EP2170358A2

EP2170358A2 - Age deglycation.

Info

Publication number: EP2170358A2
Application number: EP08786013A
Authority: EP
Inventors: Nabil Abdul-Malak; Cécile ALTOBELLI; Eric Perrier
Original assignee: BASF Beauty Care Solutions France SAS
Current assignee: BASF Beauty Care Solutions France SAS
Priority date: 2007-07-09
Filing date: 2008-07-09
Publication date: 2010-04-07
Also published as: BRPI0813925A2; CN101765432A; WO2009007412A3; US20100203175A1; WO2009007412A2; FR2918570B1; CN103816095A; FR2975495B1; KR20100047253A; JP2010533143A; JP2014028814A; FR2918570A1; FR2975495A1

Abstract

The invention relates to the use, as active ingredient, of at least one substance that promotes AGE deglycation, for the preparation of a composition, especially for limiting the presence of AGEs in a tissue. The invention relates in particular to the use of such a substance for the preparation of a composition for use in preventing and/or combating the decrease in flexibility and/or plasticity and/or elasticity and/or functionality of a tissue, and/or in preventing and/or combating ageing of a tissue, by promoting AGE deglycation in the tissue, wherein said tissue is preferably the skin, or the tissue wall of a blood vessel or of an organ.

Description

Deployment of AGEs

The invention relates to the use of active principles to promote the deglycation of glycated proteins, in other words to promote the reversion of the Maillard reaction.

The present invention relates in particular to substances which can be used topically or orally to act on glycated proteins in a tissue, such as for example in the skin, or at the level of the tissue wall of a blood vessel or the like. an organ, especially in a human being.

STATE OF THE ART

It is known in the prior art that sugar, especially in the form of glycans, induces glycation of proteins (binding of sugar to proteins), in particular at the level of the skin. This glycation is quite normal, however, when the blood sugar level increases, such as, especially in diabetic subjects, during aging, or when the diet is rich in sugars. It is known in the prior art that non-enzymatic glycation or glycosylation is a purely chemical and spontaneous reaction of covalently binding a carbohydrate to a peptide chain.

Glycation is a fundamental mechanism of aging resulting from the attachment of free sugars to amino acids or proteins.

The glycated proteins, also called advanced glycation products or AGEs (Advanced Glycation Endproducts). These compounds in particular decrease the flexibility, elasticity, and functionality of the skin. The glycation process takes place in three stages:

1- Formation of a Schiff base resulting from the fixing of a reducing sugar (glucose, ribose or fructose) or an aldehyde on the amino residues of the protein, mainly lysine and the N-terminal amino fraction.

2- Molar rearrangement, called Amadori rearrangement resulting from isomerization of the Schiff base. The rate of formation of these Amadori products is proportional to the sugar concentration. 3- slow and irreversible accumulation by rearrangements, hydrogen transfer and formation of highly reactive intermediates, glycation end products or Maillard products. This reaction results in the formation of AGEs, better known as Maillard products. The rate of formation of these compounds is independent of the sugar concentration of the medium but depends on the duration of the hyperglycemia and the rate of protein turnover. The first two stages (Schiff base and Amadori rearrangement) stabilize at a plateau and can be reversed depending on the blood glucose level. However, the third progresses regardless of the blood glucose level.

Proteins of the extracellular matrix, whose lifespan in the body is very long, are affected by glycation. Glycation modifies the properties of these proteins, making them more resistant to proteolysis and preventing their renewal. In addition, AGEs induce the formation of molecular bridges between collagen fibers, making it more rigid and less soluble. Finally, AGEs could have other actions by binding to specific receptors present in macrophages, endothelial and mesangial cells, by inducing the secretion of pro-inflammatory cytokines or growth factors. The importance of protein glycation has been underlined by the effect of drugs that inhibit glycation, resulting in slower aging of some functions in experimental animals. During diabetes mellitus, there is also an exaggerated glycation of proteins, linked to the rise in blood sugar.

The solutions proposed by the prior art concern active substances that make it possible to limit the glycation of proteins as well as the formation of AGEs.

GOALS OF THE INVENTION

The main aim of the invention is to solve the technical problem consisting in the supply of active substances making it possible to limit the presence of AGEs, by reversing the Maillard reaction, in particular at the level of a tissue, such as for example at the level of the skin. , or at the level of the tissue wall of a blood vessel or organ, and in particular the skin.

The present invention aims in particular to solve this technical problem in the context of the provision of cosmetic, dermatological or pharmaceutical compositions that prevent or fight against the reduction of the elastic and plastic properties of a tissue, such as for example at the level of the skin , or at the level of the tissue wall of a blood vessel or an organ, and in particular the skin, especially during tissue aging or diabetes.

