Cyclodextrin derivatives, process for the production thereof and applications thereof

Abstract

The invention relates to a cyclodextrin derivative which comprises: - glycosidic subunits of chemical structure (4): (4), - optionally at least one glycosidic subunit of chemical structure (5): (5), the total number of glycosidic subunits of chemical structure (4) and chemical structure (5) being equal to an integer n of between 5 and 30, and at least 2 x of the x of the glycosidic subunits of chemical structure (4) being different from one another. The invention relates to a process for producing the CD derivative and to the applications thereof.

Description

TITLE: Cyclodextrin derivatives, their manufacturing process and their applications

[0001] The present invention relates to new cyclodextrin derivatives (hereinafter abbreviated as "CDs" in the plural or "CD" in the singular), and their applications in a wide variety of fields, including pharmaceutical, cosmetic, food, plant protection, agrochemical, textile and various industrial fields (e.g. paints, pigments).

[0002] In these different fields, it is well known to encapsulate active substances (for example, pharmaceutical or cosmetic active ingredients, food additives, nutraceutical products, plant protection products, perfume essences, microorganisms, pigments, dyes) in individualized particles (micro- or nanoparticles).

[0003] Furthermore, the encapsulation of active substances is implemented in order to: - to increase their activity time, due to the improvement of their chemical stability, by protecting them from light and / or interactions with other incompatible components (oxidation...), - to mask a taste or smell; - to ensure a prolonged and controlled release, for example in the dermis, in the case of cosmetic active compounds, or in the digestive tract, in the case of active substances in the agri-food industry.

[0004] Among the many encapsulation techniques, some use "host" molecules that contain a cavity allowing the formation of inclusion complexes with "guest" molecules (e.g., active substances). These "host" molecules can be mineral molecules such as zeolites and kaolinites, as well as organic molecules such as crown ethers, cyclophanes, and CDs.

[0005] The encapsulation process, common to all these "host" molecules (also called "cage molecules"), is as follows: the "host" molecule admits one or more "guest" molecules into its cavity, either partially or completely, through weak interactions but without the formation of any covalent bonds. This also allows for easy dissociation of the resulting inclusion complex. The complexation phenomenon is the result of numerous interactions involving the host molecule, the guest molecule, and the solvent, leading to the most thermodynamically stable state.

[0006] The encapsulation of active compounds using CDs through the formation of an inclusion complex is an encapsulation technique of choice.

[0007] Indeed, a CD is a cyclic oligosaccharide obtained by the enzymatic degradation of amylose (a linear form of starch, and therefore a renewable resource) using an enzyme, cyclodextrin glucosyltransferase (CGTase), of bacterial origin (Bacillus macerans, Alkalophylic bacillus). CDs thus have the advantage of being biodegradable.

[0008] More specifically, a CD is composed of n glucopyranose units in chair conformation, which are linked together by alpha (1-4) glycosidic bonds.

[0009] The most abundant and therefore most commonly used CDs, known as natural or native CDs, are alpha-CDs (hexamers), beta-CDs (heptamers), and gamma-CDs (octamers), for which n is respectively equal to 6, 7, and 8. Other CDs exist for which: - n is smaller, for example n is equal to 5; - n is higher, and can reach values ​​from 9 to 30, or even more, for example delta-CD (n is equal to 9) and epsilon-CD (n is equal to 10).

[0010] As examples, the chemical structures of alpha-CD(1) and beta-CD(2) are as follows:

[0011] Beta-CD is the CD that complexes the most molecules and whose derivatives are the most used.

[0012] CDs generally (especially alpha-, beta- and gamma-CDs) have a three-dimensional structure in the shape of a conical cylinder (or in other words a "lampshade") whose wall is made up of glucopyranose units in chair conformation.

[0013] CDs have a central cavity, as can be seen in chemical structure (3) below.

[0014] The size of the cavity depends on the number of glucopyranose units contained in the CD.

[0015] The openings of the cavity are lined by hydroxyl groups.

[0016] More specifically, the secondary hydroxyl groups of the glucopyranose units attached to carbons C2 and C3 are located around the widest entrance of the cavity (also called the "secondary face"), or in other words, the larger side of the conical cylinder. The presence of these secondary hydroxyl groups gives the outer part of the CD a hydrophilic character (designed to be in contact with a polar solvent).

[0017] The primary hydroxyl groups, carried by the C6 carbons, are located around the other opening of the conical cylinder, also called the "primary face".

[0018] The wall of the central cavity of CDs is composed of carbon and hydrogen atoms, as well as ether bonds. The lone pairs of electrons on the oxygen atoms forming glycosidic bonds are oriented towards the interior of the cavity, where the electron density is therefore high. Consequently, the interior of the CD cavity, lined with hydrogen atoms on carbons C3 and C5, and oxygen atoms (O-4) participating in the glycosidic bond, is relatively nonpolar and hydrophobic.

[0019] Finally, the formation of hydrogen bonds between the hydroxyl groups located on the C2 and C3 carbons of two adjacent glucopyranose units contributes to the rigidity of the CD structure.

[0020] CDs thus exhibit a macrocyclic structure with a hydrophobic interior and a hydrophilic exterior.

[0021] This amphiphilic nature allows them to incorporate hydrophobic molecules into their cavity to form water-soluble inclusion complexes. Indeed, in aqueous solution, the nonpolar cavity of CDs is occupied by water molecules, which is energetically unfavorable (polar-polar interactions). These water molecules can be readily replaced by a suitable "guest" molecule that is less polar than water.

[0022] More generally, the cyclic structure and their cavity allow CDs to form inclusion complexes with a large number of highly varied molecules (neutral, charged, polar, or nonpolar). The association of a CD with a guest molecule, as well as the dissociation of the complex formed, are governed by thermodynamic equilibrium.

[0023] Therefore, encapsulation in CDs can, in certain cases, protect fragile molecules (for example, from ultraviolet radiation, oxidation, or temperature), and ensure their slow and controlled release in aqueous media based on this thermodynamic equilibrium. Furthermore, the formation of inclusion complexes of molecules that are poorly or not at all soluble in water (for example, cosmetic or pharmaceutical active ingredients) with CDs increases their apparent solubility and stability. These properties are notably used to improve the bioavailability of cosmetic or pharmaceutical active ingredients.

[0024] Furthermore, because each glucopyranose unit has three reactive hydroxyl groups which are carried by the carbons C2, C3 and C6, it is known to synthesize a multitude of CD derivatives from so-called natural CDs and synthetic reagents, by replacing certain hydroxyl groups of the said natural CDs with a wide variety of groups, neutral or ionic such as alkyl, hydroxyalkyl, sulfobutyl, glucosyl, acetyl, amine, ether or ester groups from the said synthetic reagents.

[0025] CD derivatives are generally used to satisfy at least one of the following needs that are not always perfectly met by natural CDs: - the modulation of their solubility in different solvents; - the improvement of their complexation capacity; - the fixing of a specific group (for example for a vectorization application).

[0026] Like CDs, certain water-insoluble CD derivatives are of industrial interest because they are particularly suitable for preparing dispersible systems in which CDs and their derivatives are in particulate form (micro- or nanoparticles). These particles are indeed used in a wide variety of applications.

[0027] For example, in the pharmaceutical industry, such particles are useful for stabilizing or delivering active substances. They can also be used in plant protection products, where they can be used to deliver insecticides or pesticides. In cosmetics and dermatology, these particles can transport active compounds to the dermis. In industrial sectors, such as paints, varnishes, and surface treatments, these particles provide dispersions useful for delivering pigments, reagents, and strippers in the form of very low-viscosity aqueous dispersions that are easy to spray or apply. Finally, these particles can also be used in printing, reprographics, and the surface treatment of textiles and fibers.

[0028] In order to obtain dispersible systems containing particles suitable for such applications, it is essential that: - CD derivatives are designed to self-organize in the aqueous phase to form said particles while also being able to accommodate at least one active substance within their cavity, - said particles remain stable over time.

[0029] As explained above, CDs and their derivatives have the advantage of being produced from compounds derived from natural resources, making them, in some cases, biodegradable. To limit the environmental impact of such particles obtained from CD derivatives and to ensure they are as natural as possible, it is highly beneficial to limit the use of surfactants, which are commonly used to promote the self-organization of CD derivatives but are generally non-biodegradable products of synthetic chemistry.

[0030] Therefore, given all these needs, both in terms of improving solubility, forming an inclusion complex, and self-organization to obtain particles that are stable over time, there is still a real interest in developing new bio-based CD derivatives that fully satisfy them.

[0031] The inventors of the present invention have succeeded in developing new CD derivatives that perfectly fulfill all these needs.

[0032] The invention relates to a CD derivative characterized in that it comprises: - glucosidic subunits of the following chemical structure (4): in which x is an integer between 0 and 18, preferably between 0 and 12; - optionally at least one glucoside subunit of chemical structure (5): the total number of glucoside subunits of chemical structure (4) and chemical structure (5) is equal to an integer n between 5 and 30, preferably between 6 and 8, at least 2 x among the x of the glucosidic subunits of chemical structure (4) are different from each other.

[0033] The CD derivative must have at least 2 glucosidic subunits of chemical structure (4) which are different from each other, because x is not the same integer in these at least 2 glucosidic subunits of chemical structure (4).

[0034] In embodiments of the invention, the CD derivative may not include a glucosidic subunit of chemical structure (5). The number of glucosidic subunits of chemical structure (5) is equal to 0 and the number of glucosidic subunits of chemical structure (4) is then equal to the integer n.

[0035] In embodiments of the invention in which the CD derivative comprises at least one glucosidic subunit of chemical structure (5), the total number of glucosidic subunits of chemical structure (4) and of the at least one glucosidic subunit of chemical structure (5) is equal to the integer n.

[0036] In one embodiment of the invention, n is equal to 6. The derivative of CD is a derivative of alpha-CD. In another embodiment of the invention, n is equal to 7. The derivative of CD is a derivative of beta-CD. In another embodiment of the invention, n is equal to 8. The derivative of CD is a derivative of gamma-CD.

[0037] In one embodiment of the invention, the CD derivative comprises glucosidic subunits of chemical structure (4) with 2 different x values. In another embodiment of the invention, the CD derivative comprises glucosidic subunits of chemical structure (4) with 3 different x values. In one embodiment of the invention, x may be between 4 and 10, namely x may be equal to 4, 5, 6, 7, 8, 9, or 10.

[0038] In one embodiment of the invention, n is equal to 7 and the derivative of CD comprises: - 2 glucosidic subunits of chemical structure (4) in which x is equal to 10; - 2 glucosidic subunits of chemical structure (4) in which x is equal to 4; - 3 glucosidic subunits of chemical structure (5).

[0039] In one embodiment of the invention, n is equal to 7 and the derivative of CD comprises: - 2 glucosidic subunits of chemical structure (4) in which x is equal to 10; - 1 glucosidic subunit of chemical structure (4) in which x is equal to 4; - 4 glucosidic subunits of chemical structure (5).

[0040] In one embodiment of the invention, n is equal to 7 and the derivative of CD comprises: - 3 glucosidic subunits of chemical structure (4) in which x is equal to 10; - 1 glucosidic subunit of chemical structure (4) in which x is equal to 4; - 3 glucosidic subunits of chemical structure (5).

[0041] In one embodiment of the invention, n is equal to 7 and the derivative of CD comprises: - 3 glucosidic subunits of chemical structure (4) in which x is equal to 10; - 2 glucosidic subunits of chemical structure (4) in which x is equal to 4; - 2 glucosidic subunits of chemical structure (5).

[0042] In one embodiment of the invention, n is equal to 7 and the derivative of CD comprises: - 4 glucosidic subunits of chemical structure (4) in which x is equal to 10; - 2 glucosidic subunits of chemical structure (4) in which x is equal to 4; - 1 glucosidic subunit with chemical structure (5).

[0043] In one embodiment of the invention, n is equal to 7 and the derivative of CD comprises: - 4 glucosidic subunits of chemical structure (4) in which x is equal to 10; - 1 glucosidic subunit of chemical structure (4) in which x is equal to 4; - 2 glucosidic subunits of chemical structure (5).

[0044] In one embodiment of the invention, n is equal to 7 and the derivative of CD comprises: - 5 glucosidic subunits of chemical structure (4) in which x is equal to 10; - 1 glucosidic subunit of chemical structure (4) in which x is equal to 4; - 1 glucosidic subunit with chemical structure (5).

