COMPOSITION COMPRISING A BLEND OF DHA AND / OR EPA AND A PLANT-DERIVED PHOSPHOLIPID
A composition of DHA and/or EPA from microorganisms and plant-derived phospholipids addresses the limitations of existing sources by enhancing bioavailability and accessibility, offering a vegan and eco-friendly solution for diverse health conditions.
Patent Information
- Application Number
- FR2022001122
- Authority / Receiving Office
- FR · FR
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2022-02-09
- Publication Date
- 2025-04-25
- Estimated Expiration
- 2042-02-09
AI Technical Summary
There is a disability in obtaining a DHA and/or EPA intake product that is reliable, easy to access, industrialized on a large scale, and acceptable by the greatest number of people, particularly due to limited sources and potential allergies to marine fauna, and existing forms like Krill and fish oils are complex and expensive.
A composition comprising a mixture of DHA and/or EPA in the form of glycerides or ethyl esters from microorganisms and plant-derived phospholipids, with specific content percentages, optimized for bioavailability and accessibility, including micro-algae oils and plant-derived phospholipids like phosphatidylcholine, and optionally supplemented with antioxidants and short-chain triglycerides.
The composition enhances the bioavailability and accessibility of DHA and EPA, providing a vegan and eco-friendly alternative suitable for various age groups and health conditions, including neurodegenerative diseases and cardiovascular disorders, with improved cerebral and ophthalmic accretion.
Abstract
Description
Title of the invention: COMPOSITION COMPRISING A BLEND OF DHA AND / OR EPA AND A PHOSPHOLIPID OF PLANT ORIGIN
[0001] 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 from at least one microorganism, such as a microalga, and at least one phospholipid of plant origin, its preparation process and its use as a medicinal product, 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.
[0002] DHA is an essential fatty acid for nerve tissues, particularly the brain and retina. DHA biosynthesis from precursors is very limited. Exogenous DHA supplementation is therefore necessary (hence the notion of its essential nature), especially during its formation in the embryo and newborn, but also in cases of neurodegenerative diseases.
[0003] Given the aging population and the increasing incidence of neurodegenerative diseases, the development of DHA-based nutritional approaches to prevent mental health problems in particular is an important issue.
[0004] It is now well established that the preferred form of DHA delivery to the brain via the blood-brain barrier (BBB) is lysophosphatidylcholine (Lyso-PC), in which DHA is located at the Sn-2 position (Hachem & Ail, vol. 53, Mol Neurbiol, 2016). Furthermore, a specific transporter (Mfsd2a) of Lyso-PC within the BBB has been identified, enabling preferential incorporation of DHA into the brain.
[0005] It has recently been demonstrated (Hachem & ail, 2020, vol 12 Nutrients 2020, Bernoud-Hubac N. & ail, Vol 24 OCL 2017) that oral intake of LysoPC-DHA (or L'AceDoPC molecular form mimicking lysoPC-DHA) improves cerebral uptake of DHA compared to intake of DHA in triglyceride (TG) form.
[0006] It is accepted that the plasma bioavailability of EPA and DHA is better when they are provided in the form of krill phospholipids compared to the triglyceride form (Maki et al., 2009, Nutrition Research, vol. 29, 2009). However, supplementing with one-third more EPA and DHA on the triglyceride diet compared to the phosphatidylcholine (PC) diet results in similar plasma levels of EPA and DHA (Ulven et al., 2010, vol. 46, Lipids, 2011). In other words, the phospholipid form improves bioavailability plasma EPA and DHA compared to the triglyceride form, but an additional intake (one-third increase) makes it possible to bridge this difference.
[0007] In Wu et al., Lipids in health and diseases, 2017, it was described that cerebral DHA accretion in DHA-deprived mice prior to weaning is restored after administration of DHA-PC or DHA-TG and PC, at a very slightly lower level for the latter (16.5% versus 14.72% area by gas chromatography (GC area)). DHA and glycerylphosphorylcholine (GPC) provide a level comparable to DHA-PC: separate administration of DHA and PC (or GPC) is a solution for delivering DHA to the brain.
[0008] At the liver 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.
[0009] Surprisingly, at 4 days post-weaning, the hepatic level of DHA 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 et al., Lipids in health and diseases, 2017.
[0010] Erythrocyte DHA accretion (which is said to reflect cerebral DHA accretion), 14 days post-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, without being bound by this theory, is perhaps a passage in the form of lysoPC-DHA associated with albumin after hydrolysis with phospholipase A2 (or direct passage of PC-DHA) - Wu et al., Lipids in health and diseases, 2017.
[0011] Other studies have shown little difference in tissue DHA accretion depending on the form of administration. Unlike newborns, the elderly, or those with nervous system disorders, there is little cerebral or ophthalmic DHA accretion in adults, with very little difference depending on the form of administration. Thus, it is difficult to observe significant differences in DHA accretion in target organs in healthy adults.
[0012] Sources of PL-DHA or PC-DHA are relatively rare. These are of marine origin and are found particularly in krill and fish roe (herring, cod). Lipids extracted from krill (zooplankton) are notably rich in PCs (approximately 40%), but these PCs are predominantly bound with EPA. EPA represents approximately 28% of the fatty acids in PCs, while DHA represents only about 14%. DHA is preferentially found at the Sn-2 position of the PC, while EPA is found at the Sn1 and Sn-2 positions.
[0013] Thus, such sources of DHA and / or EPA limit the quantities of products that can be obtained, or would generate complex and therefore costly industrialization. of products.