The present invention also aims to provide a method for screening active ingredients having the properties mentioned above. The present invention is intended to solve the technical problem reliably, reproducibly, providing non-toxic active substances, particularly for the cosmetics industry, dermatology, dermo-pharmacy, or pharmacy preferably topically.

The object of the invention is in particular to provide substances having a low toxicity and dermatologically acceptable.

The present invention also aims to provide active ingredients whose preparation is inexpensive, and industrially reliable and simple.

DESCRIPTION OF THE INVENTION

Glycation is implicated in many age-related progressive diseases, such as vascular diseases (such as atherosclerosis), kidney disease, arthritis, diabetes complications, scarring, and so on. It is significant that diabetic complications due to glycation, can occur even at a younger age in diabetic individuals, whose average blood sugar concentration is higher than normal.

In diabetic disease, in which the involvement of free radicals is widely documented, oxidative stress is directly related to hyperglycemia. Too much sugar in the blood oxidizes easily. This oxidation of sugars leads, among other things, to sugar / protein or glycation grafts. The increased glycated hemoglobin level in diabetes is the typical example.

The glycation products whose rate is proportional to the level of blood glucose, over a long period of time, are partly responsible for tissue aging, the reduction of elastic and plastic properties is one of the causes.

Thus, the present invention describes the use of an active substance promoting the deglycation of AGEs, or promoting the reversion of the Maillard reaction with respect to AGEs, for the preparation of a composition, in particular to limit the presence of AGEs. at the level of a fabric.

Advantageously, this composition is intended, for example, to combat the reduction of the flexibility, and / or of the elasticity, and / or the plasticity, and / or the functionality of a tissue, such as for example at the skin level. , or at the tissue wall of a blood vessel or organ.

The present invention also relates to a composition for combating and / or preventing skin aging, for preventing and / or combating the reduction of the elastic and plastic properties of tissues, and in particular of the skin, by deglycation of AGEs, or by reversal of the Maillard reaction with respect to AGEs, at the cutaneous level, comprising as active substance a substance promoting the deglycation of AGEs. The present invention relates to the use of at least one active substance promoting the deglycation of AGEs, or promoting the reversal of the Maillard reaction with respect to AGEs, chosen from the following group: 3,5-Dimethoxy-4- acid hydroxycinnamic (sinapic acid), trans-3,3 ', 4', 5,7-pentahydroxyflavane (catechin), oxindole, 3,4-dihydroxyphenylacetic acid (DOPAC), 1,3,5-trihydroxybenzene (phloroglucinol), 4 aminophenol, 2-hydroxybenzoic acid (salicylic acid), 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), nordihydroguareaic acid, 6-methyl-5,7a, 13,13b-tetraazapentaphene- 8,14-dione, 6-hydroxyindole, Hydrobromide salsolinol, 7-hydroxy-4,6-dimethyl phthalide, 3,4-dihydroxycinnamic acid (caffeic acid), Physostigmine, 2-Hydroxymethyl-5-hydroxy-γ-pyrone (Kojic acid), and plant extracts containing it, at least one extract of a plant selected from the group consisting of: Aye Wiwii, Kantiankama, Blue verbena, Cercopia, Pyrole, Cherry, Cassia, and Toloman; and any of their mixtures for the preparation of a composition for promoting the deglycation of AGEs.

Preferably, the active substance promoting the deglycation of AGEs, or promoting the reversion of the Maillard reaction with respect to AGEs, is a plant extract chosen from the group consisting of:

- Aye Wiwii (Maprounea guyanensis), and preferentially the leaves,

- Jamaica vervain (Stachytarpheta jamaicensis),

- Cercopia (Cercopia obtusa), and preferentially the leaves and / or the buds,

- Pyrole (Chimaphila umbellata).

According to an alternative preferred embodiment, the active substance promoting the deglycation of AGEs, or promoting the reversion of the Maillard reaction with respect to AGEs, is a characterized molecule chosen from the group consisting of:

3,5-Dimethoxy-4-hydroxycinnamic acid (sinapic acid)

Trans-3,3 ', 4', 5,7-Pentahydroxyflavane (catechin)

- oxindole

- 3,4-dihydroxyphenylacetic acid (DOPAC) - 1,3,5-trihydroxybenzene (phloroglucinol) and mixtures thereof, and plant extracts containing them.

Advantageously, the composition is a cosmetic, dermatological, dermopharmaceutical or pharmaceutical composition of topically applicable preference, or dietary supplement (nutraceutical).

The present invention relates to the use of an active substance for the preparation of a composition for the fight against glycation glycated proteins, especially at the cutaneous level, related to the rise in blood sugar during diabetes mellitus.

The present invention relates to the use of an active substance for the preparation of a composition for controlling AGEs formed in glomeruli, and in particular to reduce the excretion of albumin in diabetic subjects.

The active substance can be concentrated by lyophilization, atomization, etc.

