Use of microalgae extracts alone or in combination for improving cognitive abilities

Abstract

The present invention relates to the use of a Phaeodactylum tricornutum extract, alone or in combination with an extract selected from guarana extract (Paullinia cupana), ginseng extract (Panax ginseng), ginkgo extract (Ginkgo biloba), lotus extract (Nelumbo nucifera), centella extract (Centella asiatica), black pepper extract (Piper nigrum), Bacopa monnieri extract or any combination thereof, and / or a compound selected from arginine, creatine, caffeine, theanine, vitamin C, vitamin E, vitamin B, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof, for maintaining and / or enhancing information processing speed and / or concentration in healthy mammals. The present invention also relates to a combination of a P. tricornutum extract with one of these extracts or one of these compounds. The present invention also relates to a composition comprising the combination according to the present invention.

Description

Technical Field

[0001] The present invention relates to the use, alone or in combination, of extracts of the microalgae Phaeodactylum tricornutum to maintain and / or enhance data processing speed and / or concentration in healthy mammals.

Background Art

[0002] Cognitive functions correspond to the functions of the brain responsible for the acquisition, processing, storage, and use of all data from the environment. They enable inference, adaptation, and concentration, but also communication. During certain periods of life, certain habits or specific customs, it is necessary for an individual to have an increase in concentration, memory, and acquisition speed, as well as an increase in the speed of classification and selection of relevant data from memory. Specifically, the cognitive process can be divided into a learning stage (data storage) and a data processing stage in memory regarding situations requiring decision-making (speed and quality of analysis), and the decision can be executed by a motor response, which becomes real and effective. The data processing stage is important: in addition to the storage capacity and quality of an individual's memory, it is the ability to process memory data in terms of both quality (accuracy) and speed, thereby enabling optimal adaptation to its social, professional, and personal environment. A common example is the case of students in learning conditions and especially examination conditions, during which cognitive functions are highly required. Another example is video game players, who are known to require some of their cognitive functions, especially the speed of decision-making and adaptation to a changing environment, during play. These populations of individuals do not suffer from cognitive impairment or even mild cognitive impairment defined as a cognitive ability disorder without dementia. They are not the elderly population in cognitive decline. Nor are they individuals who have received any prenatal stress that could explain acquired cognitive impairment. Even less are they individuals with pathologies associated with cognitive disorders such as Alzheimer's disease.

[0003] Drug therapies based on molecules such as donepezil, rivastigmine, galantamine, memantine, donanemab, TTP488 or aducanumab are already known and their effectiveness in treating or preventing cognitive impairment or decline has been demonstrated. Food supplements, notably caffeine and vitamin-based supplements, are also commercially available to address this disorder. However, there is a need in the field of dietary supplements for alternative natural ingredients that do not prevent or treat cognitive impairment or decline and do not belong to drug therapies. The argument herein is a need for healthy individuals, young adults or adults without cognitive deficits, rather than the elderly.

[0004] Precisely, the present invention proposes to achieve this by suggesting a completely natural extract of Phaeodactylum tricornutum that is active against specific components of cognitive function. Furthermore, as shown in this patent application, the applicant has surprisingly demonstrated a synergistic effect of the extract of P. tricornutum with known extracts or compounds such as vitamin C, E, B6, B9, B12, guarana (Paullinia cupana), extract of lotus (Nelumbo nucifera), centella (Centella asiatica), black pepper (Piper nigrum), ginseng (Panax ginseng), ginkgo (G. biloba), bacopa (Bacopa monnieri), creatine, arginine, caffeine, theanine, theophylline, paraxanthine, theobromine, phenolic compounds such as rosmarinic acid, ellagic acid and cinnamaldehyde.

[0005] One of the advantages of the extract of P. tricornutum according to the present invention is that it is a completely natural extract that is non-toxic and non-allergenic to humans. It is obtained by growing microalgae under controlled conditions in a photobioreactor and can thus be easily manufactured on an industrial scale.

[0006] The microalgae P. tricornutum belongs to the microalgae genus Phaeodactylum and the family Phaeodactylaceae. It is a microalgae with three distinct morphological forms (fusiform, elliptical, triradiate) found in many marine regions of the world such as northern Europe, Oceania, and the Atlantic Ocean.

[0007] The specification of French Patent Application Publication No. 3092968A1 of the present applicant describes extracts of microalgae of the species Phaeodactylum tricornutum and Tisochrysis lutea for producing dietary supplements for preventing or suppressing age-related cognitive impairment, or cognitive impairment in children or young adults who have experienced prenatal stress. However, the goal of this patent application is to prevent a decrease in learning deficit, and notably to improve spatial working memory and long-term contextual memory. In the population of individuals with non-pathological cognitive impairment, and particularly in young adults or adults who have experienced prenatal stress, or in the elderly subjects who are not cases of the population targeted in the context of the present invention, it is possible with the described extracts to compensate for behavioral changes associated with biochemical changes (increased oxidative stress and induction of neuroinflammatory processes with the release of interleukin). The specification of this French Patent Application Publication No. 3092968A1 discloses no effect of the extract of P. tricornutum for maintaining and / or enhancing data processing speed and / or concentration within the population of individuals without cognitive impairment. Moreover, this patent application does not disclose the use of this extract in combination with another extract or compound to further enhance its effect. It should be noted that for the purpose of the present invention, a clear distinction is made between the effect on an individual's memory and the effect on the speed of processing memory data. Similarly, the effect on an individual's concentration is different from the ability of that individual to memorize data.

[0008] Thus, in French Patent Application Publication No. 3092968A1, there is no further encouragement for those skilled in the art to use one of the microalgae extracts with the hope of maintaining and / or enhancing the data processing speed and / or concentration within a population different from the population described in the patent application, and / or to use it in combination with another compound or extract that enhances its effect.

[0009] Furthermore, International Publication Pamphlet No. 2019 / 193596A1 describes a method for reducing lipid accumulation in cells for the purpose of preventing or treating liver insufficiency or renal insufficiency. In this method, an extract of the same microalgae P. tricornutum is utilized. However, the use of the present invention is completely different from that. Furthermore, the method disclosed herein is a therapeutic treatment method targeted at a specific population of individuals. Therefore, in the said document, the use of this extract of P. tricornutum to implement the present invention described in this patent application is not encouraged for those skilled in the art.

[0010] Therefore, to the best knowledge of the applicant, in the prior art, the use described in this patent application has not been disclosed. Furthermore, in the prior art, there is no description of a combination of P. tricornutum with an extract selected from the group consisting of Paullinia cupana extract, Panax ginseng extract, Ginkgo biloba extract, Nelumbo nucifera extract, Centella asiatica extract, Piper nigrum extract, Bacopa monnieri extract, or a combination with a compound selected from the group consisting of creatine, arginine, caffeine, theanine, vitamin C, vitamin E, vitamin B, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, and cinnamaldehyde. SUMMARY OF THE INVENTION

Means for Solving the Problem

[0011] Accordingly, a first subject relates to the use of an extract of Phaeodactylum tricornutum, alone or in combination, for maintaining and / or enhancing data processing speed and / or concentration in healthy mammals, in particular healthy individuals showing no cognitive decline and / or disorder. A second subject relates to a combination of an extract of P. tricornutum with an extract selected from extracts of Paullinia cupana, Panax ginseng, Ginkgo biloba, Nelumbo nucifera, Centella asiatica, Piper nigrum, Bacopa monnieri, or a compound selected from creatine, arginine, caffeine, theanine, vitamin C, vitamin E, vitamin B, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde, preferably an extract selected from extracts of Paullinia cupana, Nelumbo nucifera, Centella asiatica, Piper nigrum, or any combination thereof, and / or a compound selected from creatine, arginine, caffeine, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof. A third subject relates to a composition which is advantageously used as a food supplement comprising a combination according to the invention.