[0014] Furthermore, such sources may simply be unsuitable for some people with sensitivities, such as allergies to certain marine fauna, or who have simply made a choice regarding their dietary habits, as is the case with veganism. Thus, even if large-scale industrial production were possible for obtaining a DHA and / or EPA supplement from krill (certainly involving high R&D costs with a process that would likely be uneconomical / environmentally unsound in the end), fish, or fish eggs, the market would be limited by the very nature of the sources of such products.
[0015] Thus, there is a deficiency in the art for obtaining a DHA and / or EPA supply product that is reliable, easily accessible, industrializable on a large scale and acceptable to the greatest number of people.
[0016] In addition, a means of obtaining a form as close as possible to lysoPC-DHA could present advantages in terms of efficacy when administering the product.
[0017] The object of the present invention therefore seeks to resolve these shortcomings.
[0018] SUMMARY
[0019] The object 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 microalga, and at least one phospholipid of plant origin, characterized in that:
[0020] - 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
[0021] - the content of at least one phospholipid of plant origin, such as phosphati- dylcholine, is between 10% and 90% by mass relative to the mass of composition.
[0022] The object of the present invention thus relates to a method for manufacturing a composition according to the present invention comprising the following successive steps:
[0023] (a) obtaining an oil enriched in DHA and / or EPA in the form of glyceride(s), such than a triglyceride;
[0024] b) addition of at least one phospholipid of vegetable origin.
[0025] The oil extraction step from a microorganism, such as a microalga, is carried out by heating a suspension of microorganisms, such as microalgae, preferably ground, under vacuum, for example at 45-50°C, or even up to 60°C. Thus, at the end of fermentation, the cell walls are lysed using an enzyme (advantageously a protease) to release the fat, which is then recovered by centrifugation.
[0026] The object of the present invention also relates to a composition according to the present invention for its use as a medicinal product, preferably as a food supplement.
[0027] The object 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 related to one or more EPA-related disorders.
[0028] The object of the present invention relates more particularly to a composition as described herein for its use as a form of DHA intake for brain development, 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", it is included in the scope of the present invention the esters of glycerol with docosahexaenoic acid (DHA) and / or eicosapentaenoic acid (EPA). The glycerides may be mono-glycerides, diglycerides or triglycerides of DHA and / or EPA.
[0031] By "DHA and / or EPA in the form of ethyl ester(s)", it is understood in the context of the present invention to mean an ethanol molecule linked to DHA and / or EPA via an ester bond, i.e. DHA and / or EPA with a -COOEt group.
[0032] For the purposes of this invention, "derived from at least one microorganism, such as a microalga" means that the origin of the DHA and / or EPA in the form of glyceride(s), such as a triglyceride, is from at least one microorganism, such as a microalga. In other words, the origin of the DHA and / or EPA in the form of glyceride(s), such as a triglyceride, is traceable at each stage of the processes used to obtain the composition according to this invention.
[0033] For the purposes of this invention, "at least one phospholipid of plant origin" means that said at least one phospholipid is derived from at least one plant. In other words, the origin of the phospholipid is traceable at each stage of the processes used to obtain the composition according to the present invention.
[0034] For the purposes of this invention, "DHA and / or EPA enriched oil" means 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.
[0035] By "pathologies involving a deficiency in DHA and / or EPA", it is understood that The scope of the present invention includes pathologies linked, for example, to cardiovascular risk (thrombosis, excessive levels of triglycerides and / or cholesterol in the blood, low blood pressure), to ocular fragility (related in particular to the retina), or to neurological pathologies (such as depression, neurodegenerative diseases such as Alzheimer's disease or epilepsy).
[0036] By "brain development", it is understood in the context of the present invention to mean neural development, or in other words the process of morphological and functional maturation of the brain. DETAILED DESCRIPTION
[0037] • Composition:
[0038] The present invention therefore relates to the composition described above, its method of 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 microalga, is chosen from the list consisting of a Traustochytride, such as Shizochytrium sp or Crypthecodinium cohnii, Nannochloropsis, Isochrysis, Phaeodactylum or Nitzchia. Indeed, there are strains of microalgae, such as Crypthecodinium cohnii, Nannochloropsis, Isochrysis, Phaeodactylum or Nitzchia, which can produce PLs predominantly in PCs, with even di-DHA PCs;
[0041] - said at least one phospholipid of plant origin is chosen from the list consisting in sunflower oil, canola oil, soybean oil and their mixtures;
[0042] - preferably, said at least one phospholipid of plant origin is a vegetable extract chosen from the list consisting of sunflower oil and soybean oil.
[0043] - preferably, the phospholipid of plant origin is rich in lecithin and / or in phosphatidylcholine. Indeed, phosphatidylcholine seems to have an effect on the blood-brain barrier: it facilitates the passage of active ingredients;
[0044] - the composition further comprises DPAn-6;
[0045] - the content of DPAn-6 is between 0.1% and 20% by mass relative to weight total composition;
[0046] - the sum of the DHA contents in the form of glyceride(s), such as a triglyceride, derived from at least one microorganism, such as a microalga, and the content of phospholipid(s) of plant origin is greater than or equal to 50% by mass relative to the total weight of composition;
[0047] - the EPA content is between 10% and 90% by mass relative to the total weight composition;
[0048] - the DHA content is between 10% and 90% by mass relative to weight total composition;
[0049] - the DHA:EPA ratio is between 1:100 and 100:1 by mass, respect tively;
[0050] - said composition further comprises at least one antioxidant, the content of which is between 0.001% and 2% by mass relative to the total weight of composition;
[0051] - the antioxidant is chosen from the following list: carotenoids, astaxanthin, the zeaxanthin, and lutein, preferably astaxanthin;
[0052] - the composition comprises at least one triglyceride with chain fatty acids short MCTs with a concentration preferably between 1% and 50% by mass, such as 20% plus or minus 5% by mass; and / or
[0053] - the composition is a food composition, preferably vegan.
