Composition comprising a mixture of DHA and / or epa and a plant-derived phospholipid

Abstract

The invention relates to a composition comprising a mixture of DHA and / or EPA in the form of glyceride or ethyl ester derived from at least one microorganism, such as a microalga, and at least one plant-derived phospholipid, characterized in that: - the content of DHA and / or EPA in triglyceride form is between 10% and 90% by weight relative to the total weight of the composition, and - the content of at least one plant-derived phospholipid, such as phosphatidylcholine, is between 10% and 90% by weight relative to the weight of composition. The invention also relates to the method for manufacturing same and to the use thereof, in particular in the treatment of pathologies involving a deficiency of DHA and / or EPA, such as age-related macular degeneration or Alzheimer's disease.

Description

[0001] COMPOSITION COMPRISING A MIXTURE OF DHA AND / OR EPA AND A

[0002] PHOSPHOLIPID OF PLANT ORIGIN

[0003] The invention relates to a composition comprising a mixture of DHA (docosahexaenoic acid) and / or EPA (eicosapentaenoic acid) in the form of glycerides or ethyl ester derived from at least one microorganism, such as a microalgae, and at least one phospholipid of plant origin, its preparation process and its use as a medicament, for example in the treatment of age-related macular degeneration, the supply of DHA and / or EPA in the context of Alzheimer's disease and more generally in the treatment of pathologies involving a deficiency in DHA and / or EPA.

[0004] DHA is an essential fatty acid for nervous tissue, particularly the brain and retina. The biosynthesis of DHA from precursors is very limited. An exogenous supply of DHA is therefore necessary (hence the notion of indispensability), particularly during its formation in the embryo and newborn, but also in cases of neurodegenerative diseases.

[0005] Given the aging population and the increasing incidence of neurodegenerative diseases, the development of DHA-based nutritional approaches to prevent mental health in particular is an important issue.

[0006] It is now well accepted that the preferred form of DHA delivery to the brain via the blood-brain barrier (BBB) ​​is lyso-phosphatidyl-choline (Lyso-PC) with DHA in the Sn-2 position (Hachem & AU, vol 53 Mol Neurbiol. 2016). In addition, a specific transporter (Mfsd2a) of LysoPCs within the BBB has been identified allowing the preferential incorporation of DHA into the brain.

[0007] It has recently been demonstrated (Hachem & ail, 2020, vol 12 Nutrients 2020, Bernoud-Hubac N. & all, Vol 24 OCL 2017) that an oral intake of LysoPC-DHA (or AceDoPC molecular form mimicking lysoPC-DHA) improves cerebral uptake of DHA compared to an intake of DHA in triglyceride (TG) form.

[0008] It is accepted that the plasma bioavailability of EPA and DHA is better when supplied in krill phospholipid form compared to the triglyceride form (Maki & ail, 2009, Nutrition Research, vol 29 2009). However, supplementing the triglyceride diet with one-third more EPA and DHA than the phosphatidylcholine (PC) diet can establish a similar plasma level of EPA and DHA (Ulven & ail, 2010, Vol 46, Lipids 2011). In other words, the phospholipid form improves the plasma bioavailability of EPA and DHA compared to the triglyceride form, but an additional intake (one-third increase) can make up for this difference.

[0009] In Wu & al., Lipids in health and diseases, 2017), it was described that brain accretion of DHA in mice deprived of DHA before weaning is restored after intake of DHA-PC or DHA-TG and PC, at a very slightly lower level for the latter (16.5% vs. 14.72% in area by gas chromatography (GC area)). DHA and glycerylphosphorylcholine (GPC) give a level comparable to DHA-PC: a separate intake of DHA and PC (or GPC) is a solution to provide DHA to the brain.

[0010] At the hepatic level, the DHA level is very quickly recovered (two days after weaning) whether with DHA-PC or DHA-TG and PC or DHA-TG and GPC, for TG and for hepatic phospholipids (PL) - Wu & al., Lipids in health and diseases, 2017.

[0011] Surprisingly, at 4 days after weaning, the hepatic DHA level is higher for the TG-DHA and PC or TG-DHA and GPC diets, whether at the level of PL (increase of 3 to 4 points %; CG area) or TG (2.5% versus 3.5%) - Wu & al., Lipids in health and diseases, 2017.

[0012] Erythrocyte accretion of DHA (which is said to reflect brain accretion of DHA), at 14 days after weaning, is greater for the PC-DHA diet (9.7% DHA; CG area) than for the TG-DHA and PC or TG-DHA and GPC diets (8.3%). The interpretation is, without being bound by this theory, perhaps a passage in the form of lysoPC-DHA associated with albumin after hydrolysis with phospholipase A2 (or direct passage of PC-DHA) - Wu & al., Lipids in health and diseases, 2017.

[0013] Other studies have shown little difference in tissue accretion of DHA depending on the form of intake. Unlike in newborns or the elderly or in cases of diseases related to the nervous system, there is little cerebral or ophthalmic accretion of DHA in adults with very little difference depending on the form of intake. Thus, it is difficult to observe significant differences in DHA accretion in target organs in healthy adults.

[0014] Sources of PL-DHA or PC-DHA are relatively rare. The latter are of marine origin and are found more particularly in krill and fish eggs (herring, cod). Lipids extracted from krill (zooplankton) have the particularity of being rich in PC (approximately 40%), but these PCs are grafted mainly with EPA. EPA represents approximately 28% of the fatty acids in PC while DHA represents only approximately 14%. DHA is preferentially in the Sn-2 position of PC, EPA in the Sn1 position and in the Sn-2 position.

[0015] Thus, such sources of DHA and / or EPA limit the quantities of products that can be obtained, or would generate complex and therefore expensive industrialization of products.

[0016] Furthermore, such sources may simply be prohibited for some people with sensitivities in terms of allergies to certain marine fauna, or who have simply made a choice regarding their eating habits, as is the case with veganism. Thus, even if large-scale industrialization were possible to obtain a DHA and / or EPA supply product from krill (certainly involving high Research and Development costs with a process that is likely to be uneconomical / unfriendly in the end), fish or fish eggs, the market would be limited by the very nature of the sources of such products.

[0017] Thus, there is a deficiency in the art for obtaining a DHA and / or EPA supply product that is reliable, easy to access, can be industrialized on a large scale and is acceptable to the greatest number of people. In addition, a way to obtain a form as close as possible to lysoPC-DHA could present advantages in terms of efficiency when administering the product.