[0045] The invention also relates to a process for preparing a CD derivative according to the invention as described above, characterized in that it comprises at least the following steps: a) a mixture is prepared comprising at least: - a native CD comprising n glucopyranose units, n being an integer between 5 and 30, preferably between 6 and 8, - an enzyme configured to catalyze a transesterification reaction at the hydroxyl group on carbon C2 of the glucopyranose units of native CDs and CD derivatives; b) a 1 is added to said mixture er vinyl ester with the following chemical structure (6): in which x is an integer between 0 and 18, preferably between 0 and 12, said 1 er Given that the vinyl ester is in stoichiometry m, and ni is an integer less than n, to perform a 1 ère transesterification reaction between native CD and 1 er vinyl ester and so as to obtain at the end of this 1 ère transesterification reaction a 1 erThe so-called "intermediate" CD derivative in the reaction medium corresponds to the native CD in which neither hydroxyl groups on the C2 carbons of the glucopyranose units of said native CD have reacted with said 1 er vinyl ester; c) at least one 2 is added to the reaction medium containing the so-called "intermediate" CD derivative ème vinyl ester of chemical structure (6) whose x value is different from the x value of 1 er vinyl ester, said 2 ème vinyl ester being added in stoichiometry n2, n2 being an integer such that the sum of ni and n2 is less than or equal to n, to achieve, in the presence of said enzyme, at least one 2 ème transesterification reaction between the 1 er derived from CD called "intermediate" and at least one 2 èmevinyl ester wherein n2 hydroxyl groups among the hydroxyl groups borne by the C2 carbons of the glucopyranose units of said CD derivative called "intermediate" have reacted with said 2 ème vinyl ester so as to obtain at the end of at least one 2 ème transesterification reaction of said CD derivative according to the invention; d) optionally, step c) is repeated one or more times; all vinyl esters added to the reaction medium during said preparation process are of chemical structure (6), all x of these vinyl esters are different from each other and the sum of the stoichiometries of all these vinyl esters is less than or equal to n.

[0046] As explained above, by "native CD" we mean a natural CD or in other words a CD that has not been chemically modified.

[0047] Preferably, the native CD is chosen from the group consisting of alpha-CD (n equals 6), beta-CD (n equals 7), and gamma-CD (n equals 8). Most preferably, the native CD is beta-CD.

[0048] In an advantageous embodiment, prior to step a), the native CD can be solubilized in a non-aqueous solvent, preferably one that preserves the integrity of the enzyme and in which the native CD can be dissolved. This solvent can be an organic solvent or an ionic liquid that meets these criteria. For example, the organic solvent can be chosen from the group consisting of dimethyl sulfoxide (hereinafter abbreviated as "DMSO"), dimethyl formamide (hereinafter abbreviated as "DMF"), and pyridine. For example, the ionic liquid can be 1-n-butyl-3-methylimidazolium. The choice of a suitable solvent is perfectly within the capabilities of a person skilled in the art.

[0049] The x of the chemical structures (6) of all the vinyl esters used in the process for preparing the CD derivative according to the invention is an integer between 0 and 18, preferably between 0 and 12. Preferably, the vinyl esters used in this process are selected from the group consisting of vinyl acetate, vinyl butyrate, vinyl hexanoate, vinyl decanoate, vinyl octanoate, vinyl laurate, and vinyl myristate. Most preferably, these are vinyl butyrate and vinyl decanoate.

[0050] The enzyme is configured to catalyze a transesterification reaction at the hydroxyl groups attached to the C2 carbons of the glucopyranose units of: - any native CD and - any CD derivative, including at least one so-called "intermediate" CD derivative.

[0051] In other words, the enzyme is regioselective of the hydroxyl groups carried by the C2 carbons of the glucopyranose units of native CDs and CD derivatives, including at least one so-called "intermediate" CD derivative.

[0052] The enzyme can be a protease or a lipase.

[0053] Preferably, the enzyme is thermolysin. Thermolysin is a protease. For example, it could be the enzyme marketed by Sigma Aldrich under the trade name P1512-250mg.

[0054] In an advantageous embodiment of the invention, the enzyme is immobilized on a support. The support can be diatomaceous earth (for example, Celite®). Immobilizing the enzyme on a support is a conventional method and therefore perfectly within the capabilities of a person skilled in the art.

[0055] Immobilizing the enzyme on a support (for example, celite®) provides the following advantages: - the stabilization of the enzyme during transesterification reactions; - facilitate the purification of the CD derivative following the transesterification reactions; - the repeated use of the same enzyme for several transesterification reactions.

[0056] Without limiting the scope of the invention, the enzyme can be immobilized on a support in the following manner (the so-called "adsorption" method): - the enzyme is mixed, preferably at room temperature (e.g. 20°C), with a buffer solution (e.g. a 3-morpholino-1-propanesulfonic buffer solution with a pH of approximately 7) to obtain an enzyme suspension; - the enzyme suspension thus obtained is added to a support (for example celite®) in order to obtain a mixture; - the liquid phase of the mixture thus obtained is removed, for example under reduced pressure and preferably at room temperature, so as to obtain the immobilized enzyme.

[0057] During the 1 ère transesterification reaction, according to the stoichiometry of the 1 er vinyl ester which is implemented, part of the hydroxyl groups of the C2 carbons of the glucopyranose units is substituted to give glucosidic subunits of the chemical structure (4) as detailed above.

[0058] In other words, the degree of molecular substitution of the hydroxyl groups of the C2 carbons of the glucosidic subunits of chemical structure (4) with a determined x corresponding to the x of chemical structure (6) of the 1 er vinyl ester depends on the stoichiometry of 1 er vinyl ester which is implemented during the 1 èretransesterification reaction. Depending on the desired degree of molecular substitution for the 1 ère transesterification reaction, it is perfectly within the reach of a person skilled in the art to determine the stoichiometry of the 1 er vinyl ester to be implemented (or in other words the quantity of 1 er vinyl ester to be implemented in the reaction medium).

[0059] In this regard, within the framework of the present invention, the "degree of molecular substitution" corresponds to the number of hydroxyl groups on the C2 carbons that are substituted to give glucosidic subunits of the chemical structure (4) with a determined x corresponding to the x of the chemical structure (6) of the vinyl ester determined for a specific transesterification reaction during the preparation process according to the invention, and this per molecule of native CD used. The degree of molecular substitution thus takes into account the number of glucopyranose units that the native CD comprises.

[0060] The "total degree of molecular substitution" thus corresponds to the number of all the hydroxyl groups on the C2 carbons that are substituted to give glucosidic subunits of the chemical structure (4) with determined x values ​​corresponding to the x values ​​of the chemical structures (6) of the vinyl esters used for all the transesterification reactions carried out during the preparation process according to the invention, and this per molecule of native CD used in the step a) The total degree of molecular substitution is therefore less than or equal to n, which corresponds to the number of glucopyranose units in the native CD.

[0061] The process for preparing the CD derivative according to the invention comprises at least 2 transesterification reactions which employ vinyl esters all different from one another, namely in the value of x of their chemical structure (6).

[0062] At least one 2 èmevinyl ester different from 1 er vinyl ester, by virtue of their x values ​​of their chemical structures (6), is added to the reaction medium such that at least one 2 ème A transesterification reaction is initiated. During this 2 ème transesterification reaction, all or part of the hydroxyl groups of the C2 carbons of the glucopyranose units of the so-called "intermediate" CD derivative (in other words, the hydroxyl groups of the C2 carbons of the glucopyranose units of the native CD that were not substituted during the 1 ère transesterification reaction) are substituted to give glucosidic subunits of chemical structure (4) in which x corresponds to x of chemical structure (6) of at least one 2 ème vinyl ester.

[0063] At the end of at least one 2 èmetransesterification reaction, a CD derivative according to the invention is obtained in which all or part of the hydroxyl groups of the C2 carbons of the glucopyranose units of the so-called "intermediate" CD derivative have been substituted to give glucosidic subunits of the chemical structure (4) in which the length of the fatty chain is different.

[0064] Depending on the desired degree of substitution of the hydroxyl groups of the C2 carbons of the remaining glucopyranose units to give, from at least one 2 ème vinyl ester, glucosidic subunits of the chemical structure (4), it is perfectly within the reach of a person skilled in the art to determine the stoichiometry of at least one 2 ème vinyl ester to be implemented (or in other words the quantity of at least one 2 ème vinyl ester to be implemented in the reaction medium).

[0065] As explained above, the process for preparing a CD derivative according to the invention may include more than 2 transesterification reactions, for example 3 transesterification reactions, 4 transesterification reactions, 5 transesterification reactions, with respectively 3 different vinyl esters, 4 different vinyl esters, 5 different vinyl esters.

[0066] The vinyl esters used in the preparation of the CD derivative according to the invention must all be different from each other with respect to the x of their chemical structure (6).

[0067] Furthermore, the vinyl esters must be added to the reaction medium in determined stoichiometries such that the sum of the stoichiometries of all the vinyl esters used in the process of preparing a CD derivative according to the invention is less than or equal to n (namely the number of glucopyranose units included in the native CD used in step a) of said preparation process).

[0068] Because the hydroxyl groups of the C2 carbons of the glucopyranose units of all the native CD molecules present in the reaction medium are not all substituted to the same degree of molecular substitution during each of the transesterification reactions carried out during the preparation process, a complex mixture containing different CD derivatives according to the invention, the structure of which has been described above, is obtained at the end of this preparation process.

[0069] However, during the implementation of the process for preparing a CD derivative according to the invention, it was found that, because the enzyme (preferably thermolysin) was very regioselective, the number of different types of CD derivatives thus obtained was relatively small (about six) compared to the theoretical number expected considering all possible combinations of substitution of hydroxyl groups according to various degrees of molecular substitution.

[0070] All or part of the transesterification reactions of the process for preparing a CD derivative can be carried out simultaneously or sequentially.

[0071] In one embodiment of the invention, all transesterification reactions are carried out simultaneously. Thus, in this embodiment of the invention, steps b) and c) and, optionally d) are performed simultaneously.

[0072] In one embodiment of the invention, all transesterification reactions are carried out sequentially. In other words, in this embodiment of the invention, all transesterification reactions are carried out one after the other (i.e., successively).

[0073] In one embodiment of the invention, at the end of step b) and before the execution of step c), the so-called "intermediate" CD derivative can be recovered after precipitation (for example by centrifugation or filtration) of the reaction medium of the 1 èretransesterification reaction and, optionally, be purified (for example, as described below). Step c) is then carried out in a reaction medium comprising at least the so-called "intermediate" CD derivative thus recovered (and optionally purified) and said enzyme configured to catalyze a transesterification reaction at the hydroxyl group on carbon C2 of the glucopyranose units of native CDs and CD derivatives, to which said at least one 2 is added ème vinyl ester of chemical structure (6) so as to carry out at least one 2 ème transesterification reaction.

[0074] In other words, in this embodiment of the invention, the transesterification reactions are carried out sequentially, and between each transesterification reaction, the so-called "intermediate" CD derivatives thus synthesized are recovered and possibly purified so that each new transesterification reaction is initiated with purified "intermediate" CD derivatives. In other words, the "intermediate" CD derivatives are purified as they are obtained in the reaction medium. continue transesterification reactions based on purified so-called "intermediate" CD derivatives.

[0075] In another embodiment of the invention, the transesterification reactions are carried out sequentially by directly and progressively adding the other vinyl ester(s) to the reaction medium, without having recovered or possibly purified the so-called "intermediate" CD derivatives obtained during the addition of the vinyl ester(s). In other words, in this embodiment of the invention, there is no intermediate purification of the CD derivatives obtained in the reaction medium.

[0076] In one embodiment of the invention, some of the transesterification reactions are carried out sequentially and the remaining transesterification reactions are carried out simultaneously.

[0077] In one embodiment of the invention, at the end of step c) or optionally at the end of step d), the CD derivative according to the invention thus obtained is recovered and optionally purified.

[0078] The conditions for the transesterification reactions implemented during the process of preparing a CD derivative according to the invention may advantageously be at least one of the following, taken alone or in combination thereof: - the temperature of the reaction medium can be between 20°C and 70°C, preferably between 40°C and 45°C; for example 45°C; - the reaction medium can be subjected to agitation, for example at an agitation speed of between 1 revolution / minute and 500 revolutions / minute, preferably between 200 revolutions / minute and 250 revolutions / minute.

[0079] Following the transesterification reactions, advantageously, the CD derivative thus prepared can be recovered and purified.

[0080] Indeed, at the end of the transesterification reactions, a synthetic product containing the unpurified CD derivative according to the invention is obtained.

[0081] Without limiting the scope of the invention, in a 1 er According to the embodiment of the invention, the recovery and purification of the CD derivative can be carried out in the following manner: 1) the enzyme is removed by centrifugation or filtration from the reaction medium thus obtained at the end of the last transesterification reaction and the supernatant or filtrate is recovered; 2) the synthesis product is precipitated from the supernatant (or filtrate) thus recovered by mixing in a non-solvent (i.e. a solvent in which the CD derivative according to the invention is not soluble) of the synthesis product (for example by adding a volume of an aqueous solution of methanol containing 35% by volume of methanol for a volume of supernatant); 3) in order to eliminate any possible traces of synthesis solvent (for example the solvent in which the native CD was optionally solubilized, in particular DMSO), the synthesis product is then isolated by solubilization cycles in a volatile organic solvent (for example tetrahydrofuran (hereafter abbreviated as "THF") or acetone) and then by precipitation in acetonitrile; 4) The isolated product obtained at the end of step 3) is then solubilized in a solvent (by example ethanol, acetone, THF), then filtered and dried (for example under reduced pressure or under vacuum) so as to obtain the CD derivative in a purified form.

[0082] Without limiting the scope of the invention, in a 2 ème According to the embodiment of the invention, the recovery and purification of the CD derivative can be carried out in the following manner: 1) the enzyme is removed by centrifugation or filtration from the reaction medium thus obtained at the end of the last transesterification reaction and the supernatant or filtrate is recovered; 2) the supernatant or filtrate thus obtained is diluted 1 / 3 to 1 / 4 in water, preferably distilled water, which is then frozen (for example at -80°C); 3) The solvent in which the native CD and water were solubilized is removed by sublimation under reduced pressure (e.g. 0.002 mbar), e.g. at room temperature (20°C), so as to obtain the CD derivative in a purified form.