[0054] More specifically, the composition according to the present invention may have the following characteristics.
[0055] In the current context of the strong trend of "vegan" diets, the composition according to the present invention is optimally suited for an intake of DHA and / or EPA of microalgal origin and phosphatidylcholine (PC) (i.e. also an intake of choline) promoting the cerebral accretion of DHA.
[0056] Thus, the object 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.
[0057] Thus, microalgal oils containing DHA, for example based on shizo-chytrium, or the EPA fraction after fractionation of EPA and DHA oil which contains some DHA, are characterized by the presence of n-6 DPA. n-6 DPA is not present in fish oils (or very weakly <0.3% of fatty acids), characteristic of microalgal oils (for example, base oils at 400 mg of DHA / g of oil contain about 80 g of n-6 DPA / g of oil).
[0058] 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%, or 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.
[0059] 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.
[0060] It should be noted that in the case of phospholipids with a lower PC content, more will need to be added to reach the above quantities, and therefore the quantity of DHA will be less. Thus, for oils rich in EPA, there is very little n-6 DPA.
[0061] Certain microalgal 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) or C22:1 docosenoic acid (C22:1 W9 erucic and C22:1 W1 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).
[0062] Thus, in a particular embodiment, the composition (which may be vegan) according to the present invention comprises:
[0063] - of 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
[0064] - of docosenoic acid C22:1 in a content less than or equal to 5%, preferably less than or equal to 1%, relative to the total weight of composition.
[0065] Preferably, the composition (which may be vegan) according to the present invention is:
[0066] - free from C20:1 eicosenoic acid; and / or
[0067] - free of docosenoic acid C22:1.
[0068] 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, from at least one microorganism, such as a microalga, 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%.
[0069] In a particular embodiment, the EPA content included in the composition (which may be vegan) according to the present invention is between 10 and 70%, preferably between 20% and 60% by mass relative to the total weight of the composition, for example between 30% and 50%, between 35% and 40% such that 37.5% plus or minus 2% by mass relative to the total weight of the composition.
[0070] In a particular embodiment, the DHA content included in the composition (which may be vegan) according to the present invention is between 20% and 80% by mass relative to the total weight of the composition, for example between 30% and 70%, between 40% and 60% such that 50% plus or minus 5% by mass relative to the total weight of the composition.
[0071] In a particular embodiment, the composition (which may be vegan) according to the present invention comprises a DHA:EPA ratio of between 1:9 and 75: 1 in 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 in mass.
[0072] 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 that 0.8% plus or minus 0.05% by mass relative to the total weight of the composition.
[0073] In a particular embodiment, the object of the present invention relates to a composition (which may be vegan) comprising between 10% to 90% by mass of DHA from a microorganism, such as a microalga, and between 10% to 80% by mass of phosphatidylcholine.
[0074] In a particular embodiment, the object of the present invention relates to a composition (which may be vegan) comprising 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.
[0075] Preferably, the object 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 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.
[0076] In a particular embodiment, the object of the present invention relates to a composition (which may be vegan) comprising between 10% to 90% by mass of EPA from a microorganism, such as a microalga, and between 10% to 80% by mass of phosphatidylcholine.
[0077] Preferably, the object 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 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.
[0078] In a particular embodiment, the object of the present invention relates to a composition (which may be vegan) of DHA and / or EPA derived from a microorganism, such as a microalga, comprising phosphatidylcholine and at least one antioxidant, such as astaxanthin, at least one carotenoid, zeaxanthin, the lutein, vitamin E, for example tocopherol acetate or tocotrienol; vitamin C or one of its analogues, natural polyphenols.
[0079] In a particular embodiment, the object of the present invention relates to a composition (which may be vegan) of DHA and / or EPA derived from a microorganism, such as a microalga, with a chlorophyll content of 5% or less by mass, preferably 4% or less, 3% or less, 2% or less, or 1% or less. More preferably, the vegan composition of DHA and / or EPA derived from a microorganism, such as a microalga, is chlorophyll-free.
[0080] In a particular embodiment, the object 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 5% or less by mass, preferably 4% or less, 3% or less, 2% or less, or 1% or less. More preferably, the vegan composition of DHA and / or EPA from a microorganism, such as a microalga, and phosphatidylcholine is chlorophyll-free.
[0081] In a particular embodiment, the object of the present invention relates to a composition (which may be vegan) of DHA and / or EPA derived 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%, or less than or equal to 1%. More preferably, the vegan composition of DHA and / or EPA derived from a microorganism, such as a microalga, is free of glycolipids.
[0082] In a particular embodiment, the object 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 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%, or less than or equal to 1%. More preferably, the vegan composition comprising DHA and / or EPA from an alga or microalga and phosphatidylcholine is free of glycolipids.
[0083] Indeed, glycolipids do not come from microalgal oil obtained from their heterotrophic culture.
[0084] In a particular embodiment, the object 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 at least one triglyceride with short-chain fatty acids (MCTs), i.e., C1-C10, preferably, in C2-C8, or even C4-C6.
[0085] In a particular embodiment, the object 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 (MCTs), i.e. C1-C10, preferably C2-C8, or C4-C6.
