FR2728563A1 - New ester(s) of aromatic poly:hydroxyl cpds. - Google Patents

Abstract

Esters of aromatic polyhydroxyl cpds., formed as prods. of reticulation, such as by reaction of aromatic polyhydroxyl derivs. with polyacids or their derivs., are new.

Description

ESTERS OF AROMATIC POLYHYDROXYL COMPOUNDS,
THEIR PREPARATION AND THEIR APPLICATIONS
The invention relates to esters of aromatic polyhydroxy compounds (phenols) and to their preparation.

 Many families of aroma chemical compounds have free -OH groups (phenols).

The reactivity of these groups is often a problem with regard to the applications envisaged for the products.

 The use of protective groups is often used to solve the problem of their instability.

 It is known that phenols, in general, oxidize spontaneously, in contact with oxygen in the air and / or in the presence of light, giving radical condensation products and quinone forms.

 These compounds are responsible for the appearance of red-brown colors that are incompatible with certain applications, for example in therapeutics and cosmetics.

 This is the case for proanthocyanidols, which are natural polyphenol derivatives widely used in plants, including vines and pines.

These are polymeric derivatives having the 2-phenylchromane ring, or flavane ring, substituted by a hydroxyl group at the 3-position, with catechin 1 and epicatechin Z as base unit as shown below.

catechine 1 epicatechin 2
The crude extracts of proanthocyanidols are forms of comolexes mixtures comprising monomers and polymers, more particularly oligomers ranging from dimers and most generally up to decamers.

The association of the monomers is, most generally, by interflavanic carbonecarbon bonds 4-6 or 4-8. Formula 3 below gives an example of a dimer.

 The industrial extraction processes aim to provide fractions consisting mainly of oligomers. These fractions will be called indifferently hereinafter flavanolic oligomers, or alternatively procyanolidic oligomers and abbreviated OPC.

 Many properties have been attributed to them: physicochemical properties (instability related to anti-radical and anti-oxidant properties, chelating effect vis-à-vis heavy metals), and biological and therapeutic properties (collagen stabilizers). vascular protective effect, antibacterial, antitumor and others).

 Here again, their instability is such that their conservation must be done in the dark and in an inert atmosphere, and that their use can be considered in the native state, only in galenic forms ensuring their protection.

 Another family of unstable aromatic polyphenolic derivatives includes gallotanins and ellagitannins, more or less polymerized molecules, from pentagalloylglucose. The galloyl residues may be esterified in turn by other galloyl groups in the form of depsides (gallotannins). They can also be linked together as a result of oxidative phenolic coupling (ellagitannins).

Their formulas are given below

<tb><SEP> OH
<tb><SEP></ NOH
<tb><SEP> HO <SEP> j <SEP> CH
<tb><SEP> Ho <SEP> OH
<tb><SEP> O <SEP> OH
<tb><SEP> HO <SEP> X <SEP><<SEP> ZG <SEP> CCH <SEP><<SEP> fromPSIdeS
<tb> HO <SEP> thooooooo
<tb> HO <SEP> EO <SEP> 0E [EA ': 0 <SEP> ÀEN! IOH
<tb><SEP> OH <SEP> OHÉ &num; OHOEoHOH
<tb> gallotannins: n = 0, 1, 2, 3, ...

ellagitannin
It is therefore possible to measure the value of derivatives which make it possible, on the one hand, to stabilize such aromatic polyhydroxy compounds, to preserve them under normal atmospheric conditions, and, on the other hand, to take advantage of their various properties, in particular their use as antiradicals and antioxidant within a system.

 The inventors' research in this field has led them to note that the use of certain esterification agents by blocking the free -OH groups to form crosslinked structures of great interest as solutions to the problems mentioned above.

 The object of the invention is therefore to provide new esters of aromatic polyhydroxy derivatives in crosslinked form and making it possible to exploit the properties of the aromatic polyhydroxy derivatives and, where appropriate, of active compounds retained in the crosslinked structure.

 It also aims to provide a process for the preparation of such exploitable derivatives on an industrial scale.

 The invention also aims the applications of these new esters in various fields, including therapeutics, cosmetics and food.

