FR3129295A1 - Deep eutectic solvent of supramolecular natural origin - Google Patents

Abstract

Supramolecular naturally occurring deep eutectic solvent comprising at least one acyclic polymerized naturally occurring carbohydrate (GPPa) and a plurality of different naturally occurring organic acids including malic acid and citric acid.

Description

Deep eutectic solvent of supramolecular natural origin

The present invention relates to the field of natural eutectic solvents, allowing the solubilization and the extraction of compounds of natural origin (for example of vegetable origin), as well as the obtaining of extracts (for example of vegetable extracts) at from raw material(s) of natural origin (for example from raw material(s) of plant, fungal, animal and/or microbial origin).

State of the art

In the field of extraction on an industrial scale (implementation, for example, in the chemical, food, pharmaceutical, cosmetics and perfumery, phytopharmaceutical industries), and in particular plant extraction, organic solvents from petrochemicals (known as "solvents of petrochemical origin" or "Volatile Organic Compounds (VOCs)") are widely used for the extraction of compounds, active principles or substances from raw material(s) of vegetable. Depending on the nature of the compounds, active principles or substances targeted, organic solvents, such as alcohols, hexane and ethyl acetate, are generally used in the extraction processes. However, these solvents can be toxic, flammable, explosive and/or poorly biodegradable.

In particular due to the above-mentioned issues, binding national and supranational regulations (such as Directive 1999/13/EC relating to VOC emissions, Directive 67/548/EEC relating to hazardous substances, Directive 1999/45/ EC, relating to dangerous products and, since June ¹ , 2007, the European regulation REACH ("Registration, Evaluation, Authorization and Restriction of Chemicals", in English language)) have come to regulate, in a strict manner, the use of solvents of petrochemical origin, leading to the need to substitute said solvents of petrochemical origin with alternative extraction solvents that are renewable and weakly toxic (or even devoid of toxicity), commonly referred to as “green solvents”. Moreover, in certain areas, such as that of liquid mixtures packaged in ampoules or single-doses, the regulations are even more restrictive concerning the solvent used, which is part of the final product consumed. Furthermore, with regard to products in solid/dry form resulting from the drying of plant extracts, the addition of technical agent(s) is generally necessary at the end of the process, in particular to facilitate drying. of the extract and/or following said drying, before carrying out the stage - or stages - of formulation strictly speaking. For example, the preparation of tablets from products in solid form resulting from the drying of plant extracts traditionally requires the addition of technical agent(s) - and more precisely of compression agent(s) - before to perform the compression step. The technical agents (for example one or more compression agents) thus used are more or less natural, which, if necessary, can give rise to problems of compatibility with the appropriate regulations in terms of biological products. In addition, the addition of such technical agent(s) before the formulation step(s) tends to complicate the formulation process as a whole, which is in particular likely to generate a significant overhead. Indeed, the person skilled in the art does not have, in the current state of knowledge, an extraction solvent which would integrate at least one technical agent, such as a compression agent, which, once the solvent has dried , would make it possible to obtain a solid dosage form—such as a tablet—having satisfactory pharmaco-technical properties.

Faced with the above-mentioned problems, those skilled in the art naturally turned to the use of water as a solvent to carry out the extraction of compounds of natural origin (and in particular of bioactive compounds). Indeed, water remains the safest solvent (i.e. the least toxic) and the least expensive. Nevertheless, its very polar character limits its power of solubilization to natural polar (hydrophilic) compounds, de facto excluding natural compounds that are not very polar (also called “compounds with intermediate polarity”) and apolar ones. Moreover, if one is interested in the extraction of bioactive compounds from plant raw material(s) (plant material), those skilled in the art know that the effectiveness of the use of water as extraction solvent will inevitably be affected by the poor diffusion of water in the plant tissue. For example, in the case of plants containing lipids or molecules that are apolar or of intermediate polarity, it is difficult - or even very difficult - for water to wet the surface of the plant and penetrate within the plant tissue, due to the non-miscibility and non-solvation of apolar molecules present in large quantities in the plant. Finally, the fact of using water as an extraction solvent would not make it possible to have a real support to carry out the compression of the dry matter obtained by drying of the corresponding extract, with a view to producing tablets.

In this search for alternatives to extraction solvents of petrochemical origin, other extraction solvents - and categories of extraction solvents - have been explored. In this regard, it is possible to cite, for example, the PCT application published under the reference WO 2018/122514 A1, which discloses the use of coconut water (whose Brix degree is between 4 and 6, at 20°C) as extraction solvent and the extracts obtained by extraction with this coconut water. It is also possible to mention a famous family of solvents, namely ionic liquids (ILs), consisting of liquid salts differing from all molten salts by a melting temperature below 100°C [1 ]. Many of them are liquid at room temperature. These ionic liquids consist of a cation, most often organic, associated with an organic or inorganic anion. They were first discovered by Paul Walden in 1914 in the case of ethylammonium nitrate, obtained by neutralization of ethylamine with concentrated nitric acid. Although LIs have interesting properties (non-flammability, thermal stability, low vapor pressure, etc.), they cannot however be considered as true "green" extraction solvents, in particular because of their low biocompatibility and biodegradability, as well as their toxicity [2] [3].

Since the early 2000s, deep eutectic solvents (SEPs; “Deep Eutectic Solvents” in English, whose acronym is DESs) have been developed. Generally defined as a sub-category of LIs ([4] and [5]), these SEPs consist of mixtures of at least two species which associate with each other by non-covalent intermolecular bonds (in particular by hydrogens). These interactions lead to an energy decrease characterized by the melting point of the mixture. The term “eutectic mixture” is used when the melting point of the mixture (or eutectic point), at a well-determined molar ratio, is lower than that of the two compounds of the mixture taken individually [6].

The properties of SEPs are similar to those of Lis (or close to them); the main advantages inherent in SEPs being their ease of preparation and the low cost of their constituents. Among these SEPs, we can cite choline chloride, which acts as a hydrogen bond acceptor (ALH), and makes it possible to form a eutectic mixture with most hydrogen bond donors (DLH). Thus, it is possible to cite a SEP formed by the mixture of choline chloride and urea (in a 1/2 molar ratio), which was historically one of the first SEPs demonstrated.

However, and although SEPs have already been tested with a view to extracting molecules of interest from plant raw material(s) (for example to extract quercetin and kaempferol, cf. [ 7]), it should be noted that the viscosity of these SEPs (and in particular of those comprising choline chloride such as ALH) remains problematic for natural extraction, and in particular plant extraction, to the point that certain systems require adding additive(s) such as water for use. Added to this is the absence of established proof concerning the non-toxicity of SEPs in comparison with “traditional” LI solvents, the toxicological profile of which has been widely questioned in the past. In addition, SEPs include ALHs compounds (such as choline chloride) and DLHs compounds obtained by synthetic chemistry, which does not guarantee safety (or at the very least compatibility with the appropriate regulations in with regard to organic products, see in particular EC regulation no. organic products with regard to organic production, labeling and controls - and its modifications/rectifications, as well as the new Regulation (EU) 2018/848, which entered into force on 1 ^January 2021), compounds and/or extracts obtained from natural raw material(s) (for example vegetable raw material(s)) by extraction using these SEPs.