[0012] Accordingly, a first subject matter of the present invention is for maintaining and / or enhancing data processing speed and / or concentration in a healthy mammal, preferably a healthy individual not showing cognitive decline and / or disorder, alone or in combination with an extract selected from Paullinia cupana extract, Panax ginseng extract, Ginkgo biloba extract, Nelumbo nucifera extract, Centella asiatica extract, Piper nigrum extract, Bacopa monnieri or any combination thereof, and / or a compound selected from creatine, arginine, caffeine, theanine, vitamin C, vitamin E, vitamin B, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof, preferably an extract selected from Paullinia cupana extract, Nelumbo nucifera extract, Centella asiatica extract, Piper nigrum extract or any combination thereof, and / or a compound selected from creatine, arginine, caffeine, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof, regarding the use of an extract of Phaeodactylum tricornutum. Advantageously, this is a non-therapeutic use, particularly a nutraceutical use.

[0013] The term "mammal" as used herein means a human or an animal, preferably a domestic animal, more preferably a dog or a cat. Most preferably, it is a human. The term "healthy individual" means an individual who does not exhibit cognitive decline and / or impairment. Thus, this population excludes elderly individuals, particularly elderly humans, i.e., humans over 60 years old, preferably over 70 years old, individuals suffering from depression such as chronic depression, but mammals showing cognitive impairment following stroke, cancer, diabetes, physical trauma to the brain, chronic kidney disease, or Alzheimer's disease, individuals showing cognitive and behavioral changes associated with oxidative stress or inflammatory conditions, children or young adults who have undergone prenatal stress that induces non-pathological diseases such as hyperactivity, attention deficit and memory impairment, language development delay and anxious behavior.

[0014] The term "non-therapeutic use" means non-pharmacological use and thus is not intended as a therapeutic treatment within the understanding of experts in the field. It is directed to the population of individuals recognized as healthy as defined above.

[0015] The term "vitamin B" means vitamin B6, B9, B12 or any combination thereof. The term "oral route" also means the ingestion of the extract of P. tricornutum alone or in combination, or the ingestion of a composition containing it.

[0016] "Increase in data processing speed in healthy mammals" means a reduction in the time required by a healthy mammal to analyze information from an external stimulus selected from visual, auditory, olfactory or gustatory stimuli for making a judgment. In a preferred embodiment, this includes a reduction in the reaction time preferentially in healthy individuals in response to visual stimuli.

[0017] Thus, advantageously, the reduction of said reaction time is a significant decrease in response time of at least 9 milliseconds, preferably at least 30 milliseconds, very preferably at least 60 milliseconds, measured in a population of healthy individuals administered a combination of guarana and P. tricornutum according to the invention, compared to the reaction time measured in the same population administered a placebo component.

[0018] The measurement is advantageously carried out within the framework of a clinical trial using the Sternberg test (Sternberg S., 1969). It consists of presenting visual stimuli to each participant one by one and identifying them as present or absent in a sequence of 3, 6, 9, 12, 15 or 18 seconds: the number of visual stimuli (data to be processed) increases over a short time interval and thus the level of difficulty increases. To avoid repetition, the participants are instructed to count backwards from a specific random number by 3 and 4 until they see a red light appear on the computer screen. In this test, accuracy and reaction time are specifically measured.

[0019] In an advantageous embodiment, the reduction of the reaction time is in individuals with an average age of 17.7 - 25.7 years, a weight of 60 - 86 kg, and a body mass index of 20.6 - 27.8 kg / m 2It is measured within a population consisting of 51 healthy men and 10 healthy women recognized as experienced players having a body mass index within the range. Advantageously, the individual does not ingest nutritional supplements containing stimulants, theophylline, paraxanthine, theobromine, vitamins, creatine, caffeine, theanine, or any other substance or extract containing any of the above compounds alone or in combination for two weeks before the start of the clinical trial, nor does it ingest guarana extract or wild yam extract or ginkgo (G. biloba) extract, or P. tricornutum extract, or foods rich in arginine or nitrate. More advantageously, the administered combination is a combination of 500 mg of guarana extract and 436 mg / day or 872 mg / day of a composition containing the P. tricornutum extract according to the present invention, tocopherol, and the MCT oil described in the remainder of this patent application under the conditions described in Example 3. Most advantageously, the extract of P. tricornutum contained in the composition is the extract prepared in Example 1, and the guarana extract is the extract of guarana seeds prepared in Example 2. In an alternative embodiment, "increase in data processing speed in healthy individuals" means an increase in the protein expression of synaptotagmin selected from SYT1, SYT2, SYT3, SYT4, SYT5, SYT6, SYT7, SYT8, SYT9, SYT10, SYT11, SYT12, SYT13, SYT14, SYT15, SYT16, SYT17 in neuronal culture in the presence of the extract of P. tricornutum according to the present invention. Advantageously, the protein expression increases by at least 2%, advantageously at least 4% in the presence of the extract according to the present invention compared to a control without the extract. Advantageously, this is an increase in the protein expression of synaptotagmin measured in the presence of the extract of P. tricornutum prepared according to Example 1.

[0020] In another alternative embodiment, "an increase in the data processing speed in a healthy individual" means increasing the density of the network structure of nerve cells at the nerve cell level by increasing the length of the extension and / or the dendricity of nerve cells in a healthy individual. The term "dendricity" means the formation of dendrites (the extension of the cell body of a nerve cell). Specifically, it is well known that all cognitive components, especially the speed at which an individual processes data, are closely related to nerve cell density.

[0021] Advantageously, therefore, the extract of P. tricornutum according to the invention increases the length of the extension of nerve cells in vitro by at least 2.5%, preferably at least 5%, in the culture of nerve cells, compared to the length of the extension measured without the extract. Advantageously, the increase in the extension of nerve cells is measured in the culture of nerve cells in the presence of an extract according to the invention in an amount of 0.0005 to 1.5%, advantageously 0.001 to 0.5%, based on the total weight of the medium and the extract. Advantageously, the extract of P. tricornutum is the extract prepared in Example 1. Very advantageously, the length of the nerve cells is measured after visualization using a secondary antibody conjugated to a fluorescent dye, by using a photograph taken by an automated microscope, especially under the conditions described in Example 5a), after labeling the nerve cells with an anti-β-tubulin antibody.

[0022] Alternatively, an increase in the data processing speed in a healthy individual is evaluated by measuring the neuronal dendricity in the same in vitro nerve cell culture model as described above, in the presence of an extract according to the invention in an amount of 0.0005 to 1.5%, advantageously 0.001 to 0.5%, based on the total weight of the medium and the extract. Advantageously, the extract of P. tricornutum is the extract prepared in Example 1. Very advantageously, the neuronal dendricity is evaluated by measuring the formation of nerve cell branches by the microscopy method detailed above.

