EP2003990A2

EP2003990A2 - Association of oleaginous substance with a mixture of at least two cyclodextrins

Info

Publication number: EP2003990A2
Application number: EP07731799A
Authority: EP
Inventors: Mohamed Skiba; Malika Lahiani; Frédéric BOUNOURE; Pierre Dechelotte
Original assignee: IN CYCLO
Current assignee: IN CYCLO
Priority date: 2006-03-23
Filing date: 2007-03-22
Publication date: 2008-12-24
Also published as: FR2898817A1; CA2647089A1; FR2898817B1; WO2007107679A3; WO2007107679A2; JP2009530357A; US20090130218A1

Abstract

The invention concerns a mixture of inclusion complexes comprising or consisting of (1) at least two different cyclodextrins selected among alpha-, beta- and gamma cyclodextrin and/or derivatives thereof, in particular derivatives thereof modified by primary and/or secondary hydroxyl groups, and (2) at least one oleaginous substance, in particular selected among animal, vegetable or synthetic oils. The invention also concerns a composition comprising or consisting of such a mixture, the use of such a mixture for preparing a medicine and a method for preparing such inclusion complexes.

Description

OLEAGINOUS SUBSTANCE ASSOCIATION WITH A MIXTURE OF AT LEAST TWO CYCLODEXTRINS

The present invention relates to the field of cosmetic, pharmaceutical, food, nutritional, nutraceutical and veterinary compositions.

More specifically, the invention relates to inclusion complexes of oleaginous substance (s), in particular of fatty acids, and a mixture of cyclodextrins, compositions comprising them and a process for the preparation of such complexes. The invention also relates to compositions comprising at least two cyclodextrins and at least one oleaginous substance.

Oleaginous substances, and in particular unsaturated fatty acids, can play a very important role in the body. For example, they may have an influence in: - cellular activity and humoral immunity,

- hormonal regulation,

- cardiovascular protection, and

- the quality of pregnancy and lactation. On the other hand, they are structural constituents of many cell membranes.

Insofar as the organism, in particular human, may have deficiencies in terms of unsaturated fatty acids, it may be useful to provide it.

However, these fatty acids may have a specific taste and / or odor.

Thus several documents describe techniques trying to reduce these disadvantages. Patent FR 2 547 829 proposes a composition containing unsaturated fatty acid compounds and a type of cyclodextrin whose role is to stabilize fatty acids and reduce the odor and bitterness associated with polyunsaturated fatty acids.

EP 0 470 452 discloses a product comprising gamma-cyclodextrin for complexing an oleaginous substance containing a mixture EPA and DHA, polyunsaturated fatty acids of different structures. US 5189149 and US 6878696 disclose a method of encapsulating polyunsaturated fatty acid-rich animal or plant oils and their derivatives using a type of cyclodextrin. However, the protection of oils composed of a mixture of different polyunsaturated fatty acids may be insufficient.

The foregoing documents thus have inclusions of unsaturated fatty acids with gamma-cyclodextrin.

Patent FR 2,850,040 for its part describes an acid complex with alpha-cyclodextrin alone.

However, the inclusion complexes described above may have insufficient stability, or insufficiently mask the taste and / or odor of certain types of oleaginous substances, such as fatty acids.

On the other hand, the methods described may have problems related to:

the polymerization of unsaturated fatty acids, and especially polyunsaturated fatty acids, the migration of cis-double bonds in trans, and

- the peroxidation of unsaturated fatty acids. On the other hand, incorporation of unsaturated fatty acids into compositions may be difficult because of their immiscibility or low miscibility in water.

There is therefore a need for inclusion complexes, and methods for obtaining them, to overcome all or part of the problems mentioned above.

According to a first aspect, the subject of the invention is a mixture of inclusion complexes comprising, or consisting of:

at least two different cyclodextrins chosen from alpha-, beta- and gamma-cyclodextrin and / or their derivatives, in particular their modified derivatives on the primary and / or secondary hydroxyl groups, and

at least one oleaginous substance, chosen especially from oils of animal, plant and synthetic origin.