 The esters of aromatic polyhydroxy compounds of the invention are characterized in that they consist essentially of a crosslinking product, as obtained by reaction of polyhydroxy aromatic compounds with polyacids or derivatives thereof.

These esters are thus characterized in that they comprise structural crosslinking bridges

These bridges connect distinct oxygenated positions on the same molecule, and / or on different molecules.

 In the structure forming the crosslinking bridge, R represents an aliphatic chain of 2 to 10 carbon atoms and / or 1 to 3 aromatic rings and / or heterocycles. The aliphatic chain and the rings are, where appropriate, substituted and in particular carry one or more -COOH groups or groups derived from such a group.

 The aromatic polyhydroxy compounds are more particularly polyphenols chosen from condensed tannins, their gallic esters, gallotannins and ellagitannins.

 In condensed tannins, mention will in particular be made of the OPCs mentioned above.

 In order to modify their biodegradability, the aromatic polyhydroxy derivatives may be used in admixture with proteins or polysaccharides.

 Thus, the use of water-soluble proteins, for example gelatins, ovalbumin, milk proteins, such as casein, makes it possible in particular to increase the digestive biodegradability; on the contrary, it may be reduced by using polysaccharides, such as dextran, hydroxyethyl starch, sodium alginate or carboxymethylcellulose.

 The aromatic polyhydroxy compounds are generally obtained by extraction from plant species. Among these are the maritime pine, the vine, but also cocoa, acacia, chestnut, oak, walnut, witch hazel, mimosa, myrobolan, quebracho, tara, or tea.

 These are preferably purified fractions.

A conventional extraction process derives from that described in patent FR 1 427 100 of December 14, 1964. The OPC are extracted from the plant material by a saturated aqueous solution of NaCl. Liquid ethyl acetate extraction is then carried out, and the OPCs are precipitated by adding excess chloroform. After filtration, the precipitate is taken up in ethyl acetate and subjected, if necessary, for additional purification, to several cycles of reprecipitation with excess chloroform, taken up in ethyl acetate, the solvent being evaporated at the end.

 Alternatively, these compositions are extracted from the plant material with water, and then Nazi is added. The impurities are precipitated, removed by filtration and liquid liquid extraction of the OPCs is carried out with ethyl acetate. The solvent is evaporated and the residue taken up in water. After the steps of washing the aqueous solution with chloroform, spray drying or taking up with ethyl acetate, the flavanolic compositions are precipitated by adding excess chloroform, then filtered and dried in an oven.

 According to the plant species concerned and the extraction techniques used, the OPCs include a sugar motif. It is an ose such as for example glucose or galactose, or polyoses formed of several of these oses, identical or different.

The extraction of these glycosylated derivatives is carried out from the plant material with water, an alcohol such as ethanol or methanol, or a water-acetone mixture (2/3). After washing with ethyl acetate, the extract is redissolved in aqueous solution. Liquid-liquid extraction is carried out with n-butanol, and the solvent is then removed by evaporation. The residue is subjected to a countercurrent chromatographic purification or on
Fractogel TSK HW40, Sephadex LH20, MCI gel CHP 20P, silica gel RP C18.

 The polyacids or their derivatives constitute the crosslinking agents. The polyacids are more especially selected from halides, especially chlorides, or anhydrides, or isocyanates.

 It is advantageously dicarboxylic acids such as malic acid, malonic acid, glutaric acid, phthalic acid, diacid chlorides, such as terephthaloyl dichloride, succinyl dichloride, sebacoyl dichloride, and adipoyl dichloride, anhydrides. or the corresponding isocyanates, such as toluene diisocyanate or hexamethylene diisocyanate.

 According to one embodiment of the invention, the crosslinking product corresponds to a spongy mass.

 According to another embodiment of the invention, the crosslinked esters are in the form of microcapsules of which they constitute the wall.

This wall forms a particularly dense three-dimensional network, since the polyhydroxylated derivative has numerous reactive functions, which constitutes a major difference between the microparticles of the invention and those generally produced by crosslinking a diamine (piperazine,
L-lysine, 1,6-hexamethylenediamine and others) and an acyl dichloride.

 These microcapsules generally have a mean diameter of the order of 25 to 300 p. Their size may vary according to that of the particles that constitute the emulsion, which depends, in particular on the speed of the rotor and the shape of the container.