[0023] In yet another alternative embodiment of the present invention, "increase in data processing speed in a healthy individual" means an in vitro increase in the calcium mobilization rate at synapses during synaptic transmission (transmission of nerve impulses between two nerve cells). Specifically, calcium channels are essential for the transmission of nerve impulses; when they open as a result of the depolarization of synaptic buttons following an action potential, calcium ions can flow into the synaptic buttons, causing the fusion of synaptic vesicles, thereby releasing neurotransmitters such as acetylcholine. Therefore, by measuring in vitro the level of calcium mobilized in the culture of nerve cells in the presence of the extract according to the present invention, it is reasonably possible to represent an increase in data processing speed. In an advantageous embodiment, the measurement of the level of mobilized calcium is carried out using a fluorescent probe that binds to calcium under the action of its release following the activation of nerve cell receptors, particularly under conditions such as those described in Example 5b). Advantageously, the increase in data processing speed by the extract according to the present invention is measured in the presence of an amount of 0.0005 to 1.5%, advantageously 0.001 to 0.5%, in nerve cell culture. Advantageously, the extract according to the present invention is the extract of P. tricornutum prepared in Example 1.

[0024] On the one hand, "maintaining the data processing speed in a healthy mammal" means maintaining the reaction time required by a healthy mammal, and preferably a healthy individual, in response to an increase in the number of stimuli (data to be processed). In a preferred embodiment, this means maintaining the reaction time measured in the presence of the combination of guarana and P. tricornutum extract according to the present invention, as compared to the reaction time measured within a population administered a placebo component. Advantageously, "maintaining the data processing speed in a healthy individual" means maintaining the reaction time measured in the presence of the combination of guarana and P. tricornutum extract when the number of visual stimuli (data to be processed) increases by 4 to 6 over a given period of time. More advantageously, this is the measurement of the reaction time as measured in the above-described clinical trial. Even more advantageously, the combination to be administered is a combination of 500 mg of guarana extract and 436 mg / day or 872 mg / day of a composition containing the P. tricornutum extract according to the present invention, tocopherol, and the MCT oil described in the remainder of this patent application under the conditions described in Example 3. Very advantageously, the extract of P. tricornutum contained in the composition is the extract prepared in Example 1, and the guarana extract is the extract of guarana seeds prepared in Example 2.

[0025] Furthermore, "maintaining and / or increasing the concentration of a healthy mammal" means, with the intention of making a decision in a healthy mammal, maintaining and / or enhancing the accuracy of information analysis from external stimuli selected from visual stimuli, auditory stimuli, olfactory stimuli, or gustatory stimuli. In an advantageous embodiment, it is, advantageously, an increase in the accuracy of response to visual stimuli in a healthy individual. Thus, the improvement in concentration is at least 0.02%, preferably at least 0.05%, of the percentage of accuracy in the population of healthy individuals measured 30 days after supplementation in the population of healthy individuals administered the combination of the guarana extract and the extract of P. tricornutum according to the present invention, compared to the population administered the placebo component. The measurement is specifically by means of a Go-NoGo test (Donders, 1969; Wessel, 2017) that evaluates the ability to maintain sustained attention (concentration), the control of the response (decision-making) by measuring the accuracy of the response to visual stimuli by pressing a key meaning "Go", or the suppression of the response by not pressing a key meaning "No-Go", but is carried out within the framework of the above-mentioned clinical trial. This evaluation is carried out in the same study population as described above and under exactly the same conditions. More advantageously, the combination administered is a combination of 500 mg of guarana extract and a composition containing 436 mg / day or 872 mg / day of the extract of P. tricornutum according to the present invention, tocopherol, and MCT oil as described in the remainder of this patent application under the conditions described in Example 4. Very advantageously, the extract of P. tricornutum contained in the composition is the extract prepared in Example 1, and the guarana extract is the extract of guarana seeds prepared in Example 2.

[0026] In one embodiment of the present invention, the extract of P. tricornutum is used as it is.

[0027] Advantageously, the extract is obtained by extraction methods known to those skilled in the art. Advantageously, the extract is obtained from the biomass of a microalgae culture. The biomass can first be centrifuged and then filtered to remove water. Subsequently, a solid-liquid extraction step can be carried out. Preferentially, the extract is in a solvent or solvent mixture, preferably water, acetone, hexane, ethyl acetate, methyltetrahydrofuran, 2-methyloxolane, heptane, and an alcohol selected from ethanol, methanol, isopropanol alcohol, natural or branched-chain oils, glycols, polyols, a water / alcohol mixture in a ratio of 100 / 1 to 1 / 100 (w / w), a water / glycol mixture, or by any other solvent capable of extracting all or part of the hydrophobic and amphiphilic compounds. Very preferentially, the extract of P. tricornutum is obtained by extraction in a water / ethanol ratio of 40 / 60 to 1 / 100 (w / w), for example 30 / 70 (w / w) and 20 / 80 (w / w). The solvent or solvent mixture is separated from the residual biomass after extraction by a process such as centrifugation or filtration, and subsequently concentrated, or the solvent can be removed by a technique such as vacuum evaporation or other techniques that allow for the selective evaporation of the solvent. As an alternative, the extract of P. tricornutum according to the present invention is obtained by extraction under subcritical or supercritical conditions. Advantageously, in this case, the extract is obtained by supercritical CO2 extraction. The extraction can be carried out at a temperature in the range of 4 to 300 °C, including room temperature, i.e., 20 °C. In a preferred embodiment of the present invention, the extraction is carried out at room temperature. In all cases, the obtained extract is filtered and optionally dried. Advantageously, in this case, the drying step is carried out by freeze-drying, vacuum drying, drum drying, or spray drying, by a fluidized bed using coupling, by any technique that allows for encapsulation or microencapsulation with a support matrix and / or the formation of an emulsion. Then, the extract according to the present invention is in powder form. As described below, it can be incorporated into a composition alone or in combination.Instead, the extract of P. tricornutum is filtered but not dried and is in a liquid state.

[0028] In another embodiment, the extract of P. tricornutum is used in combination with an extract selected from a Paullinia cupana extract, a Panax ginseng extract, a Ginkgo biloba extract, a Nelumbo nucifera extract, a Centella asiatica extract, a Piper nigrum extract, a Bacopa monnieri or any combination thereof, and / or a compound selected from creatine, arginine, caffeine, theanine, vitamin C, vitamin E, vitamin B, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof.

[0029] In particular, the extract of P. tricornutum is used in combination with an extract selected from a Paullinia cupana extract, a Nelumbo nucifera extract, a Centella asiatica extract, a Piper nigrum extract, or any combination thereof, and / or a compound selected from creatine, arginine, caffeine, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof.