[0083] The implementation of the recovery and purification of the CD derivative according to the invention is perfectly within the capabilities of a person skilled in the art.

[0084] As explained above, the inventors discovered that the characteristics of the CD derivatives according to the invention, as detailed above, enabled them to spontaneously self-organize satisfactorily in a solvent (e.g., water) to obtain particles of the CD derivative.

[0085] Therefore, the invention also relates to a particle (micro- or nanoparticle) which is characterized in that it comprises at least one CD derivative according to the invention as described above or at least one CD derivative obtained according to the preparation process as described above.

[0086] Depending on its size, the particle according to the invention can be a microparticle or a nanoparticle.

[0087] In one embodiment of the invention, said particle may further comprise at least one active substance.

[0088] As mentioned above, CDs and CD derivatives are host molecules that can form inclusion complexes with at least one guest molecule such as an active substance.

[0089] In one embodiment of the invention, said CD derivative according to the invention and at least one active substance can form an inclusion complex.

[0090] In another embodiment of the invention, said particle further comprises at least one active substance that does not form an inclusion complex with said CD derivative according to the invention. In this embodiment, the active substance is encapsulated within the particle based on the CD derivative according to the invention.

[0091] The active substance may be chosen from the group consisting of pharmaceutical active ingredients (for human or animal use), cosmetic active ingredients, plant protection active compounds, food active compounds, food active compounds, biological active compounds, colorants and pigments.

[0092] The active substance can be any suitable molecule, whether or not it forms an inclusion complex with the CD derivative according to the invention. The choice of the active substance is perfectly within the capabilities of a person skilled in the art.

[0093] The particle according to the invention may comprise one or more different active substances.

[0094] In one embodiment of the invention, the particle comprises an active substance that may or may not form an inclusion complex with the CD derivative. In another embodiment of the invention, the particle comprises two different active substances that may or may not form an inclusion complex with the CD derivative.

[0095] The particle size according to the invention can be between 0.1 pm and 2 pm, preferably between 0.15 pm and 1 pm.

[0096] Advantageously, the particles according to the invention can be spheroidal.

[0097] The invention also relates to a method for manufacturing particles according to the invention, which is characterized in that it comprises at least the following steps: a) a 1 era mixture comprising at least one CD derivative according to the invention as described above or at least one CD derivative obtained according to the preparation process according to the invention as described above, a polar organic solvent and, optionally at least one er surfactant and / or at least one 1 ère active substance; b) a 2 is prepared ème a mixture comprising at least water and, optionally at least one 2 ème surfactant and / or at least one 2 ème active substance; c) one of the 1 is added er or 2 ème mixing with the other mixture, so as to obtain a suspension of said particles.

[0098] In other words, in the 1 er mixture, the presence of 1 er surfactant, as well as the 1 ère The active substance is optional. In the 2 ème mixture, the presence of 2 ème surfactant, as well as the 2 ème The active substance is optional.

[0099] In one embodiment of the invention, said 1 er mixture may include a 1 ère active substance.

[0100] In one embodiment of the invention, said 1 er mixture may include two 1 ères active substances.

[0101] In step a), the polar organic solvent is advantageously miscible in any proportion with water, preferably distilled water.

[0102] In step a), the polar organic solvent can be chosen from the group consisting of acetone, methanol, ethanol, isopropanol and THF, taken alone or in mixtures thereof.

[0103] In step a), the 1 er The surfactant can be a non-ionic lipophilic surfactant, preferably with an HLB between 4 and 8. HLB is the English acronym for "Hydrophilic-Lipophilic Balance," which translates to "hydrophilic / lipophilic equilibrium." The aforementioned 1 erThe surfactant can be a sorbitan ester (for example, sorbitan oleate).

[0104] In step a), the 1 ère The active substance is preferably a molecule soluble and / or miscible in the 1 er mixture. Said 1 ère The active substance is insoluble in water. Thus, the 1 ère The active substance is preferably fat-soluble. 1 ère The active substance can be chosen from among pharmaceutical (human or animal) or cosmetic active ingredients, plant protection product active compounds, food active compounds, food processing active compounds, biological active compounds, colorants, and pigments. For example, it could be a derivative of vitamin C, vitamin E, curcumin, or a lipophilic preservative.

[0105] In step a), the 1 erThe mixture may also include at least one lipophilic compound. This may be a vegetable oil (e.g. olive oil, sunflower oil), a synthetic oil (e.g. Miglyol®), an essential oil (e.g. tea tree essential oil), a butter, or any other lipophilic compound (e.g. benzyl benzoate, isopropyl myristate, a hydrocarbon).

[0106] In this embodiment of the invention, namely when the 1 er If the mixture further comprises at least one lipophilic compound, a capsular-type particle suspension is obtained. These particles include: - an outer envelope containing at least one CD derivative according to the invention as described above or obtained according to the preparation process as described above, and optionally the 1 er surfactant and the 2 ème surfactant; - a core based on the lipophilic compound in which the 1 is optionally dispersed or solubilized ère active substance, said core is surrounded by the outer shell.

[0107] If a 2 ème the active substance is present in the 2 ème When mixed, it ends up in the aqueous phase of the particle suspension.

[0108] The outer envelope is in the form of a wall of very regular thickness.

[0109] Capsular-type particles have the advantage that their nucleus allows for a greater capacity to carry active substances.

[0110] In this regard, it should be noted that when the 1 er If the mixture lacks lipophilic compounds, a suspension of matrix-like particles is obtained. These particles are dense and composed of a matrix, or in other words, a network. In other words, these matrix-like particles do not have cell walls.

[0111] In step b), the 2 ème The surfactant may be a non-ionic hydrophilic surfactant, preferably with an HLB greater than or equal to 10. Said 2 ème For example, the surfactant can be chosen from the group consisting of sugar-derived surfactants, for example alkyl glucosides such as decyl glucoside.

[0112] In step b), the 2 ème The active substance is preferably a molecule soluble in 2 ème mixture. The 2 ème active substance may be chosen from pharmaceutical active compounds (for human or animal use), cosmetic active compounds, plant protection active compounds, food active compounds, food active compounds, biological active compounds, colorants, pigments and preservatives that are hydrophilic.

[0113] In step b), the water can be distilled, salted, acidified or alkalized water.

[0114] The particle preparation process according to the invention can be carried out at a temperature that has little or no effect on its proper execution. This temperature can be any temperature at which the 1 er and the 2 ème The mixtures are liquid. Choosing the temperature is perfectly within the capabilities of a skilled professional. The temperature can be ambient temperature (approximately 20°C).

[0115] The ratio of the volume of 1 er mix on the 2 ème The mixture can be between 3 / 1 and 1 / 5, preferably between 1 / 2 and 2 / 1.

[0116] The mass percentage of at least one 1 er surfactant and / or at least one 2 ème surfactant (if used during the particle preparation process according to the invention), expressed as a percentage of the total mass of the particle suspension obtained at the end of step c), may be between 0.1% and 10%, preferably between 0.2% and 2%.

[0117] Preferably, step c) is carried out under agitation, for example at an agitation speed of between 50 rpm and 1000 rpm, preferably between 250 rpm and 500 rpm.

[0118] Agitation can be achieved by means of a magnetic stir bar.

[0119] In step c), the particle suspension forms almost instantaneously. In other words, in the aqueous phase, the CD derivatives according to the invention spontaneously self-organize.

[0120] In one embodiment of the invention, at the end of step c), all or part of the polar organic solvent can be removed. The removal of all or part of the polar organic solvent can, for example, be carried out under reduced pressure. This step of removing the polar organic solvent is perfectly within the capabilities of a person skilled in the art.

[0121] Furthermore, at the end of step c), or possibly at the end of this polar organic solvent removal step if this step is performed, all or part of the water can be removed under vacuum until a suspension of particles according to the invention is obtained at a desired concentration, or the particles are in solid form. This step of concentrating the particle suspension is perfectly within the capabilities of a person skilled in the art.

[0122] The particle suspension obtained at the end of step c), or possibly at the end of the polar organic solvent removal step, or even at the end of the particle suspension concentration step if this or these steps are carried out, can be filtered. The filtration of the particle suspension is perfectly within the capabilities of a person skilled in the art.

[0123] At the end of step c), the suspension of particles thus obtained can also be sterilized, buffered (for example to physiological pH), and lyophilized.

[0124] The particles according to the invention, whether of matrix or capsular type, have the advantage of allowing a high incorporation rate of the 1 ère active substance. This is due to the possibility of two systems of incorporation (i.e., molecular or particulate encapsulation) of the active substances into said particles: - firstly, a charge from the 1 ère active substance in the matrix in the case of matrix-type particles or, in the nucleus in the case of capsular-type particles, and - Secondly, a possible charge of the 1 ère active substance in the cavity of the CD derivative, due to the fact that said 1 ère active substance may have a suitable conformation relative to the cavity of the CD derivative.

[0125] Thanks to the particles according to the invention, the 1 ères active substances exhibit improved physicochemical stability due to their integration within particles that remain stable over time, which are obtained by spontaneous and durable self-organization of CD derivatives according to the invention and which can further form inclusion complexes with said 1 ère active substances.

[0126] Advantageously, no surfactant is used during the manufacturing process of particles according to the invention so that said particles are as natural and biodegradable as possible.

[0127] Because the particles according to the invention comprise CD derivatives capable of forming inclusion complexes with one or more active substances, they offer the following advantages: - they allow the bioavailability of said active substances to be modulated; - they improve the chemical stability of said active substances, by protecting them from light and / or interactions with other incompatible components; - they ensure a prolonged and controlled release of said active substances, for example in the dermis, in the case of cosmetic active compounds.

[0128] The particles according to the invention are therefore particularly suitable for incorporation into compositions requiring the encapsulation of active substances for the reasons detailed in particular in the introduction to the description of the present invention.

[0129] Therefore, the invention also relates to a composition, preferably a composition chosen from pharmaceutical, cosmetic, food, agri-food, phytosanitary, paint, varnish, textile dye compositions, which is characterized in that it comprises at least particles according to the invention as described above or obtained according to the manufacturing process as described above.

[0130] The invention and its advantages are illustrated in the examples below.

[0131] Product summary: comparative CD derivatives and CD derivatives according to the invention:

[0132] For all the syntheses described below, the enzyme used was thermolysin, more specifically, the type X protease isolated from Bacillus thermoproteolyticus rokko marketed by the company Sigma Aldrich under the trade name P1512-250mg.

[0133] Regeneration of celite® (diatomaceous earth):

[0134] The thermolysin immobilization support was celite®, which was regenerated as follows: 10 g of celite® were regenerated in 6 hours at 80°C in 100 mL of an acid solution Nitric acid (with a volume percentage of 69.5%) was used in a reflux setup. The nitric acid was then removed by filtration, and the celite® was washed with distilled water until a stable pH of 6.5–7 was reached. The regenerated celite® was then oven-dried at 80°C before being stored in an airtight container.

[0135] Immobilization of thermolysine on celite®:

[0136] Thermolysin was immobilized on celite® as follows: 100 mg of thermolysin was mixed at 20°C in 5 mL of a 3-morpholino-1-propanesulfonic acid buffer solution (concentration of 50 mmol / L and pH 7.5). The resulting preparation was added to 1 g of regenerated celite®. The liquid phase of this preparation was slowly removed at 25°C under reduced pressure to obtain 100 mg of thermolysin immobilized on 1 g of celite®.

[0137] Summary of comparative product 1: derivative of comparative CD 1:

[0138] 1.00015 g (782 pmol) of native beta-CD was solubilized in 9.0981 g of DMSO, then mixed with 100.08 mg of thermolysin immobilized on 1 g celite® under stirring (250 rpm) at a temperature of 45°C so as to obtain a beta-CD solution in the presence of the thermolysin immobilized on celite® suspended in the reaction medium.

[0139] Next, with a view to a single transesterification reaction with a degree of molecular substitution of 4, 0.63007 g (313 mmol) of vinyl decanoate was introduced into the reaction medium.

[0140] The reaction medium thus obtained was incubated at a temperature of 45°C during which the transesterification reaction took place.

[0141] The transesterification reaction of CD was monitored by thin-layer chromatography by comparison with native beta-CD dissolved in DMSO. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (6 / 1 / 3 / 1 v / v / v / v) and was detected with a developer comprising 5 g of potassium dichromate in 100 mL of an aqueous sulfuric acid solution containing 40% by volume of said sulfuric acid.

[0142] At the end of the transesterification reaction, the comparative product 1 thus synthesized was recovered in the following way from the reaction medium: it was separated from the thermolysin immobilized on celite® by recovering the centrifugation supernatant from the reaction medium.

[0143] The CD derivatives synthesized in solution in the supernatant were precipitated by mixing one volume of this supernatant with the same volume of a methanol solution (more precisely a mixture of methanol and distilled water, the volume of methanol representing 30% of the volume of the methanol solution).

[0144] The precipitate obtained was isolated (centrifugation) and traces of DMSO were removed by 3 cycles of solubilization of the product in THF / precipitation in acetonitrile and filtration.