[0086] Indeed, triglycerides with short-chain fatty acids (MCTs) can exhibit ketogenic activity, which is advantageous in certain brain disorders. Short-chain fatty acids can thus become the brain's energy source.
[0087] By way of illustration, in the case of Alzheimer's disease, the use of glucose (supplied via the digestive system) is reduced in the brain. MCTs then act as an energy source for the brain. Thus, in certain pathologies such as Alzheimer's disease or at the extremes of age, it appears that the brain's energy supply is dysregulated or inefficient. In the case of Alzheimer's disease, the brain's reduced uptake of glucose for energy is impaired. This reduction appears before the onset of cognitive decline and before the decrease in neuronal function. Beta-amyloid (present in aggregates with Alzheimer's disease) has shown inhibitory activity on pyruvate dehydrogenase, thus limiting the production of acetyl-CoA, the fuel for the Krebs cycle for energy production. The ketogenic pathway to compensate for the glucose energy deficit becomes particularly relevant.Medium and short chain fatty acids are ketogenic. They are broken down by the mitochondria of the liver into ketone bodies (acetoacetate, β-hydroxybutyrate) which, transported to the brain by the blood, are used as an alternative fuel by regenerating acetyl CoA, which is then available for the Krebs cycle and energy production.
[0088] The addition of these medium-chain fatty acids (MCFAs) to the formulation is a significant advantage. This can be in their fatty acid form or in triglyceride form (such as MCTs). Furthermore, these MCFAs have the advantage of being rapidly absorbed and transported to the liver compared to longer-chain fatty acids, which require activation via the camitin system. Capric acids, and more specifically caprylic acids, are preferred.
[0089] Preferably, the object 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 at least one triglyceride with short-chain fatty acids (MCTs) with a rate 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.
[0090] Preferably, the object 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 (MCTs) with a rate 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.
[0091] In a particular embodiment, the object of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA derived from a microorganism, such as a microalga, characterized in that this composition is adapted to allow for increased 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 (micro- / nano-) oil-in-water or water-in-oil emulsion.
[0092] Preferably, the composition according to the invention is a self-emulsifying composition.
[0093] Preferably, the composition according to the invention is an oil-in-water emulsion.
[0094] Preferably, the object 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 suitable for self-emulsification, i.e. the composition emulsifies without external mechanical input.
[0095] In a particular embodiment, the object of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA derived from a microorganism, such as a microalga, and phosphatidylcholine, characterized in that this composition is adapted to allow for increased 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 (micro- / nano-) oil-in-water or water-in-oil emulsion.
[0096] Preferably, the object of the present invention relates to a composition (which may be vegan) comprising DHA and / or EPA and derived from a microorganism, such as a microalga, and phosphatidylcholine, characterized in that this composition is suitable for self-emulsification.
[0097] In a particular embodiment, the object 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.
[0098] Preferably, the food composition (which may be vegan) according to the present invention may be in a pre-dosed form.
[0099] Preferably, the food composition (which may be vegan) according to the The present invention may take the form of a capsule, a tablet, an encapsulated liquid or a liquid contained in an ampoule. • Obtaining processes
[0100] Oils enriched with DHA and / or EPA may be commercial (marketed for example under the brand name Omegavie Algae oils® of the company Polaris).
[0101] However, the following three procedures (referred to below as "options") allow the oils enriched in DHA and / or EPA to be obtained.
[0102] The first option (as illustrated in Example 1 below) consists of a process comprising the following steps: - (al) 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,
[0103] - (bl) a step of concentration of omega-3 polyunsaturated fatty acids by dis high-vacuum molecular tillation in a scraped-film evaporator coupled to a rectification column with at least seven theoretical plates, thus allowing DHA to be obtained in the form of ethyl esters (EE); and
[0104] - (cl) a step of converting DHA to glycerides comprising the steps additional (dl) and (el):
[0105] - (dl) a step of restructuring monoglycerides, diglycerides and triglycerides of omega-3 polyunsaturated fatty acids in the presence of enzyme and glycerol; and
[0106] - (el) a short path molecular distillation step under vacuum.
[0107] An illustration of this first option is given in example 1.1 below.
[0108] The second option (as illustrated in Example 2 below) consists of a process for enriching with DHA or EPA starting from the same source as Option 1. In particular, the process according to Option 2 is a process for fractionating fatty acids with a two-carbon difference by molecular distillation (including fractionation between EPA and DHA), characterized in that it comprises the following steps:
[0109] (a2) a reaction step between an oil of microorganisms comprising omega-3 polyunsaturated fatty acids in the form of triglycerides and an alcohol in the presence of a chemical or enzymatic catalyst;
[0110] (b2) a (e.g., 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 trays, and recovery of a first residue and a (first) distillate;
[0111] (c2) a subsequent step (e.g., second) of vacuum molecular distillation pushed, of the residue recovered in step (b2), into said scraped film evaporator coupled to the rectification column comprising at least seven theoretical trays, and recovery of a second residue and a (second) distillate;
[0112] (d2) an optional step of restructuring monoglycerides, diglycerides and sorting glycerides of omega-3 polyunsaturated fatty acids in the presence of enzyme and glycerol; and
[0113] (e2) a short path molecular distillation step under vacuum.
[0114] The two steps (b2) and (c2) allow the separation of DHA from EPA. With a single This step doesn't seem possible. The equipment (7 trays) appears to be the determining factor.
[0115] At step (c2), DHA and EPA are in the form of ethyl esters. It is therefore possible to convert them back into diglycerides.