 They form a wall whose thickness is of the order of 2 to 5 p.

entre des positions oxygénées distinctes d'une même molécule et/ou de molécules voisines, R étant tel que défini plus haut.According to the invention, the aromatic polyhydroxylated ester esters defined above are obtained by reaction of polyhydroxy aromatic derivatives with a polyacid or a polyacid derivative, under conditions leading to the formation of a bridge.

between distinct oxygen positions of the same molecule and / or neighboring molecules, R being as defined above.

 The aromatic polyhydroxy derivatives and crosslinking agents used in the process of the invention are as identified above.

 Where appropriate, the aromatic polyhydroxy derivatives are used in admixture with proteins or polysaccharides as already defined.

 When the acid is used as the acylating agent, the reaction is advantageously carried out in the presence of an activating agent of the latter.

 Most conventionally, this agent is dicyclohexylcarbodiimide, but other agents imparting the same activating effect can be used as tert-butylchloroformate (for the formation of a mixed anhydride).

 The acylation reaction is carried out in the presence of a solvent allowing partial solubilization of the aromatic polyhydroxy starting compounds.

 Suitable solvents are selected from halogenated derivatives such as dichloromethane, chloroform, 1,2-dichloroethane or an amine such as pyridine.

 The reaction is preferably carried out at room temperature.

 The reaction with the acid chloride or anhydride may alternatively be carried out in an aqueous alkaline medium according to the Schotten Baumann reaction.

 Aromatic polyhydroxylated derivatives are then placed in the aqueous phase at a pH of 7.5 to 12, in particular from 8 to 10, the acylating agent dissolved in the organic phase and a phase transfer agent.

 The organic phase in which the acylating agent is dissolved is advantageously an organochlorine solvent such as chloroform or dichloromethane.

 Suitable phase transfer agents include halides or hydroxides such as tetrabutylammonium or tetrabutyl phosphonium, benzyltriethylammonium chloride, or hydrogen sulphates, for example tetrabutylammonium.

 The resulting crosslinked esters are in the form of a spongy mass.

 They are separated from the reaction mixture by filtration and purified for the intended purposes.

In a variant, the reaction of the aromatic polyhydroxy derivatives with the crosslinking agents is carried out according to a process characterized in that,
a water-in-oil (W / O) emulsion is formed, and for this purpose
an aqueous alkaline solution of at least one polyhydroxy aromatic derivative in an immiscible organic solvent is dispersed in the form of an emulsion, the emulsion obtained being subjected to agitation, and
at least one polyacid or a polyacid derivative, in solution in said immiscible organic solvent, is added as a crosslinking agent, or
an oil-in-water emulsion (O / W) is formed, and for this purpose
an organic solution containing at least one polyacid or a polyacid derivative is dispersed in the form of an emulsion as a crosslinking agent in an aqueous solution of at least one polyhydroxy aromatic derivative, the emulsion obtained being subjected to agitation, and
an alkaline agent in aqueous solution is added capable of bringing the pH of the dispersing phase to between 9 and 11.5,
the stirred mixture is subjected to agitation, and
the crosslinked product formed is recovered, in which -CO-R-CO- bridges connect the oxygen groups occupying two distinct positions on the same polyhydroxylated derivative and / or the oxygen groups of two different derivatives.

 The crosslinking reaction occurs at the interface of the emulsified droplets.

 The alkaline aqueous solution of these derivatives has a pH of preferably 9 to 11.5.

 To form the emulsion, an emulsifying agent is used in a proportion of 3 to 12% by weight of the dispersion, in particular 5 to 7.5%.

Conventionally, use is made of surfactants formed by esterification of hexyl alcohols such as those sold under the brand names.
SpanR or to condensation products of fatty acid esters and sorbitol with ethylene oxide as the
Tween®.

 The emulsion obtained is kept stirring.

 The organic solution used during the emulsion stage is formed of one or more organic solvents immiscible with water, and advantageously chosen from those in which the crosslinking agent is soluble.

 Suitable solvents are selected from organochlorine products such as chloroform, methylene chloride or trichlorethylene, or hydrocarbons such as hexane or cyclohexane.