This is why, in recent years, particular attention has been paid to SEPs consisting solely of natural molecules. The acronym "NADES" (for "Natural Deep Eutectic Solvents", the French translation of which is "deep eutectic solvent of natural origin" (SEPNa)) was proposed in the PCT application published under the reference WO 2011/155829 A1). WO 2011/155829 A1 discloses in particular an extraction process carried out from a biological material (for example of plant origin), implemented by means of an extraction agent consisting of a deep eutectic solvent of natural or an ionic liquid of natural origin. According to one embodiment, said deep eutectic solvent is defined as comprising the combination of at least two compounds, substantially without chemical or ionic bond, namely:

- a natural organic acid or an inorganic compound, and

- a natural mono- or dimeric sugar, a polyol, an amino acid, a di or trialkanol, or choline or its derivatives, such as phosphatidylcholine.

Different NADES and/or extraction processes including these NADES have subsequently been developed. By way of example, we can cite the teaching of the PCT application published under the reference WO 2016/162703 A1. The latter relates to a eutectic extraction solvent for extracting, for example, plant, animal and/or prokaryotic biological material, said eutectic extraction solvent being a mixture, described as transparent, stable and fluid, comprising:

(a) betaine or a hydrated form of betaine;

(b) at least one hydrogen bond donor compound selected from the group consisting of polyols and organic acids; And

(c) water provided that the eutectic extraction solvent does not contain exogenous sugar and/or amine salt and/or anion.

Even more recently, new SEPs have been described. The acronym "SUPRADES" for "Supramolecular Deep Eutectic Solvents", whose French translation is "Supramolecular deep eutectics solvents" (SEPsSup), was proposed in 2020 (cf. [8]). These SUPRADES are obtained by mixing a DLH with an ALH (the ALH being a cyclodextrin). These low melting temperature mixtures (e.g. at room temperature) are described as having a supramolecular structure. According to the authors, the SUPRADES thus obtained would make it possible to maintain the encapsulating properties of the cyclodextrins composing these SEPs. Soon after, the same research team discovered new SUPRADES made from various chemically modified cyclodextrins (cf. [9]). According to these authors, such SUPRADES would make it possible to solubilize trans-anethole by a factor of more than 1000 times greater than water. It is important to remember that these SUPRADES are obtained by mixing only a DLH (for example levulinic acid) with only an ALH (in this case a cyclodextrin). These mixtures therefore consist of 2 molecules (binary mixtures) between which a well-defined and limited number of hydrogen bonds are established. Finally, these SUPRADES based on the use of cyclodextrins, although presented as "green solvents", are likely not to comply with the appropriate regulations for biological products, insofar as the cyclodextrins themselves do not do not comply with the relevant regulations for organic products.

In light of the foregoing, there is therefore a significant need to design and develop new SEPNas:

i) making it possible to obtain a better efficiency of solubilization and/or extraction (advantageously of solubilization and extraction),

ii) capable of encapsulating - totally or partially - all or part of the compounds, active principles or substances targeted,

iii) satisfying the criteria of naturalness, biocompatibility and biodegradability - in order to guarantee consumer health safety and minimize the environmental impact associated with the use of such solvents,

iv) compatible with relevant regulations for organic products, and/or

v) of which at least one of the constituents plays the role of technical agent (for example of compression agent) - which moreover complies with the appropriate regulations in terms of biological products - thus avoiding the need to proceed with the addition of agent (s) conventional technique(s) (for example of compression agent(s)) at the end of the preparation process, within the framework of the development of a solid form traditionally requiring such an addition (for example during the tablet formulation process by compression, during the drying step or after it).

The present invention aims to meet this need. This relates to a naturally occurring eutectic solvent, in particular a naturally occurring deep eutectic solvent, such as a supramolecular naturally occurring deep eutectic solvent, said solvent comprising (or consisting essentially of or consisting of):

1. at least one acyclic polymerized naturally occurring carbohydrate (GNPa) (as compound ALH), and
2. a plurality of different naturally occurring organic acids, said plurality b) comprising malic acid and citric acid (as DLH compounds);

said at least one GNPa being selected from:

1. non-cyclic homogeneous oligosaccharides and/or polysaccharides,
2. non-cyclic heterogeneous oligosaccharides and/or polysaccharides, and
3. their mixtures.

Indeed, the inventors have discovered that the combination of constituents a) and b) as defined above made it possible to prepare a deep eutectic solvent of natural origin (such as a deep eutectic solvent of supramolecular natural origin) meeting the abovementioned need. .

The aforesaid oligosaccharides comprise from 2 to 10 saccharide residues, preferably from 3 to 10 saccharide residues (for example from 4 to 9 saccharide residues). The aforesaid polysaccharides, for their part, comprise at least 11 saccharide residues.

According to one embodiment, the aforesaid plurality of different organic acids of natural origin b) consists essentially of, or consists of, malic acid and citric acid.

According to one embodiment of the invention, the aforementioned plurality of different organic acids of natural origin b) also comprises tartaric acid.

According to one embodiment:

• said non-cyclic homogeneous oligosaccharides and/or polysaccharides are selected from: inulin, modified starches, preferably having a Dextrose Equivalent of less than 20, advantageously less than 20 and greater than or equal to 18, and mixtures thereof, and/or
• said non-cyclic heterogeneous polysaccharides are selected from acemannan and the non-cyclic heterogeneous polysaccharides of acacia gum (namely present within acacia gum), and mixtures thereof.

According to one embodiment of the invention, said at least one GNPa is at least "soluble in water" within the meaning of the European Pharmacopoeia (cf. definition below) and, preferably, at least "easily soluble in water” within the meaning of the said European Pharmacopoeia (see definition below). Advantageously, said at least one GNPa is “easily soluble in water” within the meaning of said European Pharmacopoeia (cf. definition below).

According to one embodiment of the invention, said at least one GNPa is selected from inulin, a maltodextrin, non-cyclic heterogeneous polysaccharides of acacia gum, acemannan (for example present in a powder of Aloe vera, such as a powder of Aloe vera leaf juice (preferably without HAD)) and mixtures thereof, preferably from a maltodextrin, the non-cyclic heterogeneous polysaccharides of acacia gum, acemannan and mixtures thereof; preferably said at least one GNPa consisting of a maltodextrin and/or acemannan.

According to one embodiment, the aforesaid eutectic solvent of natural origin according to the invention comprises at least one source of GNPa (comprising or consisting essentially of said at least one GNPa), such as for example acacia gum and/or an Aloe vera powder, such as an Aloe vera leaf juice powder (preferably without HAD).

According to one embodiment, the eutectic solvent of natural origin according to the invention further comprises:

c) a plurality of monosaccharides, preferably said plurality c) comprising glucose and/or fructose, advantageously both, and

d) optionally amino acids and/or vitamins.

The association between the constituents a) to c) or a) to d) makes it possible to obtain respectively ternary (a+b+c) or quaternary (a+b+c+d) systems which appear to further promote the solubilization of target compounds (typically compounds with intermediate polarity) in the solvent according to the invention, via the formation of supramolecular complexes characterized by the multiplicity of hydrogen bonds formed between the various ALH and DLH of these ternary or quaternary systems.

In addition to glucose and/or fructose, the aforementioned plurality of monosaccharides c) can comprise other monosaccharides such as mannose.

According to one embodiment, the solvent according to the invention comprises one or more disaccharides such as sucrose.

According to a particular embodiment, the eutectic solvent of natural origin according to the invention does not comprise any polyol.

According to one embodiment of the invention:

- said at least one GNPa represents at least 5% by mass, preferably at least 10% by mass (for example at least 20% by mass, 30% by mass, 40% by mass, 50% by mass), relative to the total mass of said solvent, and/or

- said plurality of different organic acids of natural origin b) represents at least 3% by mass, preferably at least 5% by mass, preferably at least 10% by mass, advantageously at least 20% by mass, relative to the total mass of said solvent.