[0116] An illustration of this second option is given in example 1.2 below.
[0117] The third option (as illustrated in Example 3 below) consists of a process for enriching an oil with EPA comprising the following steps:
[0118] (a3) a reaction step between an oil of microorganisms comprising EPA and an alcohol in the presence of a chemical catalyst;
[0119] (b3) a step of concentration and purification of fatty acid ethyl esters including ethyl esters of EPA by short-path molecular distillation under high vacuum;
[0120] (c3) a step of concentration of eicosapentaenoic acid by distillation mo lecular on rectification column;
[0121] (d3) a step of restructuring monoglycerides, diglycerides and triglycerides of omega-3 polyunsaturated fatty acids in the presence of enzyme and glycerol; and
[0122] (e3) a short path molecular distillation step under vacuum.
[0123] The starting oil in step (a3) can be, for example, a microalgae oil of the genera Nannochloropsis, Isochrysis, Phaeodactylum or Nitzchia.
[0124] An illustration of this third option is given in example 1.3 below.
[0125] In step (e3) of the process, EPA in the form of ethyl esters (EE) is obtained.
[0126] It is possible to put it in the form of glycerides by adding the following steps:
[0127] (f3) a step of restructuring monoglycerides, diglycerides and triglycerides of omega-3 polyunsaturated fatty acids in the presence of enzyme and glycerol; and
[0128] (g3) a short path molecular distillation step under vacuum.
[0129] Another aspect of the present invention relates to a method for manufacturing a composition such as the one described above. This method may comprise the following successive steps:
[0130] (a) obtaining an oil enriched in DHA and / or EPA in the form of glyceride(s), such than a triglyceride, for example by any of the processes mentioned above;
[0131] (b) the addition of at least one phospholipid of plant origin.
[0132] Any addition technique applicable in this case may be used. Preferably, DHA and / or EPA oils and at least one phospholipid of origin The plant-based ingredients are mixed at high speed and / or for a sufficient time to achieve adequate homogeneity of the mixture. In particular, a gradual vacuum can be applied while heating and stirring until the phospholipid is completely dissolved in the mixture.
[0133] In particular, DHA and / or EPA oils and at least one phospholipid of vegetable origin are mixed under vacuum to avoid their oxidation or more generally the incorporation of gas into the mixture.
[0134] Preferably, the process includes 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 being mixed under vacuum, to a temperature between 5°C and 60°C, preferably between 45°C and 50°C.
[0135] Advantageously, the process includes 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 an inert gas, such as nitrogen, or preferably under vacuum. • Applications
[0136] The object 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.
[0137] In particular, the intake of PC and DHA will allow the body to synthesize Lyso-PC-DHA which is a preferred molecular form of DHA vectorization to the brain in particular (PC is also a source of choline).
[0138] Preferably, the object 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 aged 40 years or older, 45 years or older, 50 years or older, 55 years or older, 60 years or older, 65 years or older, 70 years or older, 75 years or older, 80 years or older, 85 years or older, 90 years or older, or 95 years or older.
[0139] In a particular embodiment, the object of the present invention relates to a composition as described herein for its use in the treatment of cardiovascular disorders.
[0140] Preferably, the object of the present invention relates to a composition as described herein for its use in the treatment of cardiovascular disorders in a patient aged 40 years or older, 45 years or older, 50 years or older, 55 years or older, 60 years or older years, 65 years or older, 70 years or older, 75 years or older, 80 years or older, 85 years or older, 90 years or older, or 95 years or older.
[0141] Preferably, the object of the present invention relates to a composition as described herein for its use in the treatment of thrombosis.
[0142] Preferably, the object of the present invention relates to a composition as described herein for its use in the treatment of thrombosis in a patient aged 40 years or older, or 45 years or older, aged 50 or older, aged 55 or older, aged 60 or older, aged 65 or older, aged 70 or older, aged 75 or older, 80 years or older, 85 years or older, 90 years or older, or still over or equal to 95 years old.
[0143] Preferably, the object of the present invention relates to a composition as described herein for its use in the treatment of disorders related to excessive levels of triglycerides and / or cholesterol in the blood.
[0144] Preferably, the object of the present invention relates to a composition as described herein for its use in the treatment of disorders related to excessive levels of triglycerides and / or cholesterol in the blood, in a patient aged 40 years or older, 45 years or older, 50 years or older, 55 years or older, 60 years or older, 65 years or older, 70 years or older, 75 years or older, 80 years or older, 85 years or older, 90 years or older, or 95 years or older.
[0145] In a particular embodiment, the object of the present invention relates to a composition as described herein for its use in the treatment of disorders related to ocular fragility, in particular having a link with the retina.
[0146] In a particular embodiment, the object of the present invention relates to a composition as described herein for its use in the treatment of macular degeneration, particularly age-related macular degeneration. Indeed, PC-DHA intake is also important from a very young age and during gestation for the development of the retina (visual acuity). Thus, one of the objectives of the present invention may be to provide PC-DHA to the mother and also to the infant through the administration of the composition according to the present invention.
[0147] Preferably, the object of the present invention relates to a composition as described herein for its use in the treatment of disorders related to ocular fragility, in particular those related to the retina, such as macular degeneration, particularly age-related macular degeneration, in a patient aged 40 years or older, 45 years or older, 50 years or older, or older. at 55 years, 60 years or older, 65 years or older, 70 years or older, 75 years or older, 80 years or older, 85 years or older, 90 years or older, or 95 years or older.
[0148] In a particular embodiment, the object 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.
