table 4]

Claims

Claims

1. Extract of Phaeodacty / um tricornutum or composition comprising it for its use to facilitate the resumption of physical activity, advantageously sporting, and / or reduce cardiovascular risks and / or risks linked to bone and / or joint fragility when resuming physical activity, advantageously sporting.

2. Extract or composition for use thereof according to claim 1, for maintaining and / or decreasing heart rate, and / or preventing a decrease in bone mineral content.

3. Extract or composition for use thereof according to any one of claims 1 or 2 for maintaining and / or decreasing resting heart rate.

4. Extract or composition for its use according to any one of claims 1 to 3 for: - strengthen cardiovascular capacities and / or - reduce cardiovascular risk and / or - prevent bone and / or joint fragility and / or - preserve bone capital and / or joints.

5. Extract or composition for its use according to any one of claims 1 to 4, characterized in that the extract is a lipophilic extract, advantageously obtained by extraction in a solvent or mixture of solvents chosen from water, acetone, hexane, ethyl acetate, methyltetrahydrofuran, 2-methyloxolane, heptane, an alcohol chosen from ethanol, methanol, isopropanol, a natural or branched oil, a glycol, a polyol and a water / alcohol or water / glycol mixture in a proportion of 99 / 1 to 1 / 99 (w / w).

6. Extract or composition for its use according to any one of claims 1 to 5, characterized in that the extract is an oily extract obtained by extraction in a water / ethanol mixture in a proportion of 40 / 60 (w / w) to 1 / 99 (w / w), advantageously in ethanol.

7. Extract or composition for its use according to one of any of claims 1 to 6, characterized in that the extract comprises a docosahexaenoic acid (DHA) content of at most 4% by weight, advantageously at most 2% by weight, in particular at most 1% by weight, relative to the total weight of the extract.

8. Extract or composition for its use according to any one of claims 1 to 7, characterized in that the extract comprises an eicosapentaenoic acid (EPA) content of between 4% and 20% by weight, preferably between 5% and 15% by weight, still preferably between 7% and 13% by weight, still preferably 12.4% by weight, relative to the total weight of the extract.

9. Extract or composition for its use according to any one of claims 1 to 8, characterized in that the EPA / DHA weight ratio of the extract is between 5 / 4 and 50 / 1, advantageously between 7 / 4 and 40 / 1, still advantageously between 3 / 1 and 30 / 1 and particularly advantageously it is 28.33 / 1.

10. Extract or composition for its use according to any one of claims 1 to 9 in healthy mammals, advantageously healthy humans.

11. Extract or composition for its use according to claim 10 in healthy mammals who are overweight and / or following a slimming diet, advantageously healthy humans who are overweight and / or following a slimming diet.

12. Extract or composition for its use according to any one of claims 1 to 11 by oral route.

13. Extract or composition for its use according to any one of claims 1 to 12, characterized in that the extract or composition is in the form of a food supplement.

14. Composition for its use according to any one of claims 1 to 13, characterized in that the extract content of the composition is between 20% and 70% by weight, preferably between 30% and 65% by weight, still preferably between 45% and 60% by weight.

15. Composition for its use according to any one of claims 1 to 14, characterized in that the composition further comprises a vegetable oil and vitamin E, advantageously coconut oil and o-tocopherol.

16. Composition for its use according to any one of claims 1 to 15, characterized in that the composition is in solid form, advantageously in powder form, still advantageously in the form of cold dispersible powder, or alternatively in liquid form.

17. Composition for its use according to any one of claims 1 to 16, characterized in that the composition is in the form of a gel cap, a capsule, a tablet, a tablet, a candy, a chewing gum, a granule, a lozenge, a pill, an energy bar, a kibble, a pâté, a treat, granules, a soft capsule, a syrup, a spray, an ampoule, a suspension, an emulsion, a hot or cold drink such as a fruit juice, in particular an energy drink.

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