[0030] Therefore, extracts of guarana (P. cupana), ginseng (P. ginseng), ginkgo (G. biloba), lotus (N. nucifera), centella (C. asiatica) or black pepper (P. nigrum) can be obtained by extracting all or part of the target plant selected from buds, leaves, stems, flowers, seeds or rhizomes. The extraction of guarana is preferably the extraction of seeds, and the extract of ginkgo (G. biloba) is preferably the extraction of rhizomes or leaves, preferably the extraction of leaves. The extraction of ginseng (P. ginseng) is preferably the extraction of rhizomes, the extraction of lotus (N. nucifera) is preferably the extraction of flowers, and the extraction of black pepper (P. nigrum) is preferably the extraction of seeds.

[0031] The extraction can be carried out by any method known to those skilled in the art selected from maceration, hot decoction, grinding such as ultrasonic grinding using a blender, or alternatively, can be obtained by extraction in water under subcritical or supercritical conditions (carbon dioxide). Extraction can be carried out using dry or fresh material, preferably dry material, in an amount of 0.1 to 20% by weight, preferably 1 to 20% by weight, very preferably 5 to 15% by weight, and even more preferably 15% by weight, based on the total weight of the material and the extraction solvent. For the purposes of the present invention, the term "dry matter" means a dehydrated plant containing less than 15%, preferably less than 10%, even more preferably less than 5%, and very preferably less than 1% water. The extraction can be carried out at a temperature in the range of 4 to 300 °C, including room temperature, i.e., 20 °C. In a preferred embodiment of the present invention, the extraction is carried out at room temperature.

[0032] In one embodiment of the present invention, the extraction is carried out in water under sub-critical conditions at a temperature in the range of 100 to 300 °C, advantageously 120 to 250 °C, and even more advantageously at 120 °C. The extraction can be carried out at a predetermined temperature or at a continuously increasing temperature. In an advantageous embodiment of the present invention, the extraction is carried out at a temperature of 120 °C. In an alternative embodiment, it can be carried out using one of three increasing temperature gradients of 100 to 200 °C, for example 120 °C, 140 °C, then 160 °C, or 110 °C, 130 °C, then 150 °C, or 120 °C, 145 °C, then 170 °C.

[0033] Extraction under "sub-critical conditions" means extraction in the presence of water under conditions of a temperature above 100 °C and a pressure below 221 bar, which has a lower viscosity and surface tension than water at room temperature, but remains in the liquid state and increases its dielectric constant. Thus, the extraction pressure is advantageously 150 to 250 bar, preferably 200 to 221 bar, in a pressurized extraction autoclave.

[0034] In alternative embodiments, extracts of guarana (P. cupana), Asian ginseng (P. ginseng), ginkgo (G. biloba), lotus (N. nucifera), centella (C. asiatica) or black pepper (P. nigrum) are obtained by extraction in a solvent or solvent mixture, preferably water, acetone, hexane, ethyl acetate, methyltetrahydrofuran, 2-methyloxolane, heptane, and an alcohol selected from ethanol, methanol, isopropanol, a natural or branched oil, a glycol, a polyol, a water / alcohol mixture in a ratio of 100 / 1 to 1 / 100 (w / w), a water / glycol mixture, or by any other solvent, such as an ionic liquid, for example an imidazolium or pyrrolidinium cation combined with chloride, acetate and tosylate anions, which makes it possible to extract all or some of the hydrophobic and amphiphilic compounds. The resulting extract is then filtered and optionally dried by freeze-drying, vacuum drying, drum drying or spray drying. Thus, the dried extract is in powder form. Alternatively, it may be in liquid form.

[0035] In a preferred embodiment of the invention, the extract of P. tricornutum is used in combination with an extract of guarana (Paullinia cupana), an extract of lotus (Nelumbo nucifera), an extract of centella (Centella asiatica), an extract of black pepper (Piper nigrum), or any combination thereof. In a preferred embodiment of the invention, the extract of P. tricornutum is used in combination with an extract of guarana, preferably an extract of guarana seeds.

[0036] In yet another embodiment, the P. tricornutum extract is used in combination with a compound selected from creatine, arginine, caffeine, theanine, vitamin C, vitamin E, vitamin B, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof, preferably in combination with a compound selected from creatine, arginine, caffeine, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof.

[0037] Caffeine (C8H 10 N4O2; molar mass: 194.19 g / mol, CAS number 58-08-2), theophylline (C7H8N4O2; molar mass: 180.164 g / mol; CAS number: 58-55-9), paraxanthine (C5H4N4O2; molar mass: CAS number: 69-89-6) and theanine (C7H 14 N2O; molar mass: 174.2 g / mol, CAS number: 3081-61-6) can be obtained by extraction from any plant selected from Coffea arabica, Paullinia cupana, Camellia sinensis, Theobroma cacao. Theobromine (C7H8N4O2; molar mass: 180.164 g / mol, CAS number: 83-67-0) can be obtained by extraction of Theobroma cacao (T. cacao). Creatine (C4H7N3O; molar mass: 113.1 g / mol, CAS number: 60-27-5) and arginine (C6H 14 N4O2; molar mass: 174.2 g / mol, CAS number: 7200-25-1 or 157-06-2 for the D- or R-form) are commercially available. Rosmarinic acid (C18H 16 O8; molar mass: 360.31 g / mol, CAS number: 20283-92-5) can be extracted from the Salvia rosmarinus plant. Ellagic acid (C 14H6O8; molar mass: 302.19 g / mol, CAS number: 476-66-4) can be extracted from red fruits such as strawberries, raspberries and blackberries. Cinnamaldehyde (C9H8O; molar mass: 132.16 g / mol, CAS number: 104-55-2) is the main component of cinnamon oil.

[0038] These compounds can be extracted using a non-polar organic solvent or a non-polar organic solvent selected from hexane, cyclohexane, heptane, trichloromethane, dichloromethane, acetone, 2-methyloxolane or an ionic liquid, such as an imidazolium or pyrrolidinium cation combined with chloride, acetate and tosylate anions, in a ratio of 100 / 1 to 1 / 100 (w / w). They can be purified by preparative high performance liquid chromatography (HPCL). Alternatively, they can be obtained commercially. Vitamin C (L-ascorbic acid, C6H8O6, molar mass 176.12 g / mol, CAS number 50-81-7) can be obtained commercially.

[0039] The use of the P. tricornutum extract according to the invention alone or in combination is preferably via the oral route. The extract alone or in combination can preferably be contained in a composition used as a food supplement.

[0040] The present invention also relates to a combination of an extract of Phaeodactylum tricornutum and an extract selected from an extract of Paullinia cupana, an extract of Panax ginseng, an extract of Ginkgo biloba, an extract of Nelumbo nucifera, an extract of Centella asiatica, an extract of Piper nigrum, an extract of Bacopa monnieri, or a compound selected from creatine, arginine, caffeine, theanine, vitamin C, vitamin E, vitamin B, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde, and any combination thereof. In an advantageous embodiment of the present invention, the present invention also relates to a combination of an extract of Phaeodactylum tricornutum and an extract selected from an extract of Paullinia cupana, an extract of Nelumbo nucifera, an extract of Centella asiatica, an extract of Piper nigrum, or a compound selected from creatine, arginine, caffeine, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde, and any combination thereof.