[0149] Preferably, the object 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 a sclerosis, such as amyotrophic sclerosis.
[0150] Preferably, the object 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 a sclerosis, such as amyotrophic sclerosis, in a patient aged 40 years or older, 45 years or older, 50 years or older, 55 years or older, 60 years or older, 65 years or older, 70 years or older, 75 years or older, 80 years or older, 85 years or older, 90 years or older or 95 years or older.
[0151] In a particular embodiment, the object of the present invention relates to a composition as described herein for its use in the treatment of a patient aged 40 years or older, 45 years or older, 50 years or older, 55 years or older, 60 years or older, 65 years or older, 70 years or older, 75 years or older, 80 years or older, 85 years or older, 90 years or older, or 95 years or older.
[0152] Preferably, the object of the present invention relates to a composition as described herein for use in the treatment of a patient over 60 years of age with a pathology or risk selected from among cardiovascular disorders, thrombosis, disorders related to excessively high levels of triglycerides and / or cholesterol in the blood, disorders related to ocular fragility, disorders related 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 multiple sclerosis. EXAMPLES
[0153] Some embodiments of the present invention will be described below by way of non-limiting examples.
[0154] Example 1: Process for obtaining microalgae oils
[0155] Example 1.1.: concentration of a microalgae oil in DHA predominantly in the form of glycerides.
[0156] This is the process for manufacturing an oil according to option 1 described above. This process is detailed in patent document FR3103355.
[0157] The process is implemented using crude oil produced by the microalgae strain Schizochytrium sp T18 marketed by Mara Renewables Corporation.
[0158] The oil initially contains 329 mg / g of DHA. The objective here is to at least double the DHA concentration.
[0159] Step (i): transesterification
[0160] A transesterification reaction is carried out on a biomass of 1800 kg of microalgae oil using 450 kg of ethanol and 21.6 kg of sodium ethoxide, in a suitable reactor.
[0161] The reaction temperature is 50°C and the reaction time is 1 h. After the reaction, the excess ethanol is evaporated under vacuum, then the mixture is cooled to a temperature of approximately 30°C and allowed to settle for 1 h. The light phase is collected, and the glycerol is drained off. A second settling is carried out for 30 seconds. The residual glycerol and monoglycerides are drained off.
[0162] An acid 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 time exceeding 2 hours.
[0163] At the end of this step, the oil contains 329 m / g of DHA in the form of ethyl esters.
[0164] Step (ii): Concentration of DHA by molecular distillation
[0165] The oil is then conveyed to a deaerator and subsequently passes through a scraped-film evaporator. The vapors are then distilled through a rectification column coupled to the evaporator supplied by UIC GmbH. Refluxing the distillate, i.e., reintroducing the distillate into the column, can increase its separation efficiency. The column used contains approximately seven theoretical plates. The distillation residue is recovered and represents the fraction enriched in DHA.
[0166] The operating conditions are as follows: Evaporator temperature: 225°C; Rectification column vacuum: 0.1 mbar; Reflux rate 75%, Temperature (top of column): 195°C.
[0167] 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.
[0168] [Table 1] Fatty acid composition before step (i) Fatty acid composition after step (ii) C4:0 1.867 - C6:0 1.808 - C12:0 7.542 - C14:0 89.582 4.428 C15:0 2.478 - C16:0 153.76 10.206 C16:1 69.696 5.611 C18:0 6.133 - C18:1 n9 cis 19.555 8.442 C18:1 n7 cis 89.271 17.745 C18:2 n6 cis 10.651 3.487 C20:4 n3 3.055 5.572 EPA 11.294 18.856 C22:5 n6 55,904 125,453 DHA 329,162 757,958
[0169] More than 97% of the DHA is 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.
[0170] Step (iii): synthesis of triglycerides, diglycerides and monoglycerides
[0171] The reaction takes place in a reactor in the presence of immobilized enzyme. This is a lipase from fraction B of Candida antarctica (marketed under the name Lipozym 435 by the company Novozym).
[0172] 480 g of distillation residue containing approximately 758 mg / g of DHA, 33 g of glycerol and 20g of enzyme are introduced into the reactor.
[0173] The reaction takes place under moderate stirring, at a controlled temperature of around 60°C, under vacuum with evaporation and condensation of the ethanol generated. The reaction time is 25 hours.
[0174] The reaction yield is over 95%.
[0175] At the end of this step, the oil has the following glyceride profile (Table 2):
[0176] [Tables2] Ethyl esters Monoglycerides Diglycerides Triglycerides 8.6% 5.7% 35.8% 49.9%
[0177] Step (iv): Short path molecular distillation
[0178] After synthesis, the product is taken up for passage in a short path distiller (marketed by UIC GmbH) to eliminate residual ethyl esters, odorous volatiles but also to inactivate any potential residual enzymatic activity.
[0179] 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 for a lower distillation temperature.
[0180] At the end of this step, the oil has the profile shown in Table 3:
[0181] [Tables3] Compounds Units Values (Example 1) DHA mg / g 758 Saturated fatty acids (SFA) mg / g 15 Triglycerides (TG) % 63 Diglycerides (DG) % 36 Monoglycerides (MG) % 2 Ethyl esters / free fatty acids (EE / FFA) mg / g 1.2 EPA mg / g 20 ETA n-3 mg / g 6 DPA n-6 mg / g 105
[0182] Example 1.2: EPA / DHA fractionation by molecular distillation and obtaining microbial oil compositions enriched in eicosapentaenoic acid and docosahexaenoic acid
[0183] This is the process for manufacturing an oil according to option 2 described above. This process is detailed in patent document FR3108622.