[0145] The recovered product was dissolved in ethanol, filtered, and dried under reduced pressure. It was a 1 erderived from comparative CD 1 (i.e. comparative product 1).

[0146] Product synthesis of invention 1: CD derivative according to invention 1:

[0147] 200.2 mg (20.6 pmol) of comparator product 1 were solubilized in 5.1035 g of DMSO, then mixed with 83.33 mg of thermolysin immobilized on 1 g of celite® under agitation (250 rpm) at a temperature of 45°C so as to obtain a solution of comparator product 1 in the presence of the immobilized thermolysin.

[0148] Next, 0.0623 g (103 pmol) of vinyl butyrate were introduced into the comparator product 1 solution in the presence of immobilized thermolysin.

[0149] The reaction medium thus obtained was incubated at a temperature of 45°C for a period of 96 hours during which a transesterification reaction took place.

[0150] The transesterification reaction was monitored by thin-layer chromatography in the same manner as for comparator product 1. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (by volume in the proportions 9 / 1 / 2 / 1 v / v / v / v) and was revealed with a developer comprising 5 g of potassium dichromate in 100 mL of an aqueous sulfuric acid solution containing 40% by volume of said sulfuric acid.

[0151] Following the transesterification reaction, the product of invention 1 thus synthesized was recovered and purified in the same way as for the comparative product 1. It was a 1 er CD derivative according to the invention.

[0152] Summary of comparative product 2: derivative of comparative CD 2:

[0153] 1.00018 g (881 pmol) of beta-CD was solubilized in 8.4681 g of DMSO, then mixed with 83.16 mg of thermolysin immobilized on 1 g of celite® under agitation (250 rpm) at a temperature of 45°C so as to obtain a beta-CD solution in the presence of the immobilized thermolysin.

[0154] Next, 1.2647 g (3.13 mmol) of vinyl decanoate was introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0155] The reaction medium thus obtained was incubated in a microwave at a temperature of 45°C for a period of 6 hours during which the transesterification reaction took place.

[0156] The transesterification reaction was monitored by thin-layer chromatography in the same way as for comparator product 1.

[0157] Following the transesterification reaction, the comparative product 2 thus synthesized was recovered from the reaction medium as follows: it was separated from the thermolysin immobilized on Celite® by collecting the centrifugation supernatant from the reaction medium. The centrifugation supernatant was precipitated in 30 mL of distilled water. The resulting precipitate was washed in about 70 mL of distilled water, then solubilized in about 50 mL of ethanol, then filtered through pleated filter paper.

[0158] The filtrate was dried under reduced pressure to remove the ethanol, thus obtaining the comparative product 2 in a purified form. This was a 2 ème derivative of comparative CD.

[0159] Product synthesis of invention 2: CD derivative according to invention 2:

[0160] 1 g (881 pmol) of native beta-CD was solubilized in 9.5233 g of DMSO, then mixed with 83.33 mg of thermolysin immobilized on 1 g celite® under agitation (250 rpm) at a temperature of 45°C so as to obtain a beta-CD solution in the presence of the immobilized thermolysin.

[0161] Next, 0.1893 g of vinyl butyrate (1.65 mmol) was introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0162] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for a period of 25 days during which the 1 ère transesterification reaction.

[0163] The 1 ère transesterification reaction was monitored by thin layer chromatography in the same way as for comparator product 1.

[0164] At the end of the 1 èretransesterification reaction, the intermediate product thus synthesized was recovered in the following way in the reaction medium: it was separated from the thermolysin immobilized on celite® by recovering the centrifugation supernatant from the reaction medium.

[0165] An extemporaneous preparation of 83.33 mg of thermolysine immobilized on 1 g of celite® was added to the centrifugation supernatant.

[0166] Then 0.9703 g (4.89 mmols) of vinyl decanoate was added.

[0167] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 144 hours, during which the 2nd reaction occurred. ème transesterification reaction.

[0168] At the end of the 2 èmetransesterification reaction, the synthesis product present in the reaction medium was precipitated by mixing a volume of said reaction medium with an equal volume of a methanol solution (more precisely a mixture of methanol and distilled water, the volume of methanol representing 30% of the volume of the methanol solution).

[0169] The precipitate obtained was isolated (centrifugation) and traces of DMSO were removed by 3 cycles of solubilization of the product in THF / precipitation in itrile aceton and filtration.

[0170] The recovered product of invention 2 was purified as follows: it was dissolved in ethanol, filtered, and dried under reduced pressure. It was a 2 ème CD derivative according to the invention.

[0171] Product synthesis of invention 3: CD derivative according to invention 3:

[0172] 1 g (881 pmol) of native beta-CD was solubilized in 9.5233 g of DMSO, then mixed with 83.33 mg of thermolysin immobilized on 1 g celite® under agitation (250 rpm) at a temperature of 45°C so as to obtain a beta-CD solution in the presence of the immobilized thermolysin.

[0173] Next, 0.3645 g of vinyl butyrate (3.19 mmol) was introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0174] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for a period of 25 days, during which the 1st reaction occurred ère transesterification reaction.

[0175] The 1 ère transesterification reaction was monitored by thin layer chromatography in the same way as for comparator product 1.

[0176] At the end of the 1 èretransesterification reaction, the intermediate product thus synthesized was recovered in the following way in the reaction medium: it was separated from the thermolysin immobilized on celite® by recovering the centrifugation supernatant from the reaction medium.

[0177] An extemporaneous preparation of 83.33 mg of thermolysine immobilized on 1 g of celite® was added to the centrifugation supernatant.

[0178] Then 0.9821 g (4.95 mmols) of vinyl decanoate was added.

[0179] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 144 hours, during which the 2nd reaction occurred. ème transesterification reaction.

[0180] At the end of the 2 èmeIn the transesterification reaction, the synthesis product present in the reaction medium was precipitated by mixing one volume of said reaction medium with an equal volume of a methanol solution (specifically, a mixture of methanol and distilled water, with the volume of methanol representing 30% of the volume of the methanol solution). Then, the DMSO was removed by solubilization / precipitation in a THF / acetonitrile system.

[0181] The recovered product of invention 3 was purified as follows: it was dissolved in ethanol, filtered, and dried under reduced pressure. It was a 3 ème CD derivative according to the invention.

[0182] Product synthesis of invention 4: CD derivative according to invention 4:

[0183] 1 g (881 pmol) of native beta-CD was solubilized in 9.1070 g of DMSO, then mixed with 83.33 mg of thermolysin immobilized on 1 g celite® under agitation (250 rpm) at a temperature of 45°C so as to obtain a beta-CD solution in the presence of the immobilized thermolysin.

[0184] Next, 0.4522 g (3.96 mmol) of vinyl butyrate was introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0185] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for a period of 3 days, during which the 1st reaction occurred ère transesterification reaction.

[0186] Then, after these 3 days of incubation, 0.6309 g of vinyl decanoate (3.18 mmols) was added to the reaction medium.

[0187] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 114 hours, during which the 2nd reaction occurred. ème transesterification reaction.

[0188] At the end of the 2 ème transesterification reaction, the synthesis product present in the reaction medium was precipitated by mixing a volume of said reaction medium with an equal volume of a methanol solution (more precisely a mixture of methanol and distilled water, the volume of methanol representing 30% of the volume of the methanol solution).

[0189] The precipitate obtained was isolated (centrifugation) and traces of DMSO were removed by 3 cycles of solubilization of the product in THF / precipitation in itrile aceton and filtration.

[0190] The recovered product of invention 4 was purified as follows: it was dissolved in ethanol, filtered, and dried under reduced pressure. It was a 4 ème CD derivative according to the invention.

[0191] Product synthesis of invention 5: CD derivative according to invention 5:

[0192] 1.00017 g (881 pmol) of native beta-CD was solubilized in 8.2855 g of DMSO, then mixed with 83.33 mg of thermolysin immobilized on 1 g celite® under agitation (250 rpm) at a temperature of 45°C so as to obtain a beta-CD solution in the presence of the immobilized thermolysin.

[0193] Next, 0.1810 g (1.58 mmol) of vinyl butyrate and 1.2560 g (6.33 mmol) of vinyl decanoate were introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0194] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for a period of 114 hours during which 2 transesterification reactions occurred with the 2 aforementioned vinyl esters.

[0195] Following these 2 transesterification reactions, the synthesis product present in the reaction medium was precipitated by mixing a volume of said reaction medium with an equal volume of a methanol solution (more precisely a mixture of methanol and distilled water, the volume of methanol representing 30% of the volume of the methanol solution).

[0196] The precipitate obtained was isolated (centrifugation) and traces of DMSO were removed by 3 cycles of solubilization of the product in THF / precipitation in itrile aceton and filtration.

[0197] Product synthesis of invention 6: CD derivative according to invention 6:

[0198] 1.00111 g (881 pmol) of native beta-CD was solubilized in 9.0665 g of DMSO, then mixed with 83.33 mg of thermolysin immobilized on 1 g of celite® under agitation (250 rpm) at a temperature of 45°C in order to obtain a beta-CD solution in the presence of immobilized thermolysin.

[0199] Next, 0.3244 g (2.84 mmol) of vinyl butyrate and 0.6397 g (3.22 mmol) of vinyl decanoate were introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0200] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for a period of 114 hours during which 2 transesterification reactions occurred with the 2 aforementioned vinyl esters.

[0201] Following these 2 transesterification reactions, the synthesis product present in the reaction medium was precipitated by mixing a volume of said reaction medium with an equal volume of a methanol solution (more precisely a mixture of methanol and distilled water, the volume of methanol representing 30% of the volume of the methanol solution).

[0202] The precipitate obtained was isolated (centrifugation) and traces of DMSO were removed by 3 cycles of solubilization of the product in THF / precipitation in acetonitrile and filtration.

[0203] Product synthesis of invention 7: CD derivative according to invention 7:

[0204] 1 g (881 pmol) of native beta-CD was solubilized in 9.0915 g of DMSO, then mixed with 83.33 mg of thermolysin immobilized on 1 g celite® under agitation (250 rpm) at a temperature of 45°C to obtain a beta-CD solution in the presence of the catalyst in suspension.

[0205] Next, 0.6293 g (3.17 mmol) of vinyl decanoate was introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0206] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for a period of 3 days, during which the 1st reaction occurred ère transesterification reaction.

[0207] Then, after these 3 days of incubation, 0.5781 g of vinyl butyrate (5.06 mmols) was added to the reaction medium.

[0208] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 114 hours, during which the 2nd reaction occurred. ème transesterification reaction.

[0209] At the end of the 2 èmetransesterification reaction, the synthesis product present in the reaction medium was precipitated by mixing a volume of said reaction medium with an equal volume of a methanol solution (more precisely a mixture of methanol and distilled water, the volume of methanol representing 30% of the volume of the methanol solution).

[0210] The precipitate obtained was isolated (centrifugation) and traces of DMSO were removed by 3 cycles of solubilization of the product in THF / precipitation in acetonitrile and filtration.

[0211] The recovered product of invention 7 was purified as follows: it was dissolved in ethanol, filtered, and dried under reduced pressure. It was a 7 ème CD derivative according to the invention.

[0212] Characterization of the synthesized products:

[0213] All synthesized products were characterized by a MALDI-TOF type mass spectrometry method (abbreviated "MS", as it is the English acronym for "mass spectrometry"): - "MALDI" being the English acronym for "Matrix Assisted Laser Desorption Ionisation"; - "TOF" being the English acronym for "Time-Of-Flight".

[0214] This method is generally referred to by the English acronym "MALDI-TOF-MS" and can be translated as "matrix-assisted laser desorption / ionization time-of-flight mass spectrometry analysis method." It therefore consists of a mass spectrometer coupling a matrix-assisted laser ionization source and a time-of-flight analyzer.

[0215] We describe below the characterization of comparative product 1. All other synthesized products were characterized in the same way.

[0216] Comparative product 1 was solubilized in THF (10 pg / pL) to obtain a solution of comparative product 1.

[0217] A matrix solution was prepared by solubilizing 2,5-dihydroxybenzoic acid (hereafter abbreviated "DHB") in THF (20 mg / mL).

[0218] For the analysis, a mixture of 0.5 pL of the comparator product 1 solution and 0.5 pL of the matrix solution was deposited on a MALDI plate and dried in cold air to crystallize the product on the sample holder (analysis in vacuum).

[0219] Mass spectra were acquired using a time-of-flight mass spectrometer equipped with a reflectron (i.e., an electrostatic mirror or "ion mirror") that deflected positive ions with an electric field, thus doubling the ion's flight path length and increasing the spectrometer's resolution. The time-of-flight spectra were generated by averaging the signals from 10 repetitions of 10 different points (non-homogeneous deposition and desorption of the material at the location of the previous shot) at a frequency of 1000 shots / second.

[0220] The MALDI-TOF-MS method has the advantage of achieving resolutions of 20,000 and thus being able to visualize molecules of similar masses.

[0221] MALDI / TOF analysis of all synthesized products showed for each of them a set of signals confirming the presence of a statistical mixture of differently acylated CD derivatives.

[0222] Indeed, as explained above, the synthetic products obtained from the preparation process of a CD derivative according to the invention are actually a complex mixture of different CD derivatives because the hydroxyl groups of the C2 carbons of the glucopyranose units not all native CD molecules present in the reaction medium have been substituted to the same degree of molecular substitution.