[0018] The object of the present invention therefore seeks to resolve these shortcomings.

[0019] SUMMARY

[0020] The subject of the present invention relates to a composition comprising a mixture of DHA and / or EPA in the form of glyceride(s) or ethyl ester(s) derived from at least one microorganism, such as a micro-algae, and at least one phospholipid of plant origin, characterized in that:

[0021] - the content of DHA and / or EPA in the form of glyceride(s), such as a triglyceride, or ethyl ester(s) is between 10% and 90% by mass relative to the total weight of the composition, and

[0022] - the content of at least one phospholipid of plant origin, such as phosphatidylcholine, is between 10% and 90% by mass relative to the mass of the composition.

[0023] The subject of the present invention thus relates to a method of manufacturing a composition according to the present invention comprising the following successive steps:

[0024] (a) obtaining an oil enriched with DHA and / or EPA in the form of glyceride(s), such as a triglyceride; b) adding at least one phospholipid of plant origin.

[0025] The step of extracting oil from a microorganism, such as a micro-algae, is carried out by heating under vacuum a suspension of microorganisms, such as micro-algae, preferably ground, for example to 45-50°C, or even up to 60°C. Thus, at the end of the fermentation, the cell walls are lysed using an enzyme (advantageously a protease) to release the fat which is then recovered by centrifugation.

[0026] The subject of the present invention also relates to a composition according to the present invention for its use as a medicament, preferably as a food supplement.

[0027] The subject of the present invention relates more particularly to a composition as described herein for its use in the treatment of pathologies involving a deficiency in DHA and / or EPA, such as age-related macular degeneration, psychiatric disorders such as Alzheimer's disease, or more generally for psychiatric disorders, in particular pathologies linked to one or more disorders linked to EPA.

[0028] The subject of the present invention relates more particularly to a composition as described herein for its use as a form of DHA supply for the development of the brain, in particular the brain of a human being, preferably from the fetal stage and a later stage, such as the newborn stage.

[0029] DEFINITIONS

[0030] By "DHA and / or EPA in the form of glycerides" is included within the scope of the present invention the esters of glycerol with docosahexaenoic acid (DHA) and / or eicosapentaenoic acid (EPA). The glycerides may be monoglycerides, diglycerides or triglycerides of DHA and / or EPA.

[0031] By "DHA and / or EPA in the form of ethyl ester(s)" is understood within the scope of the present invention an ethanol molecule linked to DHA and / or EPA via an ester bond, i.e. DHA and / or EPA with a -COOEt group.

[0032] By "derived from at least one microorganism, such as a micro-alga", it is understood within the scope of the present invention that the origin of the DHA and / or EPA in the form of glyceride(s), such as a triglyceride, comes from at least one microorganism, such as a micro-alga. In other words, the origin of the DHA and / or EPA in the form of glyceride(s), such as a triglyceride, is traceable in the different stages of the processes for obtaining the composition according to the present invention.

[0033] By "at least one phospholipid of plant origin", it is understood within the scope of the present invention that said at least one phospholipid comes from at least one plant. In other words, the origin of the phospholipid is traceable in the different stages of the processes for obtaining the composition according to the present invention. By "oil enriched with DHA and / or EPA", it is understood within the context of the present invention an oil having an EPA or DHA content greater than or equal to 300 mg / g, such as between 350 and 800 mg / g, for example 400 mg / L or 700 mg / g.

[0034] By "pathologies involving a deficiency in DHA and / or EPA", the scope of the present invention includes pathologies linked for example to a cardiovascular risk (thrombosis, excessively high levels of triglycerides and / or cholesterol in the blood, drop in blood pressure), to ocular fragility (linked in particular to the retina), or to neurological pathologies (such as depression, neurodegenerative diseases such as Alzheimer's disease or epilepsy).

[0035] By "brain development" is understood in the context of the present invention neural development, or in other words the process of morphological and functional maturation of the brain.

[0036] DETAILED DESCRIPTION

[0037] • Composition :

[0038] The present invention therefore relates to the composition described above, its process for obtaining and its uses as described above.

[0039] Preferably, the composition can further be characterized in that:

[0040] - said at least one microorganism, such as a microalgae, is chosen from the list consisting of a Traustochytrid, such as Shizochytrium sp or Crythecodinium cohnii, Nannochloropsis, Isochrysis, Phaeodactylum or Nitzchia. Indeed, there are strains of microalgae, such as for example Crypthecodinium cohnii, Nannochloropsis, Isochrysis, Phaeodactylum or Nitzchia, which can produce PLs predominantly in PC, with even di-DHA PCs;

[0041] - said at least one phospholipid of plant origin is chosen from the list consisting of sunflower oil, canola oil, soybean oil and their mixtures;

[0042] - preferably, said at least one phospholipid of plant origin is a plant extract chosen from the list consisting of sunflower oil and soybean oil. - preferably, the phospholipid of plant origin is rich in lecithin and / or phosphatidylcholine. Indeed, phosphatidylcholine seems to have an effect at the blood-brain barrier: it facilitates the passage of active ingredients;

[0043] - the composition further comprises DPAn-6;

[0044] - the content of DPAn-6 is between 0.1% and 20% by mass relative to the total weight of the composition;

[0045] - the sum of the DHA contents in the form of glyceride(s), such as a triglyceride, from at least one microorganism, such as a micro-algae, and the content of phospholipid(s) of plant origin are greater than or equal to 50% by mass relative to the total weight of the composition;

[0046] - the EPA content is between 10% and 90% by mass relative to the total weight of the composition;

[0047] - the DHA content is between 10% and 90% by mass relative to the total weight of the composition;

[0048] - the DHA:EPA ratio is between 1:100 and 100:1 by mass, respectively;

[0049] - said composition further comprises at least one antioxidant whose content is between 0.001% and 2% by mass relative to the total weight of the composition;

[0050] - the antioxidant is chosen from the following list: carotenoids, astaxanthin, zeaxanthin, and lutein, preferably astaxanthin;

[0051] - the composition comprises at least one triglyceride with short-chain MCT fatty acids with a rate preferably between 1% and 50% by mass, such as 20% plus or minus 5% by mass; and / or

[0052] - the composition is a food composition, preferably vegan.

[0053] More specifically, the composition according to the present invention may have the following characteristics.

