FR3087657A1 - COSMETIC OR NUTRACEUTICAL COMPOSITIONS CONTAINING PRIMEVERE EXTRACT - Google Patents

Abstract

The invention relates to the production and cosmetic and nutraceutical applications of a primrose extract as an agent for reducing the level of cortisol in order to improve the suppleness of the skin and fight against aging.

Description

The present invention relates to the use of extracts from a very widespread plant, in particular in Europe, in cosmetic or nutraceutical compositions.

More specifically, it relates to new extracts and new Mons apps from primroses to decrease cortisol levels and thus reduce stress; component harmful to organs such as skin, hair.

Primrose is understood to mean all species of the genus Primula, such as, for example, Prirnula yetis, Prirreula vulgaris, Prie-nul ° sikkineensis ...

In Frante, the most frequent species of Primuia is the primrose known as * .g coucoo ”. primrose is known for its softening and calming properties of flowers.

The leaves are anti-ecchymotlques.

The whole plant and particularly the root have analgesic, anti-spasmodic, diuretic, pectoral and expectorant properties.

The flowers and leaves are corrstible.

The scientific literature mentions the presence of various phytochemical families, in particular glycosylated flavonoids (Planta Med. 1981 an; 41 (1): 96-9).

Saponosides have also been described there.

Cortisol has been shown to be the chronic stress hormone and its levels increase with stress levels.

In addition, the level of cortisol, .7u; increases with age and in women during menopause (Menopause.

2009 Jul-Aug., 16 (4): 701-18).

It also has an impact on hair loss.

Cortisol is harmful to muscle mass in humans.

Cortisol can impact testosterone levels (Int J Sports Med.

1996 Aug: 17 (6): 423-8).

A high level of cortisol would be related to a decrease in the level of testosterone.

In men aged 60 and over, chronic treatment with glucocorticoids has been shown to decrease testosterone levels.

The level of cortisol reduces the thickness of the skin, decreases the synthesis of collagen and the extracellular matrix in general.

It thus causes a delay in healing.

In addition to these elements, an enzyme has been identified, 11-Beta-HydroxySteroidDeshydrogenase type 1 (11BFISD1) which catalyzes the biosynthesis of cortisol.

This protein is present in the skin at the level of keratinocytes and fibroblasts (i Invest Dermatol.

2011 Jan; 131 (1): 30-6.

Epub 2010 Aug 26), Enzyme increases with age and with photoexposure a: thus increases the level of cor tisol.

Cortisol causes delayed wound healing.

By simulating the synthesis of enzymes for degradation of the extracellular matrix such as metalloproteinases and the inhibition of genes encoding collagens, chronic hypercortisolism also has a dermal degradation effect, characterized by a decrease in the mechanical properties of the skin. skin (decrease in underlying connective tissue thickness) (PLoS One, 2011; 6 (9): e25039, Epub 2011 Sep 20).

The present invention describes new extracts of primrose as well as their applications for reducing the level of cortisol and exerting an antistre_ss role on the organs of the treated animal, in particular the skin and hair in humans. therefore play a favorable role in anti-aging cosmetic or nutraceutical compositions.

According to the invention, it has been discovered that the primrose extracts are capable of inhibiting the enzymes involved in the synthesis of cortisol, such as the HSD1 mentioned above.

Blocking the biosynthesis of cortisol amounts to reducing its content in cells and limiting its deleterious action on tissues.

This action is manifested on the skin by the increase of key blomargueurs, such as collagen, hyaluronic acid or elastin.

The present invention is specifically aimed at providing novel cosmetic compositions which are nutraceuticals capable of limiting the production of cortisol.

The invention therefore relates to a nutraceutical cc smetic composition of 31: inée to reduce the level of cortisol in a living animal, characterized in that it contains at least one active agent containing at least one plant extract of the genus itimulo.

In one embodiment, the plant extract is selected from the group formed by the exols Prirnula yetis, Primula Prienula sikkirreensis and mixtures thereof.

The composition according to the invention may comprise 0.01 Vèrsion. .1) -23/10/18 2 2.5% by dry weight of at least one plant extract of the genus Prirnula in powder form or 0.01 25% by weight of a plant extract . of the genus Primula if this extract is in encapsulated form. composition according to the invention can, when it is intended for topical application, constitute a cream, an oil or a solution, the plant extract of the genus Priroula being mixed with 5 ingredients known in cosmetics to obtain the desired presentation for the 'intended use.