[0223] The identification of the different CD derivatives was carried out by comparison with the theoretical molecular masses of native β-CD, substituted 1 to 7 times at the hydroxyl groups of the C2 carbons of its glucopyranose units by the aliphatic chains provided by vinyl decanoate and / or vinyl butyrate, taking into account the stoichiometries of these two vinyl esters used in the transesterification reactions of the syntheses of the products according to the invention and the comparative products. Subsequently, the relative strength of the different CD derivatives was calculated.

[0224] Table 1 below details, for comparative product 1, the number of substitutions of the hydroxyl groups of the C2 carbons of the glucopyranose units of native beta-CD to give glucosidic subunits of chemical structure (4) with x equal to 10 (because it is derived from vinyl decanoate): - the theoretical molecular masses of CD derivatives; - the molecular masses of CD derivatives determined by MALDI-TOF analysis; - the relative intensities of CD derivatives determined by MALDI-TOF analysis.

[0225] Table 1

[0226] Table 2 below details for product invention 1, as a function of the number of substitutions of the hydroxyl groups of the C2 carbons of the glucopyranose units of native beta-CD to give glucosidic subunits of chemical structure (4) with x equal to 10 (because derived from vinyl decanoate and noted "C10") or with x equal to 4 (because derived from vinyl butyrate and noted "C4"), the molecular masses of the CD derivatives determined by MALDI-TOF analysis.

[0227] Table 2

[0228] Table 3 below details the average molecular masses in g / mol calculated from the results of the MALDI-TOF analyses for comparative products 1 and 2, as well as for invention products 1 to 7. The average molecular mass of a given product thus corresponds to the average of the molecular masses of all the CD derivatives present in said given product.

[0229] Table 3

[0230] Preparation of particles from comparative product 2 and invention products 2 and 4:

[0231] 1 ère preparation of particles from the product of invention 2 (acetone solvent):

[0232] 2.51 mg of product of invention 2 were solubilized at 25°C in 2.5 mL of acetone to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25°C and then poured into 2.5 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm.

[0233] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.

[0234] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0235] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the acetone.

[0236] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0237] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0238] 2 ème preparation of particles from the product of invention 4 (acetone solvent):

[0239] 2.52 mg of product of invention 4 were solubilized at 25°C in 2.5 mL of acetone to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25°C and then poured into 2.5 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm.

[0240] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1. Tl

[0241] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0242] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the acetone.

[0243] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0244] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0245] Characterization of the particles obtained from the products of inventions 2 and 4:

[0246] Particle size was measured by quasi-elastic light scattering, using an instrument marketed by Malvern Panalytical under the trade name Zetasizer Nano ZS, after appropriate dilution of the samples.

[0247] Three analyses of the same sample were carried out. The experimental conditions were as follows: temperature 25 ± 0.1 °C, reference angle 173°, viscosity 0.899 * 10-3 Pa.s and refractive index 1.330.

[0248] Table 4 below details, according to the storage time (i.e., at the initial time "T=0"), then after 1 day, 4 days, 5 days, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks and 13 weeks) of the particles obtained from the product of invention 2, the 3 measurements of their size (nm) obtained, as well as the polydispersity index (hereafter abbreviated "PDI" because it is an English acronym for "PolyDispersity Index") calculated from these measurements.

[0249] The PDI is the ratio between the standard deviation and the mean particle size obtained from the three measurements taken. A low polydispersity index indicates a narrow particle size distribution, while a high polydispersity index indicates a wide distribution with a broad range of particle sizes.

[0250] Table 4

[0251] In view of the results detailed in Table 4 above, it can be noted that the particles obtained from the product of invention 2 remain stable at room temperature over time (namely at least up to 13 weeks).

[0252] Table 5 below details the 3 measurements of the size (nm) of the particles obtained from the product invention 2 and the product invention 4 at T= 0, as well as the PDI calculated from these measurements.

[0253] Table 5

[0254] In view of the results detailed in Table 5 above, it is possible to obtain particles in acetone from products of the invention having different substitutions.

[0255] 3 ème preparation of particles from the product of invention 2 (ethanol solvent):

[0256] Next, particles were prepared in the same way as for the 1 ère preparation of particles except that acetone has been replaced by ethanol.

[0257] 5.09 mg of product of invention 2 were solubilized at 25°C in 5 mL of ethanol to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25°C and then poured into 10 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm.

[0258] The ratio of the volume of the aqueous phase to the volume of the organic phase was 2 / 1.

[0259] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0260] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the ethanol.

[0261] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0262] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0263] 4 ème preparation of particles from the product of invention 4 (ethanol solvent):

[0264] Next, particles were prepared in the same way as for the 2 ème preparation of particles except that acetone has been replaced by ethanol.

[0265] 2.52 mg of product of invention 4 were solubilized at 25°C in 2.5 mL of ethanol to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25°C and then poured into 2.5 mL of distilled water subjected to magnetic stirring at a speed of 420 revolutions per minute.

[0266] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.

[0267] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0268] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the ethanol.

[0269] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0270] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0271] Characterization of the particles obtained from the products of inventions 2 and 4:

[0272] The particle size was measured in the same way as for the 1 ère particle preparation.

[0273] Table 6 below details the 3 measurements of the size (nm) of the particles obtained, as well as the PDI calculated from these measurements.

[0274] Table 6

[0275] Based on the results detailed in Table 6 above, it is possible to obtain particles in ethanol from products of the invention with different substitutions. The particles obtained in ethanol are larger than those obtained in acetone.

[0276] 5 èmepreparation of particles from the product of invention 4 (acetone solvent and by varying the ratio of the volume of the aqueous phase to the volume of the organic phase):

[0277] 5 ème Preparation A: ratio of the volume of the aqueous phase to the volume of the organic phase (1 / 2)

[0278] 2.55 mg of product of invention 4 were solubilized at 25°C in 2.5 mL of acetone to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25°C and then poured into 1.25 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm.

[0279] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 2.

[0280] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0281] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the acetone.

[0282] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0283] The resulting particle suspension was stored in sealed bottles at room temperature.

[0284] 5 ème Preparation B: ratio of the volume of the aqueous phase to the volume of the organic phase (1 / 3)

[0285] 2.50 mg of product of invention 4 were solubilized at 25°C in 2.5 mL of acetone to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25°C and then poured into 0.835 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm.

[0286] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 3.

[0287] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0288] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the acetone.

[0289] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0290] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0291] Characterization of the particles obtained from the product of invention 4:

[0292] The particle size was measured in the same way as for the 1 èreparticle preparation.

[0293] Table 7 below details the 3 measurements of the size (nm) of the particles obtained, as well as the PDI calculated from these measurements.

[0294] Table 7

[0295] In view of the results detailed in Table 7 above, an increase in the size of the particles prepared from the product of invention 4 in acetone is possible by decreasing the ratio of the volume of the aqueous phase to the volume of the organic phase.

[0296] 6 ème Particle preparation (variation of the concentration of the invention product in the organic phase):

[0297] 6 ème Preparation A: concentration of 1 mq / mL of product of invention 4 in the organic phase

[0298] The 6th ème Preparation A of particles corresponds to the 2 ème particle preparation as detailed above.

[0299] 6ème Preparation B: concentration of 2 mq / mL of product of invention 4 in the organic phase

[0300] 5.16 mg of product of invention 4 were solubilized at 25°C in 2.5 mL of acetone to obtain an organic solution with a concentration of 2 mg / mL. This organic solution was stored at 25°C and then poured into 2.5 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm.

[0301] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.

[0302] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0303] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the acetone.

[0304] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0305] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0306] 6 ème Preparation C: concentration of 3 mq / mL of product of invention 4 in the organic phase

[0307] 7.53 mg of product of invention 4 were solubilized at 25°C in 2.5 mL of acetone to obtain an organic solution with a concentration of 3 mg / mL. This organic solution was stored at 25°C and then poured into 2.5 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm.

[0308] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.

[0309] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0310] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the acetone.

[0311] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0312] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0313] Characterization of the particles obtained from the product of invention 4:

[0314] The particle size was measured in the same way as for the 1 ère particle preparation.

[0315] Table 8 below details the 3 measurements of the size (nm) of the particles obtained, as well as the PDI calculated from these measurements.

[0316] Table 8

[0317] In view of the detailed results in Table 8 above, it is possible to vary the particle size by varying the concentration of the invention product in the organic phase.

[0318] 7 ème preparation of particles with a lipophilic compound (tea tree essential oil):

[0319] 6.12 mg of product of invention 2 were solubilized at 25°C in 1.5 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 25 pL of tea tree essential oil and 20 mg of sorbitan oleate (Montane® 80, namely a non-ionic lipophilic surfactant) were added to this mixture to obtain an organic solution.

[0320] This organic solution was stored at 25°C and then added to 0.860 mL of distilled water. The resulting mixture was then stirred magnetically at a speed of 420 rpm.

[0321] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.75.

[0322] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0323] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0324] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0325] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0326] Characterization of the particles obtained from the product of invention 2:

[0327] The particle size was measured in the same way as for the 1 ère particle preparation.

[0328] Table 9 below details, according to the storage duration (namely initially at T=0, then after 1 day, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 12 weeks and 18 weeks) of the particles obtained from the product of invention 2, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements. Table 9

[0330] Based on the detailed results in Table 9 above, it can be seen that capsular-type particles remain stable over time (at least up to 18 weeks).

[0331] 8 ème particle preparation (variation in the nature of the lipophilic compound)

[0332] 8ème Preparation A: 25 µL of tea tree essential oil:

[0333] The 8 ème Preparation A of particles corresponds to the 7th ème particle preparation as detailed above.

[0334] 8 ème Preparation B: 50 µL of tea tree essential oil:

[0335] 6.09 mg of product of invention 4 were solubilized at 25°C in 3 mL of ethanol to obtain an organic solution with a concentration of 2 mg / mL. Then, 50 pL of tea tree essential oil and 20 mg of sorbitan oleate (Montane® 80) were added to this mixture to obtain an organic solution.

[0336] This organic solution was stored at 25°C and then added to 1.72 mL of distilled water. The resulting mixture was then stirred magnetically at a speed of 420 rpm.

[0337] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.75.

[0338] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0339] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0340] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0341] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0342] 8 ème Preparation C: 25 µL of benzyl benzoate:

[0343] 12.09 mg of product of invention 4 were solubilized at 25°C in 3 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 25 pL of benzyl benzoate and 20 mg of sorbitan oleate (Montane® 80) were added to this mixture to obtain an organic solution.

[0344] This organic solution was stored at 25°C and then added to 1.72 mL of distilled water. The resulting mixture was then stirred magnetically at a speed of 420 rpm.

[0345] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.75.

[0346] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0347] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0348] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0349] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0350] 8 ème Preparation D: 50 pL of sunflower oil:

[0351] 12.09 mg of product of invention 4 were solubilized at 25°C in 3 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 50 pL of sunflower oil and 20 mg of sorbitan oleate (Montane® 80) were added to this mixture to obtain an organic solution.

[0352] This organic solution was stored at 25°C and then added to 1.72 mL of distilled water. The resulting mixture was then stirred magnetically at a speed of 420 rpm.

[0353] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.75.

[0354] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0355] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0356] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0357] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0358] Characterization of the particles obtained from the products of inventions 2 and 4:

[0359] The particle size was measured in the same way as for the 1 èreparticle preparation.

[0360] Table 10 below details the 3 measurements of the size (nm) of the particles obtained, as well as the PDI calculated from these measurements.

[0361] Table 10

[0362] Based on the detailed results in Table 10 above, it is possible to obtain particles with different types of lipophilic compound.

[0363] 9 ème preparation of particles encapsulating or not an active substance (vitamin C palmitate) solubilized in tea tree essential oil:

[0364] The active substance vitamin C palmitate is a derivative of vitamin C.

[0365] In these experiments, vitamin C palmitate was first solubilized in tea tree essential oil at a concentration of 100 mg / mL.

[0366] 9 ème Preparation A:

[0367] 6.14 mg of product of invention 4 were solubilized at 25°C in 1.5 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 25 pL of tea tree essential oil and 20 mg of sorbitan oleate (Montane® 80) were added to this mixture to obtain an organic solution.

[0368] This organic solution was stored at 25°C and then added to 0.860 mL of distilled water. The resulting mixture was then stirred magnetically at a speed of 420 rpm.

[0369] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.75.

[0370] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0371] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0372] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0373] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0374] 9 ème Preparation B:

[0375] 6.06 mg of product of invention 4 were solubilized at 25°C in 1.5 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 25 pL of tea tree essential oil (in which 2.5 mg of vitamin C palmitate were solubilized), as well as 20 mg of sorbitan oleate (Montane® 80) were added to this mixture to obtain an organic solution.

[0376] This organic solution was stored at 25°C and then added to 0.860 mL of distilled water. The resulting mixture was then stirred magnetically at a speed of 420 rpm.

[0377] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.75.

[0378] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0379] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0380] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0381] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0382] 9 ème Preparation C:

[0383] 6.08 mg of product of invention 4 were solubilized at 25°C in 1.5 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 12.5 pL of tea tree essential oil (in which 1.25 mg of vitamin C palmitate were solubilized), as well as 20 mg of sorbitan oleate (Montane® 80) were added to this mixture to obtain an organic solution.