[0054] In the current context of the strong trend of "vegan" diets, the composition according to the present invention is optimally suited for a supply of DHA and / or EPA of microalgal origin and phosphatidylcholine (PC) (also a supply of choline) promoting cerebral accretion of DHA. Thus, the subject of the present invention relates to a composition as described, presently characterized in that it is a vegan composition, that is to say that it does not contain any material directly of animal origin, and preferably ecologically responsible.

[0055] Thus, microalgal oils containing DHA, for example based on shizochytrium, or the EPA fraction after fractionation of EPA and DHA oil which contains some DHA, are characterized by the presence of DPA n-6. DPA n-6 is not present in fish oils (or very weakly <0.3% of fatty acids), characteristic of microalgal oils (for example, base oils with 400 mg DHA / g oil contain about 80 g DPA n-6 / g oil).

[0056] In a particular embodiment, the composition (which may be vegan) according to the present invention comprises DPAn-6 in a content of between 0.5% and 19% by mass relative to the total weight of the composition, such as between 1% and 18%, between 5% and 17%, between 10% and 16% by mass relative to the total weight of the composition. More preferably, the composition (which may be vegan) according to the present invention comprises DPAn-6 in a content of 15% plus or minus 3% by mass relative to the total weight of the composition.

[0057] Even more preferably, the composition (which may be vegan) according to the present invention comprises DPAn-6 in a content of 10% plus or minus 3% by mass relative to the total weight of the composition.

[0058] It should be noted that in the case of phospholipids with a lower PC content, more will need to be added to achieve the above quantities and therefore the quantity of DHA will be lower. Thus, for oils rich in EPA, there is very little n-6 DPA.

[0059] Some microalgae oils, such as nannochloropsis (photoautotrophic) or schizochytrium (heterotrophic) (after EPA fractionation), do not contain C20:1 eicosenoic acid (C20:1 W7 eicosnoic and C20:1 W9 gadoleic) and C22:1 docosenoic acid (C22:1 W9 erucic and C22:1 W11 ketoleic). Indeed, C20:1 and C22:1 are more specific to zooplankton and copepods in particular (via the food chain, C20:1 and C22:1 are found in fish).

[0060] Thus, in a particular embodiment, the composition (which may be vegan) according to the present invention comprises:

[0061] - C20:1 eicosenoic acid in a content less than or equal to 5%, preferably less than or equal to 1%, relative to the total weight of the composition; and / or

[0062] - C22:1 docosenoic acid in a content less than or equal to 5%, preferably less than or equal to 1%, relative to the total weight of the composition.

[0063] Preferably, the composition (which may be vegan) according to the present invention is:

[0064] - free from eicosenoic acid C20:1; and / or

[0065] - free from C22:1 docosenoic acid.

[0066] In a particular embodiment, in the composition (which may be vegan) according to the present invention, the sum of the contents of DHA in the form of glyceride(s), such as a triglyceride, derived from at least one microorganism, such as a microalgae, and the content of phospholipid(s) of plant origin is greater than or equal to 55% by mass relative to the total weight of the composition, preferably greater than or equal to 60%, greater than or equal to 65%, greater than or equal to 70%, greater than or equal to 75%, greater than or equal to 80%, greater than or equal to 85%, greater than or equal to 90%, greater than or equal to 95%, or even greater than or equal to 98%.

[0067] In a particular embodiment, the EPA content included in the composition (which may be vegan) according to the present invention is between 10 to 70%, preferably between 20% to 60% by mass relative to the total weight of the composition, for example between 30% to 50%, between 35% to 40% such as 37.5% plus or minus 2% by mass relative to the total weight of the composition.

[0068] In a particular embodiment, the DHA content included in the composition (which may be vegan) according to the present invention is between 20% to 80% by mass relative to the total weight of the composition, for example between 30% to 70%, between 40% to 60% such as 50% plus or minus 5% by mass relative to the total weight of the composition.

[0069] In a particular embodiment, the composition (which may be vegan) according to the present invention comprises a DHA:EPA proportion of between 1:9 and 75:1 by mass, respectively, preferably between 1:8 and 50:1, between 1:7 and 25:1, between 1:6 and 10:1, between 1:5 and 5:1, between 1:4 and 4:1, between 1:3 and 3:1, between 1:2 and 2:1 or between 1.5:1 and 1.5:1 by mass.

[0070] In a particular embodiment, the composition (which may be vegan) according to the present invention further comprises at least one antioxidant whose content is between 0.003% and 1.5% by mass, preferably between 0.005% and 1.4% by mass, between 0.01% and 1.3%, between 0.02% and 1.3%, between 0.05% and 1.2%, between 0.1% and 1.1%, between 0.5% and 1.0%, between 0.7% and 0.9%, such as 0.8% plus or minus 0.05% by mass relative to the total weight of the composition.

[0071] In a particular embodiment, the subject matter of the present invention relates to a composition (which may be vegan) which comprises between 10% to 90% by mass of DHA originating from a microorganism, such as a microalgae, and between 10% to 80% by mass of phosphatidylcholine.

[0072] In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) which comprises DPAn-6 in a content of between 1% and 19% by mass, preferably between 5% and 18%, between 10% and 17%, between 12% and 16% or 15% plus or minus 0.5% by mass relative to the total weight of the composition.

[0073] Preferably, the subject of the present invention relates to a composition (which may be vegan) comprising between 20% to 80% by mass, for example between 30% to 70%, between 40% to 60% such as 50% plus or minus 5% by mass, of DHA originating from a microorganism, such as a micro-alga, and between 20% to 70% by mass, for example between 30% to 60%, between 40% to 50% such as 40% plus or minus 5% by mass, of phosphatidylcholine.

[0074] In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) comprising between 10% to 90% by mass of EPA originating from a microorganism, such as a microalga, and between 10% to 80% by mass of phosphatidylcholine. Preferably, the subject of the present invention relates to a composition (which may be vegan) comprising between 20% to 80% by mass, for example between 30% to 70%, between 40% to 60% such as 50% plus or minus 5% by mass, of EPA originating from a microorganism, such as a microalga, and between 20% to 70% by mass, for example between 30% to 60%, between 40% to 50% such as 40% plus or minus 5% by mass of phosphatidylcholine.

[0075] In a particular embodiment, the subject matter of the present invention relates to a composition (which may be vegan) of DHA and / or EPA from a microorganism, such as a microalgae, comprising phosphatidylcholine and at least one antioxidant, such as astaxanthin, at least one carotenoid, zeaxanthin, lutein, vitamin E, for example tocopherol acetate or tocotrienol; vitamin C or one of its analogues, natural polyphenols.