The term “primrose extract” is understood to mean an extract or a mixture of plant extracts of the genus Primula sp of the family Primulaceae. It is more especially an extract or a mixture of extracts of cells of Prirmeia sp.

This cellular material can be obtained by in vitro or in vivo culture.

By in vitro culture is meant all of the techniques known to those skilled in the art, which make it possible to artificially obtain a plant or a part of a plant.

Thus, the extract can be an extract or a mixture of organ extracts (root, stem, leaf), or even organ cells, at least one plant of the genus Primuia sp of the Primulaceae family. , or else an extract of undifferentiated cells of at least one such plant.

The applications according to reference extend to the treatment of human skin.

The subject of the present invention is therefore a cosmetic use of a primrose extract for improving the condition of the skin or the hair by topical or oral administration, for reducing the cortisol content.

It also relates to a cosmetic treatment for combating aging of a skin or for cosmetic treatment of young or aged skin, this treatment comprising auoins.une step according to which a primrose extract is applied to the skin. , to restore its flexibility and / or elasticity, [the invention therefore relates to a cosmetic use, characterized in that (condition of the skin or hair by topical or oral administration of a composition according to invention as previously defined.

In this use, the barrier function of the skin is protected or enhanced against an external physical, chemical or biological agent by topical or oral administration.

The invention also relates to an anti-aging cosmetic treatment for the skin or a cosmetic treatment for aged skin, comprising a step according to which at least one primrose extract is applied to the skin.

This treatment makes it possible to delay the phenomena of aging of the skin, but also to repair aged skin by restoring its suppleness and elasticity.

In any cosmetic application of the invention, a primrose extract can be combined. at least one other prcdifferentiante agent of the skin, such as calcium, vitamin D and their derivatives or at least one other complementary anti-aging or depigmenting agent known to those skilled in the art.

According to another aspect, the invention also relates to the nutraceutical applications of a primrose extract, as defined above.

An object according to the invention is therefore a nutraceutical composition comprising an extract of primrose, for reducing the cortisol content in order to combat stress.

In the nutraceutical aim of the invention, the extract of primrose can be administered orally.

In a composition of the invention, the extract of primrose can also be combined with at least one anti-inflammatory, anti-aging agent used in the treatment of skin inflammation.

A primrose extract according to the invention can be obtained by any method of extraction or purification known to those skilled in the art.

Mention may in particular be made of solid-liquid extraction processes in alcoholic (in particular ethanolic) and aqueous media, as well as in media using solvents such as ketones, esters, ethers, polyols, chlorinated solvents: and mixtures of at least two of the abovementioned solvents, such as hydroalcoholic media.

A subject of the invention is therefore also a process for obtaining plant extract (s) of the composition according to the invention, characterized in that a solid / liquid extraction of the plant is carried out, possibly ground, in a solvent medium comprising at least one solvent taken from the group formed by water, alcohols, ketones, ethers, polyols, chlorinated solvents versibn ree-23.10 / 18 3 and CO, supercritical .

In such a process, the extract can be produced in a water / glycerin mixture in a proportion ranging from 10% to 90% water by volume, for a time of between 1 and 4 hours with gentle stirring, at room temperature. .

Advantageously, the solid / liquid extraction is carried out on the aerial parts of the plarte of the genus Primai °.

5 Alternative methods to solvents can also be considered such as CO., Supercritical or microwaves.

Plant extracts of the genus Primula can be used as such, in liquid or powder form, unpurified or purified.

If the extract is in powder form, its drying can be carried out by any technique well known to those skilled in the art.

The extract can be dried by atomization, evaporation or lyophilization.

The powder thus obtained can be encapsulated in liposomes or other vectors and supports for better homogeneity of the composition and better diffusion of the active principle, in particular on the skin.

The primrose extracts can be combined in the compositions according to the invention with substances which increase skin protection.

By way of example, but in a nonlimiting manner, mention may be made of associations with mucopolysaccharides, vitamins, ceramides, anti-radical substances or UV filters.