According to one embodiment, the eutectic solvent of natural origin according to the invention comprises, essentially consists of, or consists of a mixture between said at least one GNPa and at least one ingredient of natural origin, said at least one ingredient of natural origin comprising said plurality of different organic acids of natural origin b). Preferably, said at least one ingredient of natural origin also comprises said plurality of monosaccharides c), when the latter is present in the solvent according to the invention. Advantageously, when the solvent according to the invention comprises amino acids and/or vitamins d), said at least one ingredient of natural origin comprises said amino acids and/or vitamins d). According to one embodiment of the invention, said at least one ingredient of natural origin comprises, in addition to said plurality of different organic acids of natural origin b), said plurality of monosaccharides c) and said amino acids and/ or vitamins d).

According to one embodiment of the invention, said at least one ingredient of natural origin is:

i) a fruit juice, for example a concentrated fruit juice, preferably a lemon, orange or apple juice, preferably a lemon or orange juice, advantageously a lemon juice; Or

ii) a mixture of fruit juices, for example a mixture of concentrated fruit juices, preferably a mixture of fruit juices selected from lemon, orange and apple juices, preferably a mixture of lemon and of orange juice.

The inventors have discovered that this embodiment proves to be particularly advantageous in that it makes it possible to obtain supramolecular deep eutectic solvents of natural origin that are particularly effective in terms of solubilization and/or extraction of the target compounds. More broadly, the inventors have discovered that the fact of using at least one ingredient of natural origin as defined in points i) and ii) above proved to be particularly advantageous in terms of increasing the power of solubilization and/or extraction observed during the implementation of the solvent according to the invention. Without being bound by theory, this can probably be explained by the fact that said at least one ingredient of natural origin represents a complex chemical environment, comprising in particular other primary metabolites such as amino acids, vitamins but also, and very interestingly, a plurality of carbohydrates other than glucose (fructose, sucrose, etc.) and a plurality of different natural organic acids (malic acid, citric acid, etc.). This complex chemical environment would explain, in all likelihood, the significant increase in the power of solubilization and/or extraction of an eutectic solvent of natural origin comprising it.

According to one embodiment, the eutectic solvent of natural origin according to the invention comprises exogenous water, for example distilled water, preferably in a mass percentage less than or equal to 90%, for example less than or equal at 80% or 75%, relative to the total mass of the solvent; preferably the exogenous water representing a mass percentage greater than or equal to 50% relative to the total mass of the solvent. In particular depending on the nature of the biological material (plant, fungal, animal and/or microbial material), the person skilled in the art will know whether it is appropriate to make an exogenous supply of water, under the conditions mentioned above, at the eutectic solvent of natural origin according to the invention.

A subject of the invention is also the use of a eutectic solvent of natural origin as defined previously, to solubilize and/or extract, preferably to solubilize and extract, for example by solid-liquid extraction such as the extraction by maceration, one or more compound(s) of a plant, fungal, animal and/or microbial material, preferably of a plant or fungal material, advantageously of a plant material.

According to one embodiment, the aforementioned use consists in dissolving, extracting and encapsulating (totally or partially) said one or more compound(s).

The invention also relates to a method for extracting one or more compound(s) from a plant, fungal, animal and/or microbial material, preferably from a plant or fungal material, advantageously from a plant material, said method comprising the following steps:

a) supply of plant, fungal, animal and/or microbial material,

b) bringing said plant, fungal, animal and/or microbial material into contact with at least one eutectic solvent of natural origin according to the invention for a sufficient period of time (for example between 30 and 90 minutes; duration easily determined by the person skilled in the art depending on the specific case), preferably with stirring, to allow the solubilization/extraction of said compound(s) and to obtain a liquid extract,

b') optionally separating, for example by pressing or by filtration, the liquid extract obtained in step b) and the residual plant, fungal, animal and/or microbial material, and

c) recovery, after step b) or step b′), when said step b′) is present, of the liquid extract, optionally after a purification step, for example by centrifugation.

According to one embodiment, at least one operation to reduce the size of the plant, fungal, animal and/or microbial material (advantageously plant, fungal and/or animal material) is carried out prior to step a). Preferably, said size reduction operation must be sufficiently successful to obtain a fine powder no longer containing coarse particles. In this embodiment, the liquid extract - comprising the target compound(s) in the solvent according to the invention - can optionally be recovered directly after step b).

Without being bound by theory, during step b) of bringing said plant, fungal, animal and/or microbial material into contact with at least one (deep) eutectic solvent of natural origin according to the invention, said solvent penetrates inside the cells of the material considered and manages to solubilize said one or more compound(s). This constitutes the solubilization step, which can be advantageously optimized by stirring the mixture of said material under consideration with said solvent (for example at 350 rpm). Once solubilized, said one or more compound(s) undergo desorption (allowing them to be detached from the cellular structures to which they are initially attached) then diffusion (allowing them to be transferred from the interior of the cells to the outside the cells which corresponds to said solvent), these two phenomena subsequent to solubilization correspond to extraction. The extraction can also be advantageously optimized by stirring the mixture of said material under consideration with said solvent (for example at 350 rpm). The two stages of solubilization and extraction ultimately make it possible to isolate in said solvent part of said one or more compounds initially contained in the material considered.

According to one embodiment, the above method comprises after step c):

d) a drying step, for example by freeze-drying and/or atomization, of said liquid extract, so as to obtain a dry extract, and

e) advantageously at least one formulation step suitable for obtaining a solid dosage form, such as a tablet, a granule, a lozenge, a capsule, a gum, a powder, a granule, a patch; preferably said formulation step being a compression step, for example direct compression, and said solid dosage form thus obtained being a tablet.

The fact that at least one of the constituents of the solvent according to the invention plays the role, in a completely innovative way, of technical agent (for example of compression agent) - what is more, very likely to comply with the appropriate regulations in terms of biological products - advantageously makes it possible to avoid resorting to the addition of exogenous technical agent(s) at the end of the process (i.e. during step d) or e) above) , in the context of the development of a solid form traditionally requiring such an addition (for example during the process for formulating tablets by compression, after the drying step). This makes it possible in particular to simplify the stage - or the stages - of formulation, to avoid the additional cost linked to the complexification of the process to allow the addition of such exogenous technical agent(s) ) and to maximize the chances of obtaining a solid dosage form compatible with the appropriate regulations for biological products.

According to one embodiment of the invention, said at least one acyclic polymerized carbohydrate of natural origin (GNPa) plays the role of technical agent (for example of compression agent) during step d) or e) above.

The invention also relates to a process for the extraction and (total or partial) encapsulation of one or more compounds from a plant, fungal, animal and/or microbial material, preferably from a material plant or fungal, advantageously plant material, said process implementing the abovementioned process, in which:

• in step b) said plant, fungal, animal and/or microbial material is brought into contact with said at least one eutectic solvent of natural origin according to the invention for a sufficient period of time (duration easily determinable by humans of the trade according to the specific case) to allow the solubilization/extraction and the encapsulation, total or partial, of said compound(s) by a supramolecular complex formed between at least the constituents a) and b) of said at least a eutectic solvent of natural origin, and obtaining a liquid extract comprising said compound(s) thus encapsulated.