[0076] In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) of DHA and / or EPA originating from a microorganism, such as a micro-alga, with a chlorophyll content of less than or equal to 5% by mass, preferably less than or equal to 4%, less than or equal to 3%, less than or equal to 2%, less than or equal to 1%. More preferably, the vegan composition of DHA and / or EPA originating from a microorganism, such as a micro-alga, is free of chlorophyll.

[0077] In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA from a microorganism, such as a microalga, and phosphatidylcholine, with a chlorophyll content of less than or equal to 5% by mass, preferably less than or equal to 4%, less than or equal to 3%, less than or equal to 2%, less than or equal to 1%. More preferably, the vegan composition of DHA and / or EPA from a microorganism, such as a microalga, and phosphatidylcholine is free of chlorophyll.

[0078] In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) of DHA and / or EPA originating from a microorganism, such as a microalga, with a glycolipid content of less than or equal to 5% by mass, preferably less than or equal to 4%, less than or equal to 3%, less than or equal to 2%, less than or equal to 1%. More preferably, the vegan composition of DHA and / or EPA originating from a microorganism, such as a microalga, is free of glycolipids.

[0079] In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA originating from a microorganism, such as a microalga, and phosphatidylcholine, with a glycolipid content of less than or equal to 5% by mass, preferably less than or equal to 4%, less than or equal to 3%, less than or equal to 2%, less than or equal to 1%. More preferably, the vegan composition comprising DHA and / or EPA originating from an algae or microalga and phosphatidylcholine is free of glycolipids. Indeed, the glycolipids do not originate from microalgae oil resulting from their cultivation in heterotrophic mode.

[0080] In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA originating from a microorganism, such as a micro-algae, and at least one triglyceride with short-chain fatty acids (MCT), i.e. C1-C10, preferably C2-C8, or C4-C6.

[0081] In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA originating from a microorganism, such as a micro-algae, phosphatidylcholine and at least one triglyceride with short-chain fatty acids (MCT), i.e. C1-C10, preferably C2-C8, or C4-C6.

[0082] Indeed, triglycerides with short-chain fatty acids (MCTs) can exhibit ketogenic action, which is beneficial in certain brain pathologies. Short-chain fatty acids can thus become the brain's energy source.

[0083] As an illustration, in the case of Alzheimer's disease, the use of glucose (supplied via the digestive system) is reduced in the brain. MCTs then intervene as a source of energy for the brain. Thus, in certain pathologies such as Alzheimer's disease or at extreme ages of life, it appears that the brain's energy supply is deregulated or inefficient. In the case of Alzheimer's disease, the reduction in the brain's uptake of glucose for energy is impaired. This reduction appears before cognitive decline syndromes and before the decline in neuronal functions. Amyloid beta (presence of aggregate with Alzheimer's disease) has shown inhibitory activities on pyruvate dehydrogenase, thus limiting the production of acetyl-CoA, fuel for the Krebs cycle for energy production. The ketogenic pathway to fill the deficit in glucose energy supply makes perfect sense.Medium- and short-chain fatty acids are ketogenic. They are broken down by liver mitochondria into ketone bodies (acetoacetate, B-hydroxybutyrate), which, when delivered to the brain by the blood, are used as an alternative fuel by regenerating the acetyl CoA then available for the Krebs cycle and energy production.

[0084] Adding these medium-chain fatty acids (MCFAs) to the formulation is a real advantage. This can be in their fatty acid form or in triglyceride form (such as MCTs). These MCFAs also have the particularity of being rapidly absorbed and transported to the liver compared to longer fatty acids which require activation via the carnitine system. Capric acids and especially caprylic acids are preferred.

[0085] Preferably, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA from a microorganism, such as a micro-algae, and at least one triglyceride with short-chain fatty acids (MCT) with a level of between 1% to 50% by mass, for example between 5% to 40%, between 10% to 30% such as 20% plus or minus 5% by mass.

[0086] Preferably, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA from a microorganism, such as a microalga, phosphatidylcholine and at least one triglyceride with short-chain fatty acids (MCT) with a level of between 1% and 50% by mass, for example between 5% and 40%, between 10% and 30% such as 20% plus or minus 5% by mass. In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA from a microorganism, such as a microalga, characterized in that this composition is adapted to allow an increase in bioavailability. Thus, preferably, the composition according to the invention is an emulsion, such as an emulsion, a microemulsion or a nanoemulsion, which may be an oil-in-water or water-in-oil (micro- / nano-) emulsion.

[0087] Preferably, the composition according to the invention is a self-emulsifiable composition.

[0088] Preferably, the composition according to the invention is an oil-in-water emulsion.

[0089] Preferably, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA originating from a microorganism, such as a micro-alga, characterized in that this composition is suitable for self-emulsification, that is to say that the composition emulsifies without external mechanical input.

[0090] In a particular embodiment, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA from a microorganism, such as a microalgae, and phosphatidylcholine, characterized in that this composition is adapted to allow an increase in bioavailability. Thus, preferably, the composition according to the invention is an emulsion, such as an emulsion, a microemulsion or a nanoemulsion, which may be an oil-in-water or water-in-oil (micro- / nano-) emulsion.

[0091] Preferably, the subject of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA and originating from a microorganism, such as a micro-algae, and phosphatidylcholin, characterized in that this composition is suitable for self-emulsification.

[0092] In a particular embodiment, the subject matter of the present invention relates to a food composition (which may be vegan), such as a food supplement which may take the form of a solid or a liquid. Preferably, the food composition (which may be vegan) according to the present invention may be in a pre-dosed form.

[0093] Preferably, the food composition (which may be vegan) according to the present invention may take the form of a capsule, a tablet, an encapsulated liquid or a liquid contained in an ampoule.

[0094] • Obtaining processes

[0095] Oils enriched with DHA and / or EPA can be commercial (marketed for example under the brand name Omegavie Algae oils® from the Polaris company).

[0096] However, the following three procedures (hereinafter called "options") allow you to obtain oils enriched with DHA and / or EPA.

[0097] The first option (as illustrated in Example 1 below) consists of a process comprising the following steps:

[0098] (a1) a reaction step between a microorganism oil comprising omega-3 polyunsaturated fatty acids in the form of triglycerides and an alcohol in the presence of a chemical or enzymatic catalyst,

[0099] - (b1) a step of concentration of omega-3 polyunsaturated fatty acids by molecular distillation under high vacuum in a scraped film evaporator coupled to a rectification column comprising at least seven theoretical plates, thus making it possible to obtain DHA in the form of ethyl esters (EE); and

[0100] - (c1) a step of converting DHA into glycerides comprising the additional steps (d1) and (e1):

[0101] - (d1) a step of restructuring monoglycerides, diglycerides and triglycerides of omega-3 polyunsaturated fatty acids in the presence of enzyme and glycerol; and

[0102] - (e1) a short path molecular distillation step under vacuum.