[0041] In one embodiment, the combination is characterized in that the weight ratio of the extract of P. tricornutum to the extract or compound selected from the extract of guarana, the extract of burdock root, the extract of Ginkgo biloba, the extract of N. nucifera, the extract of C. asiatica, and the extract of B. monnieri is respectively 1 / 6 to 6 / 1, preferably 2 / 1 to 4 / 1, and even more preferably 3 / 1 to 7 / 2. This combination is a synergistic combination. Very advantageously, according to the present invention, it is a combination of the extract of P. tricornutum and the extract of guarana (P. cupana). Preferably, the guarana extract is a seed extract (P. cupana). Therefore, a particularly advantageous combination is, with respect to the total weight of the combination: - an extract of P. tricornutum present in an amount of 50 to 600 mg, preferably 220 to 440 mg, - a guarana (P. cupana) extract present in an amount of 300 to 700 mg, preferably 500 mg.

[0042] In a preferred embodiment, the extract of P. tricornutum is prepared by the solid-liquid extraction already described above in the present invention. Preferably, the extract of P. tricornutum is obtained by extraction in a water / ethanol mixture at a ratio of 40 / 60 to 1 / 100 (w / w), for example 30 / 70 (w / w) and 20 / 80 (w / w), preferably extraction in ethanol. Even more preferably, the guarana extract (P. cupana) is obtained by concentration by evaporation under vacuum following hot water-alcohol extraction. The two extracts are filtered and then dried by freeze-drying, vacuum drying, drum drying or spray drying. Each of the two extracts is in powder form and can be combined in the described ratio to obtain the combination.

[0043] The combination according to the present invention is particularly useful for maintaining and / or enhancing data processing speed and / or concentration in healthy mammals, preferably healthy individuals not suffering from cognitive decline and / or disorders. Specifically, the Applicant has unexpectedly demonstrated a synergistic effect of a combination of P. tricornutum extract and P. cupana extract in a weight ratio of 1 / 6 to 6 / 1, preferably 2 / 1 to 4 / 1, very preferably 3 / 1 to 7 / 2, respectively.

[0044] Accordingly, in one embodiment, "increase in data processing speed in a healthy mammal" means, in this specification, the time required to analyze information from an external stimulus selected from visual, auditory, olfactory or gustatory stimuli, intended for decision-making in a healthy mammal, preferably a healthy individual, is significantly reduced by at least 5 milliseconds, preferably at least 10 milliseconds, very preferably at least 20 milliseconds.

[0045] Advantageously, this decrease in reaction time is measured within the population of healthy individuals administered the combination according to the present invention, compared to the reaction time measured within the population administered the placebo component. This measurement is preferably carried out within the framework of a clinical trial using the above-mentioned Sternberg test (Sternberg S., 1969). Four populations of healthy individuals are formed, the first population receives placebo administration, the second population receives administration of a combination of P. tricornutum extract and P. cupana extract, the third population is administered the extract of P. tricornutum alone, and the fourth population is administered the P. cupana extract alone. Also advantageously, the combination is a combination of P. tricornutum extract and P. cupana extract, preferably seed extract, in a weight ratio of 1 / 6 to 6 / 1, preferably 2 / 1 to 4 / 1, very preferably 3 / 1 to 7 / 2, respectively.

[0046] Very advantageously, it is an extract of P. tricornutum prepared according to Example 1, and the guarana extract is the extract prepared in Example 2. In an alternative embodiment, a combination of an extract of P. tricornutum and an extract of guarana (P. cupana) increases the protein expression of synaptotagmin selected from SYT1, SYT2, SYT3, SYT4, SYT5, SYT6, SYT7, SYT8, SYT9, SYT10, SYT11, SYT12, SYT13, SYT14, SYT15, SYT16, SYT17 in neuronal culture.

[0047] Advantageously, said increase in protein expression is at least 3%, advantageously at least 5% of the protein expression of synaptotagmin in the nerve culture, compared to a control not containing said combination, and the protein expression is increased by only 2% by the extract of P. tricornutum alone. Similarly, by the guarana extract alone, the synaptotagmin protein expression is increased by only 1% compared to a control containing no guarana extract at all. In a particularly advantageous embodiment, it is an increase in the protein expression of synaptotagmin measured in the presence of P. tricornutum and guarana (P. cupana) extracts, advantageously seed extracts, at a weight ratio of 2 / 1 to 4 / 1, very advantageously 3 / 1 to 7 / 2, respectively. Even more advantageously, it is an extract of P. tricornutum prepared according to Example 1 and the guarana extract is an extract prepared in Example 2. In another alternative embodiment, the synergistic combination of P. tricornutum and guarana (P. cupana) increases the data processing speed in a healthy mammal, advantageously a healthy individual, by an increase in the length and / or dendriticity of in vitro extended nerve cells. Thus, advantageously, the length of the extended nerve cells is at least 2.5%, preferentially at least 5% increased in the in vitro culture of nerve cells in the presence of a combination of an extract of P. tricornutum and an extract of guarana (P. cupana), compared to the increase in the length of the extended nerve cells measured in the presence of the extract of P. tricornutum alone or the extract of guarana alone. In an advantageous embodiment, the synergistic combination is a combination such that the weight ratio of the extract of P. tricornutum and the extract of guarana (P. cupana) is 1 / 6 to 6 / 1, advantageously 2 / 1 to 4 / 1, and very advantageously 3 / 1 to 7 / 2, respectively.

[0048] Very advantageously, it is an extract of P. tricornutum prepared according to Example 1, and the guarana extract is the extract prepared in Example 2. In yet another alternative embodiment, the combination of the P. tricornutum extract and the guarana (P. cupana) extract increases the in vitro calcium mobilization rate at synapses during synaptic transmission, resulting in an increase in the data processing speed in healthy mammals, preferably healthy individuals. By measuring in vitro the level of calcium mobilized in a culture of nerve cells in the presence of the association or in the presence of each of the extracts characterizing it, it is reasonably possible to represent the increase in the data processing speed. In an advantageous embodiment, the measurement of the mobilized calcium level is carried out using a fluorescent probe that binds to calcium under the action of its release following the activation of a nerve cell receptor. Advantageously, the increase in the data processing speed is measured in an in vitro culture of nerve cells in the presence of a combination of an extract of P. tricornutum and a guarana extract such that their weight ratio is respectively from 1 / 6 to 6 / 1, preferably from 2 / 1 to 4 / 1, very preferably from 3 / 1 to 7 / 2. Very advantageously, it is an extract of P. tricornutum prepared according to Example 1, and the guarana extract is the extract prepared in Example 2.

[0049] Another subject of the present invention also relates to a composition comprising the combination according to the present invention. In one embodiment, the composition is a composition for use as a food supplement.

[0050] Therefore, the composition particularly comprises a combination of an extract of P. tricornutum and an extract selected from an extract of P. cupana, an extract of P. ginseng, an extract of G. biloba, an extract of N. nucifera, an extract of C. asiatica, an extract of P. nigrum, an extract of B. monnieri or any combination thereof, and / or a compound selected from creatine, arginine, caffeine, theanine, vitamin C, vitamin E, vitamin B, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof, such that the weight ratio of the extract of P. tricornutum to the selected extract or compound is from 1 / 6 to 6 / 1, preferably from 2 / 1 to 4 / 1, and very preferably from 3 / 1 to 7 / 2. Very preferably, the composition comprises a combination of an extract of P. tricornutum and an extract selected from an extract of Paullinia cupana, an extract of Nelumbo nucifera, an extract of Centella asiatica, an extract of Piper nigrum or any combination thereof, or a compound selected from creatine, arginine, caffeine, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof. More preferably, the composition particularly comprises a combination of an extract of P. tricornutum and an extract of P. cupana, preferably a seed extract, at a weight ratio of from 1 / 6 to 6 / 1, preferably from 2 / 1 to 4 / 1, and very preferably from 3 / 1 to 7 / 2, respectively.