Said active substance is usually used at a concentration between 0.001 and 10%, preferably between 0.01 and 5%, more particularly 1% for plant extracts, and between 1.10 ^"7 and 1%, and preferably ^{1.10" 7} and 1.10 ^"1%, more preferably ^{IOL" 5} and 1.10 ^"lo / o for the characterized molecules, by weight of the total composition, without this being limiting concentration to use. Among all of these active substances, Those which promote the deglycation of AGEs are at least 50% preferred, with reference to the action produced by aminoguanidine at 15mM.

The present invention also relates to a cosmetic composition, applicable topically or as a dietary supplement, or a pharmaceutical composition in particular for preventing and / or combating the reduction of flexibility, and / or plasticity, and / or the elasticity, and / or the functionality of the skin, and / or to prevent and / or fight against skin aging, by promoting the reversal of the Maillard reaction with respect to AGEs at the cutaneous level, said composition comprising as active ingredient at least one substance promoting the degeneration of AGEs at the cutaneous level, preferably selected from the group consisting of: 3,5-Dimethoxy-4-hydroxycinnamic acid (sinapic acid), Trans-3,3 ', 4 ', 5,7-Pentahydroxy-flavane (catechin), oxindole, 3,4-dihydroxyphenylacetic acid (DOPAC), 1,3,5-trihydroxybenzene (phloroglucinol) 4-aminophenol, 2-hydroxybenzoic acid (salicylic acid), 6-acid 2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), nordihydroguareaic acid, 6-methyl-5,7a, 13,13b-tetraazapentaphene-8,14-dione, 6-hydroxyindole, salsolinol hydrobromide, 7-hydroxy-4,6-dimethyl phthalide, Physostigmine, and any of their mixtures, or at least one extract of a plant selected from the group consisting of: Aye Wiwii, Kantiankama, Jamaica vervain, Cercopia, Pyrole, Cherry, Cassia, and Toloman; optionally in admixture with a glycation inhibiting compound, in particular by mineralization, such as EDTA derivatives, phytic acid, or azelaic acid, or promoting the protection of skin proteins, such as aminoguanidine, guanidine, or enzyme inhibitors such as pentosidine, or substances decreasing the level of sugar available to participate in the glycation reaction, such as carnosine, ascorbic acid, or alpha-tocopherol.

In a preferred composition according to the present invention, the active substance promoting the deglycation of AGEs, or promoting the reversion of the Maillard reaction with respect to AGEs, is a plant extract chosen from the group consisting of: - Aye Wiwii (Maprounea guyanensis), and preferably the leaves

- Jamaica vervain (Stachytarpheta jamaicensis),

- Cercopia (Cercopia obtusa), and preferably the leaves and / or buds, - Pyrole (Chimaphila umbellata).

3,5-Dimethoxy-4-hydroxycinnamic acid (sinapic acid)

Trans-3,3 ', 4', 5,7-Pentahydroxyflavane (catechin)

- oxindole

3,4-dihydroxyphenylacetic acid (DOPAC) 1,3,5-trihydroxybenzene (phloroglucinol)

According to the plants, it is advantageous to use the whole vegetable or part of the plant chosen from a root, a rhizome, a stem, a bark, a flower, a fruit, a seed, a seed, and a leaf, preferably at 1-10% (w / w) in a solvent or a mixture of solvents, preferably a protic polar solvent, and advantageously in water, an alcohol, a glycol, a polyol, a water / alcohol mixture, water / glycol, or water / polyol (such as water mixed with ethanol, glycerol, butylene glycol or other glycols, such as xylitol etc.) from 100/0 to 0/100 (v / v). The extracts obtained are then preferably filtered or distilled to recover the soluble fraction which is then filtered. The active substance is advantageously the plant extract in a solvent, such as water, an alcohol, a polyol, a glycol, or a mixture thereof, preferably diluted to a concentration of between 0.01 and 10% (v / v ).

Among the glycation-inhibiting compounds (ie reducing the formation of AGEs), it is also possible to use an extracted compound, preferably by maceration, in a solvent or a mixture of solvents such as water, an alcohol or a glycol. , a polyol, a mixture of these solvents, and preferably water, (preferably the compounds soluble in these solvents, preferably after filtration), a plant selected from: a Guarana extract (Paullinia cupana), preferentially seeds, Epimede (Epimedium brevicornum), preferentially leaves, crimped looper (Rumex crispus), preferentially bark, Sarsaparilla (Smilax Ornata), preferentially the root, Liana of natives (Davilla rugosa), preferentially the leaves, Cachou (preferably wood), Sylmarin (preferably fruit), Pin, preferential pinus species (preferably root), Rhubarb of China (preferably root),, Hawthorn (preferably sheet), leucocyanidins (preferably seeds), Aréquier (preferably seeds), Bilberry (preferably fruit), Elderberry (preferably fruit), Walnut (preferably leaf), Willow (preferably bark), Salad (leaf preference), and Lespedeza (preference sheet); and / or a compound selected from sodium erythrosine, 1,4-anthraquinone, catechol, 4-hydroxychalcone, 4-aminophenol, OPC (procyanidolic oligomers), such as strawberry OPC, prunin and 1-amino-2-hydroxymethylanthraquinone, or a mixture of these substances.