Likewise, the anti-aging activity of the extracts according to the invention is particularly advantageous when they are associated with substances: having a healing effect such as proteins, hyaluronic acid, amino acids, and / or with anti-aging substances. -inflammatory, anti-aging, after-sun or with active anti-acne and anti-den latoses.

The protective activity of the extracts of the invention against free radicals and UV rays. is also very interesting in the hair field, no laminate in the case of associaton with substances facilitating the good condition of the scalp and that of the hair, such as minerals, vitamins, ceramides, protein extracts, mucm : olysaccharides, flower or fruit acids.

The compositions of the invention are very particularly suitable for topical application for preventing and / or treating numerous skin alterations.

For cosmetic use, the compositions of the invention may be in the form of creams, gels, lotions, milks, HIE and E / I-1 emulsions, solutions, ointments, sprays, body oils, hair lotions, shampoos, etc. aftershave lotions, soaps, lip protection sticks, makeup sticks and pencils.

The compositions can comprise any excipients necessary for their formulation. Thus, when in gel form, they include suitable excipients such as cellulose esters or other gelling agents, such as Carbopol ', guar gum, or the like.

These cosmetic compositions can also take the form of a lotion or: solution in which the extracts and / or molecules are in encapsulated form, for example in microspheres.

These microspheres can for example consist of fatty substances, agar-agar and water.

The active agents can also be incorporated in vectors of the liposome type, 40 glycospheres, in chylomicrons, macro-, micro-, name-particles as well as macro-, micro- and nanocapsules and can also be adsorbed on paffins: powdery organic eras, more talcs, bentonites and other mineral supports.

These emulsions have good stability and can be stored for the time necessary for unification at temperatures between 0 and 50 without sedimentation of the constituents or separation of the phases.

The cosmetic compositions of the invention contain of the order of 0.01 to 5% by weight, preferably between 0.1 and 2.5%, of prienevère extract when they are in the form of powder and of powder. 'of the order of 0.01 to 25% by weight, preferably between 0.5 and 10%, when they are in encapsulated form.

The percentages given above are expressed by weight of dry extract of primrose relative to the weight of the final composition.

Vèrs ion 23/10118 4 For the preparation of these compositions, the primrose extracts are mixed with the excipient generally used in cosmetics.

The cosmetic compositions of the invention can also contain additives or adjuvants customary in cosmetology, such as, for example, antibacterial agents or perfumes, but also extraction and / or synthetic lipids, gelling and viscosifying polymers, surfactants. - active ingredients and emulsifiers, water-soluble or liposoluble active ingredients, plant extracts, tissue extracts, marine extracts and synthetic active ingredients.

The cosmetic or derrnocosmetic use of extracts includes all the care of the body and the skin including sun products, protectors and bronzers, anti-aging products, anti-seborrheics, tonics, products ensuring the improvement of the skin. appearance of the skin including acne treatment, skin redness, scalp treatment and hair loss treatment.

The cosmetic compositions of the present invention can also comprise other complementary active principles chosen for their action, for example for sun protection, anti-wrinkle effect, anti-free radical and antioxidant activity, anti-irritant activity, cellular nutrition, cellular respiration, hydration and cellular regeneration, anti-seborrheic treatments, as well as other active principles having an action on skin tone, hair protection.

The cosmetic compositions of the present invention are preferably for daily use by applying them one or more times per day.

The cosmetic compositions of the present invention are very well tolerated, they exhibit no phototoxicity and their application to the skin, for prolonged periods of time, does not involve any systemic effect.

Consequently, in general, the invention relates in particular to the use of a primrose extract, for the preparation of a cosmetic or nutraceutical composition intended to reduce the level of cortisol and consequently to limit the effect of stress. chronic on the natural or induced aging of the organism.

The present invention is now illustrated, without limitation, by the following Examples 1 to 4.

Example 1 illustrates a process for preparing a cuckoo extract according to the invention.

Examples 2 to 4 illustrate the biological properties claimed according to the invention.

Example 5 illustrates an example of formulation from a cuckoo extract according to Example 1: Obtaining An extract of cuckoo PrImula 'such 330 g of dry and crushed green Primula flowers are macerated in 6 kg of water and 4kg of glycerin, for a period of 2 hours.