[0103] An illustration of this first option is given in example 1.1 below.

[0104] The second option (as illustrated in Example 2 below) consists of a DHA or EPA enrichment process starting from the same source as Option 1. In particular, the process according to Option 2 is a process for fractionating two-carbon fatty acids by molecular distillation (including fractionation between EPA and DHA), characterized in that it comprises the following steps:

[0105] (a2) a reaction step between a microorganism oil comprising omega-3 polyunsaturated fatty acids in the form of triglycerides and an alcohol in the presence of a chemical or enzymatic catalyst;

[0106] (b2) a (eg first) step of molecular distillation under high vacuum of the oil from step (a2), in a scraped film evaporator coupled to a rectification column comprising at least seven theoretical plates, and recovery of a first residue and a (first) distillate;

[0107] (c2) a subsequent step (eg second) of molecular distillation under high vacuum, of the residue recovered in step (b2), in said scraped film evaporator coupled to the rectification column comprising at least seven theoretical plates, and recovery of a second residue and a (second) distillate;

[0108] (d2) an optional step of restructuring monoglycerides, diglycerides and triglycerides of omega-3 polyunsaturated fatty acids in the presence of enzyme and glycerol; and

[0109] (e2) a short path molecular distillation step under vacuum.

[0110] The two steps (b2) and (c2) allow the separation of DHA from EPA. This does not seem to be possible with a single step. The equipment (7 trays) seems to be decisive.

[0111] In step (c2), DHA and EPA are in the form of ethyl esters. It is therefore possible to return them to the form of diglycerides.

[0112] An illustration of this second option is given in example 1.2 below.

[0113] The third option (as illustrated in Example 3 below) consists of a process for enriching an oil with EPA comprising the following steps:

[0114] (a3) a reaction step between a microorganism oil comprising EPA and an alcohol in the presence of a chemical catalyst;

[0115] (b3) a step of concentration and purification of fatty acid ethyl esters including EPA ethyl esters by short-path molecular distillation under high vacuum; (c3) a step of concentration of eicosapentaenoic acid by molecular distillation on a rectification column;

[0116] (d3) a step of restructuring monoglycerides, diglycerides and triglycerides of omega-3 polyunsaturated fatty acids in the presence of enzyme and glycerol; and

[0117] (e3) a short path molecular distillation step under vacuum.

[0118] The starting oil in step (a3) ​​can be, for example, a microalgal oil from the genera Nannochloropsis, Isochrysis, Phaeodactylum or Nitzchia. An illustration of this third option is given in example 1.3 below.

[0119] In step (e3) of the process, EPA in the form of ethyl esters (EE) is obtained. It can be converted into glycerides by adding the following steps:

[0120] (f3) a step of restructuring monoglycerides, diglycerides and triglycerides of omega-3 polyunsaturated fatty acids in the presence of enzyme and glycerol; and

[0121] (g3) a short path molecular distillation step under vacuum.

[0122] Another aspect of the present invention relates to a method of manufacturing a composition as described above. This method may comprise the following successive steps:

[0123] (a) obtaining an oil enriched with DHA and / or EPA in the form of glyceride(s), such as a triglyceride, for example by any of the processes cited above;

[0124] (b) the addition of at least one phospholipid of plant origin.

[0125] Any addition technique applicable in this case may be used. Preferably, the DHA and / or EPA oils and at least one phospholipid of plant origin are mixed at high speed and / or for a sufficient time to obtain sufficient homogeneity of the mixture. In particular, a gradual vacuuming with heating and stirring until the phospholipid is completely dissolved in the mixture may be carried out. In particular, the DHA and / or EPA oils and at least one phospholipid of plant origin are mixed under vacuum in order to avoid their oxidation or more generally the incorporation of gas into the mixture.

[0126] Preferably, the method comprises a step in which the mixture of DHA and / or EPA oils and at least one phospholipid of plant origin is heated at atmospheric pressure, for example after having been mixed under vacuum, at a temperature between 5°C and 60°C, preferably between 45°C and 50°C.

[0127] Advantageously, the method comprises a step in which the mixture of DHA and / or EPA oils and at least one phospholipid of plant origin is heated at atmospheric pressure under inert gas, such as nitrogen, or preferably under vacuum.

[0128] • Applications

[0129] The subject of the present invention thus relates to a composition as described herein for its use in the treatment of pathologies involving a deficiency in DHA and / or EPA.

[0130] In particular, the intake of PC and DHA will allow the body to synthesize Lyso-PC-DHA which is a preferred molecular form for vectorizing DHA to the brain in particular (PC is also a source of choline).

[0131] Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of pathologies involving a deficiency in DHA and / or EPA, in a patient having an age greater than or equal to 40 years, greater than or equal to 45 years, greater than or equal to 50 years, greater than or equal to 55 years, greater than or equal to 60 years, greater than or equal to 65 years, greater than or equal to 70 years, greater than or equal to 75 years, greater than or equal to 80 years, greater than or equal to 85 years, greater than or equal to 90 years or even greater than or equal to 95 years.

[0132] In a particular embodiment, the subject of the present invention relates to a composition as described herein for its use in the treatment of cardiovascular disorders. Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of cardiovascular disorders, in a patient having an age greater than or equal to 40 years, greater than or equal to 45 years, greater than or equal to 50 years, greater than or equal to 55 years, greater than or equal to 60 years, greater than or equal to 65 years, greater than or equal to 70 years, greater than or equal to 75 years, greater than or equal to 80 years, greater than or equal to 85 years, greater than or equal to 90 years or even greater than or equal to 95 years.

[0133] Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of thrombosis.

[0134] Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of thrombosis, in a patient having an age greater than or equal to 40 years, greater than or equal to 45 years, greater than or equal to 50 years, greater than or equal to 55 years, greater than or equal to 60 years, greater than or equal to 65 years, greater than or equal to 70 years, greater than or equal to 75 years, greater than or equal to 80 years, greater than or equal to 85 years, greater than or equal to 90 years or even greater than or equal to 95 years.

[0135] Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of disorders linked to an excessively high level of triglycerides and / or cholesterol in the blood.