[0051] The composition may also contain vegetable oil and / or vitamin E. The term "vegetable oil" means an oil extracted from seaweeds such as plants or microalgae, notably selected from olive oil, rapeseed oil, linseed oil, sunflower oil and medium-chain triglyceride (MCT) oil. Medium-chain triglycerides (MCT) are esters of glycerol and saturated fatty acids having a hydrocarbon-based chain of 6 to 12 carbon atoms. Thus, MCT oil may be selected from coconut oil, advantageously palm oil, palm kernel oil and palm oil, but can also be obtained from other fats or oils. Advantageously, for the purposes of the present invention, the vegetable oil is MCT oil, more advantageously coconut oil and very advantageously palm oil. In a particularly advantageous embodiment of the invention, the vegetable oil is present in an amount of 20 to 80% by weight, advantageously 30 to 60% by weight, relative to the total weight of the composition. The term "vitamin E" means a tocopherol selected from α-tocopherol, γ-tocopherol, β-tocopherol or δ-tocopherol, or a tocotrienol selected from α-tocotrienol, β-tocotrienol, γ-tocotrienol or δ-tocotrienol. Advantageously, it is α-tocopherol. In an advantageous embodiment, vitamin E is present in the composition in an amount of 0.15 to 1.25% by weight, advantageously 0.25 to 1% by weight and very advantageously 0.5% by weight, relative to the total weight of the composition. Thus, an advantageous composition of the invention comprises, relative to the total weight of the composition, at least: - an extract of P. tricornutum in an amount of 10 to 25%, advantageously 11 to 16%, - MCT oil present in an amount of 30 to 60%, - α-tocopherol present in an amount of 0.25 to 1%, advantageously 0.5%, - caffeine or theine in an amount of 5 to 25%, advantageously 12%, and comprises.

[0052] Another particularly advantageous composition comprises, relative to the total weight of the composition, at least: - an extract of P. tricornutum in an amount of 10 to 25%, advantageously 11 to 16%, - MCT oil present in an amount of 30 to 60%, - α-tocopherol present in an amount of 0.25 to 1%, preferably 0.5%, - arginine in an amount of 5 to 25% and contains.

[0053] Another advantageous composition is, based on the total weight of the composition, at least: - an extract of P. tricornutum in an amount of 10 to 25%, preferably 11 to 16%, - MCT oil present in an amount of 30 to 60%, - α-tocopherol present in an amount of 0.5%, - an extract of P. cupana, preferably an extract of P. cupana seeds, in an amount of 35 to 55% and further contains.

[0054] Furthermore, the composition of the present invention contains at least one additive selected from preservatives, colorants, flavorings, disintegrants, lubricants and coating or encapsulating agents. The composition takes the form of gel capsules, wafer capsules, tablets, pellets, liquids or loose powders. It is preferably packaged in dosages of unit weight of 11 mg to 2 g, preferably 20 mg to 2 g. In the liquid state, the composition can be incorporated into energy drinks, fruit juices, syrups, water, or formulated in the form of "soft gel" capsules.

[0055] In particular, it is used as a food supplement for athletes, video game players and students. In this case, the composition is orally administered in dosages of 1 g and 2 g for a period of at least 1 day, preferably at least 15 days, very preferably 1 month. Alternatively, the composition is used as a food supplement in animals, preferably livestock, more preferably dogs and cats. In this case, the composition is orally administered alone or mixed with food at a daily dosage of 11 to 25 mg / kg body weight.

[0056] The composition according to the invention is used to maintain and / or increase data processing speed and / or concentration in a healthy mammal, preferably a healthy individual.

[0057] Examples referred to herein are shown below. These examples are illustrative and are not intended to limit the scope of the invention. The examples form part of the invention and, taken as a whole, the novel features over the prior art from this specification form part of the invention.

[0058] Unless otherwise specified, percentages are given as weight / weight, temperatures are in degrees Celsius, and times are in milliseconds (ms).

Brief Description of the Drawings

[0059]

Figure 1

Figure 2

Mode for Carrying Out the Invention

[0060] Example Example 1: Method for preparing an extract of Phaeodactylum tricornutum An extract of the microalgae P. tricornutum is obtained from the biomass of a microalgae culture from a strain of French origin. The biomass is first centrifuged and then filtered to remove water. Then, a solid-liquid extraction step is carried out. Thus, an extract is obtained by extracting at a temperature of 20 °C, i.e., at room temperature, in a water / ethanol mixture at a ratio of 40 / 60 to 1 / 100 (w / w) for 2 hours. Then, it is filtered and dried by lyophilization. It is in powder form.

[0061] Example 2: Method for producing an extract of Paullina cupana, and a combination of an extract of Phaeodactylum tricornutum and an extract of Paullina cupana 2.a): Preparation of the Paullina cupana extract: The guarana extract is obtained by extracting the seeds of the guarana (Paullinia cupana) plant, which has its origin in France, in a water / ethanol mixture (20 / 80; v / v). The extraction is carried out at a temperature of 80 °C for 2 hours. The extract is then filtered and dried by lyophilization. It is in powder form. 2.b): Commercially available guarana extract The hydro-alcoholic extract (water / ethanol) of the seeds of the guarana (Paullinia cupana) plant can be purchased from Natac or Nexira. It is in powder form. 2.c): Preparation of a combination of Phaeodactylum tricornutum extract and guarana (P. cupana) extract The guarana extract obtained according to Example 2.a) or 2.b) is mixed with the powder obtained in Example 1, and a combination according to the invention of P. tricornutum extract and guarana can be obtained in ratios of 2 / 9 to 3 / 7 (Example 2c1) or 3 / 1 to 7 / 2 (Example 2c2), respectively.

[0062] Example 3: Effect of the extract of Phaeodactylum tricornutum on maintaining and / or enhancing data processing speed and / or concentration in healthy individuals. Protocol: A double-blind, placebo-controlled clinical trial was conducted in a population of 51 men and 10 women (mean age 21.7 ± 4 years, mean weight 73.0 ± 13 kg, mean mass distribution 24.2 ± 3.6 kg / m 2 ) recruited as experienced video game players. The population of subjects was randomly divided into three groups and supplemented as follows: - Control group: Two placebo gel capsules of 436 mg / day (sunflower oil 436 mg in a capsule similar to a capsule containing the extract of P. tricornutum) and one capsule containing microcrystalline cellulose (similar to a guarana capsule) of 500 mg / day. - Treatment 1 - Known as low dose: A combination of one capsule containing an extract of P. tricornutum prepared according to Example 1 (dose: 436 mg), α-tocopherol, and MCT oil, a placebo capsule at 436 mg / day, and one capsule of a garana extract at 500 mg / day. - Treatment 2 - Known as high dose: A combination of two capsules each containing an extract of P. tricornutum prepared according to Example 1 (dose: 436 mg), α-tocopherol, and MCT oil, and one capsule of a garana extract (500 mg / day).