[0384] This organic solution was stored at 25°C and then added to 0.860 mL of distilled water. The resulting mixture was then stirred magnetically at a speed of 420 rpm.

[0385] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.75.

[0386] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0387] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0388] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0389] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0390] Characterization of the particles obtained from the product of invention 4:

[0391] The particle size was measured in the same way as for the 1 ère particle preparation

[0392] Table 11 below details the 3 measurements of particle sizes (nm) obtained with these 9 èmes preparations A to C, as well as the PDI calculated from these measurements.

[0393] Table 11

[0394] In view of the results detailed in Table 11 above, it can be noted that it is possible for the particles according to the invention to simultaneously carry a lipophilic compound (tea tree essential oil) and an active substance (vitamin C palmitate).

[0395] 10 ème preparation of particles manufactured in the absence of the decyl glucoside surfactant in the aqueous phase:

[0396] The objective of this io ème The particle preparation was intended to show that: - the particles according to the invention, prepared from the product according to the invention 4, remained perfectly stable over time, even in the absence of the decyl glucoside surfactant in the aqueous phase during their manufacture, - unlike particles prepared from comparative product 2.

[0397] 10 ème Preparation A: particles according to the invention manufactured in the absence of decyl glucoside:

[0398] The io ème Preparation A of particles corresponds to the 9th ème Particle preparation A.

[0399] 10 ème Preparation B: Comparative particles produced in the absence of decyl glucoside:

[0400] 6.17 mg of comparator product 2 were solubilized at 25°C in 1.5 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 25 pL of tea tree essential oil and 20 mg of sorbitan oleate (Montane® 80) were added to obtain an organic solution.

[0401] This organic solution was stored at 25°C and then added to 0.860 mL of distilled water. The resulting mixture was then stirred magnetically at a speed of 420 rpm.

[0402] The ratio of the volume of the aqueous phase to the volume of the organic phase was 1 / 1.75.

[0403] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0404] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0405] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0406] The suspension of particles thus obtained was stored in closed bottles at room temperature.

[0407] Particle characterization:

[0408] The particle size was measured in the same way as for the 1 ère particle preparation

[0409] Table 12 below details the 3 measurements of particle sizes (nm) obtained with these io èmes preparations A and B, as well as the PDI calculated from these measurements.

[0410] Table 12

[0411] The particles obtained from product 4 of invention remain stable over time, even though they were obtained in the absence of the decyl glucoside surfactant. In contrast, the particle size obtained from comparative product 2, also in the absence of the decyl glucoside surfactant, is more polydisperse and changes over time. These particles are not stable over time.

[0412] This io ème Particle preparation demonstrates that with particles according to the invention prepared from CD derivatives according to the invention, it is possible to avoid adding a surfactant to the aqueous phase during their manufacture.

[0413] This demonstrates the great value of CD derivatives according to the invention, which make it possible to manufacture particles that are as natural as possible.

[0414] Product synthesis of invention 8: CD derivative according to invention 8:

[0415] 1 g (771 pmol) of native gamma-CD was solubilized in 10 mL of DMSO, then mixed with 100 mg of thermolysin immobilized on 1 g of celite® under stirring (250 rpm) at a temperature of 45 °C to obtain a gamma-CD solution in the presence of the catalyst in suspension.

[0416] Next, 0.176 g (1.54 mmol) of vinyl butyrate was introduced into the gamma-CD solution in the presence of immobilized thermolysin.

[0417] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for 64 hours, during which the 1st reaction occurred ère transesterification reaction.

[0418] The transesterification reaction of CD was monitored by thin-layer chromatography by comparison with native gamma-CD dissolved in DMSO. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (6 / 1 / 3 / 1 v / v / v / v) and was detected with a developer comprising 5 g of potassium dichromate in 100 mL of an aqueous sulfuric acid solution containing 40% by volume of said sulfuric acid.

[0419] After 64 hours of incubation, 1.0709 g of vinyl decanoate (5.40 mmols) was added to the reaction medium.

[0420] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 141 hours, during which the 2nd reaction occurred. èmetransesterification reaction. The reaction was monitored by thin-layer chromatography and analyzed with the same developer. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (8 / 1 / 1 / 1 v / v / v / v).

[0421] At the end of the 2 ème For the transesterification reaction, the reaction mixture was centrifuged (4000 g, 10 minutes) to allow the Celite® and immobilized thermolysin to settle. 75 mL of distilled water were added to the supernatant containing 10 mL of DMSO and the synthesis product, and the resulting solution was stirred at 300 rpm at room temperature for 30 minutes. It was then frozen at -65°C before being lyophilized.

[0422] The freeze-dried solid was dissolved in 50 mL of absolute ethanol, stirred at 300 rpm and left at room temperature for 2 hours, then filtered through a sintered glass flask under reduced pressure. The precipitate obtained on the sintered glass flask was washed with an additional 25 mL of absolute ethanol, and the light yellow filtrate was concentrated under reduced pressure using a rotary evaporator.

[0423] To eliminate the last traces of DMSO, 20 mL of distilled water were added to the dried product and, after freezing at -65 °C, the mixture was lyophilized to give product invention 8, namely an 8 ème CD derivative according to the invention. It was a white solid with a mass of 1.3559 g.

[0424] Product synthesis of invention 9: CD derivative according to invention 9:

[0425] 1 g (881 pmol) of native beta-CD was solubilized in 10 mL of DMSO, then mixed with 100 mg of thermolysin immobilized on 1 g of celite® under stirring (250 rpm) at a temperature of 45 °C to obtain a beta-CD solution in the presence of the catalyst in suspension.

[0426] Next, 0.152 g (1.76 mmol) of vinyl acetate was introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0427] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for a period of 70 hours, during which the 1st reaction occurred ère transesterification reaction.

[0428] The transesterification reaction of CD was monitored by thin-layer chromatography by comparison with native beta-CD dissolved in DMSO. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (6 / 1 / 3 / 1 v / v / v / v) and was detected with the same developer as previously described.

[0429] After 70 hours of incubation, 1.197 g of vinyl laurate (5.29 mmols) was added to the reaction medium.

[0430] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 161 hours, during which the 2nd reaction occurred. ème transesterification reaction. The reaction was monitored by thin-layer chromatography with a mobile phase composed of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (7 / 1 / 2 / 1 v / v / v / v).

[0431] At the end of the 2 èmeFor the transesterification reaction, the reaction medium was centrifuged (4000 g, 10 minutes) to allow the Celite® and immobilized thermolysin to settle. 85 mL of distilled water were added to the supernatant containing 10 mL of DMSO and the synthesis product, and the resulting solution was stirred at 300 rpm at room temperature for 30 minutes. It was then frozen at -65 °C before being lyophilized.

[0432] The freeze-dried solid was dissolved in 50 mL of absolute ethanol, stirred at 300 rpm and left at room temperature for 30 minutes, and then filtered through a sintered glass flask under reduced pressure. The precipitate obtained on the sintered glass flask was washed with an additional 25 mL of absolute ethanol, and the light yellow filtrate was concentrated under reduced pressure using a rotary evaporator.

[0433] To eliminate the last traces of DMSO, 20 mL of distilled water were added to the dried product and, after freezing at -65 °C, the mixture was lyophilized to give product invention 9, namely a 9 ème CD derivative according to the invention. It was a pale yellow solid with a mass of 1.0645 g-

[0434] Product synthesis of invention 10: CD derivative according to invention 10:

[0435] 1 g (771 pmol) of native gamma-CD was solubilized in 10 mL of DMSO, then mixed with 100 mg of thermolysin immobilized on 1 g of celite® under stirring (250 rpm) at a temperature of 45°C to obtain a gamma-CD solution in the presence of the catalyst in suspension.

[0436] Next, 0.133 g (1.54 mmol) of vinyl acetate was introduced into the gamma-CD solution in the presence of immobilized thermolysin.

[0437] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for 50 hours, during which the 1st reaction occurred ère transesterification reaction.

[0438] The transesterification reaction of CD was monitored by thin-layer chromatography by comparison with native gamma-CD dissolved in DMSO. The mobile phase was composed of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (6 / 1 / 3 / 1 v / v / v / v) and it was revealed with the same developer as previously described.

[0439] After 50 hours of incubation, 1.222 g of vinyl laurate (5.40 mmols) was added to the reaction medium.

[0440] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 161 hours, during which the 2nd reaction occurred. èmetransesterification reaction. The reaction was monitored by thin-layer chromatography with a mobile phase composed of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (7 / 1 / 2 / 1 v / v / v / v).

[0441] At the end of the 2 ème For the transesterification reaction, the reaction medium was centrifuged (4000 g, 10 min) to allow the Celite® and immobilized thermolysin to settle. 75 mL of distilled water were added to the supernatant containing 10 mL of DMSO and the synthesis product, and the resulting solution was stirred at 300 rpm at room temperature for 30 minutes. It was then frozen at -65 °C before being lyophilized.

[0442] The freeze-dried solid was dissolved in 50 mL of absolute ethanol, stirred at 300 rpm and left at room temperature for 30 minutes, and then filtered through a sintered glass flask under reduced pressure. The precipitate obtained on the sintered glass flask was washed with an additional 25 mL of absolute ethanol, and the colorless filtrate was concentrated under reduced pressure using a rotary evaporator.

[0443] To eliminate the last traces of DMSO, 10 mL of distilled water were added to the dried product and, after freezing at -65°C, the mixture was lyophilized to give product invention 10, namely a 10 ème CD derivative according to the invention. It was a white solid with a mass of 1.3212 g-

[0444] Product synthesis of invention 11: CD derivative according to invention 11:

[0445] 1 g (771 pmol) of native gamma-CD was solubilized in 10 mL of DMSO, then mixed with 100 mg of thermolysin immobilized on 1 g of celite® under stirring (250 rpm) at a temperature of 45°C to obtain a gamma-CD solution in the presence of the catalyst in suspension.

[0446] Next, 0.199 g (2.31 mmol) of vinyl acetate was introduced into the gamma-CD solution in the presence of immobilized thermolysin.

[0447] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for a period of 53 hours, during which the 1st reaction occurred ère transesterification reaction.

[0448] The transesterification reaction of CD was monitored by thin-layer chromatography by comparison with native gamma-CD dissolved in DMSO. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (6 / 1 / 3 / 1 v / v / v / v) and was detected with the same developer as previously described.

[0449] After 53 hours of incubation, 1.047 g of vinyl laurate (4.63 mmols) was added to the reaction medium.

[0450] The reaction medium thus obtained was incubated again at 45 °C with stirring at 250 rpm for a period of 136 hours, during which the 2nd reaction occurred. ème transesterification reaction. The reaction was monitored by thin-layer chromatography with a mobile phase composed of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (7 / 1 / 2 / 1 v / v / v / v).

[0451] At the end of the 2 èmeFor the transesterification reaction, the reaction mixture was centrifuged (5000 g, 15 minutes) to allow the Celite® and immobilized thermolysin to settle. The supernatant, containing 10 mL of DMSO and the synthesis product, was then concentrated under reduced pressure using a rotary evaporator. 30 mL of distilled water were added to the resulting viscous oil, and the resulting suspension was stirred at 250 rpm and room temperature for 21 hours. After freezing in liquid nitrogen, the suspension was lyophilized.

[0452] The solid obtained after freeze-drying was dissolved in 50 mL of absolute ethanol, stirred at 300 rpm and left at room temperature for 45 minutes, then filtered through a sintered glass slurry under reduced pressure. The precipitate obtained on the sintered glass was then washed with an additional 40 mL of absolute ethanol, and the colorless filtrate was concentrated under reduced pressure in a rotary evaporator, leading to the product of invention 11, namely a 11 ème CD derivative according to the invention. It was a whitish solid with a mass of 1.3076 g.

[0453] Product synthesis of invention 12: CD derivative according to invention 12:

[0454] 1 g (881 pmol) of native beta-CD was solubilized in 10 mL of DMSO, then mixed with 100 mg of thermolysin immobilized on 1 g of celite® under stirring (250 rpm) at a temperature of 45 °C to obtain a beta-CD solution in the presence of the catalyst in suspension.

[0455] Next, 0.228 g (2.643 mmol) of vinyl acetate was introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0456] The reaction medium thus obtained was incubated at a temperature of 45 °C with stirring at 250 rpm for a period of 49 hours, during which the 1st reaction occurred ère transesterification reaction.

[0457] The transesterification reaction of CD was monitored by thin-layer chromatography by comparison with native beta-CD dissolved in DMSO. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (6 / 1 / 3 / 1 v / v / v / v) and was detected with the same developer as previously described.

[0458] After 49 hours of incubation, 0.997 g of vinyl laurate (4.41 mmols) was added to the reaction medium.

[0459] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 136 hours, during which the 2nd reaction occurred. ème reaction of transesterification. The reaction was monitored by thin-layer chromatography with a mobile phase composed of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (7 / 1 / 2 / 1 v / v / v / v).

[0460] At the end of the 2 èmeFor the transesterification reaction, the reaction medium was centrifuged (5000 g, 15 minutes) to allow the Celite® and immobilized thermolysin to settle. The supernatant, containing 10 mL of DMSO and the synthesis product, was then concentrated under reduced pressure using a rotary evaporator. 30 mL of distilled water were added to the resulting viscous oil, and the resulting suspension was stirred at 300 rpm at room temperature for 2 hours. After freezing in liquid nitrogen, the suspension was lyophilized.