The mixture of complexes according to the invention may comprise an oleaginous substance content greater than or equal to 40% by weight, in particular greater than or equal to 50% by weight, in particular greater than or equal to 60% by weight, or even greater than or equal to 70% by weight relative to the total weight of complexes.

The oleaginous substance may especially comprise or consist of at least one fatty acid, especially saturated and / or unsaturated fatty acid, a corresponding ester or triglyceride, in particular a mono- or poly-unsaturated fatty acid. For the purposes of the present invention, the term "fatty acids" is intended to mean carboxylic acids comprising from 6 to 50 carbon atoms, in particular from 10 to 30 carbon atoms, and in particular from 12 to 22 carbon atoms. The name of this class of compounds recalls their natural origin, the fatty substances, which are esters of long-chain carboxylic acids, in particular fats of animal or vegetable origin which can be triesters of glycerol. For the purposes of the present invention, the term "unsaturated fatty acids" means monounsaturated or polyunsaturated fatty acids.

In particular, the fatty acid may come from a vegetable, animal or synthetic oil or a mixture thereof, in particular from fish oil, linseed oil and / or camelina oil, and in particular the fatty acid may be from an oil selected from the group consisting of:

linseed oil, which may comprise an alpha-linolenic acid content of about 56%, nut, rapeseed and soybean oil, which may comprise an alpha-linolenic acid content ranging from 8% to 14%

- blackcurrant seed oil, which may comprise about 12 to 24% linoleic acid, 15 to 19% gamma-linolenic acid but also 30 to 40% alpha-linolenic acid and 3 to 4 % of stearidonic acid (omega 3),

- camelina oil, which may contain 12 to 24% linoleic acid, but also 30 to 40% alpha-linolenic acid, 10 to 24% oleic acid and 500 to 800 mg / kg of tocopherol and tocorienol,

- Corn, sunflower and grapeseed oils, which can be very rich, especially in linoleic acid, and - fish oils, which may contain large proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

The oleaginous substance may comprise an unsaturated fatty acid content greater than or equal to 30% by weight, in particular greater than or equal to 50% by weight, in particular greater than or equal to 70% by particular weight, more particularly greater than or equal to 90% by weight.

% by weight, or even greater than or equal to 95% by weight, relative to the total weight of oleaginous substance.

Unsaturated fatty acids include fatty acids selected from the group consisting of:

undecene-10-oic acid (11: 1),

hexadecene-9-oic acid (16: 1, omega-7), octadecene-9-oic acid (18: 1, omega-9),

octadecene-11-oic acid (18: 1, omega-7),

octadecadiene-9, 12-oic acid (18: 2, omega-6),

octadecatriene-9, 12, 15-oic acid (18: 3, omega-3),

- gadoleic acid (20: 1), - eicosatetraene-5, 8, 11, 14-oic acid (20: 4, omega-6),

eicosapentaene-5, 8, 11, 14, 17-oic acid (20: 5, omega-3),

docosene-13-oic acid (22: 1, omega-9), docosahexaene-4, 7, 10, 13, 16, 19-oic acid (22: 6, omega-3),

tetracosene-15-oic acid (24: 1 omega-9), and

- a mixture of these.

In particular, the oleaginous substance may comprise a content of omega fatty acid (s), in particular omega-3, omega-6 and / or omega-9, greater than or equal to 50% by weight, in particular greater than or equal to 75% by weight. weight, in particular greater than or equal to 90% weight, or even greater than or equal to 99% by weight relative to the total weight of oleaginous substance.

Natural cyclodextrins (alpha, beta and gamma) are most often derived from the bioconversion of maize starch by a bacterial enzyme, cycloglycosyltransferase (CGTase).