[0063] Supplements were prepared to maintain double-blind administration throughout the study. The inclusion criteria were as follows: 1.) Healthy men and women; 2.) Aged 18 - 40 years; 3.) A self-reported history of playing video games for more than 5 hours per week in the 6 months prior to screening; 4.) A body mass index (BMI) of 18 - 34.9 kg / m 2 ; 5.) Subjects who agreed to provide their own operator-oriented action or strategy video games that they had played at least 21 times in the 3 months prior to the start of the clinical trial; 6.) Had not recently (<2 weeks) consumed food supplements that affect cognitive function; 7.) Could submit written informed consent and could take the experimental product daily during the study period; 8.) Living freely (alone at home or living with family and able to maintain their own health and hygiene without assistance); 9.) Maintaining a regular sleep schedule in the evening before coming to the test; 10.) Agreeing to continue the normal use of games between test visits.

[0064] The non-inclusion criteria were as follows (participants were not allowed to participate in the study in the following cases): 1.) Intake of caffeine and alcohol 12 hours before each test visit; 2.) Intake of food supplements that may affect cognition and / or have a stimulating effect for at least 7 days before Visit 2; 3.) Pregnant women, lactating women, or women who wish to become pregnant; 4.) Presence of a history of untreated major psychotic or depressive disorders, or cognitive impairment; 5.) Hypertension, diabetes, thyroid diseases, untreated heart diseases, cancer; 6.) Severe neurological diseases; 7.) Predicted major changes in lifestyle (diet, exercise level, travel) during the study period; 8.) History of alcohol or drug abuse in the past 12 months; 9.) Known allergies to one of the components of the supplement product; 10.) Individuals who do not advance their own game system and / or provide all their games.

[0065] During the familiarization session (first visit), participants were provided with an explanation of the study and signed an informed consent form. Participants completed a questionnaire about their medical history, underwent a general physical examination including measurement of height, weight, resting heart rate, and blood pressure, and were provided with an explanation of the general study procedures. Eligible participants completed a baseline assessment and were scheduled for study evaluations. Participants were asked to record their diet and beverages for four days prior to the test, refrain from consuming a normal amount of caffeine and other stimulants not normally consumed in the diet for 48 hours, and fast for 12 hours prior to the test. At this visit, the classification of the video game (action or strategy-oriented) was confirmed. Each subject was selected and required to bring a pre-approved video game, as well as a compatible gaming platform and accessories. Subjects were required to have played the selected game at least 21 times in the three months prior to selection. Subjects agreed to bring and play the same video game at Visit 1 and Visit 2, and to play the selected game regularly between test visits to minimize bias in the learning curve. The final score of the selected game prior to administration was recorded. It was provided in the form of a photo or screenshot, rather than an oral response.

[0066] Experiment 1 (second visit): Participants who reported to the laboratory and submitted a four-day food diary had their weight measured, completed a questionnaire about stimulus sensitivity and side effects, and underwent a Go-NoGo Sternberg test. Participants were then randomly assigned to take the supplement as described. Fifteen minutes after ingestion, participants repeated the test (post 15-SUPP). The time between ingestion of the treatment and the start of the video game was recorded. Participants then played their video game for one hour. Immediately thereafter, participants again underwent a set of test equipment and tests for stimulants and side effects. Participants then left the laboratory and received the appropriate amount of the assigned treatment, along with instructions on how to take it (post gaming).

[0067] Experiment 2 (Clinic Visit 3): Four weeks after daily supplementation, participants who reported to the laboratory and submitted a four-day food diary had their weight measured and performed a set of the same tests as described above (Experiment 1) (before SUPP). Next, the participants ingested the treatment assigned to the study and / or placebo immediately after the pre-game test and waited for the same length of time as recorded in Example 1. Then, the participants played their video game (the same video game as in Experiment 1) for one hour. Immediately afterwards, the participants repeated the set of tests, filled out questionnaires about stimulus sensitivity and side effects, and also filled out a questionnaire about the test for stimulants (after gaming). This study was conducted in accordance with the guidelines and principles of the Food and Drug Administration (FDA), the International Conference on Harmonization (ICH), and Good Clinical Practice (GCP) for the conduct of pharmaceutical clinical trials.

[0068] Subjects were instructed to take the designated supplement once a day for one month (±2 days). The first and last doses were administered at the clinical site at Clinic Visit 2 (Experiment 1) and Clinic Visit 3 (Experiment 2), respectively. Univariate, multivariate, and repeated measures general linear models (GLMs) were used to analyze the data, taking into account each baseline characteristic as a covariate where appropriate. Additionally, changes relative to the baseline were evaluated by means of means with 95% confidence intervals and analyzed by one-way analysis of variance. A power analysis was also performed at the end of the study.

[0069] Results: The results of the Sternberg test are shown in the following two tables (the corresponding graphs are shown in Figure 1 corresponding thereto), corresponding to the results of Experiment 1 (having received one supplementation).

[0070] [Table 1]

[0071] [Table 2]

[0072] Conclusion: From these results, the effect of the combination of guarana and the extract of P. tricornutum on the increase in data processing speed in healthy individuals compared to the placebo component was shown. Among this combination, the effect of the extract of P. tricornutum was dominant, and this effect was: - The reaction time of individuals administered with a low-dose or high-dose composition in response to visual stimuli for individuals in the placebo group was short; - The reaction time was significantly reduced by the composition containing the extract of P. tricornutum at a high dose (872 mg) rather than at a low dose (436 mg), indicating a major advantage of the extract of P. tricornutum; - When the number d of visual stimuli (data to be analyzed) increased, this reaction time remained constant; which is characteristic. It should be noted that the change in reaction time associated with supplementation as a function of the number (n) of visual stimuli was the opposite of the results usually obtained in the Sternberg test. In fact, when the number of incoming stimuli (the amount of data to be evaluated before making a decision) increases, the reaction time mechanically increases because the data processing process is sequential and exhaustive (Sternberg, 1966), and each individual has a certain intrinsic processing time per data unit. Supplementation with a combination of a low-dose extract (436 mg) of P. tricornutum and a guarana extract induced a constant reaction time for 4 to 6 stimuli. On the other hand, supplementation with a combination of a high-dose extract (872 mg) of P. tricornutum and a guarana extract induced a decrease in reaction time from 2 to 6 stimuli.

[0073] Example 4: Effect of the extract of Phaeodactylum tricornutum on maintaining and / or increasing concentration in healthy individuals. Protocol: The protocol is the one shown in Example 3. Results: The results are shown in Table 3 (Figure 2) (Go-NoGo test).

[0074]

Table 3

[0075] Conclusion: By supplementation using a combination of guarana extract and a composition containing an extract of P. tricornutum, regardless of the dose (low or high) of the composition containing the extract of P. tricornutum, the level of accuracy of the response 30 days after supplementation was improved, whereas the level of accuracy decreased in the placebo group (Figure 2). The benefit regarding the level of concentration was greater with the composition containing a high-dose extract of P. tricornutum (right side of Figure 2).