 The crosslinking agent added to the emulsion is in solution in one or more organic solvents. This or these are advantageously the same as those used to produce the emulsion of the polyhydroxylated derivative.

 Depending on the relative amounts of the aqueous and organic phases and the emulsifier, an emulsion of the O / W or W / O type is formed.

 Stirring is carried out so as to rapidly homogenize the aqueous and organic solutions, for example by using a magnetic bar at 500-1000 rpm or a propeller at 800-2000 rpm. The duration of this step is generally of the order of 30 min.

 The crosslinked esters obtained are washed and dried and are in the form of a fluid powder.

 Their recovery is advantageously carried out by subjecting the reaction mixture to at least one centrifugation step, so as to separate the solid interface formed between the droplets.

 Alternatively, the formed esters are isolated by diluting the reaction mixture with one or more solvents followed by decantation and / or centrifugation and washing steps.

 The microcapsules obtained are presented under the microscope in the form of substantially spherical particles, of homogeneous size.

 Depending on the operating conditions, the diameter may vary from 25 to 300 p approximately.

 When it is desired to prepare microcapsules containing active ingredients, the latter are preferably added to the organic or aqueous phase in which it is soluble.

 This active ingredient, as will be developed hereafter, is constituted by a compound possessing properties in human or animal therapeutics, a product for the diagnosis, or an active product, in particular, in the phytosanitary fields.

 Advantageously, the esters of the invention allow the use of the properties of polyhydroxy aromatic derivatives, especially the antioxidant and anti-radical properties of polyphenols, in many industrial sectors and, in addition, those of principles various actives that can be incorporated into the crosslinked structure of these esters.

 According to a first aspect, the invention relates to the application of esters of aromatic polyhydroxy derivatives as defined above, in the fields where these derivatives are exploitable, such as in therapeutics, cosmetology, phytopharmacy, agrochemistry or agri-food, and as agents of chelation of heavy metals for depollution purposes.

 The biological and therapeutic properties of these derivatives are thus used, their crosslinking providing a solution to their original instability, as well as their physico-chemical properties, especially antiradical and antioxidant properties, to protect air-sensitive active principles. and light and their chelating effect against heavy metals (requiring their use in a totally insoluble form).

 In these various applications, the esters are in the form of compositions in which they are present in an effective amount for a given application and are associated with suitable inert and / or diluent carriers.

 Advantageous compositions are formed solely from esters of aromatic polyhydroxy derivatives.

 Other preferred compositions are prepared from esters of aromatic polyhydroxy derivatives and proteins or polysaccharides.

 According to another aspect, the invention relates to the use of the above esters as vectors of active principles. The latter are more especially incorporated into the crosslinked structure of the esters and are contained in the spongy mass of the crosslinking product or in the microcapsules constituted by these esters.

 In particular, the invention relates to microcapsules containing compounds or compositions that are active in human or animal therapy, or that can be used in the food or dietetic field.

 These are advantageously water-soluble products, or fat-soluble products, or oily products.

 Examples include alkali metal salts of carboxylic acids, such as salicylic acid, vegetable oils such as olive oil, or animal oils such as fish liver oils, for example cod, essential oils, vitamins , molecules with an antimitotic or antineoplastic effect, hormones, antibiotics, antigens, attenuated bacteria that can be used as vaccines.

 The guarantees of innocuousness offered by the microcapsules, taking into account the nature of their constituent elements, as well as their biodegradability make them particularly suitable for the inclusion of the active principles mentioned above and many other pharmaceutically acceptable products.

 This form has the advantage of facilitating access to action sites and also makes it possible to administer certain active ingredients according to new routes of administration and to protect them transiently vis-à-vis, for example, d digestive enzymes, or the action of oxidizing agents.

 These microcapsules also make it possible to mask the unpleasant taste of an active ingredient to be administered.

 The galenic forms, for their administration, are liquid or pasty, the microcapsules being in suspension, or solid, for example capsules containing the microcapsules. Dosage form is administered by the oral, dermal, subcutaneous, intradermal, intramuscular or intravenous routes.

 In the field of diagnosis, the microcapsules of the invention are appropriate for the encapsulation of colored or fluorescent reagents such as fluorescein, or radioactive markers.