These are cyclic oligosaccharides having respectively, for alpha, beta and gamma: 6, 7 or 8 alpha-D-glucopyranose units, the bonds connecting these units are of the alpha- (1 4) glucosidic type.

alpha beta gamma

Number of units 6 7 8 glucopyranose

Relative mass 972 1135 1297

Internal diameter (A) 4.7- 5.2 6.0- 6.4 7, 5-8.3

Outer diameter (A) 14.6 ± 15.4 ± 17 _r 5 ± 0.4

0.4 0.4

Depth (A) 7.9-8.0 7.9-8.0 7, 9-8.0

Aqueous solubility (g / 100 14.5 1.85 23.2 mL, 25 ° C)

The cyclodextrin derivatives can be obtained by substitution of primary or secondary hydroxyl groups, for example by alkyl radicals, in particular comprising from 1 to 12 carbon atoms, for example methyl (-CH ₃ ) or propyl (-C ₃ H ₉ ) . These substitutions may make it possible to increase the lipophilicity of the cavity and increase the aqueous solubility of the cyclodextrin. The structure of cyclodextrins can be represented as a conical trunk with a hydrophobic cavity. The exterior of the cyclodextrin molecule is generally hydrophilic, they are pseudo-amphiphilic molecules.

This pseudo-amphiphilic structure can allow the formation of inclusion complexes. The inclusion complex may have physicochemical properties independent of the guest molecule and thus improve the apparent solubility in water of this molecule. This improvement in solubility may allow, for example, an improvement in the bioavailability of the molecule, in particular by improving the dissolution rate of the molecule.

The mixture of complexes according to the invention comprises at least two different cyclodextrins, which may each be present in a content greater than or equal to 1% by weight, especially at a content greater than or equal to 10% by weight, or even a higher content. or equal to 20% by weight, or even a content greater than or equal to 30% relative to the total weight of cyclodextrin.

According to one variant, the mixture of complexes comprises two cyclodextrins, in particular: an alpha-cyclodextrin / beta-cyclodextrin mixture, in particular in a ratio ranging from 10/1 to 1/10, or even from 4/1 to 1/4,

an alpha-cyclodextrin / gamma-cyclodextrin mixture, in particular in a ratio ranging from 10/1 to 1/10, or even from 4/1 to 1/4, or a beta-cyclodextrin / gamma-cyclodextrin mixture, in particular in a ratio ranging from 10/1 to 1/10, or even from 4/1 to 1/4.

According to another variant, the mixture of complexes comprises three cyclodextrins, in particular an alpha-cyclodextrin / beta-cyclodextrin / gamma-cyclodextrin mixture, in particular with an alpha-cyclodextrin / beta-cyclodextrin ratio ranging from 10/1 to 1/10, or even from 4/1 to 1/4, with an alpha-cyclodextrin / gamma-cyclodextrin ratio ranging from 10/1 to 1/10, or even from 4/1 to 1/4, and / or with a beta-cyclodextrin / gamma-cyclodextrin ratio ranging from 10/1 to 1/10, or even 4/1 to 1/4.

According to another of its aspects, the subject of the invention is also a composition comprising or consisting of a mixture of at least two cyclodextrins chosen from alpha-, beta- and gamma-cyclodextrin and / or their derivatives, and at least one oleaginous substance.

This composition may have an oleaginous substance / cyclodextrin weight ratio greater than or equal to 0.5, in particular greater than or equal to 1, or even greater than or equal to 2.

In particular, the composition comprises an oleaginous substance content greater than or equal to 10% by weight, in particular greater than or equal to 20% by weight, advantageously greater than or equal to 30% by weight, in particular greater than or equal to 40% by weight, more especially greater than or equal to 50% by weight, especially greater than or equal to 60% by weight, or even greater than or equal to 70% by weight relative to the total weight of the composition.

The composition may comprise at least two different cyclodextrins, each present in a content greater than or equal to 1% by weight, especially at a content greater than or equal to 10% by weight, or even a content greater than or equal to 20% by weight, even at a content greater than or equal to 30% relative to the total weight of cyclodextrin.