It is particularly advantageous to combine the active substances that make it possible to limit the presence of AGEs, by reversing the Maillard reaction, with at least one of the above active substances that inhibit glycation, preferably chosen from a Guarana extract (Paullinia cupana). , preferentially seeds, of Epimedium (Epimedium brevicornum), preferentially the leaves, of crimped sorrel (Rumex crispus), preferentially the bark, of Sarsaparilla (Smilax Ornata), preferentially the root, of the vine of the natives (Davilla rugosa) preferentially the leaves, 3,5-Dimethoxy-4-hydroxycinnamic acid (sinapic acid), trans-3,3 ', 4', 5,7-pentahydroxy-flavane (catechin), oxindole, 3,4-dihydroxyphenylacetic acid (DOPAC) ), 1,3,5-Trihydroxybenzene (phloroglucinol), taken individually or in combination. Thus, the present invention relates to a method of cosmetic care comprising the topical application, or as a dietary supplement (nutraceutical), a composition comprising as cosmetic active ingredient at least one of the active ingredients mentioned above or cited below.

The present invention further relates to a method of treating the human body comprising administering a pharmaceutical composition mentioned above or cited below, preferably topically, to prevent and / or fight against the glycation of proteins at a level of tissue, especially when the blood sugar level rises and / or is high, as for example during diabetes. The invention particularly relates to a method for reducing albumin excretion in a diabetic subject.

The present invention also relates to a method for screening active principles promoting the deglycation of AGEs, comprising: a) producing AGEs; b) bringing the AGEs into contact with a substance to be screened for its activity with respect to the deglycation of AGEs; c) the selection of at least one active ingredient promoting the deglycation of AGEs.

Advantageously, step a) comprises an incubation of at least one type of protein of the skin or of blood vessel walls in the presence of a sugar (for example: glucose, ribose, fructose, etc.) under conditions allowing the AGEs formation, and preferably at a temperature between 40 and 60 ⁰ C, and more preferably at about 50 ⁰ C, for a period of between 1 and 5 weeks and preferably 3 weeks. Advantageously, step b) comprises incubating the AGEs in the presence of at least one substance to be screened at a temperature of between 40 and 60 ^° C., and preferably at approximately 50 ^° C.

The selection of the active ingredient is carried out by comparing the results obtained in the presence of the tested active with respect to a control or control.

The compounds according to the present invention are prepared in the form of topical compositions, in particular of cosmetic, dermopharmaceutical or pharmaceutical compositions. As a result, for these compositions, the excipient contains, for example, at least one compound chosen from the group consisting of preservatives, emollients, emulsifiers, surfactants, moisturizers, thickeners, conditioners, mattifying agents, stabilizers, antioxidants, texture agents, gloss agents, film formers, solubilizers, pigments, dyes, fragrances and sunscreens.

These excipients are preferably chosen from the group consisting of amino acids and their derivatives, polyglycerols, esters, polymers and cellulose derivatives, lanolin derivatives, phospholipids, lactoferrins, lactoperoxidases, stabilizers based on sucrose, vitamins E and its derivatives, natural and synthetic waxes, vegetable oils, triglycerides, unsaponifiables, phytosterols, vegetable esters, silicones and its derivatives, protein hydrolysates, Jojoba oil and its derivatives, lipo / water-soluble esters, betaines, aminoxides, plant extracts, sucrose esters, titanium dioxides, glycines, and parabens, and more preferably from the group consisting of butylene glycol, steareth -2, steareth-21, glycol-15 stearyl ether, cetearyl alcohol, phenoxyethanol, methylparaben, ethylparaben, propylparaben, buty lparaben, butylene glycol, natural tocopherols, glycerin, dihydroxycetyl sodium phosphate, isopropyl hydroxyketyl ether, glycol stearate, triisononanoin, octyl cocoate, polyacrylamide, isoparaffin, laureth-7, carbomer, propylene glycol, glycerol, bisabolol, dimethicone, sodium hydroxide, PEG-30-dipolyhydroxystate, capric / caprylic triglycerides, cetearyl octanoate, dibutyl adipate, grape seed oil, jojoba oil, magnesium sulfate, EDTA, cyclomethicone, xanthan gum, citric acid, sodium lauryl sulfate, waxes and mineral oils, isostearyl isostearate, propylene glycol dipelargonate, propylene glycol isostearate, PEG 8 Beewax, glycerides of hydrogenated palm heart oil, glycerides of hydrogenated palm oil, lanolin oil, sesame oil, cetyl lactate, lanolin alcohol, castor oil, titanium dioxide, lactose, sucrose, low polyethylene ensité, a salty isotonic solution. It is particularly advantageous to combine the active substances according to the present invention with other active agents with complementary properties in order to further improve the efficacy against cutaneous aging, against the reduction in flexibility, and / or plasticity, and / or elasticity, and / or the functionality of the skin. Advantageously, these other assets are chosen from:

the active substances stimulating cell proliferation and / or differentiation, having an anti-aging effect, in particular the following molecules: NGF, alpha-MSH, beta-endorphin or their derivatives, in particular those described in the patent application FR2857874, the active substances protecting fibroblast growth factor (FGF), in particular FGF2, in particular those described in the patent application on behalf of the Applicant published under No. GB244036, in particular an extract of Hibiscus Abelmoscus, the active substances stimulating the activity and / or the proliferation of fibroblasts, in particular a fermented soybean peptide, in particular that marketed by the Applicant under the name Phytokine ™, advantageously in combination with a Hibiscus Abelmoscus extract. the active substances stimulating Hyaluronase synthase, in particular

HAS2, in particular those described in patent FR2893252,

the active substances stimulating the activity and / or the synthesis of Lysyl Oxidase, in particular LOX, in particular those described in the patent application FR2855968, and preferentially the dill extract, the active substances having anti-inflammatory properties , such as the one inhibiting PLA2, in particular an extract of roots of pueraria lobata as described in patent FR2847267 (Inhipase®);

Advantageously, the abovementioned compositions are formulated in a form chosen from the group consisting of an aqueous or oily solution, an aqueous cream or gel or an oily gel, in particular in a pot or in a tube, in particular a shower gel, a shampoo; a milk ; an emulsion, a microemulsion or a nanoemulsion, especially oil-in-water or water-in-oil or multiple or silicone; a lotion, in particular in a glass or plastic bottle or in a measuring or aerosol flask; a lightbulb ; a liquid soap; a dermatological bread; an ointment ; a mousse; an anhydrous product, preferably liquid, pasty or solid, for example in the form of a stick, especially in the form of lipstick.

The term "topical application" as used herein means applying or vaporizing the composition according to the present invention on the surface of the skin.

The terms "dermatologically acceptable", used herein, mean that the composition or components thereof are adapted to use in contact with human skin without toxicity, incompatibility, instability, allergic response, or their equivalents, undue.

The terms "favoring the degassing of AG Es" or "promoting the reversal of the Maillard reaction with respect to AGEs" mean that the substance makes it possible to obtain, from an advanced glycation product (AGE), a protein not glycated in an amount greater than a negative control (absence of active principle), for example as estimated by a difference in fluorescence according to Example 1 between a control sample (absence of active ingredient) and a sample comprising the presence of the substance promoting the deglycation of AGEs. Preferably, the fluorescence obtained with the sample comprising the presence of the substance promoting the deglycation of the AGEs is compared with the fluorescence obtained obtained in the presence of aminoguanidine. The terms "substance promoting the deglycation of AGEs" relate in particular to substances whose fluorescence obtained in the presence of the substance is at least equal to 70% of the fluorescence obtained in the presence of aminoguanidine at 15 mM and in the absence of active principle . The term "deglycation of AGEs" means the reversal of the Maillard reaction.

Many cosmetically active ingredients are known to man to improve the health and / or physical appearance of the skin. The person skilled in the art is formulated the cosmetic or dermatological compositions to obtain the best effects. On the other hand, the compounds described in the present invention can have a synergistic effect when combined with each other. These combinations are also covered by the present invention. The CTFA Cosmetic Ingredient Handbook, Second Edition (1992) describes various cosmetic and pharmaceutical ingredients commonly used in the cosmetic and pharmaceutical industry, which are particularly suitable for topical use. Examples of these classes of ingredients include, but are not limited to, the following: abrasive, absorbent, aesthetic compound such as perfumes, pigments, dyes, essential oils, astringents, etc. (eg clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel distillate), anti-acne agents, anti-flocculants, antifoam agents, antimicrobial agents (eg examples: iodopropyl butylcarbamate), antioxidants, binders, biological additives, buffering agents, blowing agents, chelating agents, additives, biocides, denaturants, external analgesics, film-forming materials, polymers , opacifying agents, pH adjusters, reducing agents, depigmenting or brightening agents (eg hydroquinone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl glucosamine), conditioning agents (eg humectants) skin-soothing agents and / or healing agents (eg panthenol and its derivatives (eg ethyl panthenol), aloe vera, pantothenic acid and its derivatives ivés, allantoin, bisabolol, and dipotassium glycyrrhizinate), thickeners, and vitamins, and derivatives or equivalents thereof.