[0184] The process according to the invention is implemented using crude oil produced by the microalgae strain Schizochytrium sp marketed by the company DSM under the brand name Life's DHA 60.
[0185] The oil profile is as follows:
[0186] - 360 mg / g of DHA, in mg / g of composition,
[0187] - 184 mg / g of EPA, in mg / g of composition,
[0188] - 94.1% triglycerides,
[0189] - 5.4% diglycerides,
[0190] - 0.4% monoglycerides.
[0191] The objective here is at least to double the concentration of EPA and DHA.
[0192] Step (i): transesterification
[0193] A transesterification reaction is carried out on a biomass of 19 kg of microalgae oil using 4.75 kg of ethanol and 222 g of sodium ethoxide, in a suitable reactor.
[0194] The reaction temperature is 50°C and the reaction time is 1 h. After the reaction, the excess ethanol is evaporated under vacuum, then the mixture is cooled to a temperature of approximately 30°C and allowed to settle for 1 h. The light phase is collected, and the glycerol is drained off. A second settling is carried out for 30 seconds. The residual glycerol and monoglycerides are drained off.
[0195] An acid 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 drying under vacuum (pressure < 90 mbar) at 60°C for a time exceeding 2 hours.
[0196] At the end of this step, the oil contains 192 mg / g of EPA and 374 mg / g of DHA in the form of ethyl esters.
[0197] Step (ii): first molecular distillation step
[0198] The oil is then conveyed to a deaerator and subsequently passes through a scraped-film evaporator. The vapors are then distilled through a rectification column coupled to the evaporator supplied by UIC GmbH. The aim here is to remove the lighter fatty acids while retaining the DHA and EPA. The column used contains seven theoretical plates. The distillation residue is collected and represents the fraction enriched in EPA and DHA.
[0199] 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.
[0200] 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%.
[0201] Step (iii): Second molecular distillation step
[0202] The operation of step (II) is repeated on the residue. The residue is then returned to the degasser and subsequently passes through the scraped-film evaporator. The vapors are then distilled through the rectification column coupled to the evaporator, as in the previous step (ii). The aim here is to separate the DHA and the EPA.
[0203] 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.
[0204] 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% for EPA and 4% for DHA. The residue fraction contains 706 mg / g of DHA and 83 mg / g of EPA. The yield of this fraction is 93% for DHA and 22% for EPA.
[0205] In Table 4 below, the detailed fatty acid profile of the distillate and residue fractions obtained at the end of step (iii) is shown (in mg / g of composition).
[0206] [Tables4] RESIDUE DISTILLATE C14:0 0 0 C15:0 0 0 C16:0 5.3 0 C18:0 13.5 0 C18:1 n9 cis 27.6 0 C18:2 n6 cis 2.6 0 C20:0 12.2 3.5 C20:3 n6 2.1 0.3 C21:0 5.0 0 C20:1 n7 0.0 0.3 C20:4 n6 54.9 4.4 C20:3 n3 5.9 0 UNKNOWN 0.0 0 UNKNOWN 1.8 0.8 C20:4 n3 22.4 3.7 EPA 733.4 83.2 C22:0 0 2.6 UNKNOWN 5.0 5.2 C22:4 n6 0.0 0 C22:5 n6 4.4 30.7 UNKNOWN 0.0 1.8 C22:5 n3 5.9 85.3 DHA 70.1 730
[0207] Example 1.3: Obtaining microalgae oil containing EPA
[0208] This is the process for manufacturing an oil according to option 3 described above.
[0209] The starting oil is a crude oil produced by the Nannochloropsis sp. strain obtained after culturing the biomass for approximately eight days under photoautotrophic conditions. The fat is extracted from the biomass by ethanolic maceration. After separation of the remaining solid phase, the ethanol is evaporated under empty.
[0210] EPA produced by photoautotrophy is incorporated into membrane lipids, either as glycolipids, phospholipids, or free fatty acids. The triglyceride form is not very common.
[0211] Step (i): transesterification
[0212] A transesterification reaction is carried out on 100 kg of microalgae oil biomass using approximately 200 kg of ethanol and 10 kg of sulfuric acid, in a suitable reactor (reflux 60°C > 100°C). The transesterification is carried out via an acidic route, using sulfuric acid.
[0213] Step (ii): EPA concentration by short path molecular distillation under vacuum
[0214] The conditions are an evaporator wall temperature between 175 and 180°C and a vacuum of less than 0.1 mbar.
[0215] 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.
[0216] The amount of EPA in the form of ethyl esters is 735 mg / g.