According to a particular embodiment, the composition comprises inclusion complexes according to the invention, especially in a content ranging from 1 to 99.9% by weight, in particular ranging from 15 to 99% by weight, or even from 25 to at 95% by weight relative to the total weight of the composition.

The composition according to the invention may be in the form of a liquid, in particular aqueous, a semi-solid, a solid. It may especially be in the form of a powder, tablets, capsules, a cream, an emulsion, especially oil-in-water or water-in-oil, or even a multiple emulsion, liposomes, nanoparticles, microparticles or a suspension.

The compositions according to the invention may be pharmaceutical, nutritional, veterinary, nutraceutical, food or cosmetic compositions comprising a mixture of inclusion complexes according to the invention. The inclusion of oleaginous substance, and in particular of fatty acids, in particular polyunsaturated fatty acids, or of their triglycerides, salts and / or esters in mixtures of cyclodextrins, according to the invention, may make it possible to obtain aqueous, solid formulations or semi-solid, at 20 ^° C. and atmospheric pressure, containing this oleaginous substance, and in particular these polyunsaturated fatty acids and / or their triglycerides, salts and esters while suppressing or greatly reducing the problems related to their oxidability and their instability as well as reducing or eliminating their taste and / or smell.

Thus, the subject of the invention is also the use of a mixture of at least two cyclodextrins as an agent for stabilizing and / or masking the taste and / or odor of oleaginous substance, in particular of acid unsaturated fats, in a composition, especially food, nutraceutical, cosmetic, pharmaceutical, veterinary, further comprising at least one oleaginous substance.

The subject of the invention is also the use of a mixture of at least two cyclodextrins and an oleaginous substance, in particular at least one unsaturated fatty acid, for the preparation of a medicinal product, in particular intended to treat or to prevent cardiovascular diseases.

The subject of the invention is a method for preparing inclusion complexes comprising at least the steps of: solubilizing at least two cyclodextrins chosen from alpha-, beta- and gamma-cyclodextrin and / or their derivatives, in particular in degassed water

adding to this solution at least one oleaginous substance,

the mixture is agitated, in particular under an inert atmosphere and / or absence of light, in particular at a temperature ranging from 10 to 40 ^° C.,

- recover the formed complexes.

The complexes can be recovered directly in emulsion form, or in powder form, in particular by lyophilization of the emulsion or by spray drying.

The following examples are given for illustrative and not limiting.

Examples

Example 1: Inclusion complexes of 60% camelina oil with a binary mixture of 40% cyclodextrins composed of 50% alpha-cyclodextrin and 50% β-cyclodextrin.

1 g of the mixture of cyclodextrins based on 50% of alpha-cyclodextrin and 50% of beta-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

1.5 g of camelina oil are then added, and stirring is kept constant at 300 rpm in the absence of light on a turntable for 24 hours. hours, at room temperature. A stable white suspension consisting of 40% binary mixture of cyclodextrin and 60% camelina oil is formed.

After lyophilization, a rich powder of 60% of oil is recovered with a yield of 76%.

The solubility of the lyophilized complexes is then examined, by dissolving in water, it leads to an opalescent solution.

Example 2: Inclusion complexes of 60% camelina oil with a binary mixture of 40% cyclodextrins composed of 30% α-cyclodextrin and 10% β-cyclodextrin.

1 g of the cyclodextrin mixture composed of 0.75 g of α-cyclodextrin and 0.25 g of β-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved. 1.5 g of camelina oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 40% binary mixture of cyclodextrin and 60% camelina oil is formed.

After freeze-drying, a powder rich with 60% of oil is recovered with a yield of 75%.

The solubility of the lyophilized complexes is then examined, by dissolving in water, it leads to an opalescent solution. Example 3: Inclusion complexes of 70% camelina oil with a binary mixture of 30% cyclodextrins composed of 15% α-cyclodextrin and 15% β-cyclodextrin.