[0136] Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of disorders linked to an excessively high level of triglycerides and / or cholesterol in the blood, in a patient having an age greater than or equal to 40 years, greater than or equal to 45 years, greater than or equal to 50 years, greater than or equal to 55 years, greater than or equal to 60 years, greater than or equal to 65 years, greater than or equal to 70 years, greater than or equal to 75 years, greater than or equal to 80 years, greater than or equal to 85 years, greater than or equal to 90 years or even greater than or equal to 95 years. In a particular embodiment, the subject of the present invention relates to a composition as described herein for its use in the treatment of disorders linked to ocular fragility, in particular having a link with the retina.

[0137] In a particular embodiment, the subject of the present invention relates to a composition as described herein for its use in the treatment of macular degeneration, in particular age-related. Indeed, the intake of PC-DHA is also important from a very young age and during gestation for the constitution of the retina (visual acuity). Thus, one of the objectives of the present invention may be a supply of PC-DHA to the mother and also to the infant by administering the composition according to the present invention.

[0138] Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of disorders linked to ocular fragility, in particular having a link with the retina, such as macular degeneration, in particular age-related, in a patient having an age greater than or equal to 40 years, greater than or equal to 45 years, greater than or equal to 50 years, greater than or equal to 55 years, greater than or equal to 60 years, greater than or equal to 65 years, greater than or equal to 70 years, greater than or equal to 75 years, greater than or equal to 80 years, greater than or equal to 85 years, greater than or equal to 90 years or even greater than or equal to 95 years.

[0139] In a particular embodiment, the subject matter of the present invention relates to a composition as described herein for its use in the treatment of neurological disorders, such as depression, neurodegenerative disease or epilepsy.

[0140] Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of a neurodegenerative disease such as Alzheimer's disease, Parkinson's disease or sclerosis, such as amyotrophic sclerosis.

[0141] Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of a neurodegenerative disease such as Alzheimer's disease, Parkinson's disease or sclerosis, such as amyotrophic sclerosis, in a patient having an age greater than or equal to 40 years, greater than or equal to 45 years, greater than or equal to 50 years, greater than or equal to 55 years, greater than or equal to 60 years, greater than or equal to 65 years, greater than or equal to 70 years, greater than or equal to 75 years, greater than or equal to 80 years, greater than or equal to 85 years, greater than or equal to 90 years or even greater than or equal to 95 years.

[0142] In a particular embodiment, the subject of the present invention relates to a composition as described herein for its use in the treatment of a patient of an age greater than or equal to 40 years, greater than or equal to 45 years, greater than or equal to 50 years, greater than or equal to 55 years, greater than or equal to 60 years, greater than or equal to 65 years, greater than or equal to 70 years, greater than or equal to 75 years, greater than or equal to 80 years, greater than or equal to 85 years, greater than or equal to 90 years or even greater than or equal to 95 years.Preferably, the subject of the present invention relates to a composition as described herein for its use in the treatment of a patient aged over 60 years presenting a pathology or a risk chosen from cardiovascular disorders, thrombosis, disorders linked to an excessively high level of triglycerides and / or cholesterol in the blood, disorders linked to ocular fragility, disorders linked to the retina such as macular degeneration, neurological disorders, such as depression or epilepsy, a neurodegenerative disease such as Alzheimer's disease, Parkinson's disease or sclerosis.

[0143] EXAMPLES

[0144] Embodiments of the present invention will be described below by way of non-limiting examples.

[0145] Example 1: Process for obtaining microalgae oils

[0146] Example 1.1: concentration of a microalgae oil in DHA mainly in the form of glycerides. This is the process for manufacturing an oil according to option 1 described above. This process is detailed in patent document FR3103355.

[0147] The process is carried out using crude oil produced by the microalgae strain Schizochytrium sp T18 marketed by the company Mara Renewables Corporation.

[0148] The oil initially contains 329 mg / g of DHA. The goal here is to at least double the DHA concentration.

[0149] Step (i): transesterification

[0150] A transesterification reaction is carried out on a biomass of 1800 kg of microalgal oil using 450 kg of ethanol and 21.6 kg of sodium ethylate, in a suitable reactor.

[0151] The reaction temperature is 50°C and the reaction time is 1 hour. At the end of the reaction, the excess ethanol is evaporated under vacuum, then the mixture is cooled to a temperature of approximately 30°C and then subjected to decantation for 1 hour. The light phase is recovered and then the glycerol is drained. A second decantation is carried out for 30 seconds. The residual glycerol and monoglycerides are drained.

[0152] An acidic water wash is then carried out by adding 17% demineralized water containing 2.5% phosphoric acid (75%) while stirring for 20 seconds. The mixture is decanted for 20 seconds and the aqueous phase is drained. This is followed by vacuum drying (pressure < 90 mbar) at 60°C for a period of more than 2 hours.

[0153] At the end of this stage, the oil contains 329 m / g of DHA in the form of ethyl esters.

[0154] Step (ii): DHA concentration by molecular distillation

[0155] The oil is then passed through a degasser and then through a wiped film evaporator. The vapors are then distilled through a rectification column which is coupled to the evaporator supplied by UIC GmbH. Refluxing the distillate, i.e. reintroducing the distillate into the column, can increase the separation efficiency of the latter. The column used contains approximately seven theoretical plates. The distillation residue is recovered and represents the DHA-enriched fraction. The operating conditions are as follows: Evaporator temperature: 225°C; Rectification column vacuum: 0.1 mbar; Reflux ratio 75%, Temperature (top of column): 195°C.

[0156] Table 1 below compares the fatty acid profile of the oil obtained after this step (ii) with the initial fatty acid profile before the first step (i). The quantities are expressed in mg of each fatty acid per g of oil.

[0157] [Table.1]

[0158] More than 97% of DHA was retained in the recovered residue. The amount of DHA increased from 329 mg / g of DHA in the form of ethyl esters to 758 mg / g.

[0159] Step (iii): Synthesis of triglycerides, diglycerides and monoglycerides

[0160] The reaction takes place in a reactor in the presence of an immobilized enzyme. This is a lipase from fraction B of Candida antartica (marketed under the name Lipozym 435 by the company Novozym).

[0161] 480 g of distillation residue containing approximately 758 mg / g of DHA, 33 g of glycerol and 20 g of enzyme, are introduced into the reactor.

[0162] The reaction takes place under moderate stirring, at a controlled temperature around 60°C, under vacuum with evaporation and condensation of the ethanol generated. The reaction time is 25 hours. The reaction yield is more than 95%.