[0217] Examples of compositions according to the present invention
[0218] Vegetable oils used: - Soybean oil 50% PC - Sunflower oil 90% PC - Non-concentrated Schizochitrium sp. oil: 40% DHA - Concentrated Schizochitrium sp. oil: 70% DHA - Schizochitrium sp. oil rich in EPA and DHA: 20% EPA and 30% DHA - Palm oil with short-chain triglycerides (MCTs) - 10% concentrated astaxanthin
[0219] Method for manufacturing a composition according to the present invention: - Adding the different elements into the same container - Agitation and gradual vacuum sealing - Heat the mixture while stirring until a homogeneous mixture is obtained - Restoration to atmospheric pressure by adding inert gas
[0220] Table 5: Summary table of the compositions obtained:
[0221] [Tables5] Composition Ingredients Proportions (by mass) A Unconcentrated Schizochytrium s oil according to manufacturing process XX 50% Soybean oil 50% PC 50% B Concentrated Schizochytrium s oil according to manufacturing process XX 49.9% Soybean oil 50% PC 50% Astaxanthin 0.1% C Unconcentrated Schizochytrium s oil according to manufacturing process XX 20% Concentrated Schizochytrium s oil according to manufacturing process XX 57% Sunflower oil 90% PC 22.9% Astaxanthin 0.1% D Concentrated Schizochytrium s oil according to manufacturing process XX 25% Soybean oil 50% PC 60% Palm oil with short-chain triglycerides 15% E Schizochytrium sp oil rich in EPA and DHA: 20% EPA and 30% DHA 17% Oil Schizochytrium concentrate according to manufacturing process XX 60% Sunflower oil 90% PC 19.9% Astaxanthin 0.1%
[0222] Comparative example between a composition according to the present invention and a composition according to the prior art
[0223] Table 6: Composition C vs krill oil
[0224] [Tableauxô] Composition of Krill Oil: Phospholipid Fraction: Min 30% by mass, 40% by mass; Phosphatidylis: Min 25% by mass, 30% by mass; EPA: Min 5 mg / g as triglycerides, Min 120 mg / g; DHA: Min 340 mg / g as triglycerides, Min 55 mg / g; Total Omega-3: Min 345 mg / g, Min 220 mg / g; Astaxanthin: 10 mg / 100g, 10 mg / 100g
[0225] It has been found that the amount of phosphatidylcholine in composition C is sufficient to produce emulsifying properties similar to krill oil.
[0226] Composition C has higher levels of DHA. The EPA level can be increased if necessary. Thus, the levels of DHA and EPA can be adjusted according to the intended treatment.
[0227] The amount of astaxanthin can also be modified depending on the intended treatment.
[0228] It can nevertheless be noted that composition C includes 6 times more DHA and 1.5 times more omega 3 than krill oil.
[0229] Example 3: In vivo tests in rats: the supposed mechanism of action
[0230] 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 delivery of DHA to target tissues.
[0231] It is well known that after food intake, phospholipase A2 is very rapidly activated. Ingested phospholipids undergo rapid hydrolysis. DHA, being naturally in Sn-2 form, is released as a free fatty acid. This is then available for intestinal absorption.
[0232] Several studies have shown better incorporation of DHA into erythrocytes when it is administered as 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, the TG or Mono were not supplemented with plant-based PL.
[0233] Phospholipids are amphiphilic molecules, giving them self-emulsifying properties, similar to what occurs during the digestion of fatty acids. Emulsification is well known to improve intestinal absorption of Fatty acids in humans (Raatz SK et al., J of Am. Diet. Ass., vol. 109, 2009; Couëdelo L. et al., Food Funct. Vol. 6, 2015; Couëdelo L. et al., OCL, vol. 24, 2017; Ottestad I. et al., J. of Nutr. Sci., Vol. 5, 2016). Thus, lecithin intake improves the emulsification of lipids or fatty acids and their plasma bioavailability.
[0234] A study with DHA oils in triglyceride form supplemented with plant phospholipids (PC) compared to a phosphatidylcholine-DHA regimen extracted from cod roe (Arctic Nutrition AS- brand Romega®) with identical DHA intake, showed equivalent plasma bioavailability of DHA (identical DHA content) 10 hours after administration. Looking at the DHA levels in the plasma phospholipid fraction, a slight superiority of DHA content was noted with the PC-DHA regimen (+approximately 15%). Analyzing the distribution of DHA on the glycerol backbone of plasma phospholipids, it was observed that DHA is predominantly bound at the Sn-2 position (approximately 80% of DHA), with a very slight advantage for the PC-DHA regimen. With the TG-DHA and PL (PC) plant-based 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 PC-DHA sn-2 is indeed resynthesized in enterocytes before being released into the plasma.
[0235] A better delivery of DHA and / or EPA to the brain in a specific form has been determined here. Thus, the best known form of DHA, or even EPA, delivery 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 lyso-PC form are rare and expensive. They consist of krill oil and fish eggs. The present invention not only offers an alternative to these previous forms, but also provides 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
Claims
1. Vegan 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: - 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 phosphatidylcholine is between 10% and 90% by mass relative to the mass of the composition
2. Composition according to claim 1, characterized in that said at least one microorganism is chosen from the list consisting of a Traustochytrid, such as Shizochytrium sp or Crythecodinium cohnii, Nannochloropsis, Isochrysis, Phaeodactylum or Nitzchia.
3. 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.
4. Composition according to any one of the preceding claims, characterized in that the sum of the DHA contents in the form of glyceride(s), such as a triglyceride, derived from at least one microorganism and the phosphatidylcholine content are greater than or equal to 50% by mass relative to the total weight of the composition.
5. Composition according to any one of the preceding claims, characterized in that the DHA:EPA proportion is between 1:100 and 100:1 by mass, respectively.
6. 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 the composition and chosen from the following list: carotenoids, astaxanthin, zeaxanthin, and lutein, preferably astaxanthin.
7. Composition according to any one of the preceding claims, characterized in that the composition comprises at least one triglyceride with short-chain fatty acids MCT with a rate preferably between 1% and 50% by mass, such as 20% plus or minus 5% by mass.
8. Composition according to any one of the preceding claims, characterized in that the composition is a food composition, preferably vegan.
9. Composition according to any one of the preceding claims, for its use as a medicament, preferably as a food supplement.
10. 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 linked to one or more disorders linked to EPA.
11. A composition according to any preceding claim for use as a form of DHA supply for brain development.