0.75 g of the cyclodextrin mixture composed of 0.375 g of α-cyclodextrin and

0.375 g of β-cyclodextrin and 30 ml of degassed water. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

1.75 g of camelina oil are then added, and stirring is kept constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 30% binary mixture of cyclodextrin and 70% camelina oil is formed.

After lyophilization, a rich powder of 70% of oil is recovered with a yield of 77%.

Example 4: Inclusion complexes of 70% camelina oil with a binary mixture of 30% cyclodextrins composed of 20% α-cyclodextrin and 10% β-cyclodextrin.

0.75 g of the cyclodextrin mixture composed of 0.5 g of α-cyclodextrin and 0.25 g of β-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved. 1.75 g of camelina oil are then added, and stirring is kept constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 30% binary mixture of cyclodextrin and 70% camelina oil is formed.

Example 5: Inclusion complexes of 80% of camelina oil with a binary mixture of 20% cyclodextrins composed of 10% α-cyclodextrin and 10% β-cyclodextrin.

0.5 g of the cyclodextrin mixture composed of 0.25 g of α-cyclodextrin and 0.25 g of β-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

2 g of camelina oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 20% binary mixture of cyclodextrin and 80% camelina oil is formed.

After lyophilization, a rich powder of 80% of oil is recovered with a yield of 78%. The solubility of the lyophilized complexes is then examined, by dissolving in water, it leads to an opalescent solution.

Example 6: Inclusion complexes of 80% of camelina oil with a binary mixture of 20% of cyclodextrins composed of 15% of α-cyclodextrin and 5% of β-cyclodextrin.

0.5 g of the cyclodextrin mixture consisting of 0.375 g of α-cyclodextrin and

0.125 g of β-cyclodextrin and 30 ml of degassed water. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

2 g of camelina oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 20% binary mixture of cyclodextrin and 80% camelina oil is formed. After lyophilization, a rich powder of 80% of oil is recovered with a yield of 76%.

Example 7: Inclusion complexes of 60% camelina oil with a binary mixture of 40% cyclodextrins composed of 20% α-cyclodextrin and 20% γ-cyclodextrin.

1 g of the cyclodextrin mixture composed of 0.5 g of α-cyclodextrin and 0.5 g is introduced into a container. γ-cyclodextrin and 30 ml degassed water. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

1.5 g of camelina oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 40% binary mixture of cyclodextrin and 60% camelina oil is formed. After lyophilization, a rich powder of 60% of oil is recovered with a yield of 74%.

Example 8: 60% inclusion complexes of camelina oil with a binary mixture of 40% cyclodextrins composed of 30% α-cyclodextrin and 10% γ-cyclodextrin.

1 g of the cyclodextrin mixture composed of 0.75 g of α-cyclodextrin and 0.25 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

1.5 g of camelina oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 40% binary mixture of cyclodextrin and 60% camelina oil is formed. After freeze-drying, a powder rich with 60% of oil is recovered with a yield of 75%.

Example 9: Inclusion complexes of 70% camelina oil with a binary mixture of 30% cyclodextrins composed of 15% α-cyclodextrin and 15% γ-cyclodextrin.

0.75 g of the cyclodextrin mixture composed of 0.375 g of α-cyclodextrin and 0.375 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

After lyophilization, a rich powder of 70% of oil is recovered with a yield of 74%. The solubility of the lyophilized complexes is then examined, by dissolving in water, it leads to an opalescent solution.

Example 10: Inclusion complexes of 70% camelina oil with a binary mixture of 30% cyclodextrins composed of 20% α-cyclodextrin and 10% γ-cyclodextrin. 0.75 g of the cyclodextrin mixture composed of 0.5 g of α-cyclodextrin and 0.25 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

After lyophilization, a rich powder of 70% of oil is recovered with a yield of 75%. The solubility of the lyophilized complexes is then examined, by dissolving in water, it leads to an opalescent solution.

Example 11: Inclusion complexes of 80% camelina oil with a binary mixture of 20% cyclodextrins composed of 10% α-cyclodextrin and 10% γ-cyclodextrin.