 The microcapsules formed of a wall based on esters according to the invention, can also be used in cosmetology where they allow in particular the transport of products, in the dermis, in particular anti-radical products.

 The invention also relates to the use of these microcapsules in the field of phytopharmacy, where they can convey insecticides or pesticides. Their size ensures better penetration through the cuticle and leads to improved action of the encapsulated products. By protecting the active ingredients and by prolonging their release, these microcapsules make it possible to reduce the doses administered.

 These microcapsules are also of great interest in the sector of paints, varnishes and surface treatments.

 These microcapsules are then characterized in that they contain pigments, or surface treatment agents.

 Their very small size makes it possible to produce deposits of high quality and very high homogeneity.

 Other areas of the art in which the microcapsules can be used include printing, reprography, textile and fiber surface treatment, photography, lubrication and agriculture.

 Overall, the invention thus provides means for valuing products a raw material of plant origin.

 Examples of preparation of crosslinked polyphenol esters in spongy form and in the form of microcapsules will be given below to illustrate the invention. In these examples, reference is made to the single figure which represents a photo of microcapsules of the invention at a magnification of 100 under an optical microscope.

 EXAMPLE 1 Preparation of Grape OPC Terephthaloate in Spongy Form

 500 mg of a grape OPC fraction, as obtained from grapevine is dissolved in the method described in Patent FR 1 427 100, in 10 ml of distilled water, 50 ml of dichloromethane are added and the reaction mixture is stirred vigorously (mechanical stirring at about 1000 rpm). 50 ml of a buffered aqueous solution (pH = 9.8) are added to 0.2 M sodium hydrogen phosphate. 1/10 of catechin equivalent (60 mg) of tetrabutylammonium hydrogen sulfate (phase transfer agent) and then 2.60 ml of terephthaloyl chloride (d = 0.905, 2.37 g, 5 catechin equivalents) are added. ). It is left for 45 min with vigorous stirring. At the end of the reaction, the organic phase is recovered and washed with twice 25 ml of dichloromethane. The organic phase is recovered and evaporated on a rotary evaporator under vacuum. The residue is taken up in 50 ml of absolute ethanol and the mixture is stirred vigorously for 15 minutes. The reaction medium is then centrifuged and a solid spongy mass is recovered at the water-chloroform interface. This is washed successively with chloroform, ethanol and water and dried.

 The product obtained is in spongy form, brown in color. An IR spectrometric control shows that it has a 1735 cm-1 band corresponding to the phenylbenzoate carbonyl.

 The other I.R. characteristic strips (in KBr pellet, cm-1) are as follows: 3399, 2930, 1735, 1613, 1504, 1438, 1406, 1256, 1108, 1070, 1015, 871, 721.

The ester obtained thus corresponds to a structure of the following type

 Example: Preparation of gall tannin terephthalate in spongy form.

 The procedure is as in Example 1, replacing the OPC with oenological tannins gall water.

 EXAMPLE 3 Preparation of pine OPC adipoate in spongy form

In a beaker of l 1, we introduce
200 ml of 1,2-dichloroethane, 10 g of pine OPC (as obtained according to the method described in the patent
FR 1427100), 8.3 g of adipic acid, 11.7 g of dicyclohexylcarbodiimide, and 1 g of 4 pyrolidinopyridine are left stirring at room temperature for 24 hours in the absence of air (under a stream of nitrogen and light).

At the end of the reaction, the reaction medium is filtered, washed with hexane and then with ethanol. 9.5 g of pine OPC adipoate in spongy form are thus recovered after drying. This product is used in particular to chelate heavy metals for the purpose of depollution.

 Example: Manufacture of microcapsules from vine OPC crosslinked with terephthaloyl chloride from a water-in-oil emulsion.

 In a cylindrical tube is poured 20 ml of a chloroform solution of sorbitan trioleate (Span 85R) at 5% and stirred (T-stirrer, 1000 rpm). 50 mg of grape OPC (oligoprocyanolidic fraction as obtained from the grapevine according to the method of the FR patent mentioned above) is dissolved in 5 ml of a 0.1M solution of sodium hydrogen phosphate. The aqueous solution is poured into the chloroform solution and the emulsion is allowed to proceed for 5 minutes. One equivalent catechin of terephthaloyl chloride (70 mg) is dissolved in 15 ml of chloroform and this solution is added to the emulsion. Stirring is maintained for 30 minutes. At the end of the reaction, the reaction medium is centrifuged at 3000 rpm for 30 seconds.