[0163] At the end of this stage, the oil has the following glyceridic profile

[0164] (Table 2):

[0165] [Table 2]

[0166] Step (iv): Short path molecular distillation

[0167] After synthesis, the product is taken back for passage in a short-path distiller (marketed by the company U IC GmbH) to eliminate residual ethyl esters, odorous volatiles but also to inactivate any potential residual enzymatic activity.

[0168] The conditions are an evaporator wall temperature between 160 and 220°C and a vacuum of less than 0.02 mbar. Preferably, the vacuum is 0.005 mbar to allow the distillation temperature to be lowered.

[0169] At the end of this step, the oil has the profile indicated in Table 3:

[0170] [Table 3]

[0171] Example 1.2: EPA / DHA fractionation by molecular distillation and obtaining microorganism oil compositions enriched with eicosapentaenoic acid and docosahexaenoic acid

[0172] This is the process for manufacturing an oil according to option 2 described above. This process is detailed in patent document FR3108622. The process according to the invention is carried out from a crude oil produced by the microalgae strain Schizochytrium sp marketed by the company DSM under the brand name Life's DHA 60.

[0173] The oil profile is as follows:

[0174] - 360 mg / g of DHA, in mg / g of composition,

[0175] - 184 mg / g of EPA, in mg / g of composition, - 94.1% triglycerides,

[0176] - 5.4% diglycerides,

[0177] - 0.4% monoglycerides.

[0178] The goal here is to at least double the concentration of EPA and DHA.

[0179] Step (i): transesterification

[0180] A transesterification reaction is carried out on a biomass of 19 kg of microalgal oil using 4.75 kg of ethanol and 222 g of sodium ethoxide, in a suitable reactor.

[0181] The reaction temperature is 50°C and the reaction time is 1 h. At the end of the reaction, the excess ethanol is evaporated under vacuum, then the mixture is cooled to a temperature of approximately 30°C and then subjected to decantation for 1 h. The light phase is recovered and then the glycerol is drained. A second decantation is carried out for 30 sec. The residual glycerol and monoglycerides are drained.

[0182] An acidic water wash is then carried out by adding 3.2 kg of demineralized water containing 76.4 g of phosphoric acid (75%) while stirring for 20 seconds. The mixture is decanted for 20 seconds and the aqueous phase is drained. This is followed by vacuum drying (pressure < 90 mbar) at 60°C for a period of more than 2 hours.

[0183] At the end of this stage, the oil contains 192 mg / g of EPA and 374 mg / g of DHA in the form of ethyl esters.

[0184] Step (ii): first step of molecular distillation

[0185] The oil is then passed through a degasser and then through a wiped film evaporator. The vapors are then distilled through a rectification column, which is coupled to the evaporator supplied by U IC GmbH. The aim here is to remove the lightest fatty acids while retaining the DHA and EPA. The column used contains seven theoretical plates. The distillation residue is recovered and represents the fraction enriched in EPA and DHA.

[0186] The operating conditions are as follows: Evaporator temperature: 225°C; Rectification column vacuum: less than 0.1 mbar; Reflux rate 70%, Temperature (bottom of column): 190°C, Temperature (top of column): 135°C.

[0187] At the end of this step, a residue fraction and a distillate fraction are obtained. The residue fraction contains 256 mg / g of EPA and 520 mg / g of DHA. The yield is 68%.

[0188] Step (iii): second step of molecular distillation

[0189] The operation of step (II) is repeated on the residue. This is then returned to the degasser and then passes through the wiped film evaporator. The vapors are then distilled through the rectification column coupled to the evaporator as in the case of step (ii) above. The aim here is to separate the DHA and the EPA.

[0190] The operating conditions are as follows: Evaporator temperature: 235°C; Rectification column vacuum: less than 0.05 mbar; Reflux rate 60%, Temperature (bottom of column): 202°C, Temperature (top of column): 160°C.

[0191] At the end of this step, a residue fraction and a distillate fraction are obtained. The distillate fraction contains 733 mg / g of EPA and 70 mg / g of DHA. The yield of this fraction is 84% ​​EPA and 4% DHA. The residue fraction contains 706 mg / g of DHA and 83 mg / g of EPA. The yield of this fraction is 93% DHA and 22% EPA.

[0192] In Table 4 below, the detailed fatty acid profile of the distillate and residue fractions obtained at the end of step (iii) is indicated (in mg / g of composition).

[0193] [TABLE 4]

[0194] Example 1.3: Obtaining microalgal oil containing EPA

[0195] This is the process of making an oil according to option 3 described above.

[0196] The starting oil is a crude oil produced by the Nannochloropsis sp strain obtained after culturing the biomass for about eight days under photoautotrophic conditions. The extraction of the fat from the biomass is carried out by ethanolic maceration. After separation of the remaining solid phase, the ethanol is evaporated under vacuum.

[0197] EPA produced by photoautotrophy is found incorporated into membrane lipids, either in the form of glycolipids, phospholipids, or free fatty acids. The triglyceride form is poorly represented.

[0198] Step (i): transesterification

[0199] A transesterification reaction is carried out on a biomass of 100 kg of microalgal oil using approximately 200 kg of ethanol and 10 kg of sulfuric acid, in a suitable reactor (reflux 60°C > 10 h). The transesterification is carried out by acid means, with sulfuric acid. Step (ii): EPA concentration by short-path molecular distillation under vacuum

[0200] The conditions are an evaporator wall temperature between 175 and 180°C and a vacuum of less than 0.1 mbar.

[0201] Step (iii): EPA concentration by molecular distillation on a rectification column The operating conditions are as follows: Evaporator temperature: 230°C; Rectification column vacuum: 0.07 mbar; Reflux rate 65%, Temperature (top of column): 107°C, Temperature (bottom of column): 147°C. The quantity of EPA in the form of ethyl esters is 735 mg / g.

[0202] Examples of compositions according to the present invention

[0203] Vegetable oils used:

[0204] Soybean oil 50% PC

[0205] Sunflower oil 90% PC

[0206] Unconcentrated Schizochitrium sp. oil: 40% DHA

[0207] Concentrated Schizochitrium sp. oil: 70% DHA

[0208] Schizochitrium sp. oil rich in EPA and DHA: 20% EPA and 30% DHA Palm oil with short-chain triglycerides (MCT) Astaxanthin concentrated at 10%

[0209] Method of manufacturing a composition according to the present invention: Addition of the different elements in the same container Stirring and progressive vacuuming

[0210] Heating the mixture while stirring until a homogeneous mixture is obtained

[0211] Return to atmospheric pressure by adding inert gas

[0212] Table 5: summary table of the compositions obtained: [TABLE 5]

[0213]

[0214] Comparative example between a composition according to the present invention and a composition according to the state of the art Table 6: Composition C vs krill oil [TABLE 6] is sufficient to produce emulsifying properties similar to krill oil.