The total or partial encapsulation of said compound(s) participates in increasing, as a whole, its/their solubilization. Indeed, said compound(s), forming a supramolecular complex once encapsulated, is/are therefore more soluble in the solvent according to the invention. In addition, and in a particularly advantageous manner, said encapsulation is capable of increasing the overall stability over time of said compound(s). Namely, the encapsulation is likely to increase on the one hand the chemical stability of said compound(s) by preserving its/their chemical integrity despite the hypothetical exposure to various chemical and/or biological agents a priori likely to modify the chemical structure of said compound(s). Therefore, the chemical stability provided by the encapsulation is likely to contribute to a better preservation of the bioactive properties of said compound(s). On the other hand, encapsulation is likely to increase the thermal stability of said compound(s) by preserving it/them from hypothetical chemical transformations induced by temperature variations. Thanks to this increase in overall stability likely to be provided by encapsulation, the delivery of said compound(s) is likely to be targeted and/or controlled (or even delayed), thus maximizing the bioactive properties of said compound(s) (s).

Another object of the invention relates to a liquid or solid, preferably solid, dosage form comprising one or more compound(s) of a plant, fungal, animal and/or microbial material, preferably of a plant or fungal material. , advantageously of a plant material, encapsulated (s), totally or partially, by a supramolecular complex formed between at least the constituents a) and b) of the eutectic solvent of natural origin according to the invention.

According to one embodiment of the invention, said liquid or solid dosage form does not contain any exogenous technical agent(s), namely added(s) in addition to the (deep) eutectic solvent of natural origin according to the invention.

The invention also relates to a pharmaceutical composition, a medicament (for human or animal use, preferably for human use), a foodstuff such as a food supplement (for human or animal use, preferably for human use), a device medical device, an ADDFMS (cf. definition below), comprising, consisting essentially of, or consisting of, the liquid or solid (preferably solid) dosage form according to the invention.

The invention also relates to the use of a mixture comprising at least one acyclic polymerized carbohydrate of natural origin (GNPa) and at least one ingredient of natural origin comprising citric acid and malic acid for the preparation of a naturally occurring eutectic solvent, such as a naturally occurring deep eutectic solvent (and in particular a supramolecular naturally occurring deep eutectic solvent); said at least one GNPa and said at least one ingredient of natural origin being as defined previously.

Definitions

Ionic liquids (ILs) : these are liquid salts which differ from all molten salts by a melting temperature below 100°C. Many of them are liquid at room temperature. These solvents consist of a cation, usually organic, combined with an organic or inorganic anion. Examples of cations and anions commonly used to formulate ionic liquids are:

- concerning cations: tetraalkylammonium, tetraalkylphosphonium, alkylmethylimidazolium and trialkyl sulfinium;

- concerning the anions: hexafluorophosphate, chloride, glulycolate and tetrafluoborate.

Eutectic : the term eutectic mixture is used when the melting point, or eutectic point, of a mixture of at least two species which are associated with each other by non-covalent intermolecular bonds (in particular by hydrogen bonds) is lower than that of the two compounds of the mixture taken individually.

Ingredient of natural origin : an ingredient of natural origin is composed of at least one raw material of natural origin, present as such in nature and untreated, or else treated by physical and/or chemical processes authorized according to the repository of ISO 16128 part 1 (entitled "Guidelines relating to technical definitions and criteria applicable to natural and organic cosmetic ingredients and products - Part 1: Ingredient definitions") or described in Information Note no. 2009 -136 (communicable within the meaning of the law of July 17, 1978) of the DGCCRF. The raw material or materials constituting such an ingredient of natural origin are not obtained by chemical synthesis. They can be for example of origin: vegetable, mineral, fungal, or microbial, a product of fermentation or active substances of natural origin from the hive.

Hydrogen bond : the hydrogen bond is a weak chemical bond, involving a hydrogen atom with acidic H and an electronegative atom such as oxygen, nitrogen and fluorine (see definition below). For this bond to be established, it is necessary to be in the presence of a hydrogen bond donor and a hydrogen bond acceptor.

Compound hydrogen bond acceptor (compound ALH ) : compound comprising at least one electronegative atom carrying a non-binding doublet (such as oxygen, nitrogen and fluorine) allowing the establishment of at least one hydrogen bond with a hydrogen bond donor compound (see definition below). According to one embodiment, said electronegative atom bearing a non-binding doublet is an oxygen, nitrogen or fluorine atom.

Hydrogen bond donor compound (DLH compound) : compound comprising at least one acid H - that is to say a hydrogen atom bonded to a heteroatom (as in amines, alcohols, thiols) - allowing the establishment of at least one hydrogen bond with a hydrogen bond acceptor compound (cf. definition above). According to one embodiment, said acid H is present at the level of an amine, alcohol or thiol function.

Deep Eutectic Solvents (SEPs) (“Deep Eutectic Solvents” in English, whose acronym is DESs) : Deep Eutectic Solvents consist of a mixture of a hydrogen bond acceptor (ALH) and a hydrogen bond donor (DLH). Examples of hydrogen bond donors and acceptors commonly used to prepare SEPs include:

- as a hydrogen bond acceptor: choline chloride, and

- as a hydrogen bond donor: urea and 4-chlorophenol.

Deep eutectic solvents of natural origin (SEPsNa) (or "Natural Deep Eutectic Solvents", in English; English acronym: NADES ): deep eutectic solvents obtained from donors and hydrogen bond acceptors which are of natural origin .

Biobased : material from a renewable resource, for example plant, fungal, animal and/or microbial material. This material may or may not have undergone chemical and/or enzymatic transformation.

Supramolecular : chemical structure of a mixture of at least two molecules linked together by non-covalent bonds (for example by hydrogen bonds). None of said at least two molecules constituting the new “supermolecule” (or “supramolecular complex”) is modified in its chemical integrity. On the other hand, said “supermolecule” can acquire properties which were not present before the establishment of said non-covalent bonds.

Cyclodextrin : cyclic oligosaccharide obtained by enzymatic hydrolysis of starch (“native cyclodextrin”) then possibly chemically modified (“modified cyclodextrin”), composed of glucose monomers. Cyclodextrins have a hollow conical cylinder shape and thus exhibit a hydrophobic inner cavity and a hydrophilic outer surface.

Supramolecular Deep Eutectic Solvents (SEPsSup) : deep eutectic solvents obtained by mixing a DLH with an ALH (the ALH being a cyclodextrin) leading to a liquid supramolecular mixture at room temperature.

Modified starch : starch whose initial structure has been modified by:

• physical treatment: pregelatinized starches (prior cooking and dehydration), extruded or compacted;

• chemical treatment: oxidation, esterification, etherification, hydrogenation;

• cross-linking: treatment of starch at a temperature below the gelatinization temperature which induces the formation of a small percentage of intramolecular bridges; cross-linking reduces swelling, increases shear strength and allows sterilization;
• controlled depolymerization: the partial hydrolysis of starch, which can be obtained in an acid medium, is now often carried out enzymatically; it then uses debranching enzymes (of the pullulanase or isoamylase type) which cut the α-(16) bonds, amylases (α-amylases, producing oligosaccharides or β-amylases, inducing recurrent hydrolysis from the non-reducing end of the linear chains and producing maltose) and to amyloglucosidases, exo-enzymes hydrolyzing in a repetitive way both bonds 14 and bonds 16 and producing glucose. The field of application of these enzymatic techniques is the production of maltodextrins (dextrinization) and that of glucose syrup for example;

[Bruneton J. Pharmacognosy, phytochemistry and medicinal plants. Edition Lavoisier, Paris, 5th edition, 2016, p87-89].