Other objects, features and advantages of the invention will become apparent to those skilled in the art following the reading of the explanatory description which refers to examples which are given by way of illustration only and which can not in in no way limit the scope of the invention.

The examples are an integral part of the present invention and any feature appearing novel with respect to any state of the art from the description taken in its entirety. together, including the examples, forms an integral part of the invention in its function and in its generality.

Thus, each example has a general scope.

On the other hand, in the examples, all percentages are by weight unless otherwise indicated, and the temperature is in degrees Celsius unless otherwise indicated, and the pressure is atmospheric pressure unless otherwise indicated.

EXAMPLES

Example 1: Reversal of the Maillard reaction

1- Preparation of AGEs:

The preparation of a solution containing a protein and a reducing sugar is carried out in an extemporaneous manner as follows: a solution of bovine serum albumin (BSA) at a concentration of between 1.5 .mu.M and 1.5M, preferably between 15 .mu.M and 500 .mu.m, is incubated with a reducing sugar solution such as glucose, fructose, etc., preferably with glucose at a concentration between 0.1M and 10M and preferably between 0.5M and 5M.

The bovine serum albumin solution may be substituted with human collagen.

The incubation is maintained between 1 and 5 weeks and preferably 3 weeks. The temperature of the incubation is maintained between 20 and 70 ^° C., preferably at 50 ^° C.

2- Incubation of the AGEs with the potentially active compound and highlighting the phenomenon of reversal of the Maillard reaction: The solution containing the AGEs prepared in 1 is incubated in the presence or absence (negative control) of a test compound for its AGES deglycation activity, at a temperature of between 40 and 60 ^° C., preferably at approximately 50 ^° C. for 1 to 5 weeks, preferably for 3 weeks. The compounds are tested at a concentration of between 0.001 and 10%, preferably between 0.01 and 5%, and more particularly at 1% by weight of the total composition. The positive control used is aminoguanidine at a concentration of between 15 μM and 15 μm, preferably at a concentration of between 1.5 and 15 μm. The measurement of the AGEs inhibition is performed by measuring the fluorescence (excitation wavelength between 350 and 375 nm preferably at 355 nm, emission wavelength between 420 and 450 nm, preferably at 430nm). The reversal of the Maillard reaction is calculated by comparing the fluorescence of AGEs named 100% (maximum fluorescence) with the fluorescence of AGES + active tested.

Example 2: Deαlvcation of AGES by Characterized Molecules

The preparation of a protein / sugar reducing solution is carried out according to the method described in Example 1 (paragraph 1). The molecules are tested at a concentration of between IOL ^"7 and ^{1.10" lo} / o, and preferably between 1.10 ^{"and 5} ^{IOL" 1%,} and especially 1.10 ^"lo / o, for example in water or DMSO as described in Example 1 (paragraph 2).

The molecules that promote the deglycation of AGEs under the described conditions, in a manner at least equivalent to that of the aminoguanidine used at 15 mM are: Table 1

% Deglycation: Fluorescence obtained with the active principle versus the fluorescence obtained with the positive control (aminoguanidine 15mM), in

5%.

Example 3: Deqlvcation of AGES by plant extracts

The preparation of a protein / sugar reducing solution is carried out according to the method described in Example 1 (paragraph 1). The compounds of Table 2 are extracts obtained by maceration in water. The compounds are tested at a concentration of between 0.01 and 5%, and more particularly at 1% by weight of the total composition.

Table 2

% Degeneration: Fluorescence obtained with the active principle versus the fluorescence obtained with the positive control (aminoguanidine 15mM), in%.

Example 4 Activity of the Substances According to the Present Invention on the Degradation of Human Collaαene

The preparation of a protein / sugar reducing solution is carried out according to the method described in Example 1 (paragraph 1), with the use of human collagen instead of BSA. 1- Preparation of human collagen

The extraction of human collagen is performed from a human biopsy after plastic surgery. The collagen obtained in the form of a solution is incubated with a reducing sugar solution such as glucose, fructose, ribose, and preferably with ribose. The incubation concentrations are the same as described in the previous examples.

2- Preparation and Testing of Potentially Active Principles Potentially active principles of the "plant extract" type and of the "characterized molecules" type are used under the same conditions as those cited in Examples 2 and 3.

3- Results The molecules which promote the deglycation of AGEs under the conditions described in a manner at least equivalent to that of the aminoguanidine used 15 mM are the same as those cited in Examples 2 and 3.

Examples 5 to 10: Anti-aging composition applicable topically

In the following examples, "Products of the invention" represents the active substances according to the invention and in particular obtained according to Example 2 or 3.