The extract is filtered until a clear solution is obtained.

We get a basic extract named EX2Gi4145.

This extract is then adjusted in glycerin to respect a compound title and microbiological stability.

This procedure made it possible to obtain 9 kg of extract.

This method makes it possible to produce the S3GJ4186 extract tested below.

An alternative process is as follows: 900 g of dry and crushed Prirnula yetis flowers are macerated in 10.8L of ethanol and 7.2L of water, for a period of 24 hours.

The extract is then filtered until a clear solution is obtained.

The extract is then decolorized using 45g of activated charcoal; then the extract is filtered again.

The ethanol is then evaporated off at reduced pressure, then the extract is spray dried.

This procedure made it possible to obtain 120 g of dry extract.

45 These two extracts are titrated as glycosylated fiavonoids. invention.

Version e-23110118 a Example 2: Evaluation of the cvtotoxicity of the ex ualt carried out according to Example 1 Principle: The study of the cell viability in the presence of the active ingredients to be tested is carried out using a test with 5 MTT1 The NITT is a tetrazolium salt whose ring is transformed by mitachondrial dehydrogenases.

The yellow substrate is transformed into a dark blue product by living cells, but not by dead cells or the culture medium.

This calorimetric test makes it possible to link the intensity of the staining to the number of living cells.

I. Absorbance at 550 nm is directly proportional to the number of living fibroblasts.

Preparation of the stock solutions of the extracts: The extract (53614186) is diluted directly in the cuture medium in order to obtain a 1% solution, Procedure: 96-well plates are inoculated at a rate of 5000 fibroblasts per well, After 24 hours of culture, the active ingredients to be tested are added.

Twelve concentrations of each active principle are tested.

The active ingredients are dissolved directly = Jans of the culture medium from the snlutionsnoè / es.

Results A significant increase in cell viability is observed in the presence of 0.0075% of Active 1 (53614186) compared to the Control group, A significant decrease in cell viability is observed with 0.01%, 0.025% and 0 .05% active compared to the Control group.

However, the viability remains above 80% (Figure 1).

The concentrations of Actq observed for the rest of the study are: 0.05%; 0.25% and 1%.

Example 3: Evaluation of the anti-aging activities in cultures of normal human epidermal fibroblasts The extract according to example 1 is now tested on its capacity to modulate certain biomarkers of the extracellular matrix, Culture and treatment of monolayers A confluence, the fibroblasts are trypsinized and seeded in 6-well plates at a rate of 0.08.10c cells per well.

After 24 hours of cultures, 2 ml of medium with or without active agent are added.

The Active is diluted to the concentrations chosen in DMEMIc culture medium.

After 48 hours of culture in the presence of the active agent, the supernatant is taken on an antiprotease (10%).

Aliquots are stored at -80 ° C until assays.

The cell monolayers are washed with PBS and 400 µl of 0.1N NaOH is added.

The cell lysate is stored at -20 ° C. until the proteins are assayed.

Assays: Assay of collagen 1, fs.

Principle 40 The quantity of collagen produced by the cells is determined by ELISA assay (Enzyme-Linked immunosorbent Assay, Liscri Life Science kit).

The samples are placed in a 96-well plate pre-coated with an antibody specific for collagen III. The standards and the samples are deposited in the plate with a solution of anti-collagen III antibodies coupled to biotin.

The revelation is carried out by adding a solution of avidin coupled to etHorseradish Peroxidase ”(HRP) then 45 of TMB substrate. Finally, the enzymatic reaction is stopped by adding a solution of Version n'-23 acid. / 20/18 6 sulfuric.

The coloration obtained is proportional to the amount of collagen Ilf and the optical densities are carried out immediately <reading of 'te.

Procedure 5,100 µl of sample or standard is placed in each well.

After 2 hours of incubation at 37 ° C, the wells are emptied and 100 µl of detection reagent A is added.

After an incubation of one hour at 37 ° C., the wells are washed 3 times with the washing solution. 100 μl of detection reagent 3 are then deposited and the plate is incubated for 30 minutes at 37 ° C. 5 washes are carried out then 90 μl of the substrate solution are added to the wells.