0.5 g of the cyclodextrin mixture composed of 0.25 g of α-cyclodextrin and 0.25 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

2 g of camelina oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. It forms a Stable white suspension composed of 20% binary mixture of cyclodextrin and 80% camelina oil.

After lyophilization, a rich powder of 80% of oil is recovered with a yield of 75%. The solubility of the lyophilized complexes is then examined, by dissolving in water, it leads to an opalescent solution.

Example 12: Inclusion complexes of 80% of camelina oil with a binary mixture of 20% cyclodextrins composed of 15% α-cyclodextrin and 5% γ-cyclodextrin.

0.5 g of the cyclodextrin mixture composed of 0.375 g of α-cyclodextrin and 0.125 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a vessel. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

After lyophilization, a rich powder of 80% of oil is recovered with a yield of 75%.

Example 13: Inclusion Complexes of 60% camelina oil with a ternary mixture of 40% of cyclodextrins composed of 15% α-cyclodextrin, 10% β-cyclodextrin and 15% γ-cyclodextrin.

1 g of the cyclodextrin mixture composed of 0.375 g of α-cyclodextrin, 0.25 g of β-cyclodextrin and 0.375 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved. 1.5 g of camelina oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 40% binary mixture of cyclodextrin and 60% camelina oil is formed.

Example 14: Inclusion complexes of 70% camelina oil with a ternary mixture of 30% cyclodextrins composed of 10% α-cyclodextrin, 10% β-cyclodextrin and 10% γ-cyclodextrin.

0.75 g of the cyclodextrin mixture composed of 0.25 g of α-cyclodextrin, 0.25 g of β-cyclodextrin and 0.25 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. . The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

After lyophilization, a rich powder of 70% of oil is recovered with a yield of 75%.

Example 15: Inclusion complexes of 79% of camelina oil by a ternary mixture of 21% of cyclodextrins composed of 7% α-cyclodextrin, 7% β-cyclodextrin and 7% γ-cyclodextrin.

0.525 g of the cyclodextrin mixture consisting of 0.175 g of α-cyclodextrin, 0.175 g of β-cyclodextrin and 0.175 g of γ-cyclodextrin are introduced into a container and 30 ml of degassed water. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

1.975 g of camelina oil is then added, and stirring is kept constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 21% of cyclodextrin binary mixture and 79% of camelina oil is formed. After lyophilization, a 79% rich oil powder is recovered with a yield of 75%.

Example 16: 60% inclusion complexes of argan oil with a binary mixture of 40% cyclodextrins composed of 30% α-cyclodextrin and 10% γ-cyclodextrin.

1.5 g of argan oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension is formed consisting of 40% binary mixture of cyclodextrin and 60% argan oil. After lyophilization, a rich powder of 60% of oil is recovered with a yield of 77%.

Example 17: Inclusion complexes of 70% argan oil with a binary mixture of 30% cyclodextrins composed of 15% α-cyclodextrin and 15% γ-cyclodextrin.

0.75 g of the cyclodextrin mixture composed of 0.375 g of α-cyclodextrin and

0.375 g of γ-cyclodextrin and 30 ml of degassed water. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved. 1.75 g of argan oil are then added, and stirring is kept constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 30% binary mixture of cyclodextrin and 70% argan oil is formed.

After lyophilization, a rich powder of 70% of oil is recovered with a yield of 73%. The solubility of the lyophilized complexes is then examined, by dissolving in water, it leads to an opalescent solution.

Example 18: Inclusion complexes of 70% argan oil with a binary mixture of 30% cyclodextrins composed of 20% α-cyclodextrin and 10% γ-cyclodextrin. 0.75 g of the cyclodextrin mixture composed of 0.5 g of α-cyclodextrin and 0.25 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

1.75 g of argan oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension is formed consisting of 30% binary mixture of cyclodextrin and 70% argan oil.