According to the invention, the modified starch is selected from starches modified by physical treatment, starches modified by chemical treatment, starches modified by crosslinking, and/or starches modified by controlled depolymerization. According to one embodiment, for the purposes of the present invention, a starch modified by controlled depolymerization, such as a starch hydrolyzate (obtained by partial hydrolysis of the starch), is used.

Acyclic polymerized carbohydrates of natural origin (GNPa) : non-cyclic molecules or mixtures of molecules resulting from the more or less significant condensation of monomeric sugars, derived from plant, fungal, animal and/or microbial material. In one embodiment of the invention, these GNPa (ALH compounds) are selected from:

(i) non-cyclic oligosaccharides and/or homogeneous polysaccharides (i.e. resulting from the condensation of molecules of the same ose type),

(ii) non-cyclic heterogeneous oligosaccharides and/or polysaccharides (i.e. resulting from the condensation of molecules of at least two different types of oses), and

(iii) mixtures thereof.

The aforesaid oligosaccharides comprise from 2 to 10 saccharide residues (namely resulting from the condensation of 2 to 10 saccharide monomers), preferably from 3 to 10 saccharide residues (so-called “higher” oligosaccharides resulting from the condensation of 3 to 10 saccharide monomers). The aforesaid polysaccharides (also called “polyosides” or “glycans”), for their part, comprise at least 11 osidic residues (namely result from the condensation of at least 11 osidic monomers).

As indicated previously, non-cyclic oligosaccharides and/or polysaccharides can be:

1. Homogeneous (homoglycans), namely resulting from the condensation of molecules of the same ose type, these being advantageously selected from inulin (polymer of fructose, CAS number 9005-80-5), modified starches, preferably modified starches with a Dextrose Equivalent (DE) of less than 20 (maltodextrins), advantageously a modified starch (maltodextrin) with a DE of less than 20 and greater than or equal to 18, and mixtures thereof;
2. Heterogeneous (heteroglycans), namely resulting from the condensation of molecules belonging to at least two different types of oses, these being advantageously selected from non-cyclic heterogeneous polysaccharides of acacia gum (derived in particular from arabinose, galactose, rhamnose and glucuronic acid, CAS number 9000-01-5), acemannan (derivative of glucose and mannose, CAS number 110042-95-0), and mixtures thereof.

Dextrose Equivalent (DE) (or “Dextrose Equivalent”) : result of total hydrolysis of starch (monomers). The higher the DE, the greater the hydrolysis. A starch has a DE close to 0. Between 20 and 100, we speak of glucose syrup and we speak of maltodextrin for a DE lower than 20.

Method of the European Pharmacopoeia (Maltodextrin monograph n°1542) to determine the dextrose equivalent (in italics):

Dextrose equivalent (DE): does not differ by more than 2 DE units from the nominal value.

In a 500 mL volumetric flask, dissolve an amount of maltodextrin, corresponding to 2.85-3.15 g of reducing carbohydrates, calculated as dextrose equivalent, in water R and dilute to 500.0 mL with the same solvent . Transfer the solution to a 50 mL burette.

Introduce 25.0 mL of cupri-tartaric solution R into a 250 mL flask and add 18.5 mL of solution to be examined contained in the burette, mix and add a few glass beads. Place the flask on a hot plate previously set so that the solution starts boiling after 2 min + 15 s. Keep boiling for exactly 120 s, add 1 mL of a 1 g/L solution of methylene blue R and titrate with the solution to be examined (V ₁ ) until the blue color disappears. Keep the solution boiling throughout the titration.

Calibrate the cupri-tartaric solution with a glucose solution R at 6.00 g/L (V ₀ ).

Calculate the dextrose equivalent using the following expression:

V ₀ = total volume of glucose standard solution, in millilitres,

V ₁ = total volume of solution to be examined, in millilitres,

M = mass of the sample in grams,

D = percentage content of dry matter in the substance.

As is known in the state of the art, oligosaccharides and polysaccharides result from the condensation of several ose molecules. These are natural molecules, where each sugar is linked to its neighbor via an osidic bond, formed by the elimination of a molecule of water between the hemiacetalic hydroxyl at C-1 of a sugar and the one of the hydroxyls of the other saccharide molecule.

Unlike cyclodextrins, the GNPas according to the invention are quite likely to comply with the appropriate regulations for biological products, which represents a significant advantage.

In addition, and without being bound by theory, the GNPas according to the invention – although non-cyclic – appear capable of forming supramolecular complexes with the compounds of intermediate polarity, which promotes the solubilization of the latter.

Acemannan (commonly called “Aloeverose”) : acemannan (C66H100NO49-, CAS RN 110042-95-0), is composed of one or more polymer(s) of natural glucose and mannose. The MeSH (Medical Subject Headings), a dictionary that is a reference in the biomedical field, has classified acemannan as a gastrointestinal agent, an antiviral agent, an anticancer agent and an immunological adjuvant. [MeSH Supplementary Concept Data. Acemannan. US National Library of Medicine. 2020/11/24. https://meshb-prev.nlm.nih.gov/record/ui?ui=C058414]. The Canadian monograph references Aloe vera gel as an emollient to help soothe irritation/inflammation of the gastrointestinal tract and as a source of antioxidants [Health Canada. Natural Health Product. Aloe vera leaf gel – Oral. August 28, 2018. http://webprod.hc-sc.gc.ca/nhpid-bdipsn/atReq.do?atid=aloe.gel&lang=eng].

Inulin : inulin (CAS 9005-80-5) is a polymer of fructose, a natural, indigestible and non-absorbable polysaccharide, produced by certain plants and endowed with a recognized prebiotic activity. Inulin stimulates the growth of beneficial bacteria in the colon, including bifidobacteria and lactobacilli, thereby modulating the composition of the intestinal microflora. This microbiota protects against pathogens, toxins and toxic substances, which can cause inflammation that can become chronic [Bruneton J. Pharmacognosy, phytochemistry and medicinal plants. Edition Lavoisier, Paris, 5th edition, 2016, p103-109].

Gum acacia (or gum arabic): Acacia gum (CAS RN CAS 9001-01-5), also known as gum arabic, is the dried gummy exudate of tropical and subtropical Acacia senegal trees. Acacia is a complex and loose aggregate of sugars and hemicelluloses with a high molecular weight of about 240,000-580,000 Da. The exudate is a protein polysaccharide, which essentially consists of an arabic acid core to which are bound calcium, magnesium and potassium as well as the sugars arabinose, galactose and rhamnose. The ingredient is a white or yellowish-white powder, slowly soluble in water. Acacia gum is mainly used in oral and topical pharmaceutical formulations as a suspending agent and emulsifier. It is also used in tablet formulation, as a tablet binder, and can produce tablets with an extended disintegration time. In food, acacia gum is used as an emulsifier and thickening agent in icings, fillings, soft candies, chewing gums and other confections [Rowe RC, Sheskey PJ, Weller PJ. Acacia. In: Handbook of Pharmaceutical Excipients, 6th ed. London: Pharmaceutical Press, 2009. p 206-8].

Solubility : within the meaning of the European Pharmacopoeia (general requirements), the solubility of a substance in a liquid is defined by the terms having the following meaning for a temperature of 15 to 25°C:

Descriptive terms
Approximate volumes of solvent in milliliters per gram of substance

Very soluble
Less than 1
easily soluble
From 1 to 10
Soluble
From 10 to 30
Fairly soluble
From 30 to 100
Slightly soluble
From 100 to 1000
Very slightly soluble
From 1000 to 10,000
Practically insoluble
Over 10,000

The term “partially soluble” is used in the case of a mixture of which only certain constituents dissolve.