[0076] Example 5: In vitro effect of a synergistic combination of an extract of P. tricornutum and a guarana (P. cupana) extract on maintaining and / or increasing data processing speed in healthy individuals. Example 5a): Increase in the length of neurite outgrowth and arborization. Sensory neurons were obtained from femoral joint cells (human induced pluripotent stem cells) which are themselves obtained from human fibroblasts from healthy donors. The cells were seeded in 96-well plates and maintained for 6 days under culture in a differentiation-inducing medium at a temperature of 37 °C (5% CO2). The medium was changed every 2 days. After culturing for 8 days, the medium was changed to a maturation medium (a medium containing growth factors such as nerve growth factor). The cells were maintained under culture at 37 °C under 5% CO2.

[0077] Induce and after 1 day, remove the growth factors in the medium, and use a control containing only the NGF growth factor; or the extract of P. tricornutum according to Example 1; or the guarana extract according to Example 2a) or 2b); or the combination according to Example 2c) with a P. tricornutum / guarana weight ratio of 2 / 9 to 3 / 7 (Example 2c1) or 3 / 1 to 7 / 2 (Example 2c2); and replace.

[0078] The medium was cultured for 4 days, then the cells were collected, labeled with an anti-β-tubulin antibody, and then visualized using a fluorescent dye-conjugated secondary antibody (labeling of the neuronal structure, i.e., the cell body and neurites). The length of the neuronal outgrowth and the number of branches at the level of these outgrowths were measured using an algorithm that automatically detects neurites and their branches for 20 images obtained for each culture well. On average, 6 wells were established for each condition compared to the control, and then statistical analysis was performed (one-way ANOVA using Dunnett's correction).

[0079] Example 5b): In vitro increase in the calcium mobilization rate at the synaptic level. The sensory neurons described in Example 5a) were seeded in a 96-well plate and maintained for 6 days under culture in a differentiation induction medium at a temperature of 37°C (5% CO2). The medium was changed every 2 days. After culturing for 9 days, the medium was changed to a maturation medium (a medium containing growth factors such as nerve growth factor), and the extract of P. tricornutum according to Example 1; or the galana extract according to Example 2a) or 2b); or a combination of two extracts according to Example 2c) with a P. tricornutum / galana weight ratio of 2 / 9 to 3 / 7 (Example 2c1) or 3 / 1 to 7 / 2 (Example 2c2); or a control (NGF growth factor) was added to the medium. The cells were maintained under culture at 37°C and 5% CO2 for 19 days, after which the nerve cell receptors became functional. To specifically inhibit the TRPM8 (M (melastatin) member of the transient receptor potential cation channel subfamily) nerve cell receptor and specifically activate these receptors, the medium was incubated with a fluorescent probe (Fluo-4-AM; Thermo Fisher). An increase in fluorescence represents activation of the receptor, thus representing a large influx of calcium into the nerve cells and representing an increase in the data processing speed in healthy individuals. The fluorescence fluctuations over 2 minutes were recorded, and the average value for each condition was calculated (n = 6). Statistical analysis was performed (one-way analysis of variance).

[0080] References: ‐ Donders, F.C. (1969). On the speed of mental processes. Acta Psychologica, 30, 412-431. ‐ Sternberg S. (1966) High-speed scanning in human memory. Science. 153(3736):652-4. - Wessel, J.R. (2017). Prepotent motor activity and inhibitory control demands in different variants of the go / no-go paradigm. Psychophysiology. doi:10.1111 / psyp.12871

Claims

1. Use of an extract of Phaeodactylum tricornutum, alone or in combination with an extract selected from guarana (Paullinia cupana) extract, lotus (Nelumbo nucifera) extract, gotu kola (Centella asiatica) extract, black pepper (Piper nigrum) extract, or any combination thereof, and / or a compound selected from creatine, arginine, caffeine, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde or any combination thereof, to maintain and / or enhance data processing speed and / or concentration in healthy individuals not suffering from cognitive decline and / or impairment.

2. Use according to claim 1, characterized in that the extract of Phaeodactylum tricornutum is obtained by extraction in a solvent or solvent mixture, preferably in water, acetone, hexane, ethyl acetate, methyltetrahydrofuran, 2-methyloxolane, heptane, ethanol, methanol, an alcohol selected from isopropanol, natural or branched-chain oils, glycols, polyols, a water / alcohol or water / glycol mixture in a ratio of 100 / 1 to 1 / 100 (w / w), preferably in a water / ethanol mixture in a ratio of 40 / 60 to 1 / 100 (w / w).

3. Use according to claim 1 or 2 by the oral route.

4. Use according to claim 1 or 2 in a composition preferably used as a food supplement.

5. Combination of an extract of Phaeodactylum tricornutum with an extract selected from guarana (Paullinia cupana) extract, lotus (Nelumbo nucifera) extract, gotu kola (Centella asiatica) extract, black pepper (Piper nigrum) extract, or a compound selected from creatine, arginine, caffeine, theophylline, paraxanthine, theobromine, rosmarinic acid, ellagic acid, cinnamaldehyde and any combination thereof.

6. The combination according to claim 5, characterized in that the weight ratio of the extract of Phaeodactylum tricornutum to the extract or the compound is 1 / 6 to 6 / 1.

7. The combination according to claim 5 or 6, characterized in that the extract is an extract of Paullinia cupana, preferably a seed extract.

8. An extract of P. tricornutum present in an amount of 50 to 600 mg, preferably 220 to 440 mg, and an extract of Paullinia cupana (P. cupana) present in an amount of 300 to 700 mg, preferably 500 mg, The combination according to claim 7, characterized by containing the above.

9. A composition comprising the combination according to claim 5, a plant oil and vitamin E, preferably used as a food supplement, wherein the plant oil is present in the composition at a concentration of 30 to 60% by weight based on the total weight of the composition, and the vitamin E is present at a concentration of 0.25 to 1% by weight based on the total weight of the composition.

10. An extract of P. tricornutum in an amount of 10 to 25%, preferably 11 to 16%, MCT oil present in an amount of 30 to 60%, α-tocopherol present in an amount of 0.5%, An extract of Paullinia cupana (P. cupana), preferably a seed extract, in an amount of 35 to 55%, The composition according to claim 9, characterized by containing the above.

11. The composition according to claim 9 or 10, further comprising at least one additive selected from preservatives, colorants, flavorings, disintegrants, lubricants and coating or encapsulating agents.

12. The composition according to claim 9 or 10, characterized in that it takes the form of gel capsules, wafer capsules, tablets, pellets, liquids or loose bulk powders.

13. The composition according to claim 9 or 10, characterized in that it is packaged in a dosage having a unit weight of 20 mg to 2 g.

14. The composition according to claim 9 or 10, characterized in that it is administered at a dosage of 1 to 2 g for at least 1 day, preferably at least 15 days, and very preferably for 1 month.

15. Use of the combination according to claim 5 or 6, or the composition according to claim 9 or 10, for maintaining and / or enhancing data processing speed and / or concentration in healthy individuals not showing cognitive decline and / or impairment.

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