[0461] The solid obtained after freeze-drying was dissolved in 50 mL of absolute ethanol, stirred at 300 rpm and left at room temperature for 1.5 hours, then filtered through a sintered glass condenser under reduced pressure. The precipitate obtained on the sintered glass condenser was washed with an additional 40 mL of absolute ethanol, and the light yellow filtrate was concentrated under reduced pressure in a rotary evaporator, leading to the product of invention 12, namely I2 ème CD derivative according to the invention. It was a solid in the form of a yellow powder with a mass of 1.2869 g.

[0462] Product synthesis of invention 13: CD derivative according to invention 13:

[0463] 1 g (881 pmol) of native beta-CD was solubilized in 10 mL of DMSO, then mixed with 100 mg of thermolysin immobilized on 1 g of celite® under stirring (250 rpm) at a temperature of 45°C to obtain a beta-CD solution in the presence of the catalyst in suspension.

[0464] Next, 0.152 g (1.76 mmol) of vinyl acetate was introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0465] The reaction medium thus obtained was incubated at a temperature of 45 °C under stirring at 250 rpm for 73 hours, during which the 1st reaction occurred ère transesterification reaction.

[0466] The transesterification reaction of CD was monitored by thin-layer chromatography by comparison with native beta-CD dissolved in DMSO. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (6 / 1 / 3 / 1 v / v / v / v) and was detected with the same developer as before.

[0467] After 73 hours of incubation, 1.048 g of vinyl decanoate (5.29 mmols) was added to the reaction medium.

[0468] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 134 hours, during which the 2nd reaction occurred. ème transesterification reaction. The reaction was monitored by thin-layer chromatography with a mobile phase composed of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (7 / 1 / 2 / 1 v / v / v / v).

[0469] At the end of the 2 èmeFor the transesterification reaction, the reaction medium was centrifuged (5000 g, 15 minutes) to allow the Celite® and immobilized thermolysin to settle. The supernatant, containing 10 mL of DMSO and the synthesis product, was then concentrated under reduced pressure using a rotary evaporator. 30 mL of distilled water were added to the resulting viscous oil, and the suspension was stirred at 300 rpm at room temperature for 18 hours. After freezing in liquid nitrogen, the suspension was lyophilized.

[0470] The solid obtained after freeze-drying was dissolved in 50 mL of absolute ethanol, stirred at 300 rpm and left at room temperature for 2 hours, then filtered through a sintered glass under reduced pressure. The precipitate obtained on the sintered glass was washed with an additional 40 mL of absolute ethanol, and the light yellow filtrate was concentrated under reduced pressure in a rotary evaporator, leading to product 13 of invention, namely a 13 ème CD derivative according to the invention. It was a solid in powder form with a mass of 1.2305 g.

[0471] Product synthesis of invention 14: CD derivative according to invention 14:

[0472] 1 g (771 pmol) of native gamma-CD was solubilized in 10 mL of DMSO, then mixed with 100 mg of thermolysin immobilized on 1 g of celite® under stirring (250 rpm) at a temperature of 45°C to obtain a gamma-CD solution in the presence of the catalyst in suspension.

[0473] Next, 0.133 g (1.54 mmol) of vinyl acetate was introduced into the gamma-CD solution in the presence of immobilized thermolysin.

[0474] The reaction medium thus obtained was incubated at a temperature of 45°C with stirring at 250 rpm for a period of 71 hours, during which the 1st reaction occurred ère transesterification reaction.

[0475] The transesterification reaction of CD was monitored by thin-layer chromatography by comparison with native gamma-CD dissolved in DMSO. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (6 / 1 / 3 / 1 v / v / v / v) and was detected with the same developer as before.

[0476] After 71 hours of incubation, 1.070 g of vinyl decanoate (5.40 mmols) was added to the reaction medium.

[0477] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 134 hours, during which the 2nd reaction occurred. ème transesterification reaction. The reaction was monitored by thin-layer chromatography with a mobile phase composed of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (7 / 1 / 2 / 1 v / v / v / v).

[0478] At the end of the 2 ème For the transesterification reaction, the reaction medium was centrifuged (5000 g, 15 minutes) to allow the Celite® and immobilized thermolysin to settle. The supernatant, containing 10 mL of DMSO and the synthesis product, was then concentrated under reduced pressure using a rotary evaporator. 50 mL of distilled water was added to the viscous oil. The resulting suspension was shaken at 300 rpm and at room temperature for 18 hours. After freezing in liquid nitrogen, the suspension was lyophilized.

[0479] The solid obtained after freeze-drying was dissolved in 50 mL of absolute ethanol, stirred at 300 rpm and left at room temperature for 2 hours, and then filtered through a sintered glass condenser under reduced pressure. The precipitate obtained on the sintered glass condenser was washed with an additional 40 mL of absolute ethanol, and the colorless filtrate was concentrated under reduced pressure in a rotary evaporator, leading to the product of invention 14, namely an I4 ème CD derivative according to the invention. It was a solid in the form of a white powder with a mass of 1.2836 g.

[0480] Product synthesis of invention 15: CD derivative according to invention 15:

[0481] 1 g (881 pmol) of native beta-CD was solubilized in 10 mL of DMSO, then mixed with 83 mg of thermolysin immobilized on 1 g of celite® under agitation (250 rpm) at a temperature of 45°C to obtain a beta-CD solution in the presence of the catalyst in suspension.

[0482] Next, 0.186 g (1.63 mmol) of vinyl butyrate was introduced into the beta-CD solution in the presence of immobilized thermolysin.

[0483] The reaction medium thus obtained was incubated at a temperature of 45°C under stirring at 250 rpm for 2 days, during which the 1st reaction occurred ère transesterification reaction.

[0484] The transesterification reaction of CD was monitored by thin-layer chromatography by comparison with native beta-CD dissolved in DMSO. The mobile phase consisted of 2-propanol / pure ethyl acetate / distilled water / 30% ammonia (6:1 / 3:1 v / v / v / v) and was detected with the same developer as previously described.

[0485] After 2 days of incubation, 1.082 g of vinyl laurate (4.78 mmols) was added to the reaction medium.

[0486] The reaction medium thus obtained was incubated again at 45°C with stirring at 250 rpm for a period of 25 days, during which the 2nd reaction occurred. ème transesterification reaction. The reaction was monitored by thin-layer chromatography using the same mobile phase as before.

[0487] At the end of the 2 èmeFor the transesterification reaction, the reaction medium was centrifuged twice consecutively (5000 g, 15 minutes) to allow the Celite® and immobilized thermolysin to settle. The supernatant, containing 10 mL of DMSO and the synthesis product, was then concentrated under reduced pressure using a rotary evaporator. 30 mL of distilled water were added to the resulting viscous oil, and the resulting suspension was stirred at 300 rpm at room temperature for 2 hours. After freezing in liquid nitrogen, the suspension was lyophilized.

[0488] The solid obtained after freeze-drying was dissolved in 50 mL of absolute ethanol, stirred at 300 rpm and left at room temperature for 2 hours, then filtered through a sintered glass slurry under reduced pressure. The precipitate obtained on the sintered glass was then washed with an additional 40 mL of absolute ethanol, and the dark yellow filtrate was concentrated under reduced pressure using an evaporator. rotating, leading to product invention 15, namely a 15 ème CD derivative according to the invention. It was a solid in the form of a dark beige powder with a mass of 1.2529 g.

[0489] Particle preparation

[0490] 11 ème preparation of particles from the product of invention 8 (ethanol solvent):

[0491] 3.8 mg of product of invention 8 were dissolved at 25 °C in 3.8 mL of ethanol to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25 °C and then added to 3.8 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.

[0492] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0493] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the ethanol.

[0494] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0495] The suspension of particles thus obtained was kept in a closed bottle and stored at 4°C.

[0496] Characterization of the particles obtained from the product of invention 8:

[0497] Table 13 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week, 2 weeks and 4 weeks) of the particles obtained from the product invention 8, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements.

[0498] Table 13

[0499] Based on the results presented in Table 13 above, matrix-like particles can be obtained in ethanol with a substituted gamma-CD in the same way as the corresponding substituted beta-CD (2 C4 and 5 or 6 C10 depending on the nature of the CD). The particles obtained are monodisperse (PDI < 0.25) and their average diameter of 0.22 to 0.23 pm remains stable for at least 4 weeks.

[0500] 12 ème preparation of particles of the product of invention 8 (acetone solvent):

[0501] 3.7 mg of product of invention 8 were dissolved at 25°C in 3.7 mL of acetone to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25°C and then added to 3.7 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.

[0502] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0503] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the acetone.

[0504] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0505] The suspension of particles thus obtained was kept in a closed bottle and stored at 4 °C.

[0506] Characterization of the particles obtained from the product of invention 8:

[0507] Table 14 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week, 2 weeks and 4 weeks) of the particles obtained from the product invention 8, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements.

[0508] Table 14

[0509] Based on the results presented in Table 14 above, matrix-like particles can be obtained in acetone with a substituted gamma-CD in the same way as with the corresponding substituted beta-CD (2 C4 and 5 or 6 C10 depending on the CD species). The particles obtained are monodisperse (PDI < 0.25) and their average diameter of 0.12 pm remains stable for at least 4 weeks.

[0510] 13 ème preparation of particles of the product of invention 8 (acetone solvent):

[0511] 7.8 mg of product of invention 8 were dissolved at 25°C in 7.8 mL of acetone to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25°C and then added to 3.9 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:2.

[0512] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0513] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the acetone.

[0514] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0515] The suspension of particles thus obtained was kept in a closed bottle and stored at 4 °C.

[0516] Characterization of the particles obtained from the product of invention 8:

[0517] Table 15 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week and 2 weeks) of the particles obtained from the product invention 8, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements. Table 15

[0518] Based on the detailed results in Table 15 above and compared with those in Table 14, particles obtained in acetone from the same batch of substituted CD (namely gamma-CD(2C4,6C10)) but with different aqueous / organic phase ratios resulted in particles of different sizes. Particles prepared from a 1:2 ratio were larger than those prepared from a 1:1 ratio. They were monodisperse, and their average diameter of 0.34 to 0.35 pm remained stable for at least two weeks.

[0519] 14 ème preparation of particles of the product invention 8 (ethanol solvent):

[0520] 7.6 mg of product of invention 8 were dissolved at 25 °C in 7.6 mL of ethanol to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25 °C, and then half of it was added to 7.6 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 2:1.

[0521] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0522] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the ethanol.

[0523] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0524] The suspension of particles thus obtained was kept in a closed bottle and stored at 4 °C.

[0525] Characterization of the particles obtained from the product of invention 8:

[0526] Table 16 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week and 2 weeks) of the particles obtained from the product invention 8, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements.

[0527] Table 16

[0528] Similar to the 13th èmeParticle preparation: Particles obtained in acetone from the same batch of substituted CD (gamma-CD(2C4,6C10)) but with different aqueous / organic phase ratios result in particles of different sizes. Particles prepared from a 2:1 ratio are smaller than those prepared from a 1:1 ratio. They are monodisperse (PDI < 0.25) and their average diameter of 0.10 pm remains stable for at least two weeks.

[0529] 15 ème preparation of particles of the product invention 1 1 (acetone solvent):

[0530] 3.0 mg of product of invention 11 were dissolved at 25 °C in 3.0 mL of acetone to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25 °C and then added to 3.0 mL of distilled water subjected to magnetic stirring at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.

[0531] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0532] The suspension of particles was then subjected to evaporation under reduced pressure (40°C) to remove the acetone.

[0533] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0534] The suspension of particles thus obtained was kept in a closed bottle and stored at 4 °C.

[0535] Characterization of the particles obtained from the product of invention 11:

[0536] Table 17 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week, 2 weeks and 4 weeks) of the particles obtained from the product invention 11, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements.

[0537] Table 17

[0538] The detailed results in Table 17 above demonstrate that it is possible to formulate particles in acetone using CDs substituted with alkyl chain lengths other than C4 and C10 (from vinyl butyrate and vinyl decanoate). The resulting particles are monodisperse, and their average diameter of 0.12 pm remains stable for at least 4 weeks.

[0539] 16 ème preparation of particles of the product invention 9 (ethanol solvent):

[0540] 10.1 mg of product of invention 9 were dissolved at 25 °C in 10.1 mL of ethanol to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25 °C and then divided into three portions. One-third of this organic solution was added to 3.4 mL of distilled water and stirred magnetically at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.

[0541] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0542] The particle suspension was then subjected to evaporation under reduced pressure (40°C) to remove the ethanol.

[0543] The particle suspension was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0544] The resulting particle suspension was kept in a closed bottle and stored at 4°C.

[0545] Characterization of the particles obtained from the product of invention 9:

[0546] Table 18 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week, 2 weeks and 4 weeks) of the particles obtained from the product invention 9, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements.

[0547] Table 18

[0548] The detailed results in Table 18 above demonstrate that it is possible to formulate particles in ethanol with substituted beta-CDs using alkyl chain lengths other than C4 and C10 (from vinyl butyrate and vinyl decanoate). The resulting particles are monodisperse, and their average diameter of 0.19 to 0.20 pm remains stable for at least four weeks.