The solubilization of GNPa has been checked in water within a limit of 15% by mass, this 15% by mass representing the maximum quantity of GNPa introduced into a preparation for its functionality as a technical formulation agent.

15% by mass of GNPa corresponds approximately to a mass concentration of 150 g/L of GNPa in the solvent considered, ie approximately 6.67 mL of solvent per g of GNPa. This is why, in view of the classification of the European Pharmacopoeia, the GNPas according to the invention are considered to be “easily soluble” in water (as well as in the solvents considered in the context of the present invention).

Supramolecular Natural Deep Eutectic Solvents (SEPsNaSup) : deep eutectic solvents obtained by mixing at least one DLH with at least one ALH which are of natural origin and leading to a liquid supramolecular mixture at room temperature. The SUPRANADES according to the invention combine at least one GNPa (ALH compounds), as defined above, with a plurality of different organic acids of natural origin, said plurality b) comprising malic acid and citric acid (compounds DLH) (and also, where appropriate, monomeric sugars), said plurality b) being for example comprised within fruit juices, preferably concentrated fruit juices used alone and/or in combination, advantageously orange juice and/or apple, very advantageously lemon juice. Such preferably concentrated fruit juices are advantageously rich in organic acids such as in particular citric acid and malic acid, as well as advantageously rich in monomeric carbohydrates such as in particular glucose and fructose. These juices also advantageously contain a significant amount of water.

HydroxyAnthracene derivatives (DHA or “HydroxyAnthracene derivatives”, in English, English acronym: HAD) : natural substances present in particular in the leaves of Aloe vera, having laxative properties and whose use in human health is not desirable within the framework of the field of application of this invention. Foodstuffs containing HAD plant preparations must now have a content of aloe-emodin, emodin and aloins (A + B), less than 1 ppm according to Commission Regulation (EU) 2021/468 of March 18 2021, published in the Official Journal of March 19, 2021.

Technical agent : a raw material added for a technological purpose. The technical agent intervenes and plays the role for which it was used at the stage of manufacture, packaging or storage of the product (in particular of a product in solid/dry form). For example, these technical agents can facilitate the compression, the flow, the preservation or the stability of the product over time.

Compression agent : technical agent whose intrinsic physical characteristics confer on the preparation to which it is added, the acquisition of cohesion under the effect of a constraint, and leading to the formation of a solid compact, in particular of compressed type.

Compounds with intermediate polarity : a compound with intermediate polarity is a compound lying between polar compounds, such as water, and non-polar compounds, such as vegetable oil.

Organic acid of natural origin : by "organic acid of natural origin" is meant, within the meaning of the present invention, an organic acid (based on carbon) present as such in nature (in particular naturally present in the animal, plant and/or fungal kingdom) and compatible for pharmaceutical, nutritional, food and/or cosmetic use.

Rutin : rutin (CAS no.: 153-18-4, synonyms rutoside or quercetin 3-rutinoside) is a flavonoid found in many plants. It has shown antiallergic, anti-inflammatory, antiproliferative, antioxidant properties. This bioflavonoid has multiple effects on the body, one of the most important being to reduce the fragility and permeability of capillaries. Flavonoids also improve the action of vitamin C on the body by increasing its absorption and delaying its elimination. We find rutin and its synthetic derivatives (troxerutin for example) as active ingredients of several venotonic drugs, prescribed in case of heavy legs, varicose veins, hemorrhoids, but also reduced visual acuity linked to fragility of small children. vessels of the retina [10] . As indicated throughout this patent application, rutin is poorly soluble in water since its water solubility is 0.125 mg/mL, i.e. 1.25x10 ^-4 g/mL, according to the European Pharmacopoeia in force (see 5.11. Characters).

Fruit juice (or "fruit juice") : a fruit juice is the fermentable but unfermented product obtained from the edible parts of healthy and ripe fruit, fresh or preserved by refrigeration or freezing, of one or more species mixed species, possessing the characteristic colour, aroma and taste of the juice of the fruit from which it comes (cf. Directive 2001/112/EC of 20 December 2001 relating to fruit juices and certain similar products intended for food and its amendments in force (in particular Directive 2012/12/EU), in particular Annex I relating to Names, definitions of products and characteristics). Aromas, pulps and cells obtained by appropriate physical means from fruits of the same species can be returned to fruit juice. In the case of citrus fruits, the fruit juice must come from the endocarp. However, lime juice can be obtained from the whole fruit. When juices are obtained from fruits comprising pips, seeds and skins, the parts or components of the pips, seeds and skins are not incorporated into the juice. This provision does not apply in cases where parts or components of pips, seeds and skins cannot be removed by good manufacturing practice. The mixture of fruit juice and fruit puree is permitted in the production of fruit juice. According to one embodiment of the invention, the fruit juice is different from the coconut juice (also called “coconut water” and designating the liquid contained in the central cavity of the coconut).

Concentrated fruit juice (or "concentrated fruit juice") : a concentrated fruit juice is the product obtained from fruit juice of one or more species of fruit by the physical removal of a determined part of the constitutional water (see Directive 2001/112/EC of December 20, 2001). According to one embodiment, the elimination is at least 50% of the water of constitution. Aromas, pulps and cells obtained by appropriate physical means from fruits of the same species can be returned to concentrated fruit juice.

Concentrated lemon juice (or “concentrated lemon juice”) : concentrated fruit juice obtained from the fruit of the plant Citrus limon (L.) Burm.f.

Concentrated apple juice (or “concentrated apple juice”) : concentrated fruit juice obtained from the fruit of the Malus domestica Borkh plant.

Concentrated orange juice (or “concentrated orange juice”) : concentrated fruit juice obtained from the fruit of the plant Citrus sinensis L.

Brix scale : the Brix scale measures, in degrees Brix (°B), the fraction of dry matter in a liquid, that is to say the percentage of dry matter in a liquid.

Method for determining the Brix degree : in the context of the present invention, the Brix degree is measured at a temperature of 20° C. using a refractometer, which determines the refractive index of light from a matrix . This matrix is observed by the deflection of a light beam according to the nature of the medium in which it propagates. The angle of the beam deviates according to the rate of soluble dry matter in the medium, the higher the consumption of soluble dry matter, the greater the refraction.

Solid-liquid extraction : operation consisting in bringing into contact at least one solid and at least one liquid, and in separating, thanks to said at least one liquid, one or more soluble compound(s), "the solutes", content (s) in an insoluble solid material. The extraction liquid(s) is/are called solvent(s), the soluble compound(s) can be solid(s) or liquid(s). Finally, the insoluble solid can be massive or porous and is generally in the form of porous or cellular particles with semi-permeable membranes.

Maceration : solid-liquid extraction technique which consists in leaving at least one solid body in a liquid (solvent) or a mixture of liquids (solvents), generally cold, to extract the chemical species.

Macerate : product of maceration. It consists of a solid body/solvent(s) mixture.

Plant, fungal, animal and/or microbial material (also referred to as “plant, fungal, animal and/or microbial substrate”): means any material of a plant, fungal, animal and/or microbial nature from which one or several compound(s) of interest is/are extracted by an extraction operation.