After 20 minutes at 37 ° C and protected from light, a blue coloration proportional to the amount of collagen i appears. 50 μl of the stop solution are added and the optical densities are read immediately at 450 nm (Muitiscan Ex spectrophotometer, Thermo). All Calculations The standard curve is plotted by plotting the optical densities as a function of the amount of collagen in the standard.

The amount of collagen in each sample is determined using this standard curve.

The collagen III concentrations are expressed in ng / mg of protein.

Elastin Assay 20 tçff Principle The amount of elastin produced by the cells is determined by ELISA assay (Enzyme-Linked Immunosorbent Assay, Usai Life Science kit).

The samples are placed in a 96-well plate pre-coated with an antibody specific for elastin.

The standards and the samples are deposited in the plate with a solution of anti-elastin antibody coupled to biotin. The visualization is carried out by adding a solution of avidin coupled to 4iorseradish Peroxidase ”(HRP) then of substrate. TMB.

Finally, the enzymatic reaction is stopped by adding a solution of sulfuric acid.

The coloration obtained is proportional to the amount of elastin and the optical densities are read immediately. 30% of the sample procedure diluted to 1 / 10'1 '' o 1001.11 -de standard are placed in each well.

After 1 hour of incubation at 37 ° C, the wells are emptied and 100 µl of detection reagent A is added.

After an incubation of one hour at 37 ° C., the wells are washed 3 times with the washing solution. 100 µl of detection reagent B are then added and the plate is incubated for 30 minutes at 37 ° C.

Five washes are performed and then 90 µl of the substrate solution is added to the wells.

After 20 minutes at 37`C and protected from: a light, a blue color proportional to the amount of elastin appears. pl of the stop solution are added and the optical densities are read immediately at 450 nm (Multiscan Ex, Thermo spectrophotometer). 40 'Calculations The standard curve is plotted by representing the optical densities as a function of the amount of elastin in the standard range.

The amount of elastin in each sample is determined using this standard curve. The elastin concentrations are expressed in ng / mg of protein.

45 Determination of hyaluronic acid 9 Principle different samples is determined by ELISA assay using a TECO 'kit.

This kit is a sandwich assay The amount of sensitive hyaluronic acid d (Enzyrne-Linked Immunosorbent Ass ikrsior '-23710/1 7 which uses on the one hand microplates coated with the hyaluronic acid binding protein (HABP) and on the other hand the HABP binding protein conjugated to HRP for detection.

The HRP-conjugated HABP binding protein binds to the hyaluronic acid in the sample and then reacts with the substrate.

The intensity of the color is proportional to the level of HA contained in the samples. Procedure 100 µl of standard or 100 µl of sample diluted to 1/100 '' '' are placed in each well.

The plate is incubated for 2 hours at room temperature, with stirring.

After washing the plate, 100 μl of HRBP-HRP conjugate are deposited in each well; The plate is incubated for 30 minutes at room temperature, with stirring.

After washing the ads, 100 μl of TMB substrate are added.

The plate is incubated for 30 minutes at room temperature, in the dark and with stirring.

The reaction is stopped by adding 100 μl of stop solution per well.

The optical densities are read immediately at 450 nm. 15 Calculations The calibration line is plotted by representing the OD eo as a function of the concentration of hyaluronic acid.

A regression line is then plotted and the amounts of hyaluronic acid contained in the samples are determined by means of the line of this regression line. The concentrations of hyaluronic acid are expressed in pg / mg of proteins.

Protein assay by the Pierce 7irge method.

Principle Bicinchoninic acid (BCA) in the form of sodium salt soluble in aqueous medium reacts in a stable, sensitive and highly specific manner with copper ions.

Proteins react with cupric ions in an alkaline medium to produce cuprous ions. 1: Their BCA molecules react with a cuprous ion to form a violet complex which shows an absorption peak at 562 nm. ¶ Procedure 30 A calibration range (0-2 rngiml) is produced from a solution of bovine serum albumin. 20 µl of each point of the calibration or sample range are placed in wells of a 96-well plate, in duplicate. 200 µl of Pieral's reagent are added and the plate is incubated for 30 minutes at 37 ° C.

The absorbent is read immediately at 550 nm (Multiscan Ex spectrophotometer, Thermo). - '. 4t Calculations The range makes it possible to draw a calibration line from which the protein concentration of the samples is determined.