After lyophilization, a rich powder of 70% of oil is recovered with a yield of 76%. The solubility of the lyophilized complexes is then examined, by dissolving in water, it leads to an opalescent solution.

Example 19: 60% inclusion complexes of argan oil with a ternary mixture of 40% of cyclodextrins composed of 15% of α-cyclodextrin, 10% of β-cyclodextrin and 15% of γ-cyclodextrin.

1 g of the cyclodextrin mixture composed of 0.375 g of α-cyclodextrin, 0.25 g of β-cyclodextrin and 0.375 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved. 1.5 g of argan oil are then added, and stirring is kept constant at 300 rpm in the absence of light on a turntable during 24 hours. hours, at room temperature. A stable white suspension is formed consisting of 40% binary mixture of cyclodextrin and 60% argan oil.

After lyophilization, a rich powder of 60% of oil is recovered with a yield of 70%.

Example 20: Inclusion complexes of 70% of argan oil by a ternary mixture of 30% of cyclodextrins composed of 10% of α-cyclodextrin, 10% of β-cyclodextrin and 10% of γ-cyclodextrin.

0.75 g of the cyclodextrin mixture composed of 0.25 g of α-cyclodextrin, 0.25 g of β-cyclodextrin and 0.25 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

After lyophilization, a 70% rich oil powder is recovered with a yield of 70%.

The solubility of the lyophilized complexes is then examined, by dissolving in water, it leads to an opalescent solution. Example 21: Inclusion complexes of 79% of argan oil by a ternary mixture of 21% of cyclodextrins composed of 7% of α-cyclodextrin, 7% of β-cyclodextrin and 7% of γ-cyclodextrin.

0.525 g of the cyclodextrin mixture composed of 0.175 g of α-cyclodextrin, 0.175 g of β-cyclodextrin and 0.175 g of γ-cyclodextrin and 30 ml of degassed water are introduced into a container. The whole is stirred on a turntable at 300 rpm until the mixture of cyclodextrins has completely dissolved.

1.975 g of argan oil are then added, and stirring is maintained constant at 300 rpm in the absence of light on a turntable for 24 hours at room temperature. A stable white suspension consisting of 21% binary mixture of cyclodextrin and 79% argan oil is formed.

After lyophilization, a 79% rich oil powder is recovered with a yield of 76%.

Claims

A mixture of inclusion complexes comprising, or consisting of: at least two different cyclodextrins selected from alpha-, beta- and gamma-cyclodextrin and / or their derivatives, especially their modified derivatives on the primary hydroxyl groups and / or secondary, and at least one oleaginous substance, especially chosen from oils of animal, plant and synthetic origin.

2. Mixture of complexes according to claim 1 characterized in that it comprises an oleaginous substance content greater than or equal to 10% by weight, in particular greater than or equal to 20% by weight, advantageously greater than or equal to 30% by weight, in particular greater than or equal to 40% by weight, more particularly greater than or equal to 50% by weight, more particularly greater than or equal to 60% by weight, or even greater than or equal to 70% by weight relative to the total weight of complexes.

3. Mixture of complexes according to claim 1 or 2 characterized in that the oleaginous substance comprises at least one fatty acid, especially saturated and / or unsaturated, a corresponding ester or triglyceride, in particular a mono- or poly-unsaturated fatty acid.

4. Mixture of complexes according to any one of Claims 1 to 3, characterized in that the oleaginous substance comprises an unsaturated fatty acid content greater than or equal to 30% by weight, in particular greater than or equal to 50% by weight, in particular greater than or equal to 70% by weight, very particularly greater than or equal to 90% by weight, or even greater than or equal to 95% by weight, relative to the total weight of oleaginous substance.

5. Mixture of complexes according to any one of claims 1 to 4, characterized in that the oleaginous substance comprises a content of omega fatty acid (s), in particular omega-3, omega-6 and / or omega-9, higher or equal to 50% by weight, especially greater than or equal to 75% by weight, in particular greater than or equal to 90% by weight, or even greater than or equal to 99% by weight relative to the total weight of oleaginous substance.