Fungal material (also referred to as "fungal substrate"): means any fungal material (such as fungus(ies), lichen(s), part(s) of fungi and/or lichens) whole or whose size has been reduced if appropriate/necessary, for example by fragmentation (breaking, crushing etc.), cutting, grinding or pulverizing. Fungal material can be used in dried or fresh form.

Plant material (also referred to as "plant substrate"): means any plant material (such as plants, part(s) of plants, fruits, algae, or mixtures thereof), whole or reduced in size if appropriate/ necessary, for example by fragmentation (breaking, crushing etc.), cutting, grinding or pulverizing. Plant material can be used in dried or fresh form. According to the invention, the plant material is preferably chosen from wood, stems, petals, leaves, aerial parts, roots, rhizomes, flowering tops, flowers, germ, bark, seeds , fruit or mixtures thereof.

In the case where the biological material is a plant, the extraction can be carried out from the whole of the plant or from one or more part(s) of the plant, and in particular chosen from among the root, stem, bark, flower, seed, germ and/or leaf and mixtures thereof. According to an advantageous mode, it is preferentially the aerial parts, that is to say the leaves and the stems, and preferentially the leaves.

According to one embodiment of the invention, the plant and/or fungal material is selected from the following non-exhaustive list:

Allium sativum, Medicago sativa, Aloe barbadensis, A. ferox, A. vera, A. comosus (= A. sativus), Angelica archangelica (= A. officinalis), Hippophae rhamnoides, Artemisia vulgaris, Arnica montana, Cynara scolymus, Withania somnifera , Astragalus membranaceus, Astragalus mongholicus, Calluna vulgaris, Crataegus azarolus, Crataegus oxyacantha, Crataegus monogyna, Crataegus laevigata, Crataegus.pentagyna, Crataegus.nigra, Avena sativa, Bacopa monnieri, Ballota nigra , Bambusa bambos (= B. arundinacea), Arctium lappa (= A. majus, L. major), Ocimum sanctum, Citrus aurantium var aurantium, Verbascum thapsus, V. densiflorum, Betula pendula, Betula pubescens, Rhamnus frangula (=Frangus alnus), Boswellia carteri, B. serrata, Borago officinalis, Buxux sempervirens, Arctostaphylos uva-ursi, Theobroma cacao, Vaccinium macrocarpon, Cinnamomum verum (= C. zeylanicum), Cinnamomum cassia (= C. aromaticum), Ceratonia siliqua 29, Rhamnus purshianus (= Frangula purschiana), Ribes nigrum, Silybum marianum, Cichorium intybus, Agropyron repens 34, Chrysanthellum indicum, Cimicifuga racemosa (= Actea racemosa), Coleus forksohili, Papaver rhoeas, Cucurbita pepo, Curcuma longa, Cupressus sempervirens, Echinacea angustifolia, A. pallida, E. purpurea, Eleutherococcus senticosus, Ephedra sp, Eschscholtzia californica, Eucalyptus globulus, Eucalyptus radiata, Eupatorium cannabinum, Trigonella foenum-graecum, Ruscus aculeatus, Fraxinus excelsior, F. oxyphylla, Fucus vesiculosus, F. serratus, Fumaria officinalis, Vitex agnus-castus, Juniperus communis, Gentiana lutea, Zingiber off herenal , Ginkgo Biloba, Panax Ginseng, Tanacetum Parthenium, Chrysanthemum Parthenium), Uncaria Tomentosa, Paullinia Cupana, Viscum album, Commiphera Mukul, Hamamelis Virginiana, Harpagophytum Procumbens, Harpagophytum Zeyheri, Humulus lupulusis, Go ovata, sterculia urens, piper methodsticum, Cola nitida, Lavandula angustifolia, L. officinalis, L. vera, Hedera helix, Glechoma hederacea, Linum usitatissimum, Zea mays, Aesculus hippocastanum 73, Marrubium album, Ilex paraguariensis, Matricaria recutita, Malva sylvestris, Melilotus officinalis, Melissa officinalis, Mentha piperita , Menyanthes trifoliata, Hypericum perforatum, Commiphora molmol, Vaccinium myrtillus, Nigella sativa, Olea europaea, Oenothera biennis, Ulmus rubra (= Ulmus fulva), Orthosiphon stamineus, Urtica dioica, Sabal serrulata, Serenoa repens, Carica papaya, Passiflora incarnata, Pelargonium sidoides , Voola tricolor, V. arvensis, Vinca minor, Phyllanthus niruri, Hieracium pilosella, Pinus sylvestris, Taraxacum officinalis, Plantago major, Portulacca oleracea, Equisetum arvense, Equisetum hiemale, Artemisia annua, Cinchona sp, Raphanus sativus, Ulmaria filipendula (=Spiraea ulmaria ), Rosmarinus officinalis, Salvia officinalis, Salix sp (Salix alba, S. fragilis, S. purpurea), Scutellaria baicalensis, Cassia senna, Cassia angustifolia, Lentinus edoda, Glycine max, Solidago virga aurea, Calendula officinalis, Sambucus nigra, Camellia sinensis (= C. thea, Thea sinensis), Styphnolobium japonicum (Sophora japonica), Thymus vulgaris, Tilia cordata, T. platyphyllos, T. sylvestris, Trifolium pratense, Urtica urens, Valeriana officinalis, Erigeron canadensis, Vitis vinifera rubra, Pausinystalia yohimbe, and their mixtures.

Bioactive compound : compound possessing - or being likely to possess - pharmacological, metabolic, immunological and/or physiological activity in humans or animals.

Pressing : solid-liquid separation operation by pressure allowing the separation of the liquid extract obtained after solubilization/extraction of residual plant, fungal, animal and/or microbial material.

Reducing the size of plant, fungal, animal and/or microbial material : operation - or set of operations - consisting in reducing the size of said plant, fungal, animal and/or microbial material (in particular plant, fungal and/or or animal) from which it is desired to perform at least one solubilization and/or extraction operation. As indicated above, this reduction can be obtained, for example, by fragmentation (breaking, crushing, etc.), cutting, grinding or pulverizing the material of interest (in particular plant, fungal and/or animal material).

Medical device : any instrument, device, equipment, software, implant, reagent, material or other article, intended by the manufacturer to be used, alone or in combination, in humans for one or more of the following specific medical purposes: — diagnosis, prevention, control, prediction, prognosis, treatment or alleviation of a disease, — diagnosis, control, treatment, alleviation of an injury or handicap or compensation thereof, — investigation, replacement or modification of an anatomical structure or function or a physiological or pathological process or state, — communication of information by means of in vitro examination of samples from the human body, including organ, blood and tissues, and whose principal intended action in or on the human body is not obtained by pharmacological or immunological means or by metabolism, but whose function can be assisted by such means (cf. Regulation (EU) 2017/ 745).

The present invention finds particular application in the field of medical devices.

Food supplement : composition for human or animal use (preferably for human use) the purpose of which is to supplement the normal diet and which constitutes a concentrated source of nutrients or other substances having a nutritional or physiological effect, alone or in combination, marketed in the form of doses, namely presentation forms such as capsules, lozenges, tablets, pills and other similar forms, as well as sachets of powder, ampoules of liquid, bottles fitted with a dropper and other similar forms of liquid or powdered preparations intended to be taken in small measured units.

The present invention finds particular application in the field of food supplements for human or animal use, preferably for human use.