The results are expressed as mg of protein / ml.

40 Statistical calculations and analyzes: The values are expressed by the mean standard error of the distribution of means (sem).

A one-way analysis of variance is performed, followed if necessary by a Fisher test.

Significance is only retained when p <0.05.

45 Results: Assay of collagen Hl rsi0 8 Collagen synthesis is significantly increased in the presence of vitamin C at 50 phi compared to the control group and in the presence of Active 1 at 0.05% and 0.25%.

A significant increase in the synthesis of collagen III is observed in the presence of 1% of the Active 1p "compared to the control groups, A1-0.05% and A1-0.25% (FIG. 2).

5 Determination of elastin The synthesis of elastin is significant. ent increased in the presence of vitamin C at 100 p_M compared to the control group.

A significant increase in elastin synthesis is observed in the presence of 0.05% of Active 1 compared to the Control and Vit C groups (FIG. 3). Dosage of hyaluronic acid The synthesis of hyaluronic acid is significantly increased in the presence of USE 'at 10 ng / ml compared to the control group.

A significant increase in the synthesis of hyaluronic acid is observed in the presence of 0.05% and of Active 1 compared to the control group.

A significant decrease in the synthesis of hyaluronic acid is observed in the presence of 0.05% and 0.25% of Active 1 relative to the EGF group.

A significant increase in the synthesis of hyaluronic acid is observed in the presence of 1% of Active 1 compared to the other groups (FIG. 4).

Example 4: ff, seon '20 lexem umanesH501andH5D2isoées ple 1 on an inhibition model Protocol The assay uses HRTF (Hor) (Oogenous lime Resolved Fluorescence) fluorescence technology, which is based on the competition between unlabeled cortisol and the cortisol labeled with XL665 allowing binding to a cortisol specific antibody labeled with cryptan.

Since 1-15Di converts cortisone to cortisol and H5D2 converts cortisol to cortisone, the HTRE signal can be used to determine FISD1 and HS02 activity.

The Ff FRP signal is inversely proportional to the measured cortisol concentration.

The human enzyme FiSD1 has been tested in its active state with cortisone and NADPH while HSD2 has been tested with cortisol and NAD.

The compound EX2GJ4145 was tested on HSD1 at concentrations of 1.5, 0.5, 0.17, 0.056 and 0.019 memL and on H5D2 at concentrations of 15, 5, 1.7, 0.56 and 0.19 mg. / mL.

The IC50 was determined if possible.

The reference compound, Glycyrrhetinic Acid was taken as a reference to validate the test._ Results' The results indicate that the IC50 for the extract EX2614145 is 40.7 iternt for liSD1 while there is no effect on the H502 enzyme at the concentrations tested. The inhibition curves making it possible to calculate these IC50s are presented in FIG. 5.

Conclusion The cuckoo extract inhibits the human enzyme 11501, an enzyme responsible for the production of cortisol without affecting HSD2,, 4.5 Example 5 Dermo-cosmetic formulation of a cuckoo extract.

By way of nonlimiting, we present in Table 1 an example of a formula incorporating an extract 50 of primrose.

Skrsion n'-23/10/18 35 40 9 The water-soluble cuckoo extract is incorporated directly into the emulsion during cooling, with stirring, to a temperature below 40 ° C.

5 Table 11 Example of a formula integrating an extract of Primulu according to the invention. ittm ". wumsda / qua hnrnsseur 1% PU RIFIED WATER 77.54 MONTANOV 202 Aruz.hd cuh01 ur, d behenyi aboho! ,, nr. £ .11c.ch44 glu cusicie j 3.00 h MTANG VL Cl 4-? 2 A.,: T-inclis (Eincf) Cl 2-20 All <ACilucodde Sep = 1.50 DUO ZENO KT Propane-id chc4phiee Ste4rebede pubob 8.00 - ELLIANOL G Otlydociewnd BASE 7.00 ARISTOFLEXALIC, h5irrurburr 4cryir.hiderahhiteureei V. copohne, Garent 0.80 ExTRAIT OF COUCOU? .J. rareenphetre Cle.:.:20 r4.2è: E. 1.00 0.70 0.04 PHENO) OETOL iPherlareltec .: ISAMP40 ULTRA PC 1Tromeihrenre AGDE crrRIQUE '014h cul d Ereintb , 9 100.00. - lo ikrsicen e- 23/10/18