 The solid interface is recovered, resuspended in 30 ml of chloroform and centrifuged again at 3000 rpm. The operation is repeated once with chloroform and twice with distilled water. The centrifugation pellet is recovered and resuspended in 5 ml of distilled water.

 The microcapsules obtained are dried by lyophilization and controlled by optical microscopy. Under photonic microscopy, one observes microcapsules of homogeneous size, about 30 micrometers of which a photo is given on the single plate which represents the microcapsules at a magnification of 100, under the optical microscope. The chemical structure is controlled by IR spectrometry. The main bands are as follows (in KBr pellet, cm-1): 3390, 2924, 1727, 1623, 1519, 1448, 1367, 1262, 1142, 1089, 1016, 988, 872, 827, 722, 531.

 Example 5 Manufacture of Microcapsules from a Mixture of OPC and Casein Crosslinked with Succinyl Chloride

 The procedure is as described in Example 2, but 7 mg of casein is dissolved in the aqueous alkaline solution of OPC.

 Example: Manufacture of microcapsules from grape OPC crosslinked with terephthaloyl dichloride from an oil-in-water emulsion.

Two phase phases are prepared: chloroform 5 ml
. sorbitan trioleate (Span 85R) 0.5 ml
. terephthaloyl chloride 70 mg phase 2:. distilled water 35
. Pholyoxyethylene monostearate
sorbitan (Tween 60 R) ................ R) 1 ml
OPC of vine ......................... vine 350 mg
Phase 1 is added with mechanical stirring to phase 2 and stirring is continued for 5 minutes.

 To the O / W emulsion thus formed with permanent stirring, a solution of 500 mg of sodium hydrogenphosphate in 10 ml of distilled water is added.

 The mixture is stirred for 30 minutes and then continued as in Example 4.

 Example 7: Microencapsulation of sodium salicylate by crosslinking OPC of grapevine.

 The procedure is as for Example 4, replacing the 10 ml of distilled water with 10 ml of a 3% aqueous solution of sodium salicylate.

 Example: Microencapsulation of sodium ascorbate by crosslinking OPC of green tea.

 The procedure is as for Example 4, replacing the OPCs of vines with OPCs of green tea, adding 10 mg of sodium ascorbate to the aqueous phase, extemporaneously, and conducting the reaction under nitrogen flow under cover. light.

 Example 9: Microencapsulation of essential oil of rosemary by cross-linking OPC of vine.

 The procedure is as for Example 6, adding 75 mg of rosemary essential oil to phase 1. These microcapsules are used in the food industry.

 Example 10 Microencapsulation of linoleic acid by crosslinking pine OPC. The procedure is as for Example 6, adding 60 mg of linoleic acid to phase 1, and replacing the vine OPC with pine OPC. The microcapsules obtained are useful in dietetics as supplements of unsaturated fatty acids.

 Example 11: Microencapsulation of dinocap by crosslinking oenological tannins from chestnut to water.

 The procedure is as for Example 6 by adding 80 mg of dinocap to phase 1 and replacing the vine OPC with oenological tannins from chestnut to water.

The microcapsules obtained are useful in agrochemistry for the treatment against powdery mildew.

Claims (18)

 1 / Esters of aromatic polyhydroxy compounds, characterized in that they consist essentially of a crosslinking product, as obtained by reaction of polyhydroxy aromatic derivatives with polyacids or derivatives thereof.  2 / esters according to claim 1, characterized in that they comprise structural crosslinking bridges