Dietary foods intended for special medical purposes (ADDFMS) : in accordance with French legislation, and more particularly Article L5137-1 of the Public Health Code, "Dietary foods intended for special medical purposes means foods intended to a particular diet that are specially processed or formulated to meet the nutritional needs of patients. They are intended to constitute the exclusive or partial diet of patients whose capacities for absorption, digestion, assimilation, metabolization or excretion of ordinary foods or of some of their ingredients or metabolites are reduced, limited or disturbed. , or whose state of health calls for other special nutritional needs which cannot be satisfied by a modification of the normal diet or by a diet consisting of foods intended for particular nutritional uses or by a combination of the two”.

The present invention finds particular application in the field of ADDFMS.

Plurality : two or more.

Certain aspects of the invention will be better understood on reading the detailed description presented below, made with reference to Figures 1 to 11, in which:

• represents the chemical structure of rutin (C ₂₇ H ₃₀ O ₁₆ ) and makes it possible to understand the positive and negative charges carried by this molecule,
• is a linear regression line corresponding to the calibration curve of rutin solubilized in DMSO produced with a UV-visible spectrophotometer, the experimental results of examples 1 to 5 below are based on this calibration,
• represents the chemical structure of curcumin (C ₂₁ H ₂₀ O ₆ ),
• is a bar chart showing the (comparative) experimental results of Example 1,
• [Fig. 5-6] are bar charts showing the (comparative) experimental results of Example 2,
• is a bar chart showing the experimental (comparative) results and the theoretical calculations of Example 3,
• is a bar chart showing the (comparative) experimental results of Example 4,
• is a bar chart showing the (comparative) experimental results of Example 5,
• is a comparison of chromatograms produced with the UHPLC-DAD corresponding to the experimental results of example 6,
• is a bar chart showing the (comparative) experimental results of Example 7 performed at the UHPLC-DAD.

Claims (15)

Eutectic solvent of natural origin, such as a deep eutectic solvent of natural origin, said solvent comprising:

1. at least one acyclic polymerized carbohydrate of natural origin (GNPa), and
2. a plurality of different naturally occurring organic acids, said plurality b) comprising malic acid and citric acid;

said at least one GNPa being selected from:

1. non-cyclic homogeneous oligosaccharides and/or polysaccharides,
2. non-cyclic heterogeneous oligosaccharides and/or polysaccharides, and
3. their mixtures.

Eutectic solvent of natural origin according to claim 1, in which:

• said non-cyclic homogeneous oligosaccharides and/or polysaccharides are selected from: inulin, modified starches, preferably having a Dextrose Equivalent of less than 20, advantageously less than 20 and greater than or equal to 18, and mixtures thereof, and/or
• said non-cyclic heterogeneous polysaccharides are selected from acemannan and non-cyclic heterogeneous polysaccharides of acacia gum, and mixtures thereof.

Eutectic solvent of natural origin according to claim 1 or 2, further comprising:
c) a plurality of monosaccharides, preferably said plurality c) comprising glucose and/or fructose, advantageously both, and
d) optionally amino acids and/or vitamins. Eutectic solvent of natural origin according to one of Claims 1 to 3, in which:
- said at least one GNPa represents at least 5% by mass, preferably at least 10% by mass, relative to the total mass of said solvent, and/or
- said plurality of different organic acids of natural origin b) represents at least 3% by mass, preferably at least 5% by mass, preferably at least 10% by mass, advantageously at least 20% by mass, relative to the total mass of said solvent. Eutectic solvent of natural origin according to one of Claims 1 to 4, comprising a mixture between the said at least one GNPa and at least one ingredient of natural origin, the said at least one ingredient of natural origin comprising the said plurality of of different natural origin b). A naturally occurring eutectic solvent according to claim 5 when dependent on claim 3, wherein said at least one naturally occurring ingredient also comprises said plurality of monosaccharides c). Eutectic solvent of natural origin according to claim 5 or 6, in which said at least one ingredient of natural origin is:
i) a fruit juice, for example a concentrated fruit juice, preferably a lemon, orange or apple juice, preferably a lemon or orange juice, advantageously a lemon juice; Or
ii) a mixture of fruit juices, for example a mixture of concentrated fruit juices, preferably a mixture of fruit juices selected from lemon, orange and apple juices, preferably a mixture of lemon and of orange juice. Eutectic solvent of natural origin according to one of claims 1 to 7, said solvent comprising exogenous water, for example distilled water, preferably in a mass percentage less than or equal to 90%, for example less than or equal to 80% or 75%, relative to the total mass of the solvent; preferably the exogenous water representing a mass percentage greater than or equal to 50% relative to the total mass of the solvent. Use of a eutectic solvent of natural origin according to one of Claims 1 to 8, for solubilizing and/or extracting, preferably for solubilizing and extracting, for example by solid-liquid extraction such as extraction by maceration, a or more compound(s) of plant, fungal, animal and/or microbial material, preferably of plant or fungal material, advantageously of plant material. Use according to claim 9, for solubilizing, extracting and encapsulating said one or more compound(s). Process for extracting one or more compound(s) from plant, fungal, animal and/or microbial material, preferably from plant or fungal material, advantageously from plant material, said process comprising the following steps :
a) supply of plant, fungal, animal and/or microbial material,
b) bringing said plant, fungal, animal and/or microbial material into contact with at least one eutectic solvent of natural origin according to one of Claims 1 to 8 for a period of time sufficient to allow the solubilization of said compound or compounds ( s) and obtain a liquid extract,
b′) optionally separating, for example by pressing or by filtration, the liquid extract obtained in step b) and the residual plant, fungal, animal and/or microbial material, and
c) recovery, after step b) or step b′), when said step b′) is present, of the liquid extract, optionally after a purification step, for example by centrifugation. Method according to claim 11, said method comprising, after step c):
d) a drying step, for example by freeze-drying and/or atomization, of said liquid extract, so as to obtain a dry extract, and
e) advantageously at least one formulation step suitable for obtaining a solid dosage form, such as a tablet, a granule, a lozenge, a capsule, a gum, a powder, a granule, a patch; preferably said formulation step being a compression step, for example direct compression, and said dosage form thus obtained being a tablet. Process for extracting and encapsulating one or more compounds from plant, fungal, animal and/or microbial material, preferably plant or fungal material, advantageously plant material, said process implementing the method according to claim 11 or 12, in which:

• in step b) said plant, fungal, animal and/or microbial material is brought into contact with said at least one eutectic solvent of natural origin according to one of claims 1 to 8 for a period of time sufficient to allow the solubilization and encapsulation, total or partial, of said compound(s) by a supramolecular complex formed between at least constituents a) and b) of said at least one eutectic solvent of natural origin, and obtaining a liquid extract comprising said or said compound(s) thus encapsulated.

Liquid or solid dosage form, preferably solid, comprising one or more compound(s) of plant, fungal, animal and/or microbial material, preferably of plant or fungal material, advantageously of plant material, encapsulated (s), totally or partially, by a supramolecular complex formed between at least constituents a) and b) of the eutectic solvent of natural origin according to one of claims 1 to 8. Use of a mixture comprising at least one acyclic polymerized carbohydrate of natural origin (GNPa) and at least one ingredient of natural origin comprising citric acid and malic acid for the preparation of a eutectic solvent for naturally occurring, such as a naturally occurring deep eutectic solvent;
said at least one GNPa being selected from:

1. non-cyclic homogeneous oligosaccharides and/or polysaccharides,
2. non-cyclic heterogeneous oligosaccharides and/or polysaccharides, and
3. mixtures thereof;

advantageously said at least one ingredient of natural origin being a fruit juice, for example a concentrated fruit juice, or a mixture of fruit juices, for example a mixture of concentrated fruit juices.