6. Mixture of complexes according to any one of claims 1 to 5, characterized in that at least two cyclodextrins are each present in a content greater than or equal to 1% by weight, especially at a content greater than or equal to 10% by weight, or even a content greater than or equal to 20% by weight, or even a content greater than or equal to 30% relative to the total weight of cyclodextrin.

7. Mixture of complexes according to any one of claims 1 to 6, characterized in that it comprises two cyclodextrins, in particular: an alpha-cyclodextrin / beta-cyclodextrin mixture, in particular in a ratio ranging from 10/1 to 1 / 10, or even 4/1 to 1/4,

8. Mixture of complexes according to any one of Claims 1 to 6, characterized in that it comprises three cyclodextrins, in particular an alpha-cyclodextrin / beta-cyclodextrin / gamma-cyclodextrin mixture, in particular with an alpha-cyclodextrin / beta ratio. cyclodextrin ranging from 10/1 to 1/10, or even from 4/1 to 1/4, with an alpha-cyclodextrin / gamma-cyclodextrin ratio ranging from 10/1 to 1/10, or even from 4/1 to 1/4 and / or with beta-cyclodextrin / gamma-cyclodextrin ratio ranging from 10/1 to 1/10, or even from 4/1 to 1/4.

9. A composition comprising or consisting of a mixture of at least two cyclodextrins selected from alpha-, beta- and gamma-cyclodextrin and / or their derivatives, and at least one oleaginous substance.

10. Composition according to claim 8 characterized in that the weight ratio oleaginous substance / cyclodextrin is greater than or equal to 0.5, especially greater than or equal to 1, or even greater than or equal to 2.

11. Composition according to claim 7 or 8, characterized in that it comprises an oleaginous substance content greater than or equal to 40% by weight, in particular greater than or equal to 50% by weight, in particular greater than or equal to 60% by weight. or even greater than or equal to 70% by weight relative to the total weight of the composition.

12. Composition according to any one of claims 8 to 10 characterized in that at least two cyclodextrins are each present in a content greater than or equal to 1% by weight, especially at a content greater than or equal to 10% by weight, even at a content greater than or equal to 20% by weight, or even a content greater than or equal to 30% relative to the total weight of cyclodextrin.

13. Composition according to any one of claims 8 to 11 characterized in that it comprises inclusion complexes as defined in any one of claims 1 to 7, in particular in a content ranging from 1 to 99.9 % by weight, in particular ranging from 15 to 99% by weight, or even ranging from 25 to 95% by weight relative to the total weight of the composition.

14. A composition according to any one of claims 8 to 12 characterized in that ^Λ it is in the form of a powder, tablets, capsules, cream, emulsion, including oil-in water or water-in oil, or even a multiple emulsion, liposomes, nanoparticles, microparticles or a suspension.

15. Use of a mixture of at least two cyclodextrins as an agent for stabilizing and / or masking the taste and / or odor of oleaginous substance, in particular unsaturated fatty acid, in a composition, in particular a food composition , nutraceutical, cosmetic, pharmaceutical, veterinary, further comprising at least one oleaginous substance.

16. Use of a mixture of at least two cyclodextrins and an oleaginous substance, especially at least one unsaturated fatty acid, for the preparation of a medicament, in particular for treating or preventing cardiovascular diseases .

A process for preparing inclusion complexes comprising at least the steps of: solubilizing at least two cyclodextrins chosen from alpha-, beta- and gamma-cyclodextrin and / or their derivatives, in particular from degassed water

to add to this solution at least one oleaginous substance, to agitate the mixture, in particular under an inert atmosphere and / or absence of light, in particular at a temperature ranging from 10 to 40 ^° C.,

- recover the formed complexes.

18. The method of claim 16 characterized in that the complexes are recovered directly in emulsion form, or in powder form, in particular by lyophilization of the emulsion or by spray drying.