 these bridges connecting distinct oxygenated positions on a same molecule, or oxygen positions of different molecules.  3 / esters according to claim 2, characterized in that R represents an aliphatic chain of 2 to 10 carbon atoms and / or 1 to 3 aromatic rings and / or heterocycles, the aliphatic chain and the rings being optionally substituted and bearing especially one or more -COOH groups or derived from such a group.  4 / Esters according to one of claims 1 to 3, characterized in that they are selected from condensed tannins, their gallic esters, gallotannins and ellagitannins.  5 / esters according to claim 4, characterized in that the condensed tannins are procyanolidic oligomers formed of a mixture of monomers and oligo- and polymers belonging to the family of flavan-3-ol derivatives.  6 / Esters according to claim 5, characterized in that the aromatic polyhydroxy derivatives are used in admixture with proteins or polysaccharides.  7 / Esters according to claim 6, characterized in that the proteins are chosen from gelatins, ovalbumin, or milk proteins, such as casein.  8 / esters according to claim 6, characterized in that the polysaccharides are chosen from dextran, hydroxyethyl starch, sodium alginate or carboxymethylcellulose.  9 / esters according to one of claims 1 to 8, characterized in that the aromatic polyhydroxy derivatives are obtained by extraction from, in particular, maritime pine, vine, cocoa, acacia, chestnut, oak, gall, witch hazel, mimosa, myrobolan, quebracho, tara or tea.  10 / Esters according to one of claims 1 to 9, characterized in that polyacids are dicarboxylic acids such as malic acid, malonic, glutaric, phthalic acid.  11 / esters according to one of claims 1 to 10, characterized in that the polyacid derivatives are chosen from halides, especially chlorides, or anhydrides, or isocyanates, in particular, among the chlorides of diacids, such as terephthaloyl dichloride, succinyl chloride, sebacoyl dichloride, and adipoyl dichloride, anhydrides, or the corresponding isocyanates such as toluene or hexamethylene diisocyanate.  12 / Esters according to one of claims 1 to 11, characterized in that they are in the form of a spongy mass.  13 / Esters according to one of claims 1 to 11, characterized in that they are in the form of microcapsules which they constitute the wall.  14 / Esters according to claim 13, characterized in that the microcapsules have an average diameter of the order of 25 to 300 p, and form a wall whose thickness is of the order of 2 to 5 p.  15 / Process for obtaining esters of aromatic polyhydroxy compounds according to one of claims 1 to 12, characterized in that aromatic polyhydroxy compounds as defined in one of claims 4 to 5 are reacted, the case optionally mixed with proteins or polysaccharides according to one of claims 6 to 8, with polyacids or polyacid derivatives according to one of claims 10 or 11, under conditions leading to the formation of a bridge

 according to claim 2 or 3, between distinct oxygenated positions of the same molecule and / or of different molecules.  16 / Process for obtaining esters of aromatic polyhydroxy compounds according to claim 13 or 14, characterized in that  a water-in-oil emulsion is formed and, for this purpose,  an alkaline aqueous solution of at least one aromatic polyhydroxylated derivative, optionally used as a mixture with proteins or polysaccharides, is dispersed in the form of an emulsion in an immiscible organic solvent, the emulsion obtained being subjected to agitation, and  at least one polyacid or a polyacid derivative, in solution in said immiscible organic solvent, is added as a crosslinking agent, or  an oil-in-water emulsion (O / W) is formed, and for this purpose  an organic solution containing at least one polyacid or a polyacid derivative is dispersed in the form of an emulsion as a crosslinking agent in an aqueous solution of at least one polyhydroxy aromatic derivative, the emulsion obtained being subjected to agitation, and  an alkaline agent in aqueous solution is added capable of bringing the pH of the dispersing phase to between 9 and 11.5,  . the stirred mixture is subjected to agitation, and  . the crosslinked product formed is recovered, in which -CO-R-CO- bridges connect the oxygen groups occupying two distinct positions on one and the same aromatic polyhydroxylated derivative and / or the oxygen groups of two distinct derivatives.  17 / A method according to claim 16, characterized by the implementation of at least one of the following provisions  the pH of the aqueous alkaline solution is from 9 to 11.5,  the emulsifying agent is used in a proportion of 3 to 12% by weight of the dispersion, in particular of 5 to 7.5%,  the cross-linked esters are recovered by subjecting the reaction mixture to at least one centrifugation stage, so as to separate the solid interface formed between the droplets, or alternatively by diluting the reaction mixture with one or several solvents, followed by decantation and / or centrifugation and washing steps.  18 / Application of the esters according to one of claims 1 to 14, containing optionally one or more active ingredients, in the therapeutic, cosmetic or dietetic.