Example 5 Use of the Products of the Invention in Cosmetic or Pharmaceutical Formulations of Oil-in-Water Emulsion Type Formulation 5a:

A water qs 100

Butylene Glycol 2

Glycerin 3

Sodium Dihydroxycetyl 2

Phosphate,

Isopropyl Hydroxycetyl Ether

B Glycol Stearate SE 14

Triisononaoin 5

Octyl Cocoate 6

C Butylene Glycol, 2

methylparaben,

Ethylparaben, Propylparaben, pH adjusted to 5.5

D Products of the invention 0.001 - 10%

Formulation 5b:

A water qs 100

Butylene Glycol 2

Glycerin 3

Polyacrylamide, Isoparafin, 2.8

Laureth-7 B Butylene Glycol, 2

methylparaben,

Ethylparaben, Propylparaben;

2

phenoxyethanol,

methylparaben,

Propylparaben, Butylparaben,

Ethylparaben 0.5

Butylene Glycol

D Products of the invention 0.001 - 10%

Formulation 5c:

At Carbomer 0.50

Propylene Glycol 3

Glycerol 5

Water qs 100

B Octyl Cocoate 5

Bisabolol 0.30

Dimethicone 0.30

C Sodium Hydroxide 1.60

Phenoxyethanol, 0.50 Methylparaben, Propylparaben, Butylparaben, Ethylparaben Perfume 0.30

Products of the invention 0.001 - 10%

Example 6 Use of the Products of the Invention in a Water-in-Oil Formulation

A PEG 30 3 dipolyhydroxystearate

Capric Triglycerides 3

Cetearyl Octanoate 4

Dibutyl Adipate 3

Grape Seed OiI 1,5

Jojoba OiI 1,5

Phenoxyethanol, 0.5

methylparaben,

Propylparaben, Butylparaben,

Ethylparaben

B Glycerin 3

Butylene Glycol 3

Magnesium Sulphate 0.5

EDTA 0.05

Water qs 100

C Cyclometh icon 1

Dimethicone 1 D Perfume 0.3

Products of the invention 0.001 - 10%

Example 7 Use of the Products of the Invention in an Aqueous Gel Formulation (Contours of the Eye, etc.)

A water qs 100

Carbomer 0.5

Butylene Glycol 15

Phenoxyethanol, Methylparaben, 0.5

Propylparaben, Butylparaben, Ethylparaben

B Products of the invention 0,001 - 10%

EXAMPLE 8 Use of the Products of the Invention in a Shampoo or Shower Gel Formulation

At Xantham Gum 0.8

Water qs 100

B Butylene Glycol, 0.5

methylparaben,

Ethylparaben, Propylparaben

Phenoxyethanol, 0.5

methylparaben,

Propylparaben, Butylparaben,

Ethylparaben Citric acid 0.8

D Sodium Laureth Sulfate 40.0

Product of the invention 0.001 - 10%

EXAMPLE 9 Use of the Products of the Invention in a Formulation of the Rougue Type with Lays and Other Anhydrous Products

Wax Minerals 17.0

Isostearyl Isostearate 31.5

Propylene Glycol Dipelargonate 2,6

Propylene Glycol Isostearate 1,7

PEG 8 Beewax 3.0

Hydrogenated Palm Kernel OiI 3,4

glycerides,

Hydrogenated Palm Glycerides

Lanolin OiI 3,4

Sesame OiI 1,7

Cetyl Lactate 1.7

OiI Ore, Lanolin Alcohol 3.0

B Castor OiI qsp 100 Titanium Dioxide 3.9 CI 15850: 1 0.616 CI 45410: 1 0.256 CI 19140: 1 0.048 CI 77491 2.048

Products of the invention 0.001 - 5%

Example 10 Use of the Products of the Invention in a Tablet, Ointment or Injection Formulation

IQa formulation: tablet preparation

Excipients In grams per tablet

Lactose 0.359

Sucrose 0,240

B Active ingredient * 0.001 -0.1

* The active ingredient is obtained, for example, according to the extraction method described in the examples, followed by a drying step.

IQb formulation: preparation of an ointment

excipients

Low density polyethylene 5.5

Liquid paraffin qs 100

B Active ingredient * 0.001 -0.1

IQc formulation: preparation of an injectable formula

excipient

Salted isotonic solution 5 ml B Active ingredient * 0.001 -0.1 g

Phase A and Phase B are packaged in separate ampoules and mixed before use.

Claims

1. Use as topical active ingredient of at least one substance promoting the reversal of the Maillard reaction with respect to AGEs, for the preparation of a composition for limiting the presence of AGEs in a human skin tissue .