[0549] 17 ème preparation of particles of product invention 10 (ethanol solvent):

[0550] 9.7 mg of product of invention 10 were dissolved at 25°C in 9.7 mL of ethanol to obtain an organic solution with a concentration of 1 mg / mL. This organic solution was stored at 25°C and then divided into three portions. One-third of this organic solution was added to 3.2 mL of distilled water and stirred magnetically at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.

[0551] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said particles of matrix type.

[0552] The particle suspension was then subjected to evaporation under reduced pressure (40°C) to remove the ethanol.

[0553] The particle suspension was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0554] The resulting particle suspension was kept in a closed bottle and stored at 4°C.

[0555] Characterization of the particles obtained from the product of invention 10:

[0556] Table 19 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week, 2 weeks and 4 weeks) of the particles obtained from the product invention 10, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements. Table 19

[0557] The detailed results in Table 19 above demonstrate that it is possible to formulate particles in ethanol with gamma-CDs substituted with alkyl chain lengths other than C4 and C10 (from vinyl butyrate and vinyl decanoate). The resulting particles are monodisperse, and their average diameter of 0.23 pm remains stable for at least 4 weeks.

[0558] 18 ème preparation of particles of the product of invention 8 with a lipophilic compound (tea tree essential oil):

[0559] 18.3 mg of product of invention 8 were solubilized at 25°C in 4.6 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 75 pL of tea tree essential oil and 60 mg of sorbitan oleate (Montane® 80, namely a non-ionic lipophilic surfactant) were added to this mixture to obtain an organic solution.

[0560] This organic solution was stored at 25°C and then added to 2.7 mL of distilled water. The resulting mixture was stirred magnetically at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.75.

[0561] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0562] The suspension of particles was then subjected to vacuum evaporation (40 °C) to remove the ethanol.

[0563] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0564] The suspension of particles thus obtained was kept in a closed bottle and stored at 4 °C.

[0565] Characterization of the particles obtained from the product of invention 8:

[0566] All capsule-type formulations were analyzed by DLS on the Zetasizer Nano ZS after being diluted by 15 (280 pL distilled water + 20 uL formulation).

[0567] Table 20 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week, 2 weeks and 4 weeks) of the particles obtained from the product invention 8, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements.

[0568] Table 20

[0569] Based on the detailed results in Table 20 above, it is possible to formulate so-called capsular-type particles with a gamma-CD (2C4, 6C10) in the same way as with a beta-CD similarly substituted by C4 and C10 chains. The particles obtained are monodisperse (PDI < 0.25) and their average diameter (0.43 to 0.47 pm) remains stable for at least 2 weeks.

[0570] 19 ème preparation of particles of the product of invention 11 with a lipophilic compound (tea tree essential oil):

[0571] 18.1 mg of product of invention 11 were solubilized at 25°C in 4.5 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 75 pL of tea tree essential oil and 60 mg of sorbitan oleate (Montane® 80, namely a non-ionic lipophilic surfactant) were added to this mixture to obtain an organic solution.

[0572] This organic solution was stored at 25°C and then added to 2.6 mL of distilled water. The resulting mixture was stirred magnetically at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.75.

[0573] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0574] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0575] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0576] The suspension of particles thus obtained was kept in a closed bottle and stored at 4°C.

[0577] Characterization of the particles obtained from the product of invention 11:

[0578] Table 21 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week, 2 weeks and 4 weeks) of the particles obtained from the product invention 11, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements.

[0579] Table 21

[0580] 20 èmepreparation of particles of the product of invention 12 with a lipophilic compound (tea tree essential oil):

[0581] 18.2 mg of product of invention 12 were solubilized at 25°C in 4.6 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 75 pL of tea tree essential oil and 60 mg of sorbitan oleate (Montane® 80, namely a non-ionic lipophilic surfactant) were added to this mixture to obtain an organic solution.

[0582] This organic solution was stored at 25°C and then added to 2.7 mL of distilled water. The resulting mixture was stirred magnetically at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.75.

[0583] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0584] The suspension of particles was then subjected to vacuum evaporation (40 °C) to remove the ethanol.

[0585] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0586] The suspension of particles thus obtained was kept in a closed bottle and stored at 4°C.

[0587] Characterization of the particles obtained from the product of invention 12:

[0588] Table 22 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week and 2 weeks) of the particles obtained from the product invention 12, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements.

[0589] Table 22

[0590] 21 ème preparation of particles of the product of invention 13 with a lipophilic compound (tea tree essential oil):

[0591] 18.3 mg of product of invention 13 were solubilized at 25°C in 4.6 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 75 pL of tea tree essential oil and 60 mg of sorbitan oleate (Montane® 80, namely a non-ionic lipophilic surfactant) were added to this mixture to obtain an organic solution.

[0592] This organic solution was stored at 25°C and then added to 2.7 mL of distilled water. The resulting mixture was stirred magnetically at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.75.

[0593] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0594] The suspension of particles was then subjected to vacuum evaporation (40°C) to remove the ethanol.

[0595] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0596] The suspension of particles thus obtained was kept in a closed bottle and stored at 4°C.

[0597] Characterization of the particles obtained from the product of invention 13:

[0598] Table 23 below details, according to storage duration (initially at T=0, then after 1 day, 1 week and 2 weeks), the particles obtained from the product invention 13, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements. Table 23

[0599] 22 ème preparation of particles of the product of invention 14 with a lipophilic compound (tea tree essential oil):

[0600] 18.5 mg of product of invention 14 were solubilized at 25°C in 4.6 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 75 pL of tea tree essential oil and 60 mg of sorbitan oleate (Montane® 80, namely a non-ionic lipophilic surfactant) were added to this mixture to obtain an organic solution.

[0601] This organic solution was stored at 25°C and then added to 2.7 mL of distilled water. The resulting mixture was stirred magnetically at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.75.

[0602] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0603] The suspension of particles was then subjected to vacuum evaporation (40 °C) to remove the ethanol.

[0604] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0605] The suspension of particles thus obtained was kept in a closed bottle and stored at 4°C.

[0606] Characterization of the particles obtained from the product of invention 14:

[0607] Table 24 below details, according to the storage time (namely initially at T=0, then after 1 day, 1 week and 2 weeks) of the particles obtained from the product invention 14, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements. Table 24

[0608] Based on the detailed results in Tables 21 to 24 above, it is possible to formulate particles with different types of CDs substituted with different alkyl chain lengths (C4, C2, C10, C12). The formulated particles are observed to be stable for at least two weeks. The average diameter varies between 0.56 and 0.88 pm.

[0609] 23 èmepreparation of particles of the product of invention 8 with a lipophilic compound (tea tree essential oil) and an active substance (vitamin C palmitate):

[0610] 18.3 mg of product of invention 8 were solubilized at 25°C in 4.6 mL of ethanol to obtain an organic solution with a concentration of 4 mg / mL. Then, 75 pL of tea tree essential oil, 60 mg of sorbitan oleate (Montane® 80, namely a non-ionic lipophilic surfactant) and 7.5 mg of vitamin C palmitate were added to this mixture to obtain an organic solution.

[0611] This organic solution was stored at 25°C and then added to 2.7 mL of distilled water. The resulting mixture was stirred magnetically at a speed of 420 rpm. The ratio of the volume of the aqueous phase to the volume of the organic phase was 1:1.75.

[0612] Particles formed spontaneously upon the addition of the organic solution to the distilled water, resulting in a suspension of said capsular-type particles.

[0613] The suspension of particles was then subjected to vacuum evaporation (40 °C) to remove the ethanol.

[0614] The suspension of particles was concentrated until a final aqueous volume was obtained corresponding to approximately 50 to 80% of the initial volume of distilled water used.

[0615] The suspension of particles thus obtained was kept in a closed bottle and stored at 4°C.

[0616] Characterization of the particles obtained from the product of invention 8:

[0617] Table 25 below details, according to storage duration (initially at T=0, then after 1 day, 1 week and 2 weeks), the particles obtained from the product invention 8, the 3 measurements of their size (nm) obtained, as well as the PDI calculated from these measurements.

[0618] Table 25

[0619] Based on the detailed results in Table 25 above, it is possible to encapsulate an active ingredient such as vitamin C palmitate in capsular-type particles formed from gamma-CD (2C4, 6C10), in the same way as for beta-CD (2C4, 5C10) described above. The resulting particles are monodisperse (PDI < 0.25) and their mean diameter of 0.38 pm remains stable for at least two weeks.

Claims

DEMANDS 1. Cyclodextrin derivative (hereinafter abbreviated as "CD"), characterized in that it comprises: - glucosidic subunits with the following chemical structure (4): in which x is an integer between 0 and 18, preferably between 0 and 12; - optionally at least one glucoside subunit of chemical structure (5): the total number of glucosidic subunits of chemical structure (4) and of chemical structure (5) is equal to an integer n between 5 and 30, preferably between 6 and 8, at least 2 x among the x of the glucosidic subunits of chemical structure (4) are different from each other.

2. Derivative of CD according to claim 1, characterized in that n is equal to 6, 7 or 8.

3. A process for preparing a CD derivative according to claim 1 or 2, characterized in that it comprises at least the following steps: a) a mixture is prepared comprising at least: - a native CD comprising n glucopyranose units, n being an integer between 5 and 30, preferably between 6 and 8, - an enzyme configured to catalyze a transesterification reaction at the hydroxyl group on carbon C2 of the glucopyranose units of native CDs and CD derivatives; b) a 1 is added to said mixture er vinyl ester with the following chemical structure (6): in which x is an integer between 0 and 18, preferably between 0 and 12, said 1 er Given that the vinyl ester is in stoichiometry m, and ni is an integer less than n, to perform a 1 ère transesterification reaction between native CD and 1 ervinyl ester and so as to obtain at the end of this 1 ère transesterification reaction a 1 er The so-called "intermediate" CD derivative in the reaction medium corresponds to the native CD in which neither hydroxyl groups on the C2 carbons of the glucopyranose units of said native CD have reacted with said 1 er vinyl ester; c) at least one 2 is added to the reaction medium containing the so-called "intermediate" CD derivative ème vinyl ester of chemical structure (6) whose x value is different from the x value of 1 er vinyl ester, said 2 ème vinyl ester being added in stoichiometry n2, n2 being an integer such that the sum of ni and n2 is less than or equal to n, to achieve, in the presence of said enzyme, at least one 2 ème transesterification reaction between the 1 er derived from CD called "intermediate" and at least one 2 èmevinyl ester wherein n2 hydroxyl groups among the hydroxyl groups borne by the C2 carbons of the glucopyranose units of said CD derivative called "intermediate" have reacted with said 2 ème vinyl ester so as to obtain at the end of at least one 2 ème transesterification reaction of said CD derivative; d) optionally, step c) is repeated one or more times; all vinyl esters added to the reaction medium during said preparation process are of chemical structure (6), all x of these vinyl esters are different from each other and the sum of the stoichiometries of all these vinyl esters is less than or equal to n.

4. A method for preparing a CD derivative according to claim 3, characterized in that the native CD is chosen from the group consisting of alpha-CD, beta-CD and gamma-CD.

5. A process for preparing a CD derivative according to claim 3 or 4, characterized in that the vinyl esters are selected from the group consisting of vinyl acetate, vinyl butyrate, vinyl hexanoate, vinyl decanoate, vinyl octanoate, vinyl laurate and vinyl myristate.

6. A process for preparing a CD derivative according to any one of claims 3 to 5, characterized in that the enzyme is thermolysin.

7. A method for preparing a CD derivative according to any one of claims 3 to 6, characterized in that all or part of the transesterification reactions are carried out simultaneously or sequentially.

8. A process for preparing a CD derivative according to any one of claims 3 to 7, characterized in that at the end of step c) or optionally at the end of step d), said CD derivative thus obtained is recovered and optionally purified.

9. Particle, characterized in that it comprises at least one CD derivative according to any one of claims 1 to 2 or at least one CD derivative obtained according to the preparation process according to any one of claims 3 to 8.

10. Particle according to claim 9, characterized in that it further comprises at least one active substance.

11. Particle according to claim 9 or 10, characterized in that the size of said particle is between 0.1 pm and 2 pm, preferably between 0.15 pm and 1 pm.

12. A method for manufacturing particles according to any one of claims 9 to 11, characterized in that it comprises at least the following steps: a) a 1 era mixture comprising at least one CD derivative according to any one of claims 1 to 2 or at least one CD derivative obtained according to the preparation process according to any one of claims 3 to 8, a polar organic solvent and, optionally at least one er surfactant and / or at least one 1 ère active substance; b) a 2 is prepared ème a mixture comprising at least water and, optionally at least one 2 ème surfactant and / or at least one 2 ème active substance; c) one of the 1 is added er or 2 ème mixing with the other mixture, so as to obtain a suspension of said particles.

13. A method for manufacturing particles according to claim 12, characterized in that the 1 er the mixture further comprises at least one lipophilic compound.

14. Composition, preferably a composition selected from pharmaceutical, cosmetic, food, agri-food, phytosanitary, paint, varnish, textile dye compositions, characterized in that it comprises at least particles according to any one of claims 9 to 11 or particles obtained according to the manufacturing process according to any one of claims 12 to 13.

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