[0215] Composition C contains higher levels of DHA. EPA levels can be increased if needed. This allows DHA and EPA levels to be tailored to the treatment being treated.

[0216] The amount of astaxanthin can also be modified depending on the treatment being treated.

[0217] It can nevertheless be seen that composition C includes 6 times more DHA and 1.5 times more omega 3 than krill oil.

[0218] Example 3: in vivo tests in rats: the supposed mechanism of action Knowing that during digestion, DHA is very rapidly hydrolyzed from PC (phosphatidylcholine) and that hepatic resynthesis of LysoPC-DHA in the presence of choline is active, the composition according to the present invention comprising PC and DHA appears to be a very well-suited form for the supply of DHA to target tissues.

[0219] It is well known that after food intake, phospholipase A2 is very rapidly active. Ingested phospholipids rapidly undergo hydrolysis. DHA, being naturally in Sn-2, is released in the form of free fatty acid. The latter is then available for intestinal absorption. Several studies have shown better incorporation of DHA into erythrocytes when it is provided in the form of PL-DHA followed by Mono-DHA and then TG-DHA (erythrocyte accretion of DHA is considered a marker of its cerebral accretion). In these cases, TG or Mono were not supplemented with plant PL.

[0220] Phospholipids are amphiphilic molecules that give them self-emulsification properties, similar to what happens during the digestion of fatty acids. Emulsification is well recognized to improve the intestinal absorption of fatty acids in humans (Raatz SK & all, , J of Am. Diet. Ass., vol 109, 2009; Couëdelo L. & all, Food Funct. Vol 6, 2015; Couëdelo L. & all, OCL, vol 24, 2017; Ottestad I. & Stall, J. of Nutr. Sci, Vo 5 2016). Thus, a lecithin supplement improves the emulsification of lipids or fatty acids and their plasma bioavailability.

[0221] A study with DHA oils in triglyceride form supplemented with plant phospholipids (PC) compared to a diet of Phosphatidylcholine-DHA extracted from cod roe (composition of the company Arctic Nutrition AS - brand Romega®) with an identical intake of DHA, showed, 10 hours after intake, an equivalent plasma bioavailability of DHA (identical DHA content). Looking at the DHA contents in the phospholipid fraction of the plasma, a slight superiority of the DHA content was noted with the PC-DHA diet (+ approximately 15%). By analyzing the distribution of DHA on the glycerol skeleton of plasma phospholipids, it is observed that the DHA is very predominantly grafted in the Sn-2 position (approximately 80% of DHA) with a very slight advantage for the PC-DHA diet. With the TG-DHA and PL (PC) plant diet (without DHA), we therefore find almost as much PC-DHA as with the PC-DHA diet.This clearly proves that PC-DHA is hydrolyzed by Phospholipase A2 and that there is indeed resynthesis of PC-DHA sn-2 at the level of enterocytes before release into the plasma.

[0222] It was possible to determine here a better supply of DHA and / or EPA to the brain in a specific form. Thus, the best known form of supply of DHA, or even EPA, to the brain is lyso-Phosphatidylcholine (Lyso-PC) with DHA in the Sn2 position and / or EPA in the Sn1 and Sn2 positions. Sources of DHA in the lyso-PC form are rare and expensive. These are krill oils and fish eggs. The present invention makes it possible to offer not only an alternative to these previous forms, but also offers a composition with technical effects that can be targeted according to the level and nature of the fatty acids it contains (DHA and / or EPA).

Claims

DEMANDS 1. Composition comprising a mixture of DHA and / or EPA in the form of glyceride(s) or ethyl ester(s) derived from at least one microorganism, such as a microalga, and at least one phospholipid of plant origin, characterized in that: - the content of DHA and / or EPA in the form of glycerides, such as a triglyceride, or ethyl ester(s) is between 10% and 90% by mass relative to the total weight of the composition, and - the content of at least one phospholipid of plant origin, such as phosphatidylcholine, is between 10% and 90% by mass relative to the mass of composition.

2. Composition according to claim 1, characterized in that said at least one microorganism is selected from the list consisting of a Traustochytride, such as Shizochytrium sp or Crythecodinium cohnii, Nannochloropsis, Isochrysis, Phaeodactylum or Nitzchia.

3. Composition according to claim 1 or 2, characterized in that said at least one phospholipid of vegetable origin is selected from the list consisting of sunflower oil, canola oil, soybean oil and mixtures thereof.

4. Composition according to any one of the preceding claims, characterized in that the composition further comprises DPAn-6 and in that its content is between 0.1% and 20% by mass relative to the total weight of the composition.

5. Composition according to any one of the preceding claims, characterized in that the sum of the contents of DHA in the form of glyceride(s), such as a triglyceride, from at least one microorganism and the content of phospholipid(s) of plant origin are greater than or equal to 50% by mass relative to the total weight of the composition.

6. Composition according to any one of the preceding claims, characterized in that the proportion DHA:EPA is between 1:100 and 100:1 by mass, respectively.

7. A composition according to any one of the preceding claims, characterized in that said composition further comprises at least one antioxidant whose content is between 0.001% and 2% by mass relative to the total weight of composition and chosen from the following list: carotenoids, astaxanthin, zeaxanthin, and lutein, preferably astaxanthin.

8. Composition according to any one of the preceding claims, characterized in that the composition comprises at least one triglyceride with MCT short-chain fatty acids with a rate preferably between 1% and 50% by mass, such as 20% plus or minus 5% by mass.

9. Composition according to any one of the preceding claims, characterized in that the composition is a food composition, preferably vegan.

10. Composition according to any one of the preceding claims, for use as a medicinal product, preferably as a food supplement.

11. Composition according to any one of the preceding claims for its use in the treatment of pathologies involving a deficiency in DHA and / or EPA, such as age-related macular degeneration, psychiatric disorders such as Alzheimer's disease, in particular pathologies related to one or more EPA-related disorders.

12. Composition according to any one of the preceding claims for its use as a form of DHA intake for brain development.

Images