Claims (4)

CLAIMS of a living animal, caraXriZed in ^d ® ^{StÎne to decrease} Ιθ cortisol level at least one plant extract of the genus Primula ”™ ™ ^{3CtÎf renfermarit} 2. Composition according to claim i is chosen from the group formed by the extracts of P Γθ θ “ ^{W reXtrait of} sikkimensis ^plant and their mixtures. ^{PrimuÎO νυ} ^ ^α ™ ' ^p ”™ la 3. Composition according to one of claims 1 on. comprises from 0.01 to 2.5% by weight ser ^of, _A> ^{10 2 'caractensee in} that it / powder form or 0 01 to 25% w ^m ° ^{ins an extract of} the genus Primula If this extract are under This enœps ^ JX * * eC ^you CON® ^{_U P} X ^Y etet ° hJCte: ^e rn ^{of rafiOnS 1} * ³ '^{"ra" eris "a"} * * the plant extract dp, Stu ⁵¹ ° ^{the df} "^& æ has a topical application, rsxtiî iCu _a xc * x. ^oen ™ ^s wherein φ / IIE ™ improves réradef ^re '' ^{end 'catlo} s 1 to 4, topical or oral. ' ^{skin of the} administration ^{in œ u, n} ° ^{has d} “* · ⁶ · ^ca “ ⁱⁿ “- ^e '“ * ^ba - “-?: ΞΞΒΞΞΞΧΕΞ” - · - “es reue„ * 2nsÎ'T “* ^{Ptate of} es 1 to 4, characterized in that a solid / liquid extraction of the possibly crushed plant is carried out, in a solvent medium comprising at least one solvent taken from the group formed by water, alcohols, ketones, eXZ ethers, chlorinated solvents and supercritical CO ₂ . ' ^P I realized riX ° ^ ^{d S} r ^{b reVe dicat} ! ^{on 10} 'characterized in that the solid / liquid extract is volumA T ^{angel water} / ^{glycan in a} proportion ranging from 10% to 90% water in ^time “ ^{mpr, s} - ¹ - ⁴ -“' θ ^a * “ we,: ^{Method according to either of} claims 10 or 11, characterized in that XX ^{S0Me / SqUide is carried out on} aerial plants of the genus plant Collagen ill (ng / mg) Cell viability (% / Control) Figure 1: Cell viability (% / Control) in the presence of Active 1 at different concentrations. (Average I Week; * p <0.05 and ** p <0.01 versus Control)

Figure 2: Synthesis of collagen III in the presence or not of Active 1. (Average 1 week; *** p <0.001 versus Control; ^## * p <0.001 versus Vit C; ^a3a p <0.001 versus Al-0.05%; ^bbb p <0.001 versus Al-0.25%).

* ”P <0.001 versus Control ** ρ <0.001 versus Quick *“ p <0.001 versus A1 -0.05% “ρ <0.001 versus A1 -0.25% Active S3GJ4186 Figure 3: Synthesis of elastin in the presence or not of Active 1. (Average f Week; ** p <0.01 and *** p <0.001 versus Control; ^m p <0.001 versus Vit C).

Active S3GJ418B ”p“ 0.01 and 'p-0.001 vasts Control ^s * p <0.001 versus VS C versus A1 -0.05% Hyaluronic acid (pg / mg) Figure 4: Synthesis of hyaluronic acid in the presence or absence of Active 1. (Average t Sem; * p <0.05 and *** p <0.001 versus Control; ^s p <0.05, ** p <0.01 and ^SiMf p <0.001 versus EGF; ^aaa p <0.001 versus Al- 0.05%; ^bbb p <0.001 versus Al-0.25%).

Active S3GJ4186 * p <0.05 and *** p <0.001 versus Control ^# p <0.05, p <0.01 and * p <0.001 versus EGF “ ^a p <Q, 001 versus A1-0.05% “* P <0.001 versus A1 -0.25% Figures: Determination of the IC50s of the extract EX2GJ4145 on HSD1 and HSD2.