2. Use according to claim 1, characterized in that the active substance is selected from the group consisting of: 3,5-Dimethoxy-4-hydroxycinnamic acid (Sinapic acid), Trans-3,3 ', 4', 5 , 7-

Pentahydroxy-flavane (Catechine), Oxindole, 3,4-Dihydroxyphenylacetic acid (DOPAC), 1,3,5-Trihydroxybenzene

(Phloroglucinol), 4-aminophenol, 2-hydroxybenzoic acid (salicylic acid), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), nordihydroguareaic acid, 6-methyl 5,7a,

13, 13b-tetraazapentaphene-8,14-dione, 6-hydroxyindole, Salsolinol hydrobromide, 7-hydroxy-4,6-dimethyl phthalide, 3,4-Dihydroxycinnamic acid (caffeic acid), Physostigmine, 2-Hydroxymethyl- 5-hydroxy-γ-pyrone (Kojic acid), at least one extract of a plant selected from the group consisting of: Aye Wiwii,

Jamaica vervain, Cercopia, Pyrole, Kantiankama,, Cherry tree, Cassia, and Toloman; and any of their mixtures for the preparation of a composition for promoting the deglycation of AGEs.

3. Use according to claim 1 or 2, characterized in that the composition is a cosmetic composition applicable topically.

4. Use according to any one of the preceding claims, characterized in that the composition is intended to prevent and / or fight against the decrease in flexibility and / or plasticity and / or elasticity, and / or the functionality of a tissue, and / or to prevent and / or fight against the aging of a tissue, by promoting the deglycation of AGEs in the skin tissue.

5. Use according to any one of the preceding claims, characterized in that said substance is used at a concentration preferably between 0.001 and 10% for plant extracts, and between 10 ^"7 and 1% for the characterized molecules, by weight of the total composition.

6. A method for screening active principles promoting degeneration of AGEs, comprising: a) producing AGEs; b) bringing the AGEs into contact with a substance to be screened for its activity with respect to the deglycation of AGEs; c) the selection of at least one active ingredient promoting the deglycation of AGEs.

7. Screening method, according to claim 6, characterized in that step a) comprises an incubation of at least one type of protein of the skin or of walls of blood vessels, for example a human collagen, in the presence of a sugar under conditions allowing the formation of AGEs.

8. Screening method according to claim 6, characterized in that step b) comprises the incubation of the AGEs in the presence of at least a substance to be screened at a temperature between 40 and 60 ⁰ C, preferably at about 50 ⁰ C.

9. Cosmetic composition, applicable topically or as a dietary supplement (nutraceutical), characterized in that it is intended to prevent and / or fight against the decrease in flexibility, and / or plasticity, and / or elasticity, and / or the functionality of the skin, and / or to prevent and / or fight against skin aging, by promoting the deglycation of AGEs at the cutaneous level, said composition comprising as active ingredient a substance promoting the reversion of the skin. Maillard reaction with cutaneous AGEs, preferably selected from the group consisting of: Oxindole, 3,4-dihydroxyphenylacetic acid (DOPAC), 1,3,5-Trihydroxybenzene (Phloroglucinol), 4-aminophenol, 2-hydroxybenzoic acid (Salicylic acid), 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), Nordihydroguareaic acid, 6-methyl-5,7a, 13,13b-tetraazapentaphene-8,14-dione, 6 -hydroxyindole, Salsol hydrobromide inol, 7-hydroxy-4,6-dimethylphthalide, Physostigmine, at least one extract of a plant selected from the group consisting of: Aye Wiwii, Jamaica vervain,

Cercopia, Pyrole, Kantiankama, Cherry, Cassia, and Toloman and any of their mixtures, optionally in admixture with a compound inhibiting glycation, or promoting the protection of skin proteins, or enzyme inhibitors, or substances decreasing the available sugar level to participate in the glycation reaction.

10. Pharmaceutical composition, in particular for preventing and / or combating the reduction of flexibility, and / or plasticity, and / or elasticity, and / or functionality of the skin, characterized in that it comprises as active ingredient a substance promoting the reversal of the Maillard reaction with respect to AGEs at the cutaneous level, preferably chosen from the group consisting of: Oxindole, 3,4-dihydroxyphenylacetic acid (DOPAC), 1,3,5-trihydroxybenzene

(Phloroglucinol), 4-aminophenol, 2-hydroxybenzoic acid (salicylic acid), 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), Nordihydroguareaic acid, 6-methyl 5,7a, 13 , 13b-tetraazapentaphene-8,14-dione, 6-hydroxyindole, Salsolinol hydrobromide, 7-hydroxy-4,6-dimethylphthalide, Physostigmine, at least one extract of a plant selected from the group consisting of: Aye Wiwii, Jamaica vervain, Cercopia, Pyrole, Kantiankama, Cherry tree, Cassia, and Toloman; and any of their mixtures, optionally in admixture with a glycation inhibiting compound, or promoting the protection of skin proteins, or enzyme inhibitors, or substances decreasing the available sugar level to participate in the glycation reaction .